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Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m3) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-β1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-β1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-β1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.
This research has important implications for understanding the health risks of inhaled carbon nanotubes. The findings suggest that individuals with allergic asthma are most susceptible to airway remodeling caused by carbon nanotube exposure.
Carbon nanotubes (CNT) possess unique characteristics that make them highly desirable for applications in electronics, structural engineering, and medicine due to impressive electrical conductivity, mechanical strength, and ability to be derivatized for custom applications such as drug delivery (1). Given the enormous industrial demand for carbon nanotubes (the global market is predicted to grow to between $1 billion and $2 billion by 2014), there is growing concern that the development and use of engineered CNT might be accompanied by health risks caused by occupational or environmental exposures (1, 2). Structurally, CNT can be described as graphite sheets rolled into cylinders that are one (“single-walled,” SWCNT) or several (“multiwalled,” MWCNT) layers thick. CNT range from one to several nanometers in width and up to several microns in length. This large length to width (aspect) ratio, a property shared with asbestos fibers, has led to concern that inhaled CNT may cause asbestos-like injuries, such as pulmonary fibrosis and lung cancer (2).
A number of studies over the past 5 years have shown that liquid suspensions of CNT cause pulmonary inflammation and fibrosis when administered to the lung by intratracheal instillation or pharyngeal aspiration. These studies show that CNT, which aggregate into micron-sized bundles in aqueous media, stimulate the formation of inflammatory foci known as granulomas and fibrotic reactions within the lung parenchyma. Pulmonary fibrosis and/or granulomas have been reported in mice or rats within days after intratracheal instillation of SWCNT (3–6) or MWCNT (7). Moreover, SWCNT delivered to the lung by instillation increases production of platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-β1, two growth factors that mediate the pathogenesis of fibrosis (4, 6). Granulomas are associated with large CNT aggregates in the lung that are easily visible by light microscopy, while interstitial pulmonary fibrosis appears to be associated with dispersed CNT that are detected by electron microscopy (4). A recent study showed that SWCNT dispersed with organic solvents to disrupt Van der Waals forces resulted in less deposition in the large airways but more in the interstitium, where the fibrotic response was significantly increased (8). While instillation or aspiration experiments demonstrate that CNT are fibrogenic, these methods do not accurately model deposition patterns of CNT, and much emphasis has been placed on the need for inhalation studies.
There is recent evidence from whole-body inhalation studies in rodents that the method of pulmonary administration of MWCNT affects deposition patterns and pathology. A study that compared instillation with inhalation indicated that MWCNT inhaled by mice showed a more diffuse pattern of deposition with less severe pathologic lesions than those that were observed after intratracheal instillation of a bolus dose (9). Another recent study showed that inhaled MWCNT did not cause lung inflammation or fibrosis in rats, but did cause systemic immunosuppression and spleenic oxidative stress (10). This result greatly differed from earlier work that showed MWCNT administered by intratracheal instillation resulted in pulmonary inflammation and fibrosis (7). Therefore, it appears that MWCNT cause little inflammation or fibrosis when delivered by inhalation, but significant injury, inflammation, and fibrosis when administered by intratracheal or pharyngeal routes in normal lung tissue. Despite the reported lack of lung injury from inhaled MWCNT (10), it is reasonable to postulate that adverse effects of inhaled MWCNT might be manifested under conditions of pre-existing inflammation such as allergic asthma.
Asthma is a chronic inflammatory disease that afflicts millions of individuals in the United States and worldwide. The pathogenesis of asthma involves chronic remodeling of the airways of the lung, including eosinophilic inflammation, mucus hypersecretion from the airway epithelium, airway smooth muscle cell thickening, and airway fibrosis (11). Many of these pathologic features of asthma are mediated by IL-13, a cytokine that is secreted by Th2 lymphocytes in response to allergen challenge (12). In turn, IL-13 activates a variety of other pulmonary cell types to produce cytokines and growth factors that play a diversity of roles in inflammation and fibrosis. For example, we have reported that IL-13 stimulates lung fibroblasts, the primary target cell type in fibrosis, to increase the production of PDGF, a potent fibroblast mitogen (13). IL-13 has also been reported to increase the production and activation of TGF-β1, the primary growth factor that stimulates fibroblasts to produce collagen and promote scar formation (14).
Epidemiologic studies have shown a correlation between the incidence and severity of asthma attacks and levels of airborne particulates (15). Furthermore, it has been suggested that the ultrafine (or nanoscale) fraction of particulate matter is most important to the exacerbation of asthma (16). In the present study, we hypothesized that inhaled MWCNT produce greater injury and fibrosis in mice with pre-existing allergic lung inflammation. To test this hypothesis, we sensitized mice to ovalbumin allergen, a common mouse model of asthma, and then exposed the mice to a brief, high dose of MWCNT by nose-only inhalation. The results of our study suggest that individuals with asthma represent a susceptible subpopulation that could be at greater risk for the possible profibrotic effects of engineered nanomaterials.
Pathogen-free adult male C57BL/6 mice were obtained from Charles River Laboratories (Raleigh, NC) at 6 to 8 weeks of age. Mice were randomized by weight upon receipt and divided into eight treatment groups. Animals were individually housed in polycarbonate cages with Alphi-dri cellulose bedding (Shepherd Specialty Papers, Kalamazoo, MI) in a temperature- and humidity-controlled environment with a 12-hour light/dark cycle at an International Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)-accredited facility. Mice were given food (NIH-07 ground pellets; Zeigler Brothers, Gardners, PA) and water ad libitum when not in inhalation chambers. Bedding and food meet National Toxicology Program (NTP) standards and are certified by the manufacturer as free of pesticides, resins, or aflotoxin. All mice were acclimated to inhalation chambers 1 week before aerosol exposure by adaptation to chambers from 1 hour to 6 hours over a 5-day period. All procedures requiring animal use were approved by the Institutional Animal Care and Use Committee (IACUC) at The Hamner Institutes.
Mice (n = 40) were sensitized to ovalbumin (98% pure, grade V; Sigma-Aldrich, St. Louis, MO) over a 2-week period by intraperitoneal injection 14 days before inhalation exposure (−14 d) and 7 days before inhalation exposure (−7 d) with 20 μg of ovalbumin adsorbed onto 2 mg of alum (Accurate Chemical and Scientific Corporation, Westbury, NY) in 200 μl of sterile saline as previously described (17). Control mice (n = 40) were similarly injected with 200 μl of saline. One day before inhalation exposure (−1 d), mice were challenged intranasally with 100 μl of 1% ovalbumin in saline or saline alone while under isoflurane anesthesia. A high airborne concentration of MWCNT (~ 100 mg/m3) was intentionally chosen to deliver an alveolar dose of MWCNT within a 6-hour period that would be in the 10 mg/kg range, which would be consistent with a previous study using intratracheally instilled MWCNT (7). On the day of inhalation exposure (0 d), sensitized and unsensitized mice were exposed to aerosolized nanotubes or saline vehicle for 6 hours in nose-only inhalation chambers and returned to the vivarium for 1 day or 14 days. One hour before killing at 1 day, mice were injected (intraperitoneally) with 50 mg/kg body weight of 5′-bromodeoxyuridine (Sigma-Aldrich). Mice were anesthetized with 90 mg/kg pentobarbital (intraperitoneally) and killed by exangunation. Lungs were lavaged with Dulbecco's Phosphate Buffered Saline (DPBS) and bronchoalveolar lavage fluids (BALFs) saved for lactate dehydrogenase (LDH), total protein, and enzyme-linked immunosorbent assay (ELISA). The middle and caudal lobes of the right lung were collected for RT-PCR and stored in RNAlater as instructed by the manufacturer (Ambion, Austin, TX) and the cranial lobe frozen at −80°C for later collagen determination. The left lung was insufflated with 10% neutral buffered formalin, fixed for 72 hours, transferred to 70% ethanol, and embedded in parafin. Five-micrometer sections were processed for histopathology with a Masson's trichrome or hematoxylin and eosin stain.
MWCNT of “standard” length (0.5–40 μm) synthesized by carbon vapor deposition (CVD) with nickel and lanthanum catalysts were purchased from Helix Material Solutions, Inc. (Richardson, TX). Characterization of the size, purity, and elemental composition of the MWCNT was provided by Helix, Inc. We verified these parameters by independent analysis (Millenium Research Laboratories Inc., Woburn, MA). The characterizations of bulk MWCNT provided by the manufacturer and independently are summarized in Table 1. Size was characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Purity was determined by thermogravimetric analysis (TGA). Elemental analysis was performed by energy dispersive X-ray analysis (EDX) and inductively coupled plasma Auger electron spectroscopy (ICP-AES). EDX data were expressed as the average and SEM of three different spots for each element. The EDX data provided by both groups were in agreement for carbon, which was present at approximately 94%. Composition data for oxygen, nickel, and lanthanum differed between the two groups, which is not surprising, given the lower abundance of these elements coupled with the high variability in this technique as a result of spot measurements on a nonhomogenous sample. The manufacturer found more oxygen by this method than the contractor (6.4% versus 0.71 ± 0.19%), but less nickel (0.12% versus 5.53 ± 3.92%). The contractor did not detect lanthanum, but the manufacturer did find it present at 0.06%. The contractor also measured elemental composition by ICP-AES. Lanthanum was observed at 0.03%. Nickel values were lower than those observed by EDX, at 0.34%. Oxygen values were consistent with EDX data, and carbon content was slightly greater at 99.00%. The specific surface area was determined by Brunauer-Emmett-Teller method (BET) and reported by the manufacturer as 40 to 300 m2/g. This was consistent with independent testing at 109.29 m2/g. Purity was assessed by TGA. TGA provided by the manufacturer described MWCNT as more than 95% pure, which was in agreement with greater than 94% as determined by the contractor. The manufacturer also observed less than 2% amorphous carbon and less than 0.2% residual ash. Size was assessed by SEM (Figure 1A) and TEM (Figure 1B). The manufacturer's description of MWCNT as being 10 to 30 nm average external diameter was slightly less than the contractor's values of 30 to 50 nm. The 0.5 to 40 μm average length was consistent with the 0.3 to 50 μm values obtained independently.
Autoclaved MWCNT were dry-milled in a Retsch Mixer Mill (Retsch Inc., Newtown, PA) for 5 minutes at 30 cycles per second. The milled MWCNT were suspended in a sterile, biocompatible nonionic surfactant, 1% pluronic F-68 (Sigma-Aldrich) in sterile DPBS. The MWCNT suspensions were further diluted with DPBS to achieve the desired final concentration of approximately 5 mg/ml MWCNT in 0.1% pluronic F-68. Aerosols of MWCNT suspensions or the DPBS/0.1% pluronic F-68 vehicle were generated with a 6-Jet Collision nebulizer (Model CN-25; BGI, Inc., Waltham, MA) with compressed, hepa-filtered air (~ 21 psi) used as the carrier gas. Nebulized aerosols were passed through a trap (Model F73G-3AN-QT3; Norgren, Littleton, CO) to remove any large droplets, followed by a 85Kr source (BGI-085, 10 mCi nomial; Isotope Products, Valencia, CA) and a silica gel dryer (Model 3062; TSI, Inc., St. Paul, MN) to remove water. Ten animals were exposed to the aerosols on a Cannon nose-only tower (Lab Products, Maywood, NJ) for a 6-hour period at a flow rate of approximately 217 ml/minute per port. The pressure at the tower was monitored with a Magnehelic pressure gauge (Magnehelic; Dwyer Instruments, Inc., Michigan City, IN) and maintained near 0.0 inches of water. An Aerodynamic Particle Sizer (APS, Model 3321; TSI) and a Scanning Mobility Particle Sizer (SMPS, Model 3934; TSI) were used to monitor the particle size at the inlet of the tower during each exposure. Data merge software (Model 390069; TSI) was used to combine APS and SMPS size distributions. TEM and SEM samples of the MWCNT aerosol were captured from a tower port using an electrostatic precipitator (ESP; Intox Products, Moriarty, NM). Aerosol mass concentration was determined gravimetrically for each exposure at a tower port using 25-mm glass fiber filters (G15WP02500; Osmonics, Inc., Minnetonka, MN).
We estimate an alveolar deposition dose of approximately 12 mg/kg and a tracheobronchial deposition dose of 4 mg/kg. Assuming that an adult C57BL/6 mouse with an average body mass (M) of 24 g has a respiratory minute volume (RMV) of 0.0273 L/minute (2) and that the alveolar deposition fraction (DF) is approximately 30% particles of with an MMAD of 714 ± 328 nm (and the tracheobronchial deposition is ~ 10%) (18) at a time (T) of 6 hours, the doses at 100 mg/m3 concentration (C) can be calculated according to the formula (6):
At an RMV of 0.0273 L/minute, the aerosol flow rate of 0.217 L/minute was more than sufficient to prevent dose dilution by mixing of expired air with the aerosol.
Lungs were serially lavaged five times with 1.0 ml DPBS. Lavages 1–2 and 3–5 were combined and cells recovered by centrifugation. An aliquot of the combined lavage 1–2 supernatant (the bronchoalveolar lavage fluid, or BALF) was taken for LDH (LD Liquid Reagent; Pointe Scientific, Canton, MI) and total protein (Coomassie Plus Protein Assay Reagent; Pierce, Rockford, IL) assays with a COBAS FARA II automated analyzer (Roche Diagnostic Systems Inc., Montclair, NJ) and the remainder stored at −80°C for ELISA assays. The cell pellets from all five lavages were resuspended in Ham's F12 medium with 10% FBS and counted using a Coulter counter (Beckman-Coulter, Marietta, GA). A Shandon Cytospin (Fisher Scientific, Pittsburgh, PA) was used to plate 50,000 cells per animal on glass slides, followed by fixation and staining with the Hema 3 Stain Set (Fisher Scientific). Differential cell counts were then performed on at least 200 cells per sample.
The right cranial lobe of each mouse lung was suspended in DPBS at 50 to 100 mg tissue per ml and homogenized for 60 seconds with a Tissuemiser homogenizer (Fisher Scientific). Triton X-100 was added to 1% and the samples incubated for 18 hours at room temperature. Acetic acid was added to each sample to a final concentration of 0.5 M and incubated at room temperature for 90 minutes. Cellular debris was pelleted by centrifugation and the supernatant analyzed for total protein with the BCA Assay kit (Pierce/ThermoFisher Scientific) according to manufacturer's instructions. The Sircol Soluble Collagen Assay kit (Biocolor Ltd., Carrickfergus, UK) was used to extract collagen from duplicate samples by using 200 μl of supernatant and 800 μl of Sircol Dye Reagent according to the manufacturer's instructions. Similarly prepared collagen standards (10–50 μg) were run in parallel. Collagen pellets were washed twice with denatured alcohol and dried before suspension in Alkali reagent. Absorbance at 540 nm was read on a Multiskan EX microplate spectrophotometer (Fisher Scientific) microplate reader with Ascent software. Data were expressed as μg of soluble collagen per mg of total protein.
Quantikine ELISA kits (R&D Systems, Minneapolis, MN) were used to assay BALF for total TGF-β1 (active and inactive forms), IL-13, MCP-1/JE, eotaxin, and PDGF-AA 1 day after inhalation. Duplicate samples using 50 μl BALF were used for each animal. Assays were performed as per kit instructions and absorbances read on a Multiskan EX microplate spectrophotometer microplate reader (ThermoFisher Scientific). Values were normalized relative to total protein in BALF and were expressed as mean ± SEM.
Quantification of the thickness of collagen surrounding bronchioles was performed according to a previously published procedure developed in our laboratory (19, 20). Briefly, photomicrographs of trichrome-stained sections were digitized and the thickness of the collagen layer surrounding the bronchioles measured at eight equidistant points and averaged. Five airways per animal were analyzed in a random, blinded manner, and the data were expressed as the mean ± SEM of five animals per treatment group per time point.
Lung tissues were post-fixed in 1% osmium tetroxide in 0.1 M sodium phosphate buffer, pH 7.2, dehydrated through graded ethanol solutions, cleared in acetone, and then infiltrated and embedded in Spurr's resin. Unstained thin sections (800–1,000 μm) were mounted on copper grids and then examined on a Philips EM208S transmission electron microscope.
Two-step, TaqMan quantitative RT-PCR was used to quantify expression of genes of interest in lung tissue 1 day after inhalation. Total RNA was extracted from the right cranial and caudal lobes of each lung using an RNEasy Mini Kit (Qiagen, Valencia, CA) and converted to cDNA with the High Capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA). RT-PCR was performed on an ABI PRISM 7000 using 50 to 100 ng of cDNA per reaction, TaqMan Universal PCR Master Mix, and TaqMan Gene Expression Assays for TGF-β1 (Mm03024053_m1), IL-5 (Mm00439646_m1), IL-13 (Mm00434204_m1), MCP-1/JE/CCL2 (Mm00441242_m1), eotaxin/CCL11 (Mm00441238_m1), CXCL9/MIG (Mm0043946_m1), CXCL10/IP-10 (Mm00445235_m1), PDGF-A (Mm00833533_m1), PDGF-Rα (Mm00440701_m1), pro-collagen type 1, α2 (Col1A2, Mm00483888_m1), and connective tissue growth factor (CTGF, Mm00525790_g1). The comparative CT method was used to quantify message relative to a eukaryotic 18S ribosomal RNA (Hs99999901_s1) external sample. Each reaction was performed in duplicate and data expressed as mean ± SEM.
All graphs were constructed and statistical analysis performed using GraphPad Prism software v. 5.00 (GraphPad Software, Inc., San Diego, CA). A one-way ANOVA with a post hoc Tukey or Bonferroni test was used to identify significant differences among treatment groups. In some cases, a Kruskal-Wallace nonparametric ANOVA with a post hoc Dunn's test was used. Significance was set at P < 0.05 unless otherwise stated.
TEM and SEM clearly identified our commercial product as high purity MWCNT (Figures 1A and 1B). Next, it was important to show that we were aerosolizing the MWCNT and to define particle size and aggregation status. Particle size characterizations showed the aerosol had an average mass median aerodynamic diameter (MMAD ± SD) of 714 ± 328 nm with a geometric standard deviation of approximately 2. The particle number size distribution (± SD) was 160 ± 38.9 nm. The MWCNT aerosol deposited on collection filters during animal dosing was also characterized by TEM (Figures 1C and 1D). The average concentration of MWCNT in the aerosol (± SD) was 103 ± 8.34 mg/m3. MWCNT appeared as amorphous aggregates 2 μm in diameter or less with protruding tubes extending beyond the nexus. Smaller aggregates and individual MWCNT were also present (Figure 1C). Individual MWCNT resolved at higher magnification (Figure 1D) confirmed the identity as equivalent to the bulk material (Figure 1B).
No differences in LDH release, a measure of cytotoxicity, were observed in BALF among the treatment groups 1 day after inhalation, and MWCNT-treated animals showed a significant decrease in LDH release compared with controls 14 days after exposure (data not shown). LDH levels for unsensitized, MWCNT-treated mice (0.72 ± 0.06 U/mg total protein) were significantly less than controls (1.04 ± 0.12 U/mg). Similarly, LDH levels for ovalbumin-sensitized MWCNT-treated mice (0.65 ± 0.09 U/mg) were less than for saline-treated controls (0.97 ± 0.10 U/mg). No differences in total protein were observed at 1 day or at 14 days (data not shown).
Gross observations revealed that inhaled MWCNT were homogeneously distributed in the mouse lung (Figure 2A). In both sensitized and normal mice, histopathology showed some MWCNT agglomerates on the surfaces of alveolar ducts and within alveoli, indicating delivery of the aerosol to the distal airways (Figure 2A). Importantly, no airway obstruction by MWCNT was observed. By light microscopic evaluation, MWCNT were observed primarily as agglomerates in alveolar macrophages at 1 and 14 days after inhalation (Figures 2B–2D). However, TEM identified small aggregates and individual MWCNT within alveolar macrophages (Figures 2E and 2F). TEM also revealed that MWCNT were taken up by lung epithelial cells (Figures 2G and 2H). Importantly, these results showed that MWCNT maintained tube-like structure after aerosolization, inhalation, deposition, and uptake by lung cells.
Alveolar macrophages containing MWCNT were easily identified by light microscopy and constituted the majority of total macrophages (Figure 2, Figure 3). The numbers of MWCNT-positive macrophages in BAL cytospins were counted relative to the total number of macrophages to estimate the persistence of MWCNT in the lung phagocyte population. Greater than 80% of the total number of macrophages retrieved by BAL contained MWCNT, and the relative percentage of MWCNT-positive macrophages did not decrease by 14 days after exposure, nor were there differences in the relative percentages of MWCNT-positive macrophages between unsensitized and ovalbumin-sensitized mice (Figure 3).
The results of the BALF cell differential counts are summarized in Table 2. One day after inhalation, neutrophils were significantly elevated in unsensitized animals that inhaled MWCNT compared with controls, and were also elevated for all animals sensitized with ovalbumin. There was also a trend (P < 0.1) for increased neutrophils in sensitized animals that inhaled MWCNT compared with unsensitized, MWCNT-inhaling animals. Neutrophil counts returned to basal levels by 14 days. Eosinophil counts for all sensitized animals were elevated at 1 day, but this elevation was not statistically significant due to large variability. Lymphocyte counts remained at basal levels for all treatment groups at both time points. The number of macrophages remained largely unchanged by all treatments.
At 1 day, collagen thickness around airways was similar in all dose groups, and no significant differences were found by quantitative morphometry (data not shown). At 14 days, histopathology showed an apparent increase in the thickness of collagen in the reticulum around the basement membrane of the bronchioles in sensitized animals that inhaled MWCNT relative to unsensitized animals that inhaled MWCNT and sensitized and unsensitized saline-inhaling controls (Figures 4A–4D). This was confirmed by quantitative morphometry, which showed a statistically significant increase relative to unsensitized animals that inhaled MWCNT or sensitized animals that inhaled saline (Figure 4E). Also, un-sensitized animals that inhaled MWCNT did not have a significant increase in airway collagen deposition compared with saline-inhaling controls. No significant differences in soluble collagen production as measured by Sircol Assay in whole lung (right cranial lobe) were observed among any of the treatment groups 1 day and 14 days after inhalation (data not shown). Immunostaining for BrdU was also performed in animals killed at 1 day. The rapidly dividing epithelial cells along the basement membrane of the duodenum from each animal stained positive for BrdU, indicating successful BrdU uptake and detection. However, no focal areas of BrdU staining were observed in lung tissue for controls or MWCNT-treated animals.
IL-13 protein was quantified in the BALF by ELISA and expression of IL-13 mRNA in lung tissue was quantified by RT-PCR. One day after inhalation of saline or MWCNT, IL-13 protein levels in the BALF were not detectable by ELISA in any unsensitized animals that inhaled saline or MWCNT (threshold 7.8 pg/ml). As expected, ovalbumin challenge increased IL-13 levels, and yet the level of IL-13 detected in ovalbumin-sensitized animals was not significantly affected by MWCNT inhalation (Figure 5A). Similarly, IL-13 mRNA in lung tissue was increased by ovalbumin challenge but not different between mice that received ovalbumin or ovalbumin plus MWCNT after 1 day (Figure 5B). IL-13 mRNA and protein were not detectable in any groups at Day 14 (data not shown).
A fibrogenic response requires the combined actions of PDGF to stimulate fibroblast replication and TGF-β1 to drive collagen deposition by fibroblasts. PDGF-AA levels in the BALF were significantly elevated 1 day after MWCNT inhalation in the absence or presence of ovalbumin (Figure 6A). Ovalbumin sensitization alone did not increase PDGF-AA levels in BALF. In contrast, TGF-β1 levels in BALF were increased by ovalbumin in the absence or presence of MWCNT, but MWCNT inhalation exposure alone did not increase TGF-β1 (Figure 6B). Both PDGF-AA and TGF-β1 were simultaneously increased only with combined ovalbumin sensitization and MWCNT inhalation exposure. At Day 14, no significant differences were observed for PDGF-AA or TGF-β1 protein levels (data not shown).
IL-5 mRNA levels in whole lung tissue measured by RT-PCR were synergistically increased by combined ovalbumin challenge and MWCNT exposure, yet neither ovalbumin nor MWCNT alone increased IL-5 mRNA levels above the saline control (Figure 7A). We also evaluated mRNA levels for several chemokines (MCP-1, eotaxin, and CXCL9). MCP-1 mRNA levels were significantly increased by MWCNT exposure in the absence or presence of ovalbumin sensitization (Figure 7B). Eotaxin mRNA levels were also increased by MWCNT, but also by ovalbumin (Figure 7C). mRNA levels for CXCL9, an interferon-inducible chemokine, were increased by ovalbumin but not by MWCNT (Figure 7D). The mRNA levels for all of these cytokine/chemokine returned to basal expression levels by Day 14, with no differences between exposure groups (data not shown).
The present study was designed to test the hypothesis that inhaled MWCNT would cause greater lung injury and fibrosis in mice that had pre-existing allergic inflammation. We found that inhaled MWCNT caused no significant fibrosis in mice that did not receive ovalbumin challenge, nor did we observe any increase in total lung protein and LDH release into the BAL fluid from MWCNT-exposed mice. However, mice that received ovalbumin challenge before MWCNT inhalation exposure developed significant airway fibrosis as determined by quantitative morphometry. Some neutrophilic inflammation was observed in the lungs of mice that inhaled MWCNT, but this inflammation resolved by 2 weeks. Airway fibrosis in ovalbumin-challenged mice that inhaled MWCNT was accompanied by significant increases in two profibrogenic growth factors, PDGF-AA and TGF-β1. Ovalbumin alone induced only TGF-β1, whereas MWCNT alone only induced PDGF-AA. PDGF is the most potent fibroblast mitogen discovered to date and is important in expanding the lung population of fibroblasts (21). TGF-β1 is the primary growth factor that stimulates fibroblasts to produce collagen, which defines fibrotic lesions (22). Together, these two polypeptide growth factors orchestrate a fibrogenic response. While our study suggests potential roles for PDGF and TGF-β1, further work is needed to identify more definitive roles for these mediators in MWCNT-induced airway fibrosis using strategies such as RNAi, small molecule inhibitors, or neutralizing antibodies to knock-down or block the activity of these growth factors or their receptors in vivo.
IL-13 is a well-known mediator of allergic asthma and was increased in the lavage fluid of ovalbumin-sensitized mice and also in ovalbumin-challenged mice that received MWCNT exposure. IL-13 has been reported to stimulate lung fibrosis by increasing TGF-β1 production and activating the release of active TGF-β1 from its latent complex (14). Consistent with this report, we observed elevated TGF-β1 protein in the BAL fluid of ovalbumin-challenged mice. We did not observe a significant increase in PDGF-AA in the BAL fluid from ovalbumin-challenged mice, although we have previously reported that IL-13 stimulates the mitogenesis of human lung fibroblasts through a PDGF-AA autocrine loop (13). We have also observed by immunohistochemistry that PDGF-AA and PDGF-CC are increased in the airway epithelium of mice after ovalbumin challenge (unpublished observation). It is possible that PDGF-AA in ovalbumin-challenged mice is not secreted by the airway epithelium in detectable amounts, although we clearly observed increased PDGF-AA in the BAL fluid of MWCNT-treated mice. IL-13, TGF-β1, and PDGF-AA are all elevated in human asthma, and play important roles in cell signaling pathways that mediate airway fibrosis (23, 24). MWCNT could have their most significant effect in potentiating the effects of allergen challenge by elevating PDGF.
IL-5 mRNA was increased only in mice that received both ovalbumin challenge and MWCNT inhalation. We did not measure IL-5 protein levels due to the limited amount of BAL fluid that was exhausted in ELISAs for IL-13, PDGF-AA, and TGF-β1. Previous studies have shown a modulatory role for IL-5 in promoting pulmonary fibrosis in different animal models (23) and clinical studies indicate a similar effect in humans (25). In the mouse ovalbumin model in particular, neutralization of IL-5 with monoclonal antibodies before multiple pulmonary challenges with ovalbumin decreases peribronchiolar fibrosis (26). Based on these published reports, there is compelling evidence that IL-5 plays a role in airway fibrosis in asthma. It is therefore conceivable that IL-5, which is synergistically increased by the combination of ovalbumin and MWCNT, could play a significant role in mediating the effect of MWCNT toward potentiating airway fibrosis in allergic inflammation.
The calculated dose of MWCNT aerosol we used was an estimate of the dose used in earlier studies that employed the intratracheal instillation method for CNT delivery and which resulted in significant pulmonary fibrosis and granuloma formation (3–7). Also, unlike instillation studies, the majority of MWCNT observed by light microscopy after inhalation were contained within alveolar macrophages, which is not surprising since macrophages avidly engulf inhaled particles and the (2-μm) size of the aggregated MWCNT aerosol was in the range for phagocytic uptake. Also, unlike intratracheal instillation studies (5, 7), histopathology of lungs in the present study showed no evidence of MWCNT agglomerates obstructing the conducting airways or the alveolar region. However, TEM showed that small aggregates of MWCNT or individual nanotubes were present on or beneath the epithelial cell surface throughout the lung.
The increased MCP-1 message expression from the lung tissue of MWCNT-treated mice could play a role in the recruitment of macrophages to sites of MWCNT deposition. The result that inhaled MWCNT agglomerates were almost completely localized in macrophages is consistent with a recent MWCNT inhalation study (10). We previously reported that SWCNT delivered to the lungs of rats by intratracheal instillation stimulate a strong macrophage phagocytic response (6). In that study, we described “carbon bridges,” which are bundles of SWCNT connecting two macrophages (6). The frequency of carbon bridge formation induced by SWCNT was relatively low (< 5% of total macrophages), but provided a reliable biomarker of exposure. No such structures were found in the present study using MWCNT. This is perhaps because MWCNT are 30 to 50 nm in width, whereas SWCNT are only 1 to 3 nm in width; approximately the same width as actin filaments that compose the cytoskeleton. Effective sequestration of MWCNT agglomerates may explain why little inflammation or fibrosis was present by 14 days for unsensitized animals, since inflammation and fibrosis in response to MWCNT have previously been reported around sites where large agglomerates deposited and persisted after intratracheal instillation (9). We observed many small aggregates and individual MWCNT by TEM after inhalation. Well-dispersed SWCNT have been reported to cause interstitial fibrosis in the lungs of mice when delivered by intratracheal instillation (4, 8). However, while our inhalation study resulted in well-dispersed MWCNT as determined by light microscopy and TEM evaluation, we did not observe a significant fibrogenic effect in the absence of pre-existing inflammation.
Ovalbumin sensitization by intraperitoneal injection followed by intranasal challenge creates a proinflammatory environment in the lung. Particulate pollutants have been reported to increase allergen-induced inflammation and lung function (17, 27, 28). In particular, carbon nanoparticles can aggravate ovalbumin-induced airway inflammation and immunoglobulin production, which is more prominent with smaller particles (27). In that study, the carbon nanoparticles caused airway inflammation but not fibrosis, which is consistent with our previous observation that carbon nanoparticles do not cause lung fibrotic reactions (6). The present study is the first, to our knowledge, to show that a particulate pollutant of any kind can increase airway fibrosis in allergen-challenged mice. The fibrotic response that we observed with MWCNT and ovalbumin was confined to the bronchioles and did not extend into the interstitium, which differs from previous reports showing interstitial fibrosis at sites distant from the airways of unsensitized mice in response to SWCNT (4, 8). Although quantitative morphometry revealed a statistically significant increase in peribronchiolar fibrosis in sensitized animals that inhaled MWCNT, no significant increases in total lung collagen content were observed, which is consistent with our observation of a localized airway response. Moreover, the animals showed no signs of respiratory distress. However, we did not perform pulmonary function tests on mice as has been described previously (19). Therefore, it is unknown whether the increased airway fibrosis in ovalbumin-challenged mice that inhaled MWCNT correlates with decreased lung function. This is an important issue that should be addressed in future investigations. It is also unknown whether the airway fibrotic lesions observed in mice that received a combination of allergen and MWCNT will eventually resolve or progress. Further work should include a longer time course evaluation to address this issue.
In the present study we used an aerosol concentration of approximately 100 mg/m3 MWCNT and a single exposure 6 hours in duration on a nose-only tower. This dose is admittedly high, but was specifically chosen to fall within the dosing range of MWCNT (0.5–20 mg/kg) delivered to mice by intratracheal instillation (7) or to approximate a dose of SWCNT that we used previously administered to rats by intratracheal instillation. This type of comparison is the only way to directly assess the issue of whether inhalation exposure results in pathology similar to that of intratracheal instillation or pharyngeal aspiration. Moreover, the dose of MWCNT that we used in this study is roughly within the range of previous whole-body inhalation studies that were 0.2–2.7 mg/kg (10) and 2–10.5 mg/kg (9). We estimated an alveolar deposition dose of 12 mg/kg and a tracheobronchial dose of 4 mg/kg for an aerosol of average mass median aerodynamic diameter of approximately 700 nm. Although the airborne concentration of MWCNT in the present study is similar to those at the higher end of the dosing ranges in other MWCNT inhalation studies, it is 2,000-fold greater than the average, estimated concentration of 0.053 mg/m3 generated during the handling of SWCNT in occupational exposure scenarios (29) and 20-fold greater than the 5 mg/m3 NIOSH occupational exposure standard for unregulated particulates (30).
The MWCNT used in this study were purchased from a commercial source and characterization provided by the manufacturer and verified by an independent contract laboratory. TEM of the bulk material verified that these were nanotubes, not carbon nanofibers (31, 32), and that MWCNT were aggregated. TGA analysis from both sources were in agreement that bulk MWCNT were greater than 94% in purity. BET surface area was also consistent with an average of 109.29 m2/g. The elemental composition of the bulk material was carbon > oxygen > nickel > lanthanum. It is important to note that Ni and La values measured by ICP-AES, in which the nanotubes are treated with strong acid, reflects dissolved surface metals. This measurement is probably more reasonable than EDX measurements for discerning bioavailable metals, since EDX also measures metals embedded within MWCNT. The metal concentrations as a percentage of the bulk material as determined by ICP-AES are low, at 0.34% (Ni) and 0.03% (La). The MWCNT aerosol was also characterized. TEM of the aerosol revealed that MWCNT were mostly agglomerates of approximately 2 μm in size with protruding nanotubes. Agglomeration is likely due to Van der Waals forces between MWCNT (1) that were not disrupted by the Pluronic F-68 surfactant.
A caveat for the present study is that the high dose of MWCNT and the brief duration of exposure do not likely mimic occupational exposure scenarios, which will probably occur with airborne concentrations in the 0.05–5 mg/m3 range for up to 40 hours per week in duration over weeks to months to years. However, very high airborne concentrations and brief exposures are consistent with the use of inhalants in medicine, and MWCNT are proposed for use in drug delivery applications (33). The result that no acute observable pulmonary hazard of airway fibrosis to normal lung tissue was observed is of importance, especially at the high dose that we used, since the data indicate that the NOAEL for inhaled MWCNT is probably greater than what may be achievable in “real life” occupational or therapeutic exposures. Our data do indicate a pulmonary hazard of increased airway fibrosis in inflamed lung tissue, but the degree of fibrosis was not sufficient to cause overt signs of pulmonary distress. This result supports our original hypothesis, which was that MWCNT cause greater lung injury and fibrosis under conditions of pre-existing allergic inflammation, indicating that individuals with asthma may be more susceptible to adverse effects from MWCNT than normal populations. This study should encourage future investigations into differences in dose–response-effect relationships in normal and asthmatic lung in response to inhaled CNT at airborne concentrations relevant to occupational and medical exposures.
The authors thank David Weil, Delorise Williams, Otis Light, Duncan Wallace, Vickie Wong, Elise Barber, and Carol Bobbitt for excellent technical assistance and Joseph Lopez for attentive animal care. Special thanks to Jeanette Shipley-Phillips at NCSU for performing TEM to detect MWCNT in lung. The authors also thank Greg Parsons and Joe Spagnola at NCSU for helpful comments about MWCNT TEM and SEM data, and Ram Bhat at Millenium Research, Inc., for directing contracted MWCNT characterizations.
This study was funded by The American Chemistry Council's Long Range Research Initiative provided to The Hamner Institutes for Health Sciences, The Intramural Research Program of the National Institutes of Health, National Institute of the Environmental Health Sciences, and North Carolina State University's College of Agricultural and Life Sciences.
Originally Published in Press as DOI: 10.1165/rcmb.2008-0276OC on September 11, 2008
Conflict of Interest Statement: B.A.W. received $25,000 in 2006 and 2007 from the American Chemistry Council's Long Range Research Institute as research funding related to nanoparticle toxicity. None of the other authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.


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You will need the following things for this tutorial.
Thank You Rieneke for letting Me use Your kit in My tutorials -hugs and kisses-.
Template 101 by Rachel at Scraps of Enchantment
Thank You Rachel for sharing Your templates and other goodies with Us -hugs-.
Tubes of choice. I am using the wonderful work of Ismael Rac. You can find His tubes at AMI. You need to purchase a license in order to use any of His tubes.
Open the template and tube in psp and minimize the tube. Shift+D on the template to duplicate it closing the original now delete the copyright layer as We don't need it. Find a color from Your tube You like and with Your eye dropper tool click on it.
On the PinkGlitter layer go to adjust Hue and Saturation Colorize and from the color You used click on the materials palette and use the H and S numbers and type them into the colorize slots where You see Hue and Saturation. You might have to fiddle with the numbers in order to get something that You might like.
Choose the Glamour layer and with Your magic wand click each letter and all now should be selected with marching ants. Layers new raster layer and flood fill this layer with a color or gradient of choice. Now paste Your tubes and position them along the text. After they are in place go to selections invert and tap Your delete key on each of those layers. Selections select none. Layers merge down all those tube layers until all the tubes are merged together.
Duplicate this tube layer and go to adjust gaussian blur 4. Place the original layers blend mode on Luminance and the copy blurred one on Luminance (L) put the opacity on about 80 or whatever looks good to You. I also gave it a blinds effect by going to effects texture effects blinds.
On the glamour text layer go to selections select all selections float selections defloat selections invert and choose the tube layer and tap on Your delete key. This will get rid of the blurred area's outside of Your text. Selections select none. Now back to the glamour word text and go to effects 3D effects drop shadow vertical and horizontal 2 opacity50 blur 7.00 color black. Delete the original text layer.
On the girl layer colorize it again to a color You like. On the pink strip I pasted a paper over it and then lowered the opacity. Another option You have is floating it and adding a new layer and flood filling the spaces and lines with 2 different colors. To do the paper find one You like go to edit copy and on the template go to selections select all selections float selects defloat. Edit paste as a new layer selections invert and tap the delete key. Selections select none. I slid the opacity down to 63 but of course this will vary depending on shades and likes.
Choose the Black bg layer and using Your magic wand hold down the shift key and click both area's on Your canvas and flood fill with a color or gradient of choice. Selections select none. Effects xero fritilliary 5 30 10 0. Effects 3D effects drop shadow vertical and horizontal 2 opacity 30 blur 10.00 color black. Delete the original layer.
On the dotted lines place the blend mode on Luminance. Give it the same drop but change the blur to 7.00. Now add Your main tube to the tag. You may have to change the canvas size in order to do so. You do this by going to image canvas size 700x700 and if You have excess tube just erase it with Your eraser. Duplicate the tube after You have it placed and again do the blur and then slide the opacity to about 70 or so and add a drop shadow to the bottom tube.
On the pink circles place this layer onto Luminance. So sorry I overlooked this layer. Add a drop shadow to it. Now add any of the elements from the kit You like and Your text. Merge Your layers resize or crop if needed add Your copyright and save as png.

domain: artistic


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For many years people have been sharing their beliefs in the benefits of mindfulness meditation. Recently, as mindfulness has gained popularity, folks from all over the world have been experimenting with mindfulness meditation and claiming to have had benefits such as a reduction in stress, clarity, better relationships, etc.
While most people would agree that a regular meditation regimen does produce positive results , until now there have been very few clinical studies to actually verify these claims. Most of the “data” supporting the benefits has been handed down through word of mouth and personal experiences. Most notably, Buddhist monks have been practicing mindfulness meditation for years and shared their benefits and are often referenced by supporters sharing the benefits.
True believers can now take joy in knowing that their claims of benefitting from mindfulness mediation have been clinically proven to be the true. For the first time, a controlled study was conducted by psychiatric schools around the country including, Carnegie Melon, Ohio State University and several other well respected institutions.
The study, published in Biological Psychiatry, showed how mindfulness meditation can have a very positive effect on peoples brains and ultimately lead to better physical and mental heath.

domain: sociology


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A few months back, I was having lunch with a friend. She’s a single mom. She was talking about something a mutual friend of ours had said to her. The comment had upset her. She didn’t understand our other friend’s intent.
They’d been talking about housing and the mutual friend had made a comment that could be perceived probably a hundred different ways. She suggested that my worried friend apply for Section 8, which is a government rental assistance program.
The friend I was speaking with was miffed by our mutual friend’s comment. And I understood that. Comments about a person’s financial situation are difficult to interpret. Did our mutual friend perceive her as indigent? It struck at the core of my worried friend’s self-identity. Is that how people saw her?
My worried friend wanted my interpretation of our mutual friend’s meaning. I’m a woman with a high degree of empathy, often too high. It makes it hard for me not to jump in and try to fix things. My immediate reaction was that my heart sank, and I felt my worried friend’s angst. I reassured her that people don’t perceive her that way, and they don’t.
However, the mutual friend we were speaking about is one of the nicest people I’ve ever known. I can’t imagine a circumstance under which she’d intentionally slight or insult another person. In my heart, no matter how her comment came across, I assumed she had good intentions. She probably thought she was being helpful.
In hindsight, the conversation perturbed me. I disliked that my concerned friend was spending so much time analyzing something so insignificant. I disliked that our mutual friend hadn’t thought about how her commend could be misperceived. What I hated was that I was pulled into a situation that had nothing to do with me.
In hindsight, I should simply have said, “I’m sure she meant well.” That would have ended the conversation because there’s nowhere to go from there. My concerned friend could’ve kept pushing me to interpret and provide reassurance, but I could simply have kept repeating, “I’m sure she meant well.”
“I’m sure she meant well,” would have been a boundary. Regardless of how I felt about, or interpreted the situation, it had nothing to do with me, but I was pulled in. My friend’s concern became my concern. Her troubled energy disrupted my calm energy.
The situation got me thinking about how often we’re pulled into other people’s drama and how often we create our own by not having stronger mental and emotional boundaries. “I’m sure they meant well,” has since become my go-to phrase for self-protection. It helps me protect my energy. It helps me fight my codependent urge to jump in and, “help.”
However, “I’m sure they meant well,” not only helps shield one from other people’s unsettled energy, it can also diffuse our own. It can be used as a mental boundary when we begin to ruminate about situations or people that have upset our self-identity or sense of security.
About seven years ago, when I embarked on deep journey of healing and self-discovery, a person I admired had remarked, “Why do you always assume the worst?” Boom. What? I never thought I had. I’d always thought of myself as someone with a positive mindset. Yet, when I reflected on his comment, I realized that wasn’t true at all. I was ripe with judgments and criticisms.
My inner critic had emerged. My unresolved trauma was impacting how I perceived the world. I was analyzing everything and everyone. That was happening because I had few boundaries. You see, I wasn’t encouraged to have boundaries. I didn’t even know that was a thing until I was well into my 40s.
Unresolved trauma leaves us vulnerable. For me, it manifested as codependency, which meant everything was somehow directed at or involved me. That led to emotional reactivity. In the situation with my friend, my emotional reactivity was that I was upset for her. I felt her pain. I became enmeshed in her drama.
There were so many times, though, where I’d done exactly what my friend had: I’d overthought and overanalyzed another person’s behavior. I’d made it about me. I’d done exactly what Don Miguel Ruiz in his book, The Four Agreements, advised not to do with Agreement #2: Don’t Take Anything Personally.
We don’t talk enough in our culture about character and maturity, nor do we sufficiently value these characteristics. Our pop culture and news media talk more about what a woman looks like than about how she behaves. When coverage addresses a woman’s behavior, it’s often glorifying or scandalizing bad behavior.
“I’m sure they meant well,” is a character-building phrase because it’s about self-restraint. When we use that phrase with others, and with ourselves, we’re erecting a wall that preserves our inner calm. We’re not enmeshed in other people’s drama, and we’re not creating our own.
Regardless of whether another person’s intentions are good, or evil, “I’m sure they meant well,” protects us from enmeshment, or saying or doing the wrong thing. We might react harshly to something that wasn’t meant to offend, or we might react appropriately to something utterly offensive, but that reaction may cost us dearly.
In this way, uniformly adopting the phrase, “I’m sure they meant well,” will move us to a higher level of being and awareness. It protects our energy and when that energy is shielded from disturbance, we think more clearly and we act in ways that are more self-protective and sensitive to the situation, rather than reactive or codependent.
Becoming an, “I’m sure they meant well,” person increases character because it leads to the increased self-respect that comes from knowing we protected others, and ourselves.

domain: literature


Larger warehouses and distribution centers has for many years used Warehouse Management Systems to make their logistics more efficient. Effect Warehouse makes that possible also for small and medium sized companies. The modern technology with barcodes, wifi teminals and voice picking technology, with total control over work and flows in the warehouse, is all possible.
Effect Warehouse gives you an operative tool for the warehouse activities communicating the exact results to your ERP system where quality and control are the key-words. A standard software package, simple and fast installation on a robust and reliable platform minimizes the total cost for the installation.
Effect Warehouse has a modular design and includes receiving, put-away, order processing and shipments. The system also includes support modules for Inventory Management and easy ERP interfacing. Effect is available on Windows server using the SQL-server.


Following the successful, first-ever residential online sales launch 9 months ago, Summer Park Umhlanga officially broke ground on Thursday, 16 August. Having started with an extremely positive reaction, with R60 million sold in 42 seconds of the online launch, Summer Park Umhlanga has not slowed down in sales, resulting in this swift turnaround time to construction.
“We are thrilled to have reached this stage of the development and to have had such a great response from investors and homeowners alike. It is not often you see developments reach this milestone in this record time and we are proud to have been a part of it,” says Stefan Botha, Director of Rainmaker Marketing.
“It’s a profound moment for us, knowing that our online strategy helped fast-track the process and revolutionised residential sales. In addition to the seamless sales process, it is difficult to go wrong when you combine a sought-after area like Umhlanga Ridge Town Centre, a great product that meets modern living needs, with an attractive price; you are bound to achieve great results,” continues Botha.
Summer Park Umhlanga is situated in the heart of Umhlanga Ridge Town Centre close to all the amenities, from shopping centres, medical suites and hospitals, to trendy bars and restaurants. Summer Park Umhlanga is the only pet-friendly apartment within this area that boasts family-focused facilities like a crèche and dedicated play areas for kids. Not to mention the actual design of the apartments where every homeowner has direct access to their own enclosed private courtyard that brings in extra space and natural light.
The Umhlanga Ridge Town Centre is increasing in popularity, as a total of 322 transfers took place from February 2017 to January 2018. In the last five years, the median price of Umhlanga property has increased by 48%. With the ever-growing demand for the area, and the benefits of investing off-plan, we are delighted that those who have already purchased within Summer Park Umhlanga would already have enjoyed great capital appreciation on their Summer Park investment, which will continue to grow throughout the construction period.
“By the end of August, we will see the Summer Park Umhlanga site transform into a fully-fledged construction site, with graders and construction workers steadily at work. We anticipate completion of the development around the second half of 2019,” ends Botha.


One of the largest misconceptions (no pun intended) of the new Trojan BareSkin condoms is the product’s ambiguous shelf name. “Wait a minute”¦ these are NOT made from actual bear skin?” said History major Theo Dumont. Theo is one of the many Trojan condom users who are disappointed by the “misleading” name. Students are excited to try a new product, especially individuals who have a history of latex allergies.
“I have been using sheep skin condoms for as long as I can remember, so I am eager to wrap my hands around the bear skin condoms that I heard about on the radio”¦” remarked Shane LaBone before we told him about the product’s real name.
In the winter months college students tend to increase sexual activity, reports from University of Pennsylvania at Intercourse mentioned, due to the lack of available outdoor activities. A junior at the college noted that while he does in fact like to ski, he would rather be having sex. “I like skiing but I like the other slopes better”. Another student at UPI noted that Bears are associated with hibernation, staying warm, and winter. “The natural association of Bear Skin Condoms is quite obvious”.
This Marketing gaffe might actually help the Trojan brand, depending on how they react. The large subset looking for actual “Bearskin” condoms might search elsewhere for their warm and latex-free contraceptives. Only time will tell if this turns out to be a good sign. “We did not foreskin… I mean foresee such complications with our new product launch. We will have to reevaluate how certain consumers interpret the product name,” responded Don Sharp, a sales representative from Trojan Brand Condoms.


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After 39 years of serving the community, Mr. and Mrs. D. W Snedden have retired from their pharmacy business at 24 Mill Street and have sold the Rexall Store to Mr. Darcy Farden, recently from Ottawa and formerly of Saskatchewan. Following his graduation from the Ontario College of Pharmacy in Toronto on June 6th, 1924, Wilf Snedden served his apprenticeship at the present location, then owned by Mr. M. R. MacFarlane.
He eventually sold the business to Mr. Snedden who took over January 1st, 1934 and later purchased Mr. MacFarlane’s home at 190 Church Street where he and Mrs. Snedden still reside. For many years one of the most popular spots in Almonte on a Saturday night was the soda fountain at Snedden’s Drug Store. On many occasions the ten stools would be filled and just as many or more people waiting to be served.
As time went on, however, and the fountain equipment wore out and a wider variety of frozen treats began to appear, the soda fountain lost its appeal and was finally removed when renovations were carried out in 1967. An avid sports fan, Mr. Snedden hopes to have some time to get in a little golf and follow the baseball teams more closely. Through the years Wilf Snedden has been a staunch supporter of sports in the Almonte area.
Several changes are planned for the store by its new owner, major one being a change in name to the Almonte Pharmacy, although the outlet will remain Rexall store. Mr. Farden, a 30 year old bachelor, was born and raised on a farm in Saskatchewan. He graduated in 1965 from the College of Pharmacy, University of Saskatchew an and moved to Ottawa in 1968. For the last four years he has been manager of an Ottawa Pharmacy. An avid curler and golfer, Mr. Farden is also an active pilot.
He will shortly be receiving his commercial pilot’s licence at Bradley Air Services at Carp. Staff at the Almonte Pharmacy will remain the same, with Elenor McPhail, Elizabeth Duncan Alice Landry remaining on and’ being joined by Miss Janet Smythe who has worked with Mr. Farden in Ottawa for three years. Miss Smythe has many years of pharmacy experience, especially in the field of cosmetics.
New hours of operation will be as follows; Mondays, 1 p.m. till 9 p.m.; Tuesday to Friday, 10 a.m. till 9 p.m.; Saturdays, 10 a.m. till 6 p.m. Commencing in May, Mr. Farden indicates that the pharmacy will be open Sundays from 12 noon until 3 p.m. A grand opening sale will be held from June 5-8th, 1973
Reads as long as it takes to glimpse the passing of the torch…….
The premises of Kerry’s Furniture & Appliances / Pharma Save Pharmacy, was owned by my father John Kerry from 1954 to 2019.
It was purchased from Mr. W.E. Scott in 1954. Ed Scott had rebuilt the furniture store in 1904 following a major fire. At that time he had two storefronts constructed, which has continued to exist thru these current times.
Mr. Wilf Snedden, Pharmacist and prominent resident of Almonte, rented the smaller portion of the divided building. Many will recall that he had a wonderful old fashioned soda fountain bar and stools to compliment the drug store and pharmacy services … it would be lovely to have that service reinstated somewhere for today’s lover of everything ice cream !
In my father’s era of ownership, there has been four pharmacy businesses, to be followed by the current Quilt Supply Store. What for many years housed the Furniture & Appliances side of the store, is currently an Antique Store.
Prior to being sold, my father saw the building thru an outer face lift and some internal upgrades leaving the premises with its best foot forward for the next generation of users.
With its sale completed in 2019, the history of the bricks and mortar, along with the businesses carried out within its walls by its proprietors, becomes another chapter in the continuing story of daily commercial life carried out on Mill Street.
I remember the Soda fountain too, great milkshakes and sundaes, and yes Wilf Snedden was a great gentleman.
Then it happened, even as he knew it would. It was Monday the last day in February, 1927. He had stopped at M. R. MacFarlane’s drug store (now Wilf Snedden’s) about 11:00 a.m. He spoke to a number of people between there and the Post Office (Don Campbell was one of them), and then he drove home with the horse and cutter. He stepped out of the cutter at the door, collapsed and died on the spot.
The word ran like grassfire along the pathways of Almonte.
“In the 1890s P.C. Dowdall’s drug store was on Bridge St. in Almonte, near the railway. (It’s pictured below, far right, “PC Dowdall” on the awning.) In the entrance, the weather forecasts were posted up daily, providing a point of interest each day for the children walking to & from Church Street school.
“Jimmy Morrow worked in the pharmacy for many years. He wanted to be a druggist, but this wasn’t possible for him. Yet Jimmy was ambitious, so he studied chemistry by mail. In the absence of Mr. Dowdall, he was able to read and fill the Latin prescriptions. Having no degree in pharmacy made this a bit out of the ordinary, but everybody knew about it and there were no objections or complaints.” #SmallTownLife#LocalLore#Almonte
Source: 365 “Fun facts about MM” were co-ordinated by Tiffany MacLaren, Community Economic and Cultural Coordinator for Mississippi Mills in 2017 & posted in weekly instalments at Millstone News. The “facts” wouldn’t have been possible without amazing volunteers and history buffs who contributed information. Special thanks went to Jeff Mills, Donna Lowry, Margie Argue, Rose Mary Sarsfield, Renate Seiler, Marilyn Snedden, The North Lanark Historic Society, The Naismith Basketball Foundation, The Mississippi Valley Textile Museum, Neil & Lucy Carleton, Fern Martin and others. “The Tales of Almonte”, Linda Seccaspina’s page, also posted this anecdote, earlier.
In the 1890s P.C. Dowdall’s Drug Store was on Bridge St. in Almonte near the railway. In the entrance, the weather forecasts were posted up daily, providing a point of interest each day for the children walking to and from the Church Street school. Jimmy Morrow worked in the drug store for many years. He wanted to be a druggist but this was not possible for him. But Jimmy was ambitious, so he studied chemistry by mail. In the absence of Mr. Dowdell, he was able to read and fill the Latin prescriptions. Having no degree in pharmacy made this a bit out of the ordinary, but everybody knew about it and there were no objections or complaints. ( Facts about MM- The millstone)
Son of James Patterson and Bresaya Jane Pounder Patterson
Manassah was born February 17, 1848 and married Mary E. Peddar, born September 26, 1852. They married July 22, 1875. The marriage was announced in the Perth Courier as follows: “PATTERSON – PEDDAR At the residence of the bride’s uncle, Andrew Elliott Esq., Almonte, on the 22nd inst. by the Rev. John Bennett, minister of St. Andrew’s Church, Mr. Manasseh Patterson, Druggist, to Mary Elliott Peddar.” The Ontario Archives Microfilm lists the marriage of Manassah Patterson as follows:” Manassah PATTERSON, 27, druggist, Canada, Almonte, son of James PATTERSON and Bresaya POUNDER, married Mary Elliott PEDDAR, 22, Canada, Almonte, daughter of Joshua PEDDAR and Fanny HENLEY, witness Andrew ELLIOTT of Almonte, 22 July 1875 at Almonte.”
Two sons were born; James F.( born 1877) and Francis E.(born April 19, 1880), who was known as Frank. Manassah was a druggist and owned Patterson’s Drug Store on Mill Street in Almonte. In the 1880’s, the first telephone exchange in Almonte operated from the rear of the drug store. As an agent of the Bell Telephone Company, Manassah used a primitive switchboard to manage the calls from among the original 29 subscribers to the new service.
Manassah Patterson was involved in and promoted horse racing. An article in the Renfrew Mercury July 4, 1884 reported that a proposition had been made whereby Almonte could secure an excellent and convenient driving park and public recreation grounds at a minimum cost. “Mr. M. Patterson proposes, at his own expense, to purchase 20 acres of the Robert McFarlane farm, adjoining the corporation, at to lease it, to an association to be formed for that purpose for a term of years to be agreed on and at a minimal cost. The association will gradually fit it up with a driving track and suitable grounds for athletic sports.” In the fall of 1886, Manassah travelled to the great Glenview horse sale in Kentucky with Dr. Preston, A. C. Burgess of Carleton Place, and Mr. Lawson of Almonte. The group was looking to purchase horses and was impressed by the beauty and strength of the horses in Kentucky. In July, 1889, Manassah was a judge at the Renfrew horse races.
An interesting article in the Perth Courier dated August 7, 1896 was reprinted from the Almonte Gazette as follows. “Mr. Mannaseh Patterson has patented a new disc-adjusting, oil-retaining, dust-proof ball-bearing for bicycles that he himself invented. It has features that strongly recommend it, and it will doubtless be secured by some of the leading manufacturers in the near future. We trust the inventor may find at least a few thousand in it.”
From the Carleton Place Herald July 3, 1900, regarding Almonte affairs: “Cadet Frank Patterson has arrived home from the Royal Military College at Kingston this week and is receiving the congratulations of his friends on having graduated from that institution; he and Cadet Boyd Caldwell of Lanark being equal in number of marks won and both being well up in the list of graduates.”
From the Almonte correspondent to the Carleton Place Herald, May 7, 1901: Frank E. Patterson, son of M. Patterson, of this town, who graduated from the Royal Military College a year ago, has graduated from McGill College last week as a Bachelor of Science. He took the Civil Engineering course. Mr. Patterson returned home on Tuesday and is busy receiving the congratulations of friends.
At the 1901 census, Mannasah, druggist, and his wife Mary lived at Almonte with their son Francis E., who was at that time a student aged 20.
James Patterson married Minnie McArthur, the daughter of William McArthur and Elizabeth Manson. From the Almonte Gazette, November 23, 1906. “On Tuesday evening, the home of Mr. and Mrs. William McArthur was the scene of a happy event when their second daughter Minnie Iolene was united in the holy bonds of matrimony with James F. Patterson, eldest son of Mr. and Mrs. M. Patterson, Rev. Orr Bennett officiating. The ceremony took place in the presence of only the immediate friends of the contracting parties. The bride’s dress was pointe d’esprit over white silk and she carried a bouquet of white roses. There were no attendants. After congratulations were extended, the party repaired to the dining room which was beautifully decorated with white and pink roses, carnations, ferns and smilax and where the wedding supper was served. Rev. Mr. Bennett, in a short congratulatory speech, conveyed the felicitations of the company to the bride, and those were responded to on her behalf by the bridegroom. The bride was the recipient of many beautiful and useful tokens of esteem from friends among them being several substantial checks. The groom’s gift to the bride was a very pretty gold watch and chain. At half past ten Mr. and Mrs. Patterson, the latter gowned in a traveling suit of dark grey with hat to match left for Carleton Place where they took the midnight train to Toronto and other places. Mr. and Mrs. Patterson enjoy the hearty good wishes of many friends for a life of pleasure and prosperity such as rarely falls to human kind.” From the Carleton Place Herald December 4, 1906.”James Patterson, son of M. Patterson of Almonte, married Minnie McArthur, daughter of William McArthur last Tuesday evening. The young couple drove up here and took the train to Toronto, for their home.
The death of Manassah was reported in the Perth Courier on Friday February 15, 1907 as follows. ” M. Patterson, the well known druggist of Almonte died at Cobalt on Saturday of pneumonia.” A more complete obituary was published in the Almonte Gazette on the same date. This obituary has been provided to me by Jason Gilmore whose family currently resides in the home once owned by Manassah Patterson and his family.
“Death. At Cobalt, Feb. 9, 1907, Mr. M Patterson, of Almonte, aged 59 years.”
Another Citizen Gone
Mr. M. Patterson Dies After a Few Days’ Illness of Pneumonia
Another death following a startlingly brief illness has deprived Almonte of one more prominent citizen. Mr. Manassah Patterson, who passed away at Cobalt on Friday evening last after just one week’s illness from pneumonia. Mrs. Patterson and her sons, Mssrs. James and Frank, went up to Cobalt on Tuesday morning of last week, but on Thursday the two latter returned home, with little thought that the end was so near, on the contrary, buoyed up with the news coming home of their father’s early recovery and it was hard to believe the sad news that came Saturday morning announcing his death. Mr. Patterson had been in the Cobalt district looking after some mining property, and caught cold which developed into pneumonia and ended fatally. The remains were brought home and interment took place on Monday afternoon to St. Paul’s Church and cemetery, Rev. Rural Dean Bliss conducting the services. The pall bearers were Mssrs W. Thoburn, J.M. Rosamond, J. W. Wylie, J. B. Wylie, A. Young and A.M. Greig. Notwithstanding the bitter cold there was a large and representative gathering of townspeople to pay the last tribute of respect to one who was respected and esteemed by his fellow citizens and businessmen.
The late Mr. Patterson was born in Perth, a son of the late James Patterson of that town, and was 59 years of age. About thirty-six years ago he came to Almonte and took a position with Mr. Shaw, a druggist, and shortly afterwards he bought the business and conducted it for a time in the building now occupied by Mr. Therien. In later years he built the brick store on Mill Street, which he occupied for nearly thirty years. Mr. Patterson took a deep interest in military matters and went to the front with the Perth company in 1866, and afterwards retained continuous connection with the militia, and held the position of Staff Sargeant in the 42nd Regiment. His inclination led him into agriculture and stock-raising and for quite a few years he occupied the Lt. Col. Gemmill farm within the corporation. He was of a progressive disposition and had from time to time been connected with enterprises outside his regular business as druggist, and at the time he was taken ill he was looking after some mining properties in which he was interested. He also took an intelligent though quiet interest in public matters, and was prevailed upon one or two occasions to accept a position at the council board, which he filled in a most creditable manner.
About thirty years ago he was married to Miss Mary Peddar, of Doon, and to them two sons were born. Of these James is a druggist, and has had charge of the drug store here for the past three or four years. Frank is a civil engineer and has a good position with the government in Ottawa in the engineering department. Mr. Patterson was a quiet, unostentatious man, a good citizen and one who will be missed from the business and social circles of town.”
The Perth Courier of Sept. 17, 1909 reported that fire swept through the town of Almonte on Sept. 10th, completely destroying the chief business block on the Main Street. Patterson’s Drug Store owned by M. Patterson estate, was one of the affected businesses. J. T. Patterson, druggist lived over the store and had to hurry his family out of the building. The front wall of Patterson’s building fell over onto the sidewalk, breaking the telegraph pole which struck Mr. Henshaw. Bank Manager Henshaw of the Bank of Montreal died from his injuries.
The 1911 census shows that James Patterson, aged 33, born July, 1877, was living at 74 Argyle Street, Toronto West. He lived with his wife Minnie Patterson, aged 32, born June, 1878. James was a blacksmith, an Anglican of Scotch origin. The 1911 census also shows that Francis Patterson was living on Slater St. in Ottawa, single, aged 30 and working as a civil servant for the Dominion of Canada government. His religion was Unitarian.
Manassah Patterson’s wife, Mary Peddar Patterson died 1940 and is buried in the family plot in Almonte, Ontario. Francis E. Patterson who lived from 1880 to 1942 is buried with his parents at St. Paul’s Anglican Cemetery. –Rootsweb
Historical Notes: Druggist P.C. Dowdall opened his Almonte store in 1880, and was was still serving those with constipation in 1935. Druggist Manassah Patterson (also known as John) Manassah was a druggist and owned Patterson’s Drug Store on Mill Street in Almonte. He initially came to Almonte and took a position with Mr. Shaw, a druggist, and shortly afterwards he bought the business and conducted it for a time in the building now occupied by Mr. Therien. Read-Constipation Guaranteed to be Cured in Almonte
34, 36, and 38 Mill Street: When Stafford’s Hotel was destroyed in an 1877 fire, it was replaced by three, three-storey brick buildings, which were later also destroyed in a 1909 fire
and replaced by the current two-storey buildings.45 The first telephone service in Almonte operated from Patterson’s Drug Store, located in one of these buildings, during the late 19th century.
Ephraim George Patterson was educated at Perth Grammar School in Perth before attending Toronto University. An article in the Perth Courier on September 11, 1863 shows his potential. “Toronto University. At the recent examinations at the University College, Toronto, for the admission of students, and the distribution of Scholarships, we are pleased to observe that Master Ephraim Patterson, son of Mr. James Patterson of this town, took a scholarship for general proficiency worth $120. per year. Young Patterson possesses more than ordinary talent, and his standing in the university, where he had to compete with the cleverest students in the province, must be a source of gratification to his parents; besides it shows that the Perth Grammar School in preparing students for college, is equal if not superior to any similar institution in Canada”
From the Perth Courier, June 30, 1871. “Our Perth Readers will learn with pleasure that E.G. Patterson, son of James Patterson of this town and an assistant teacher in the Hamilton High School will deliver a lecture in the town hall of Perth on “The Progress of Astronomical Science” in about three weeks time. The subject of the lecture is a grand one for the man of thought and learning and we are confident that Mr. Patterson will do it justice. The lecture will be accompanied by a reading from Tennyson. In the future, we shall be able to name the date more definitely. In the meantime we only copy the following notice of the lecture where it was previously delivered: “Mechanics Hall E.G. Patterson, M.A., lectured to a large and intelligent audience in the Mechanics Hall last night in aid of funds of that institution, taking for his subject ‘Astronomical Science’. The lecturer sketched the progress of the science from its infancy in the times when naught but the ideas of the heathen were promulgated. He gave many of the theories and discussions of scientists, men through the centuries to the present including those of Ptolemy, Galileo, Kepler, Newton, Laplane. He pointed out the sublimity and extent of this study and referred to the various phenomenon which now present themselves. The lecture was well received and exhibited great care in its preparation. It was delivered clearly, slowly, and with great taste and the display of facts, indicating an extensive acquaintance with the subject. Times.”
An article dated May 22, 1874 in the Perth Courier stated that, “our old friend, Mr. E. G. Patterson, at an examination held at the Law School, Toronto, passed for both an attorney and a barrister, without an oral. For barrister, he passed with unusual honours–beating all competitors, and obtaining 528 marks out of a possible 600–110 more than the next highest candidate.”
George Patterson started his law practice in Hamilton, as early ads indicated he and William Laidlaw formed the law firm of Laidlaw & Patterson. On the 1881 Canadian Census, George Patterson is 35 years old, a barrister living in Burlington, Halton, Ontario. His ethnicity is listed as Scottish. His wife is shown as Anna G. Patterson, age 29, background English. The children are: Harold, age 5, Anna, age 3 and Winford, 3 months. (Note, the names Anna and Winford are misspellings by the census taker of Amy and Winifred–see the children below.)George and his young family then moved to Winnipeg in 1882. At that time, he placed an ad in the Globe and Mail Saturday May 27, 1882 as follows: George Patterson, late of Hamilton, Barrister, has removed to Winnipeg to practise his profession. Offices No. 429 Main St., over Blue Store. George became a partner in a firm with his cousin-in-law, George William Baker, and they called themselves, Patterson & Baker. Barristers, Attorneys.
For more information on E. George Patterson’s law partner, George William Baker, see the Baker page of this website.
The 1901 census shows that George Patterson and his family were living in Winnipeg. George was a widowed barrister, aged 54, born April, 1847. His grown sons and daughters lived with him, along with a female servant. The family consisted of Amy, aged 22, born August 1878; Harold, aged 24, born May, 1976; Winifred, aged 19, born January 1891; and Gordon, aged 15, born May 1885. All but Gordon were born in Ontario. Gordon was born in Manitoba. Harold is listed as a clerk.
On August 24, 1908, George Patterson, a widowed barrister, aged 62, married Gertrude Viola Geddes, aged 31, at St Mark’s Church, Niagara-On-The-Lake. George is the son of James Patterson and Jane B. Pounder. Gertrude Viola is the daughter of Forbes Geddes, and Elizabeth Begue. Witnesses were Ambrose H. Beavin of Pittsburgh, PA, and Elsie H. Geddes of Niagara.
The 1911 census shows that George Patterson and his family were living in Winnipeg at the Dorchester Block. George was aged 64, born April, 1847. He is the Deputy Attorney General for Manitoba and his workplace is the Parliament Buildings. His wife Viola was aged 34, born February, 1877. Their son George G. Patterson was aged 2, born July 1909. A nurse named Mary Phillips also lived with the family. The family is listed as Scotch in origin and of the Anglican religion.
Obituary of Ephraim George Patterson
Taken from the Manitoba Free Press, Winnipeg, Monday, August 24, 1925
GEORGE PATTERSON, K.C. DIES SUNDAY, AGED 79
Was for Many Years Deputy Attorney-General of Manitoba
Was Active in His Duties Until Recently, Death Following Brief Illness
George Patterson, K.C., aged 79 years, 162 Lilac Street, died in the Winnipeg General Hospital at 1 p.m. Sunday. He was up to the time of his death, referee and master of the court of King’s bench, and for many years the deputy attorney-general of Manitoba. He had been ill but a short time.
He was born in Perth, Ontario, where his father, James Patterson, was a carpenter. His grandfather, George Patterson, was a veteran of Wellington’s armies in Spain and at Waterloo, came to Canada about 1820 and settled in Lanark County.
Mr. Patterson was educated at the public and high schools of Perth, Ontario. He was graduated from Toronto University, winning the gold medal in mathematics. He taught mathematics for some years in Hamilton, before studying law. For several years he was examiner in mathematics at Toronto University and later on, when coming to the west to the University of Manitoba.
He was a member of the university company of the Queen’s Own Rifles, and, having taken a lieutenant’s course at the Royal Military College, Kingston, he took part in the fight at Ridgeway with the Fenians in 1866, when he was wounded and for which he received the Fenian raid medal. He obtained a first class military school certificate in the same year.
When called to the bar of Ontario in 1876, Mr. Patterson was mathematical master in the Hamilton Collegiate Institute. He practised law in Hamilton until 1882, when he came to Manitoba, where he practised for a number of years. The first firm was Patterson and Baker, then Aikins, Culver and company, Aikins, Patterson and McClenigan, and finally, Patterson and Howard.
Appointed as deputy attorney-general in 1898, he held that position until his appointment as referee and master of the court of King’s bench. While deputy attorney-general, Mr. Patterson was for a time, law clerk for the government, and as deputy attorney-general, had been chief crown attorney for the province, conducting the prosecutions of all the chief criminal cases before the Winnipeg assizes for a number of years. He was made a K.C. in 1909 and had been editor of the Manitoba Law Reports since 1903.
Mr. Patterson was one of the original members of St. Luke’s Anglican Church and he had acted as both rector’s and people’s warden. He was an ardent golfer, a member of the Winnipeg Chess club and of the Winnipeg Lawn Bowling club.
He was twice married, his first wife being Annie Gertrude Baker, daughter of the late Hugh C. Baker of Hamilton, Ontario. She died in 1897. He married, some years later, Viola Geddes, daughter of the late Forbes Geddes, of Niagara-on-the-Lake. Three children of the first marriage and one of the second survive, with his widow. The surviving children are: Harold D. Patterson, Victoria, B.C.; Mrs. Amy Edwards, Winnipeg; Mrs. Leslie Ford, Perth, Australia; and George D. Patterson of Winnipeg.
Annie Gertrude Baker (October 18, 1851-1897) was the daughter of Hugh Cossart Baker (1818-1859) and Emma Wyatt (1824-1859). Hugh Cossart Baker, descended from Sir John Baker Kt of Sissinghurst, founded the Canada Life Assurance Company. Annie Gertrude’s brother, Hugh Cossart Baker started the first telephone exchange in the British Empire. George Patterson, Hugh’s brother in law, was an early stockholder and supporter. See the Baker page of this website.
MEMORANDA June 11, 1903. Made by George Patterson of Winnipeg, Barrister, for the information of his children and descendants.
I am the eldest son of James and Jane Patterson of Perth, Ontario and was born there on 20 April, 1846. My father, who died in October 1902 at Perth, was the last surviving son of George Patterson, a Scotch soldier in the Army of Wellington, who came to Canada about 1815 and settled near Perth. My grandmother Ann Patterson was English and came out with him. My mother was also born in Canada of Irish parents named Pounder. She was a most devoted and saintly mother and until the last few years of her long life had little rest from hard work except when laid up with severe illness. She literally gave herself wholly to the work of training up and caring for her large family without a thought of self. She was perhaps the meekest, most patient and most loving wife and mother that ever lived.–Rootsweb
Enjoyed seeing this article. Bresaya Jane Pounder was the sister of my gr gr gr grandmother Sarah Allan Pounder who married John Devlin in Perth, Ontario. The Pounder family emigrated from Enniscorthy, County Wexford to settle in Perth, Upper Canada.
Last week those two large poplar trees which have stood the breeze and sheltered the building occupied by Mr. Patrick C. Dowdall’s Medical Hall and Mr. R. J . Dowdall’s residence for “ years and years,” as Miss Ophelia in Uncle Tom’s Cabin would say, were removed from public view, as well as the smaller maple ones in front of Mr. Geo. Wilson’s new store.
They were, indeed, pop(u)lar trees, and although it seemed to those who claimed the right of ownership to them that their usefulness had become a thing of the past, they were nevertheless removed with a degree of sadness to more than the owners, which carried many back in thought to the good old school days when children used to rhyme in merry glee that beautiful piece entitled “ Woodman, spare that tree.”
But the woodman did not spare the trees. He, instead, applied his axe vigorously to their trunks, and a few hours sufficed to remove from the gaze of an admiring public half-a-dozen or more ornaments, which, in days past, were the pride of their owners. The change, however, is considered an improvement, more particularly as the street is one of the principal and most public ones in town
Almonte lost its oldest businessmen, Wednesday night, in the passing of Mr. Patrick Connor Dowdall, at the age of 80 years. “P. C.” as he was known, was one of the town’s finest citizens in every sense of the word. Through the long years that he conducted his drug business, here, he built up a reputation for fair dealing and good citizenship that is seldom equalled.
Born in Perth in 1856, a son of the late Edward Dowdall and his wife, Mary O’Connor, “P. C.” came to Almonte with his parents as a young child. His grandfather, Patrick Dowdall, was one of the original settlers of Lanark County, having come out from Westmeath, Ireland, in 1818 with his wife, Judith Keating settled on land granted by the Go; ernment near the military post, Perth-on-the-Tav.
The late Mr. Dowdall received his primary education in the schools of Almonte, after which he was apprenticed to a druggist in Pembroke. Upon graduating from the College of Pharmacy at Toronto he debated for a time whether he should take a position in Pembroke or start a business of his own in Almonte, then a thriving woollen town. He finally decided on the latter course and in March of 1880, he opened the store until the time of hfs death.
For the last six months Mr. Dowdall had been confined to his home through ill health and his daughter, Miss Dorothy, a graduate pharmacist who had assisted him for some years past, carried on in his absence. Mr. Dowdall’s death was not unexpected but nonetheless caused widespread regret in this town and district where he was so well and favorably known.
While never inclined to push himself forward Mr. Dowdall showed his good citizenship by shouldering a full measure of responsibility in connection with public service. He was for some years a member of the Board of Education; a town councillor, and, as deputy-reeve in the days when Almonte by virtue of its population was entitled to a deputy, he gave his best on the local body and on the county council at Perth.
He also served for a time on the Public Utility Commission of the town, and had for their objective the advancement of civic interests. In 1891 Mr. Dowdall married Miss Anne E. Boyle of Toronto, daughter of the late Mr. and Mrs. Patrick Boyle. Two sons and two daughters were born to this union, namely, Dr. Geoffrey Francis Dowdall, a graduate of McGill University, whose early death in 1929 was a great source of grief to- the father; Edward, a barrister in Kitchener, Ont.; Miss Eileen Dowdall, B.A. of the Imperial Bank staff, Toronto, and Miss Dorothy a t home, who was associated with her father in the business.
Of Mr. Dowdall’s immediate family only two members survive, a brother Frank at Port Dalhousle and a sister Mrs. Albert Dwyer (Teresa) of Almonte. Another sister, Mrs. William McGarry, mother of the late Bob. Thomas McGarry of Renfrew and four brothers, Richard, James, Edward ‘and John predeceased “P. C ” The funeral will be held on Saturday morning a t eight o’clock from the family home on Perth street, to St; Mary’s Roman Catholic Church, thence to St. Mary’s cemetery. Almonte Gazette 1933
The first storey storefronts of this building have been modified from the original glass windows for easier viewing of merchandise–hence the different colours of brick. 127-131 Bridge Street has housed a number of different businesses including pharmacies, clothing stores, grocery stores, and poolrooms.
The Hughes family bought the pharmacy from Dr. Preston in 1905.
W. J. Hughes Rexall Drug store was located on the corner and Thomas Lloyd Hughes born in 1897 along with his brother Harold until they each decided to run a smaller store at the opposite ends of town. Lloy’s store was on Moffatt Street and Harold on Lake Ave West. For 50 years they were in groceries together and then the store was sold to Thomas’s nephew and for 12 years Thomas drove a butcher wagon. There was a dark room at the rear of the store where Mr. Hughes tested your eyes for glasses. You could buy a roll of film #116 for a Brownie Box camera for 25 cents and for $1.25 he would send it away to be developed.
The folks in Carleton Place will always remember the Rexall Drug annual 1 cent sale and every local household stocked up on cough medicine, cough drops, peroxide and all sorts of liniment. Some of the clerks that worked there were: Olive Dick, Ruby Voyce, and John Briscoe and Wilbert Robertson.
Harvey Asselstine attended the Ontario College of Pharmacy in 1929. In 1944, he returned to Carleton Place and bought the drugstore at the corner of Bridge and Franklin, from W.J. Hughes who operated it for 38 years. Betty Findlay and Mary Cook both worked at Assestine’s Pharmacy. In the rear of Asselstine’s drug store the CPR Telegraph operated during the 1950s. Asselstine expanded his drug store and bought out Hughes Grocery. In 2006 the Athen’s Corners Restaurant was located there.
Taber and McCrae operated a Men’s and Boy’s clothing store within Struther’s Block, which later became a pool hall (next door) operated by Mel Barclay. Charlie Giroux, who only had one arm took over the pool hall then Ab Dowseth from Smiths Falls operated it for a short time but when McCann and Porter gained ownership they moved the pool hall to the old Bank of Commerce.
Jeremy Stinson— That corner was, for much of my childhood, the home of the Blossom Shop. Back before the one way street.
Son of William James Hughes and Mabel Vaughan (nee Strong) Hughes, of Carleton Place, Ontario. Brother of Freda, Morley and Cyril. The Town of Carleton Place remembered Pilot Officer Hughes by naming a street for him.
While going through a box full of old photograph plates in the stockroom at the rear of D. W. Snedden’s drug store, Mr. Kenneth Johnson, who is an ardent amateur photographer, unearthed a treasure trove. Apparently the late M. R. MacFarlane, or one of his staff, followed the same hobby as Mr. Johnson. Those were the days of large cameras with glass plates almost as big as a school slate. And they made good pictures, too, as can be seen by the samples Mr. Johnson developed and which are now on display in Mr. Snedden’s drug store window.
A reproduction of one of them appears on the top section of this page. The scenes developed from the old plates recall memories for the elder generation of this town and would be appreciated by out-of town readers of the Gazette who are no longer in the junior age group.
We see among them a picture of the late Dr. Hanley sitting in his buggy in front of M. R. MacFarlane’s residence on Church Street. He wears a hard-shell hat and the horse looks tired, like most doctors’ horses did in those days.
There are pictures of Dr, Oliver MacFarlane and Jack Taylor in the knee-length pants worn by children of that period; groups of women in long skirts and big hats of their time, few of them who can be identified; splendid scenes of the old stone bridge on Main Street, the churches of the town, the town hall, the Almonte Flour Mills with the railway bridge then supported by stone piers the old steel bridge with the arches, later to be replaced by the present one; up and down views of Elgin, Church and Country Streets, and, as the auction sale bills say, many others too numerous to mention.
One of the priceless pictures shows Mr. Porritt’s ancient automobile with young MacFarlane standing on the front seat. It is said to be the first horseless carriage to arrive in Almonte, and what it did to the horses can better be imagined than described. Maybe we’ll get around to printing a picture of it one of these days. The whole collection of pictures which Mr. Johnson has resurrected is most interesting and should be grouped, framed and placed in the public library or the council chamber.
In the street scene printed above can be seen the edge of the late H. H. Cole’s store, Kelly’s Hotel which had been sold to a Mr, Me-Donald, Shorty Young’s shoe store and shoe shine, Patterson’s Drug Store, the Riddell & McAdam Building, then occupied by Wesley West; J. McKinnon’s, Shaw’s Hardware, John O’Reilly’s general store, and on the left— J . L. Hamilton, photographer, in the brick building later moved back from the street and occupied at that time as an office for Baird’s Mill, later to be used as an office for the P.U.C,, arid demolished some ten years ago; and in the distance, the clockless post office. The clock came about 1913. Read—The Mystery of the Almonte Post Office Clock –Five Minutes Fast and other Things….
The Kickapoo Indian Medicine Company, founded in 1881 by John E. “Doc” Healy, “Texas Charlie” F. Bigelow, and “Nevada Ned” Oliver, took their cure-all pitch on the road. Based in New Haven, Connecticut, the company hired hundreds of Native Americans, said to be of the Kickapoo tribe, to tour America and Europe, teaching “Indian ways” and peddling its medicines. The names of their travelling salesmen can be seen on the registry of the Queen’s Hotel from the late 1800s which is at the Carleton Place and Beckwith Heritage Museum
More and more remedy-makers began to put on their own elaborate medicine shows, like Big Sensation Medicine Company and Hamlin Wizard Oil of Chicago, which came to town with a circus-like ruckus—its caravan of wagons was led by a band.
In fact, medicine shows were major events in the towns they visited. With live skits, music, juggling, acrobatics, feats of magic, sword swallowing, and ventriloquism, it was the most excitement most places would see for months. Some shows even travelled with their own flea circus or sideshow-freak acts. Stores would close, children were allowed to skip school, and residents would don their Sunday best.
Of course, the main event was always the pitch for bottled treatments such as Professor Low’s Liniment & Worm Syrup, Dalley’s Magical Pain Extractor, Dr. Kilmer’s Swamproot, Hood’s Sarsaparilla, Wistar’s Balsam of Wild Cherry, Dr. King’s New Discovery, Edgar’s Cathartic Confection, and Schenck’s Mandrake Pills.
Many travelling “doctors” with dubious credentials knew how to create the illusion that such products worked. They would rub an arthritic’s afflicted arm or foot until the pain seemed to dull. They understood that washing out earwax improved anyone’s hearing. Some even distributed pills filled with long pieces of string so the taker would appear to expel tapeworms in their stool. Often, the medicine company would place a shill in the audience, who would pretend to be sick and claim the treatment had worked a miracle.
Toward the end of the century, the American public, fed up with being scammed by these peddlers, took to campaigning against what Collier’s magazine dubbed, in 1905, “The Great American Fraud.” Families were also concerned about the effects of alcohol and narcotics like opium on their children. Around the same time, the Germ Theory of Disease, validated by the 19th-century research of Louise Pasteur and Robert Koch, was becoming widely accepted in the practice of medicine. All of this eventually led to the Pure Food and Drug Act of 1907.
This ointment tin from the early 20th century was just added to our to the Carleton Place and Beckwith Heritage Museum’s collection! The tin was manufactured by MacDonald MFG Ltd in Toronto and it contained a mixture of mercurial ointment and petroleum jelly. We have little information on what year it was manufactured and what the ointment may have been used for specifically. If you recognize this design or have more information, please let us know!
On this date in 1927, Prime Minister Mackenzie King and British Prime Minister Baldwin inaugurated a transatlantic telephone service between Canada and Great Britain.

domain: history