Objective To observe the effect of pvrrolidine dithiocarbamate (PDTC) in the treatment of rat osteoarthritis (OA). Methods OA model was established through anterior cruciate ligment transection in 20 rats, 10 rats received muscle injection of PDTC with the dosage of 10 mg/kg,and another 10 rats received normal saline injection every 48 h after operation. Six weeks later, rats were sacrificed to observe the macroscopic,anatomic microscopic and microscopic pathologic changes. Results The macroscopic and anatomic microscopic changes in the control group were more significant than in the experimental group. Mankin' s scores based on microscopic change in experimental group and control group were 5.7 ±1.70 and 8.2 ±2.10,respectively (P<0.05). Conclusion PDTC can retard the pathologic progress of OA.
Key words:
Osteoarthritis; Model,animal; PDTC; Morphology
Huadong Yanabc, Susu Jinc, Lili Liangc, Jingyuan Duc, Guruprasad P. Aithalde & Lanjuan Lia*a State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; b Department of Hepatology, Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Hwamei Hospital, Ningbo No.2 Hospital, University of Chinese Academy of Sciences, Ningbo, China; c Department of Hepatology, Hwamei Hospital, Ningbo No.2 Hospital, Ningbo University School of Medicine, Ningbo, China; d NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK; e Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
To explore a new method for the therapy of avascular necrosis of the femoral head.The recombinant plasmid pCD-rbFGF was mixed with collagen and was implanted in the necrotic femoral head. Expression of basic fibroblast growth factor (bFGF) was examined by RT-PCR and immunohistochemical method. Repair of the femoral head was observed by histological and histomorphometric analysis.Expression of bFGF was detected in the femoral head transfected with bFGF gene, indicating significant increase of angiogenesis 2 weeks after gene transfection and increased new bone formation 8 weeks after gene transfection on histomorphometric analysis (P< 0.01).Transfection of bFGF gene enhances bone tissue angiogenesis. Repair in osteonecrosis would be accelerated accordingly.
This study aimed to investigate whether specific medications used in the treatment chronic diseases affected either the development and/ or severity of coronavirus disease 2019 (COVID-19) in a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zhejiang, China. Using a cohort of 578 COVID-19 cases and 48,667 population-based controls from Zhejiang, China, we tested the role of usage of cardiovascular, antidiabetic, and other medications on risk and severity of COVID-19. Analyses were adjusted for age, sex, and body mass index and for presence of relevant comorbidities. Individuals with hypertension taking calcium channel blockers had significantly increased risk (odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.2-2.3) of manifesting symptoms of COVID-19, whereas those taking angiotensin receptor blockers and diuretics had significantly lower disease risk (OR = 0.22, 95% CI 0.15-0.30 and OR = 0.30, 95% CI 0.19-0.58, respectively). Among those with type 2 diabetes, dipeptidyl peptidase-4 inhibitors (OR = 6.02, 95% CI 2.3-15.5) and insulin (OR = 2.71, 95% CI 1.6-5.5) were more and glucosidase inhibitors were less prevalent (OR = 0.11, 95% CI 0.1-0.3) among with patients with COVID-19. Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but, not its severity.
To explore a new method for the therapy of avascular necrosis of the femoral head.The recombinant plasmid pCD-hVEGF165 was mixed with collagen and was implanted in the necrotic femoral head. The expression of vascular endothelial growth factor (VEGF) was examined by RNA dot hybridization and immunohistochemical techniques. Repair of the femoral head was observed by histological and histomorphometric analysis.The expression of VEGF was detected in the femoral head transfected with the VEGF gene. The femoral head transfected with the VEGF gene showed a significant increase in angiogenesis 2 and 4 weeks after gene transfection and a significant increase in bone formation 6 and 8 weeks after gene transfection on histomorphometric analysis (P < 0.01).Transfection of the VEGF gene enhances bone tissue angiogenesis. Repair of osteonecrosis could be accelerated accordingly, thus providing a potential method for therapy of osteonecrosis.
Abstract The study aimed to investigate whether specific medications used in the treatment chronic diseases affected either the development and/ or severity of COVID-19 in a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zheijang, China. Using a cohort of 578 COVID-19 cases and 48,667 population-based controls from Zheijang, China we tested the role of usage of cardiovascular, antidiabetic and other medications on risk and severity of COVID 19. Analyses were adjusted for age, sex and BMI and for presence of relevant comorbidities. Individuals with hypertension taking calcium channel blockers had significantly increased risk [odds ratio (OR)= 1.73 (95% CI 1.2-2.3)] of manifesting symptoms of COVID-19 whereas those taking angiotensin receptor blockers and diuretics had significantly lower disease risk (OR=0.22; 95%CI 0.15-0.30 and OR=0.30; 95%CI 0.19-0.58 respectively). Among those with type 2 diabetes, dipeptidyl peptidase-4 inhibitors (OR= 6.02; 95% CI 2.3-15.5) and insulin (OR= 2.71; 95% CI 1.6-5.5) were more and glucosidase inhibitors were less prevalent (OR= 0.11; 95% CI 0.1-0.3) among with COVID-19 patients. Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but, not its severity. Study highlights What is the current knowledge on the topic? Cardiovascular disease and Diabetes have been highlighted as comorbidities contributing to a more severe form of COVID-19 and medication to treat them may also influence the risk of COVID-19 and its clinical outcomes. What question did this study address? Does specific medications used in the treatment of chronic diseases influence the risk for the susceptibility to SARS CoV-2 infection of severity of COVID-19? What does this study add to our knowledge? The study confirms that higher BMI, diabetes and cardio/ cerebrovascular disease as independent risk factors for the development of COVID-19. Angtiotensin Receptor Blockers (ARBs) and diuretics were associated with reduced risk and Calcium Channel Blockers (CCBs) with increased risk of developing COVID-19. Among those with type 2 diabetes, dipeptidyl peptidase-4 and were associated with increased and glucosidase inhibitors with reduced risk development of COVID-19. None of the antihypertensive or anti-diabetic drugs were associated with increased risk of severe or critical form of the infection. Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but are not associated with severity of the disease. How might this change clinical pharmacology or translational science? Findings from the current large case-control study confirmed no evidence to alter ARBs or ACEIs therapy in the context of COVID-19 severity in clinical practice. Hypertension significantly increases the risk of severe or critical SARS-CoV-2 infection indicating that carefully controlled blood pressure should be a priority to reduce the healthcare burden of COVID-19.
This study aimed to evaluate the relationship between magnesium (Mg) status, serum vitamin D (VD) concentration and mortality in congestive heart failure (CHF) patients. Data for this study were extracted from the National Health and Nutrition Examination Surveys 2007-2018. Magnesium depletion score (MDS) is a scoring system developed to predict the status of Mg deficiency that considers the pathophysiological factors influencing the reabsorption capability of the kidneys. The primary outcome was all-cause mortality of CHF patients and the secondary outcome was mortality due to cardiovascular disease (CVD). Weighted univariate and multivariate cox proportional hazards models were used to explore the association between Mg status, serum VD concentration and all-cause mortality or mortality due to CVD in CHF patients, using hazard ratios (HRs) and 95 % confidence intervals (CIs). Subgroup analyses based on age, physical activity (PA), course of CHF, race, and body mass index were further assessed with regards to the association analysis. In total, 1022 CHF patients were included, of whom 418 (40.90 %) died by 31st December 2019. After adjusting for all covariates, high MDS (>2 points) was related to a higher risk of all-cause mortality (HR = 1.72, 95 % CI: 1.30-2.29) and mortality due to CVD (HR = 1.71, 95 % CI: 1.29-2.25); a higher serum VD concentration was related to a lower risk of all-cause mortality (HR = 0.78, 95 %CI: 0.62-0.99) and mortality due to CVD (HR = 0.80, 95 % CI: 0.63-0.99). Compared to patients with high serum VD concentration and low MDS, patients with low serum VD concentration and high MDS had a high risk of all-cause mortality (HR = 2.44, 95 % CI: 1.54-3.85, p for trend = 0.043) and mortality due to CVD (HR = 2.41, 95 % CI: 1.32-4.40). Serum VD and Mg status may have a combined effect in improving the prognosis in CHF patients, thus an appropriate level of serum VD and Mg intake may be beneficial to maintain cardiovascular health, thereby improving outcome.
Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI).Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis.In the derivation cohort (n = 3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3 months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR = 1.014, 95% CI: 1.005-1.023), baseline ALT (HR = 1.014, 95% CI: 1.003-1.024), haemoglobin (HR = 1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR = 1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n = 1497) of which 85 (5.7%) developed ATDILI. Age (HR = 1.029, 95% CI: 1.003-1.056), baseline AST (HR = 1.036, 95% CI: 1.010-1.062), previous TB treatment (HR = 3.894, 95% CI: 1.304-11.625) and active drinking (HR = 3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice.Elevation of ALT of ≥3 × ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.