Marie-Odile Benoit-Biancamano | Université de Montréal (original) (raw)
Papers by Marie-Odile Benoit-Biancamano
The FASEB Journal, Mar 31, 2016
Journal of Veterinary Diagnostic Investigation, Aug 21, 2022
Glucose and trehalose are the main energy sources used by honeybees ( Apis mellifera) for daily a... more Glucose and trehalose are the main energy sources used by honeybees ( Apis mellifera) for daily activities. However, there is no validated point-of-care method to reliably measure both sugars. We performed an analytical validation of a portable human glucometer (Accu-Chek; Roche) for glucose measurement in honeybee hemolymph compared to a reference method (GluCH, UniCel DxC 600; Beckman Coulter). We used 30 pooled hemolymph samples collected from the antennae of anesthetized honeybees and diluted 1:4 in 0.9% saline. We evaluated dilution linearity, spike recovery, and inter- and intra-assay imprecision. Glucose concentration was measured over time (2 h, 4 h, 8 h, 12 h, 1 d, 2 d, 3 d, 7 d, 21 d, 28 d) at various storage temperature (25°C, 4°C, −20°C, −80°C). The trehalose concentration was measured indirectly by trehalase hydrolyzation. Glucose concentrations measured by both instruments had a strong correlation (0.985, p < 0.0001) and a bias of −7.33 mmol/L (±1.96SD: 13.70 to −28.36), with linear agreement at <20 mmol/L (physiologic value: 100 mmol/L). The accuracy of the glucometer decreased at >20 mmol/L. Recovery of 115–130% of diluted spikes indicated good specificity. Inter- and intra-assay imprecision were 2.50% and 2.21%, respectively. Glucose concentrations fluctuated in stored samples dependent on time and temperature; however, glucose concentrations were constant with storage at −80°C for ≥28 d. The Accu-Chek glucometer is an adequate instrument to measure honeybee glucose concentration in hemolymph diluted with 0.9% NaCl, with good accuracy and precision at <20 mmol/L. Hemolymph storage at −80°C is suitable for long-term conservation of glucose.
Veterinary Clinical Pathology, Mar 1, 2023
Current Zoology, Oct 1, 2019
Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here... more Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here, we report that folic acid (FA) supplementation mitigates sperm miRNA profiles transgenerationally following in utero paternal exposure to POPs in a rat model. Pregnant founder dams were exposed to an environmentally relevant POPs mixture (or corn oil) 6 FA supplementation and subsequent F1-F4 male descendants were not exposed to POPs and were fed the FA control diet. Sperm miRNA profiles of intergenerational (F1, F2) and transgenerational (F3, F4) lineages were investigated using miRNA deep sequencing. Across the F1-F4 generations, sperm miRNA profiles were less perturbed with POPsþFA compared to sperm from descendants of dams treated with POPs alone. POPs exposure consistently led to alteration of three sperm miRNAs across two generations, and similarly one sperm miRNA due to POPsþFA; which was in common with one POPs intergenerationally altered sperm miRNA. The sperm miRNAs that were affected by POPs alone are known to target genes involved in mammary gland and embryonic organ development in F1, sex differentiation and reproductive system development in F2 and
Pharmacogenomics, Jul 1, 2008
PubMed, 2022
The objective of this study was to describe the histological and histochemical characteristics of... more The objective of this study was to describe the histological and histochemical characteristics of the lacrimal glands of beluga whales. The study was carried out on the formalin-fixed ocular globes from 96 carcasses of beluga whales found stranded in the St. Lawrence estuary in Quebec, Canada. Hematoxylin and eosin (H&E) stained slides from the eyes of each whale were examined for lacrimal glands. Histological description was done with H&E and Masson Trichrome (MT) stains. Period Acid-Schiff (PAS), Alcian blue (AB) pH 1.0 and 2.5, and High Iron Diamine (HID) stains were used for histochemical characterization of glycoproteins. Thirteen ocular samples from animals ranging from neonate to 48 y included sections of lacrimal glands. The H&E stain revealed a tubuloalveolar gland architecture, separated into lobules by dense connective tissue. Each lobule contained a mixture of acini and tubules with ductules. Small and large acini were composed of low and tall columnar cells, respectively. Acinar cells contained basophilic cytoplasmic granules. The ductules were lined with a bi-layered cuboidal-to-squamous epithelium. The MT stain highlighted the connective tissue separating ductules and acini. Large acini were positive for PAS and some small acini had patchy uptake. Positive staining for AB pH 1.0 and 2.5 was mainly seen in tall columnar cells as compared to small acini that had faint to no stain uptake. High Iron Diamine stain revealed 90% staining of all acinar cells, with 10% exhibiting a mixed blue-black tinge. It was concluded that the lacrimal glands of beluga whales have similar histological and histochemical findings to those of artiodactyla and carnivora orders.
Scientific Reports, Sep 25, 2019
The paternal environment is thought to influence sperm quality and future progeny may also be imp... more The paternal environment is thought to influence sperm quality and future progeny may also be impacted. We hypothesized that prenatal exposure to environmentally-relevant contaminants impairs male reproduction, altering embryo gene expression over multiple generations. folic acid (fA) can improve sperm quality and pregnancy outcomes, thus we further hypothesized that FA mitigates the contaminants. Sprague-Dawley F0 female rats treated with persistent organic pollutants (POPs) or corn oil and fed basal or supplemented FA diets, then used to yield four generations of litters. Only F0 females received POPs and/or FA treatments. In utero POPs exposure altered sperm parameters in F1, which were partly rescued by FA supplementation. Paternal exposure to POPs reduced sperm quality in F2 males, and the fertility of F3 males was modified by both POPs and FA. Ancestral FA supplementation improved sperm parameters of F4 males, while the POPs effect diminished. Intriguingly, F3 males had the poorest pregnancy outcomes and generated the embryos with the most significantly differentially expressed genes. Early-life exposure to POPs harms male reproduction across multiple generations. FA supplementation partly mitigated the impact of POPs. The two-cell embryo transcriptome is susceptible to paternal environment and could be the foundation for later pregnancy outcomes.
Veterinary Clinics of North America-small Animal Practice, Mar 1, 2023
Lactic acid bacteria and bifidobacteria (LAB & Bifido), isolated from the gastrointestinal tract ... more Lactic acid bacteria and bifidobacteria (LAB & Bifido), isolated from the gastrointestinal tract of Apis mellifera intermissa (BGIT), honey (H), propolis (P) and bee bread (BB) of hives set in different vegetations (wildflowers, caraway, orange blossom, Marrubium vulgare, Eucalyptus and Erica cinerea), were subjected to analysis of their antibacterial potential. Isolates able to inhibit Staphylococcus aureus were selected and identified with MALDI-TOF MS leading to 154 strains representing 12 LAB & Bifido species. Lactiplantibacillus plantarum, Pediococcus pentosaceus and Enterococcus faecalis were predominantly found in all matrices. BGIT showed the highest LAB & Bifido diversity with exclusive occurrences of five species (including Bifidobacterium asteroides and Limosilactobacillus fermentum). Honey was the second origin harboring an important variety of LAB species of which Apilactobacillus kunkeei and Enterococcus mundtii were characteristic of both H and BGIT. Principal compone...
Journal of Veterinary Diagnostic Investigation
Beekeeping plays a crucial role in biodiversity, pollination, commercial farming, and the worldwi... more Beekeeping plays a crucial role in biodiversity, pollination, commercial farming, and the worldwide agricultural economy. Histopathology, which is an important tool for the investigation of diseases in vertebrates, is not commonly used in honey bees ( Apis mellifera). However, histopathology could potentially help the diagnostic investigation of high mortality in bees. We developed a tissue fixation and processing method enabling systematic production of histologic slides adequate for diagnostic and research purposes. Our method uses inexpensive, accessible products and can be realized with conventional pathology laboratory equipment. The quality of histologic slides obtained is similar to those of vertebrate animals processed routinely in pathology laboratories. Histopathology as a diagnostic and research tool will improve the services currently offered to apiarists and could help decrease the mean mortality rate, increase apiarists’ profits, and ensure long-term pollination services.
Veterinary Sciences
Transscleral retinopexy is a preventive technique used against retinal detachment. Fundus examina... more Transscleral retinopexy is a preventive technique used against retinal detachment. Fundus examination can allow the monitoring of morphological retinal changes in the progression of photocoagulation lesions, without offering details on the morphological changes by the retinal lesion. The aim of the study was to assess the progression of photocoagulation lesions induced by transscleral retinopexy (840 nm diode laser), by comparing the optical coherence tomography (OCT) and histological images over a period of six weeks on eight pigmented New Zealand healthy rabbits (four males and four females; n = 16 eyes). All rabbits underwent transscleral retinopexy on their left eye on day 0 (D0). Measurements of the photocoagulation lesions were obtained in vivo on D0, D7, D15, D21, and D42 by acquiring OCT images of both eyes from all rabbits. On D1, D7, D21, and D42, two rabbits were euthanized, and their eyes were enucleated. A significant effect by time on the decrease in the central retina...
The Canadian veterinary journal. La revue veterinaire canadienne
Canadian Journal of Physiology and Pharmacology, 2015
Islet amyloid polypeptide (IAPP) has been shown to form amyloid deposits in pancreatic islets, th... more Islet amyloid polypeptide (IAPP) has been shown to form amyloid deposits in pancreatic islets, thereby furthering type 2 diabetes disease progression. Further discovery of new molecules is needed to create a diverse set of molecules that impede pancreatic amyloidosis. We have recently designed and synthesized N-phenyl-N′-(2-ethyl)ureas (EU) that are non-cytotoxic small molecules, to evaluate the role of the aryl-substituted moiety on the inhibition of hIAPP fibrillization. Several EUs were tested in vitro for their anti-amyloidogenic activity using the fluorometric ThT assay, the photo-induced cross-linking (PIUCP) assay, and cell survival assay in pancreatic MIN-6 cells. EU-362 and EU-418 were able to significantly inhibit the formation of hIAPP fibrils and protected cells from amyloid cytotoxic effects. Our results suggest that increasing the nucleophilic potency of the aryl moiety significantly enhances the anti-amyloidogenic activity of the molecules.
Canadian Journal of Physiology and Pharmacology, 2015
Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute an important pharmacotherapeutic class t... more Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute an important pharmacotherapeutic class that, over the past decade, have expanded in application to a panoply of medical conditions. They have been tested for neurodegenerative diseases such as Alzheimer’s to reduce inflammation and also in the attempt to abrogate amyloid deposition. However, the use of NSAIDs as aggregation inhibitors has not been extensively studied in pancreatic amyloid deposition. Pancreatic amyloidosis involves the misfolding of islet amyloid polypeptide (IAPP) and contributes to the progression of type-2 diabetes in humans and felines. To ascertain their antiamyloidogenic activity, several NSAIDs were tested using fluorometric thioflavin-T assays, circular dichroism, photo-induced cross-linking assays, and cell culture. Celecoxib, diclofenac, indomethacin, meloxicam, niflumic acid, nimesulide, phenylbutazone, piroxicam, sulindac, and tenoxicam reduced fibrillization at a molar ratio of 1:10. The circular ...
International Journal of Pharmacy and Pharmaceutical Sciences
Objective: Our research program has focused on the development of promising, soft alkylating N-ph... more Objective: Our research program has focused on the development of promising, soft alkylating N-phenyl-N'-(2-chloroethyl)urea (CEU) compounds which acylate the glutamic acid-198 of β-tubulin, near the binding site of colchicum alkaloids. CEUs inhibit the motility of cancerous cells in vitro and, interestingly, exhibit antiangiogenic and anticancer activity in vivo. Mitotic arrest induced by microtubule-interfering agents such as CEUs remains the major mechanism of their anticancer activity, leading to apoptosis. However, we recently demonstrated that microtubule disruption by CEUs and other common antimicrotubule agents greatly alters the integrity and organization of microtubule-associated structures, the focal adhesion contact, thereby initiating anoikis, an apoptosis-like cell death mechanism caused by the loss of cell contact with the extracellular matrix. Methods: To ascertain the activated signaling pathway profile of CEUs, flow cytometry, Western blot, immunohistochemistry...
Veterinary dermatology, Jan 14, 2015
Alopecia X in dogs is a noninflammatory alopecia that may be caused by a hormonal dysfunction. It... more Alopecia X in dogs is a noninflammatory alopecia that may be caused by a hormonal dysfunction. It may be similar to androgenic alopecia in men that is caused by the effect of dihydrotestosterone (DHT). The 5α-reductase isoenzymes, 5αR1 and 5αR2, and a recently described 5αR3, are responsible for the conversion of testosterone into DHT. However, which 5α-reductases are present in canine skin has not yet been described. The main objective of this study was to determine the pattern of expression of 5α-reductase genes in canine skin. Skin biopsies were obtained from healthy, intact young-mature beagles (three males, four females) at three anatomical sites normally affected by alopecia X (dorsal neck, back of thighs and base of tail) and two sites generally unaffected (dorsal head and ventral thorax). Prostate samples (n = 3) were collected as positive controls for 5α-reductase mRNA abundance measurement by real-time PCR. We detected mRNA encoding 5αR1 and 5αR3 but not 5αR2. There were n...
Canadian journal of diabetes, Jan 7, 2015
Deposition of islet amyloid has been associated with beta-cell death, thereby furthering diabetes... more Deposition of islet amyloid has been associated with beta-cell death, thereby furthering diabetes progression. Several hypoglycemic agents, such as thiazolidinediones, biguanide and dipeptidyl peptidase-4 inhibitors, have been known to preserve beta-cell mass, possibly by direct inhibition of islet amyloid formation. The general objective of this study was to evaluate the impact of the major representatives of hypoglycemic agents on amyloid formation by using in vitro molecular screening approaches. Ten prototypical representatives of hypoglycemic agents were evaluated for the inhibition of amyloid formation in vitro using thioflavin fluorescence assays, far-ultraviolet circular dichroism, photo-induced cross linking assays and cell viability assays. Glyburide, repaglinide and troglitazone showed the highest potency in delaying and reducing fibril formation. Troglitazone, a thiazolidinedione, was the most effective agent abrogating amyloid fibril formation. Troglitazone affected the...
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Jan 15, 2007
A method to determine total and free mycophenolic acid (MPA) and its metabolites, the phenolic (M... more A method to determine total and free mycophenolic acid (MPA) and its metabolites, the phenolic (MPAG) and acyl (AcMPAG) glucuronides, using HPLC and mass spectrometry was developed. Mean recoveries in plasma and urine samples were >85%, and the lower limits of quantification for MPA, MPAG and AcMPAG were 0.05, 0.05 and 0.01 mg/L, respectively. For plasma, the assay was linear over 0.05-50 mg/L for MPA and MPAG, and from 0.01 to 10mg/L for AcMPAG. A validation study demonstrated good inter- and intra-day precision (CV<or=11%) and accuracy (bias<or=16%) and satisfactory specificity and stability. Pharmacokinetic parameters were assessed in plasma and urine from healthy volunteers after an oral dose of mycophenolate mofetil.
The FASEB Journal, Mar 31, 2016
Journal of Veterinary Diagnostic Investigation, Aug 21, 2022
Glucose and trehalose are the main energy sources used by honeybees ( Apis mellifera) for daily a... more Glucose and trehalose are the main energy sources used by honeybees ( Apis mellifera) for daily activities. However, there is no validated point-of-care method to reliably measure both sugars. We performed an analytical validation of a portable human glucometer (Accu-Chek; Roche) for glucose measurement in honeybee hemolymph compared to a reference method (GluCH, UniCel DxC 600; Beckman Coulter). We used 30 pooled hemolymph samples collected from the antennae of anesthetized honeybees and diluted 1:4 in 0.9% saline. We evaluated dilution linearity, spike recovery, and inter- and intra-assay imprecision. Glucose concentration was measured over time (2 h, 4 h, 8 h, 12 h, 1 d, 2 d, 3 d, 7 d, 21 d, 28 d) at various storage temperature (25°C, 4°C, −20°C, −80°C). The trehalose concentration was measured indirectly by trehalase hydrolyzation. Glucose concentrations measured by both instruments had a strong correlation (0.985, p < 0.0001) and a bias of −7.33 mmol/L (±1.96SD: 13.70 to −28.36), with linear agreement at <20 mmol/L (physiologic value: 100 mmol/L). The accuracy of the glucometer decreased at >20 mmol/L. Recovery of 115–130% of diluted spikes indicated good specificity. Inter- and intra-assay imprecision were 2.50% and 2.21%, respectively. Glucose concentrations fluctuated in stored samples dependent on time and temperature; however, glucose concentrations were constant with storage at −80°C for ≥28 d. The Accu-Chek glucometer is an adequate instrument to measure honeybee glucose concentration in hemolymph diluted with 0.9% NaCl, with good accuracy and precision at <20 mmol/L. Hemolymph storage at −80°C is suitable for long-term conservation of glucose.
Veterinary Clinical Pathology, Mar 1, 2023
Current Zoology, Oct 1, 2019
Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here... more Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here, we report that folic acid (FA) supplementation mitigates sperm miRNA profiles transgenerationally following in utero paternal exposure to POPs in a rat model. Pregnant founder dams were exposed to an environmentally relevant POPs mixture (or corn oil) 6 FA supplementation and subsequent F1-F4 male descendants were not exposed to POPs and were fed the FA control diet. Sperm miRNA profiles of intergenerational (F1, F2) and transgenerational (F3, F4) lineages were investigated using miRNA deep sequencing. Across the F1-F4 generations, sperm miRNA profiles were less perturbed with POPsþFA compared to sperm from descendants of dams treated with POPs alone. POPs exposure consistently led to alteration of three sperm miRNAs across two generations, and similarly one sperm miRNA due to POPsþFA; which was in common with one POPs intergenerationally altered sperm miRNA. The sperm miRNAs that were affected by POPs alone are known to target genes involved in mammary gland and embryonic organ development in F1, sex differentiation and reproductive system development in F2 and
Pharmacogenomics, Jul 1, 2008
PubMed, 2022
The objective of this study was to describe the histological and histochemical characteristics of... more The objective of this study was to describe the histological and histochemical characteristics of the lacrimal glands of beluga whales. The study was carried out on the formalin-fixed ocular globes from 96 carcasses of beluga whales found stranded in the St. Lawrence estuary in Quebec, Canada. Hematoxylin and eosin (H&E) stained slides from the eyes of each whale were examined for lacrimal glands. Histological description was done with H&E and Masson Trichrome (MT) stains. Period Acid-Schiff (PAS), Alcian blue (AB) pH 1.0 and 2.5, and High Iron Diamine (HID) stains were used for histochemical characterization of glycoproteins. Thirteen ocular samples from animals ranging from neonate to 48 y included sections of lacrimal glands. The H&E stain revealed a tubuloalveolar gland architecture, separated into lobules by dense connective tissue. Each lobule contained a mixture of acini and tubules with ductules. Small and large acini were composed of low and tall columnar cells, respectively. Acinar cells contained basophilic cytoplasmic granules. The ductules were lined with a bi-layered cuboidal-to-squamous epithelium. The MT stain highlighted the connective tissue separating ductules and acini. Large acini were positive for PAS and some small acini had patchy uptake. Positive staining for AB pH 1.0 and 2.5 was mainly seen in tall columnar cells as compared to small acini that had faint to no stain uptake. High Iron Diamine stain revealed 90% staining of all acinar cells, with 10% exhibiting a mixed blue-black tinge. It was concluded that the lacrimal glands of beluga whales have similar histological and histochemical findings to those of artiodactyla and carnivora orders.
Scientific Reports, Sep 25, 2019
The paternal environment is thought to influence sperm quality and future progeny may also be imp... more The paternal environment is thought to influence sperm quality and future progeny may also be impacted. We hypothesized that prenatal exposure to environmentally-relevant contaminants impairs male reproduction, altering embryo gene expression over multiple generations. folic acid (fA) can improve sperm quality and pregnancy outcomes, thus we further hypothesized that FA mitigates the contaminants. Sprague-Dawley F0 female rats treated with persistent organic pollutants (POPs) or corn oil and fed basal or supplemented FA diets, then used to yield four generations of litters. Only F0 females received POPs and/or FA treatments. In utero POPs exposure altered sperm parameters in F1, which were partly rescued by FA supplementation. Paternal exposure to POPs reduced sperm quality in F2 males, and the fertility of F3 males was modified by both POPs and FA. Ancestral FA supplementation improved sperm parameters of F4 males, while the POPs effect diminished. Intriguingly, F3 males had the poorest pregnancy outcomes and generated the embryos with the most significantly differentially expressed genes. Early-life exposure to POPs harms male reproduction across multiple generations. FA supplementation partly mitigated the impact of POPs. The two-cell embryo transcriptome is susceptible to paternal environment and could be the foundation for later pregnancy outcomes.
Veterinary Clinics of North America-small Animal Practice, Mar 1, 2023
Lactic acid bacteria and bifidobacteria (LAB & Bifido), isolated from the gastrointestinal tract ... more Lactic acid bacteria and bifidobacteria (LAB & Bifido), isolated from the gastrointestinal tract of Apis mellifera intermissa (BGIT), honey (H), propolis (P) and bee bread (BB) of hives set in different vegetations (wildflowers, caraway, orange blossom, Marrubium vulgare, Eucalyptus and Erica cinerea), were subjected to analysis of their antibacterial potential. Isolates able to inhibit Staphylococcus aureus were selected and identified with MALDI-TOF MS leading to 154 strains representing 12 LAB & Bifido species. Lactiplantibacillus plantarum, Pediococcus pentosaceus and Enterococcus faecalis were predominantly found in all matrices. BGIT showed the highest LAB & Bifido diversity with exclusive occurrences of five species (including Bifidobacterium asteroides and Limosilactobacillus fermentum). Honey was the second origin harboring an important variety of LAB species of which Apilactobacillus kunkeei and Enterococcus mundtii were characteristic of both H and BGIT. Principal compone...
Journal of Veterinary Diagnostic Investigation
Beekeeping plays a crucial role in biodiversity, pollination, commercial farming, and the worldwi... more Beekeeping plays a crucial role in biodiversity, pollination, commercial farming, and the worldwide agricultural economy. Histopathology, which is an important tool for the investigation of diseases in vertebrates, is not commonly used in honey bees ( Apis mellifera). However, histopathology could potentially help the diagnostic investigation of high mortality in bees. We developed a tissue fixation and processing method enabling systematic production of histologic slides adequate for diagnostic and research purposes. Our method uses inexpensive, accessible products and can be realized with conventional pathology laboratory equipment. The quality of histologic slides obtained is similar to those of vertebrate animals processed routinely in pathology laboratories. Histopathology as a diagnostic and research tool will improve the services currently offered to apiarists and could help decrease the mean mortality rate, increase apiarists’ profits, and ensure long-term pollination services.
Veterinary Sciences
Transscleral retinopexy is a preventive technique used against retinal detachment. Fundus examina... more Transscleral retinopexy is a preventive technique used against retinal detachment. Fundus examination can allow the monitoring of morphological retinal changes in the progression of photocoagulation lesions, without offering details on the morphological changes by the retinal lesion. The aim of the study was to assess the progression of photocoagulation lesions induced by transscleral retinopexy (840 nm diode laser), by comparing the optical coherence tomography (OCT) and histological images over a period of six weeks on eight pigmented New Zealand healthy rabbits (four males and four females; n = 16 eyes). All rabbits underwent transscleral retinopexy on their left eye on day 0 (D0). Measurements of the photocoagulation lesions were obtained in vivo on D0, D7, D15, D21, and D42 by acquiring OCT images of both eyes from all rabbits. On D1, D7, D21, and D42, two rabbits were euthanized, and their eyes were enucleated. A significant effect by time on the decrease in the central retina...
The Canadian veterinary journal. La revue veterinaire canadienne
Canadian Journal of Physiology and Pharmacology, 2015
Islet amyloid polypeptide (IAPP) has been shown to form amyloid deposits in pancreatic islets, th... more Islet amyloid polypeptide (IAPP) has been shown to form amyloid deposits in pancreatic islets, thereby furthering type 2 diabetes disease progression. Further discovery of new molecules is needed to create a diverse set of molecules that impede pancreatic amyloidosis. We have recently designed and synthesized N-phenyl-N′-(2-ethyl)ureas (EU) that are non-cytotoxic small molecules, to evaluate the role of the aryl-substituted moiety on the inhibition of hIAPP fibrillization. Several EUs were tested in vitro for their anti-amyloidogenic activity using the fluorometric ThT assay, the photo-induced cross-linking (PIUCP) assay, and cell survival assay in pancreatic MIN-6 cells. EU-362 and EU-418 were able to significantly inhibit the formation of hIAPP fibrils and protected cells from amyloid cytotoxic effects. Our results suggest that increasing the nucleophilic potency of the aryl moiety significantly enhances the anti-amyloidogenic activity of the molecules.
Canadian Journal of Physiology and Pharmacology, 2015
Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute an important pharmacotherapeutic class t... more Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute an important pharmacotherapeutic class that, over the past decade, have expanded in application to a panoply of medical conditions. They have been tested for neurodegenerative diseases such as Alzheimer’s to reduce inflammation and also in the attempt to abrogate amyloid deposition. However, the use of NSAIDs as aggregation inhibitors has not been extensively studied in pancreatic amyloid deposition. Pancreatic amyloidosis involves the misfolding of islet amyloid polypeptide (IAPP) and contributes to the progression of type-2 diabetes in humans and felines. To ascertain their antiamyloidogenic activity, several NSAIDs were tested using fluorometric thioflavin-T assays, circular dichroism, photo-induced cross-linking assays, and cell culture. Celecoxib, diclofenac, indomethacin, meloxicam, niflumic acid, nimesulide, phenylbutazone, piroxicam, sulindac, and tenoxicam reduced fibrillization at a molar ratio of 1:10. The circular ...
International Journal of Pharmacy and Pharmaceutical Sciences
Objective: Our research program has focused on the development of promising, soft alkylating N-ph... more Objective: Our research program has focused on the development of promising, soft alkylating N-phenyl-N'-(2-chloroethyl)urea (CEU) compounds which acylate the glutamic acid-198 of β-tubulin, near the binding site of colchicum alkaloids. CEUs inhibit the motility of cancerous cells in vitro and, interestingly, exhibit antiangiogenic and anticancer activity in vivo. Mitotic arrest induced by microtubule-interfering agents such as CEUs remains the major mechanism of their anticancer activity, leading to apoptosis. However, we recently demonstrated that microtubule disruption by CEUs and other common antimicrotubule agents greatly alters the integrity and organization of microtubule-associated structures, the focal adhesion contact, thereby initiating anoikis, an apoptosis-like cell death mechanism caused by the loss of cell contact with the extracellular matrix. Methods: To ascertain the activated signaling pathway profile of CEUs, flow cytometry, Western blot, immunohistochemistry...
Veterinary dermatology, Jan 14, 2015
Alopecia X in dogs is a noninflammatory alopecia that may be caused by a hormonal dysfunction. It... more Alopecia X in dogs is a noninflammatory alopecia that may be caused by a hormonal dysfunction. It may be similar to androgenic alopecia in men that is caused by the effect of dihydrotestosterone (DHT). The 5α-reductase isoenzymes, 5αR1 and 5αR2, and a recently described 5αR3, are responsible for the conversion of testosterone into DHT. However, which 5α-reductases are present in canine skin has not yet been described. The main objective of this study was to determine the pattern of expression of 5α-reductase genes in canine skin. Skin biopsies were obtained from healthy, intact young-mature beagles (three males, four females) at three anatomical sites normally affected by alopecia X (dorsal neck, back of thighs and base of tail) and two sites generally unaffected (dorsal head and ventral thorax). Prostate samples (n = 3) were collected as positive controls for 5α-reductase mRNA abundance measurement by real-time PCR. We detected mRNA encoding 5αR1 and 5αR3 but not 5αR2. There were n...
Canadian journal of diabetes, Jan 7, 2015
Deposition of islet amyloid has been associated with beta-cell death, thereby furthering diabetes... more Deposition of islet amyloid has been associated with beta-cell death, thereby furthering diabetes progression. Several hypoglycemic agents, such as thiazolidinediones, biguanide and dipeptidyl peptidase-4 inhibitors, have been known to preserve beta-cell mass, possibly by direct inhibition of islet amyloid formation. The general objective of this study was to evaluate the impact of the major representatives of hypoglycemic agents on amyloid formation by using in vitro molecular screening approaches. Ten prototypical representatives of hypoglycemic agents were evaluated for the inhibition of amyloid formation in vitro using thioflavin fluorescence assays, far-ultraviolet circular dichroism, photo-induced cross linking assays and cell viability assays. Glyburide, repaglinide and troglitazone showed the highest potency in delaying and reducing fibril formation. Troglitazone, a thiazolidinedione, was the most effective agent abrogating amyloid fibril formation. Troglitazone affected the...
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Jan 15, 2007
A method to determine total and free mycophenolic acid (MPA) and its metabolites, the phenolic (M... more A method to determine total and free mycophenolic acid (MPA) and its metabolites, the phenolic (MPAG) and acyl (AcMPAG) glucuronides, using HPLC and mass spectrometry was developed. Mean recoveries in plasma and urine samples were >85%, and the lower limits of quantification for MPA, MPAG and AcMPAG were 0.05, 0.05 and 0.01 mg/L, respectively. For plasma, the assay was linear over 0.05-50 mg/L for MPA and MPAG, and from 0.01 to 10mg/L for AcMPAG. A validation study demonstrated good inter- and intra-day precision (CV<or=11%) and accuracy (bias<or=16%) and satisfactory specificity and stability. Pharmacokinetic parameters were assessed in plasma and urine from healthy volunteers after an oral dose of mycophenolate mofetil.