METHODS: We used data from the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) study, a long-running study of a community-recruited cohort of HIV-positive PWUD, linked to comprehensive HIV clinical records in Vancouver, Canada, a setting of no-cost, universal access to HIV care. The longitudinal relationship between MMT-ART dispensation at the same facility and the odds of ≥ 95% ART adherence was analysed using multivariable generalized linear mixed-effects modelling. We conducted a further analysis using a marginal structural mode with inverse probability of treatment weights as a sensitivity analysis.
RESULTS: This study included data on 1690 interviews of 345 ART- and MMT-exposed participants carried out between June 2012 and December 2017. In the final multivariable model, MMT-ART dispensation, compared with nondispensation at the same facility, was associated with greater odds of achieving ≥ 95% adherence [adjusted odds ratio (AOR) 1.56; 95% confidence interval (CI) 1.26-1.96]. A marginal structural model estimated a 1.48 (95% CI 1.15-1.80) greater odds of ≥ 95% adherence among participants who reported MMT-ART dispensation at the same facility compared with those who did not.
CONCLUSIONS: The odds of achieving optimal adherence to ART were 56% higher during periods in which MMT and ART medications were dispensed at the same facility, in a low-barrier setting. Our findings highlight the need to consider a simpler integrated approach with medication dispensation at the same facility in low-threshold settings.
AIMS: To investigate the ability of intravaginal MP gel treatment to ameliorate VA in sex-steroid deficient condition, mimicking post-menopause.
METHODS: Ovariectomized female Sprague-Dawley rats received MP (100 μg/ml, 250 μg/ml and 500 μg/ml) and estriol (E) gels intravaginally for seven consecutive days. Rats were then euthanized and vagina was harvested and subjected for histological and protein expression and distribution analyses. Vaginal ultrastructure was observed by transmission electron microscopy (TEM).
RESULTS: Thickness of vaginal epithelium increased with increasing intravaginal MP doses. Additionally, increased in expression and distribution of proliferative protein i.e. PCNA, tight junction protein i.e. occludin, water channel proteins i.e. AQP-1 and AQP-2 and proton extruder protein i.e. V-ATPase A1 were observed in the vagina following intravaginal MP and E gels treatment. Intravaginal MP and E gels also induced desmosome formation and approximation of the intercellular spaces between the vaginal epithelium.
CONCLUSIONS: Intravaginal MP was able to ameliorate features associated with VA; thus, it has potential to be used as an agent to treat this condition.
Methods: In this study, AA was administered orally at an individual dose of 300 and 2000 mg/kg body weight to group 1 and 2 respectively, while group 3 served as normal control. All the animals were observed for 2 weeks to determine any behavioral and physical changes. On day 15, blood was collected for hematological and biochemical investigation, later animals from all the three groups were euthanized to harvest and store essential organs for histopathological analysis. Four different staining techniques; hematoxylin and eosin, Masson trichrome, Periodic acid Schiff and Oil O Red were used to investigate any alterations in different tissues through microscopical observation.
Results: The results of the study showed no morbidity and mortality at two different dosage of AA treatment. Daily food & water intake, body weight, relative organ weight, hematological and biochemical parameters were detected to be normal with no severe alteration seen through microscopical investigation in the structure of harvested tissues. Our findings support the safety profile of AA, which was well tolerated at higher dose. Thus, an in-detail study on the subacute disease model is warranted.
METHODS: Orchidectomized, adult male rats were given 125 and 250 μg/kg/day testosterone subcutaneously, with or without flutamide and finasteride for seven consecutive days. At the end of the treatment, rats were anesthetized and vas deferens were perfused. Changes in vas deferens fluid secretion rate, pH, HCO3-, Cl- and Na+ concentrations were recorded in the presence of amiloride and Cftr inh-172. Rats were then sacrificed and vas deferens were harvested and subjected for molecular biological analysis.
RESULTS: Testosterone treatment caused the fluid pH and HCO3- concentrations to decrease but secretion rate, Cl- and Na+ concentrations to increase, where upon amiloride administration, the pH and HCO3- concentration increased but Cl- and Na+ concentrations further increased. In testosterone-treated rats, administration of Cftr inh-172 caused all fluid parameters to decrease. In testosterone-treated rats co-administered with flutamide or finasteride, pH and HCO3- concentration increased but fluid secretion rate, Cl- and Na+ concentrations decreased and these parameters were not affected by amiloride or Cftr inh-172 administration. Under testosterone influence, CFTR and γ-ENaC were highly expressed at the apical membrane while NHE-1 and 4 were highly expressed at the basolateral membrane of vas deferens epithelium. Meanwhile, NHE-2 and 3 were highly expressed at the apical membrane.
CONCLUSIONS: Differential expression of ENaC, CFTR and NHE in vas deferens under testosterone influence indicated the important role of these transporters in creating optimal fluid microenvironment that is essential for preserving male fertility.
HYPOTHESIS: Consumption of Marantodes pumilum leaves helps to ameliorate increased in vaginal fluid pH in sex-steroid deficient condition.
PURPOSE: To investigate changes in vaginal fluid pH and expression of proteins that participate in pH changes i.e vacoular (V)-ATPases and carbonic anhydrases (CA) in the vagina following M. pumilum leaves consumption.
METHODS: Ovariectomized adult female rats were treated orally with M. pumilum leaves extract (MPE) at 100, 250 and 500 mg/kg.b.w and estradiol at 0.2 µg/kg/b.w for 28 days. At the end of the treatment, vaginal fluid pH was measured in anesthetised rats by using micropH probe. Following sacrificed, levels of V-ATPase and CA proteins and mRNAs in the vagina were identified by Western blotting and real-time PCR, respectively. Protein distribution was visualized by immunohistochemistry.
RESULTS: Administration of MPE causes the pH of vaginal fluid to decrease and expression and distribution of vaginal V-ATPase A & B and CA II, III, IX, XII and XIII to increase.
CONCLUSIONS: The decrease in vaginal fluid pH following MPE treatment suggested that this herb has potential to be used to ameliorate vaginal fluid pH changes in sex-steroid deficient condition.
METHODS: Adult male rats with streptozotocin-nicotinamide-induced diabetes were given 50, 100 or 200 mg/kg body weight VVSEE orally for 28 days. At the end of the treatment, body weights were determined, and the blood was collected for analyses of fasting blood glucose, insulin and liver enzyme levels. Following sacrifice, livers were harvested and their wet weights and glycogen contents were measured. Histologic appearances of the livers were observed under light microscopy, and the expression and distribution of inflammatory, apoptosis and proliferative markers in the livers were identified by molecular biologic techniques.
RESULTS: Treatment of rats with diabetes by VVSEE attenuates decreased body weight, liver weight and liver glycogen content. Additionally, increases in fasting blood glucose levels and liver enzyme levels and decreases in serum insulin levels were ameliorated. Lesser histopathologic changes were also observed: decreased inflammation and apoptosis, as indicated by decreased levels of inflammatory markers (TNF-α, NF-Kβ, IKK-β, IL-6, IL-1β) and apoptosis markers (caspase-3, caspase-9 and Bax). VVSEE treatment induces increase in hepatocyte regeneration, as indicated by increased PCNA and Ki-67 distribution in the livers of rats with diabetes. Several molecules identified in VVSEE via gas chromatography mass spectrometry might contribute to these effects.
CONCLUSIONS: The anti-inflammatory, anti-apoptotic and pro-proliferative effects of VVSEE could account for its hepatoprotective actions in diabetes.
METHODS: Two rat models were used: (i) ovariectomised, sex-steroid replaced and (ii) intact, at different phases of oestrous cycle. A day after completion of sex-steroid treatment or following identification of oestrous cycle phases, rats were sacrificed and expression and distribution of these proteins in uterus were identified by Western blotting and immunohistochemistry, respectively.
RESULTS: Expression of TRα-1, TRβ-1, TSHR, VDR, RAR and ERK1/2 in uterus was higher following estradiol (E2) treatment and at estrus phase of oestrous cycle when E2levels were high. A relatively lower expression was observed following progesterone (P) treatment and at diestrus phases of oestrous cycle when P levels were high. Under E2influence, TRα, TRβ, TSHR, VDR, RAR and ERK1/2 were distributed in luminal and glandular epithelia while under P influence, TSHR, VDR abn RAR were distributed in the stroma.
CONCLUSIONS: Differential expression and distribution of TRα-1, TRβ-1, TSHR, VDR, RAR and ERK1/2 in different uterine compartments could explain differential action of thyroid hormone, TSH, vitamin D, and retinoic acid in uterus under different sex-steroid conditions.
METHODS: Orchidectomized, adult male Sprague-Dawley rats were treated subcutaneously with 125 μg/kg/day and 250 μg/kg/day testosterone with or without flutamide (androgen receptor blocker) and finasteride (5α-reductase inhibitor) for seven (7) days. Following treatment completion, in vivo perfusion of vas deferens lumen was performed and changes in fluid secretion rate, pH and HCO3- content were measured with and without bafilomycin, a V-ATPase inhibitor. Rats were then sacrificed and vas deferens were harvested and subjected for V-ATPase A1 and B1/2 protein expression and distribution analysis by western blotting and immunohistochemistry, respectively.
RESULTS: In sham-operated and testosterone-treated orchidectomized rats, higher fluid secretion rate, which was not antagonized by bafilomycin but lower HCO3- content and pH which were antagonized by bafilomycin were observed when compared to orchidectomized-only and orchidectomized, testosterone-treated rats receiving flutamide or finasteride, respectively. Bafilomycin had no effect on fluid secretion rate, HCO3- content and pH in orchidectomized and testosterone-treated orchidectomized rats receiving flutamide and finasteride. V-ATPase A1 and B1/2 proteins were expressed at high levels in vas deferens and were highly distributed at the apical membrane of luminal epithelium and in muscle layer of this organ, mainly in sham and testosterone-treated orchidectomized rats.
CONCLUSIONS: V-ATPase is involved in acidification of vas deferens fluid under testosterone influence.
METHODS: Two parameters were measured (i) rate of glucose uptake by 3T3-L1 adipocyte cells in-vitro (ii) degree of pancreatic destruction in streptozotocin-nicotinamide induced male diabetic rats receiving M. pumilum aqueous extract (M.P) (250 and 500mg/kg/day) as reflected by levels of pancreatic oxidative stress, inflammation and apoptosis. In the meantime, phyto-chemical compounds in M.P were also identified by using LC-MS.
RESULTS: M.P was found able to enhance glucose uptake by 3T3-L1 adipocyte cells in-vitro while its administration to the male diabetic rats causes decreased in the fasting blood glucose (FBG), glycated haemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) levels but causes increased in insulin and high-density lipoprotein (HDL) levels, to near normal. Levels of oxidative stress in the pancreas as reflected by levels of lipid peroxidation product (LPO) decreased while levels of anti-oxidantive enzymes (SOD, CAT and GPx) in pancreas increased. Additionally, levels of inflammation as reflected by NF-κB p65, Ikkβ and TNF-α levels decreased while apoptosis levels as reflected by caspase-9 and Bax levels decreased. Anti-apoptosis marker, Bcl-2 levels in pancreas increased.
CONCLUSIONS: The ability of M.P to enhance glucose uptake and reduces pancreatic complications could account for its beneficial effects in treating DM.
METHODS: Ovariectomized female normotensive Wistar Kyoto (WKY) and Spontaneous hypertensive (SHR) rats were given six weeks treatment with testosterone via subcutaneous silastic implant. The rats were anesthetized and mean arterial pressure (MAP) was measured via direct cannulation of the carotid artery. Animals were sacrificed and kidneys were removed and subjected for α, β and γ-ENaC protein and mRNA expression analyses by Western blotting and Real-time polymerase chain reaction (qPCR), respectively. Distributions of α, β and γ-ENaC proteins in kidneys were observed by immunofluorescence. Plasma testosterone, aldosterone, electrolytes, osmolality, urea and creatinine levels were determined by biochemical assays. Analysis were also performed in non-testosterone treated orchidectomized and sham-operated male WKY and SHR rats.
RESULTS: Treatment of ovariectomized female WKY and SHR rats with testosterone causes increased in MAP but decreased in plasma aldosterone, sodium (Na+), osmolality and expression and distribution of α, β and γ-ENaC subunits in the kidneys. Orchidectomy decreased the MAP but increased plasma aldosterone, Na+, osmolality and α, β and γ-ENaC expression and distribution in the kidneys of male WKY and SHR rats.
CONCLUSIONS: Decreased in plasma aldosterone, Na+ and ENaC levels in kidneys under testosterone influence indicated that testosterone-induced increased in MAP were not due to increased plasma aldosterone and ENaC levels in kidneys, and thus the testosterone effect on MAP likely involve other mechanisms.
METHODS: Female rats, once rendered hypothyroid via oral administration of methimazole (0.03% in drinking water) for twenty-one days were mated with fertile euthyroid male rats at 1:1 ratio. Pregnancy was confirmed by the presence of vaginal plug and this was designated as day-1. Thyroxine (20, 40 and 80 μg/kg/day) was then subcutaneously administered to pregnant, hypothyroid female rats for three days. A day after last injection (day four pregnancy), female rats were sacrificed and expression of thyroid hormone receptors (TR-α and β), retinoid X receptor (RXR) and extracellular signal-regulated kinase (ERK1/2) in uterus were quantified by Western blotting while their distribution in endometrium was visualized by immunofluorescence.
RESULTS: Expression of TRα-1, TRβ-1 and ERK1/2 proteins in uterus increased with increasing doses of thyroxine however no changes in RXR expression was observed. These proteins were found in the stroma with their distribution levels were relatively higher following thyroxine treatment.
CONCLUSIONS: Increased expression of TRα-1, TRβ-1 and ERK1/2 at day 4 pregnancy in thyroxine-treated hypothyroid pregnant rats indicate the importance of thyroxine in up-regulating expression of these proteins that could help mediate the uterine changes prior to embryo implantation.
METHODS: Female rats were treated with quercetin (10, 25 and 50mg/kg/day) subcutaneously beginning from day-1 pregnancy. Uterus was harvested at day-4 (following three days quercetin treatment) for morphological, ultra-structural, protein and mRNA expressional changes and plasma sex-steroid levels analyses. In another cohort of rats, implantation rate was determined at day-6 (following five days quercetin treatment).
RESULTS: Administration of 50mg/kg/day quercetin causes increased in uterine fluid volume and CFTR expression but decreased in γ-ENaC, AQP-5, AQP-9 claudin-4, occludin, E-cadherin, integrin αnβЗ, FGF, Ihh and Msx-1expression in the uterus. Pinopodes were poorly develop, tight junctions appear less complex and implantation rate decreased. Serum estradiol levels increased but serum progesterone levels decreased.
CONCLUSIONS: Interference in the fluid volume and receptivity development of the uterus during peri-implantation period by quercetin could adversely affect embryo implantation.
AIMS: To investigate P. niruri leaves aqueous extract (PN) effects on kidney functions, histopathological changes and levels of oxidative stress, inflammation, fibrosis, apoptosis and proliferation in DM.
METHODS: PN was orally administered to streptozotocin-nicotinamide-induced male diabetic rats for 28 days. At the end of the treatment, fasting blood glucose (FBG) and kidney functions were measured. Kidney somatic index, histopathological changes and levels of RAGE, Nrf2, oxidative stress markers (TBARS, SOD, CAT and GPx), inflammatory markers (NFkβ-p65, Ikk-β, TNF-α, IL-1β and IL-6), apoptosis markers (caspase-3, caspase-9 and Bax), fibrosis markers (TGF-β1, VEGF and FGF-1) and proliferative markers (PCNA and Ki-67) were determined by biochemical assays, qPCR, Western blotting, immunohistochemistry or immunofluorescence.
RESULTS: Administration of PN helps to maintain near normal FBG, creatinine clearance (CCr), blood urea nitrogen (BUN), BUN/Cr ratio, serum electrolytes, uric acid and urine protein levels in DM. Decreased RAGE, TBARS and increased Nrf2, SOD-1, CAT and GPx-1 were observed in PN-treated diabetic rat kidneys. Expression of inflammatory, fibrosis and apoptosis markers in the kidney reduced but expression of proliferative markers increased following PN treatment. Lesser histopathological changes were observed in the kidney of PN-treated diabetic rats.
CONCLUSION: PN helps to preserve near normal kidney function and prevents histopathological changes via ameliorating oxidative stress, inflammation, fibrosis and apoptosis while enhancing proliferation of the kidney in DM.
METHODS: SLBH at 1 and 2g/kg/b.w. was given orally to streptozotocin (STZ)-nicotinamide-induced male diabetic rats for 28days. Metabolic parameters (fasting blood glucose-FBG and lipid profiles-LP and serum insulin) were measured by biochemical assays. Distribution and expression level of insulin, oxidative stress marker i.e. catalase, inflammatory markers i.e. IKK-β, TNF-α, IL-1β and apoptosis marker i.e. caspase-9 in the pancreatic islets were identified and quantified respectively by immunohistochemistry. Levels of NF-κβ in pancreas were determined by enzyme-linked immunoassay (ELISA).
RESULTS: SLBH administration to diabetic male rats prevented increase in FBG, total cholesterols (TC), triglyceride (TG) and low density lipoprotein (LDL) levels. However, high density lipoprotein (HDL) and serum insulin levels in diabetic rats receiving SLBH increased. Additionally, histopathological changes and expression level of oxidative stress, inflammation and apoptosis markers in pancreatic islets of diabetic rats decreased with increased expression level of insulin in the islets. LC-MS analysis revealed the presence of several compounds in SLBH that might be responsible for these effects.
CONCLUSIONS: SLBH has great potential to be used as agent to protect the pancreas against damage and dysfunction where these could account for its anti-diabetic properties.