Arginase has been reported to reduce nitric oxide bioavailability in cardiovascular disease. However, its specific role in retinopathy has not been studied. In this study, we assessed the role of arginase in a mouse model of endotoxin-induced uveitis induced by lipopolysaccharide (LPS) treatment. Measurement of arginase expression and activity in the retina revealed a significant increase in arginase activity that was associated with increases in both mRNA and protein levels of arginase (Arg)1 but not Arg2. Immunofluorescence and flow cytometry confirmed this increase in Arg1, which was localized to glia and microglia. Arg1 expression and activity were also increased in cultured Muller cells and microglia treated with LPS. To test whether arginase has a role in the development of retinal inflammation, experiments were performed in mice deficient in one copy of the Arg1 gene and both copies of the Arg2 gene or in mice treated with a selective arginase inhibitor. These studies showed that LPS-induced increases in inflammatory protein production, leukostasis, retinal damage, signs of anterior uveitis, and uncoupling of nitric oxide synthase were blocked by either knockdown or inhibition of arginase. Furthermore, the LPS-induced increase in Arg1 expression was abrogated by blocking NADPH oxidase. In conclusion, these studies suggest that LPS-induced retinal inflammation in endotoxin-induced uveitis is mediated by NADPH oxidase-dependent increases in arginase activity.
Background: Peripheral artery disease(PAD) is a major macrovascular complication of diabetes mellitus. Patients with diabetes mellitus have an increased prevalence of PAD. However, due to associated neuropathy, common symptoms such as claudication are often masked and such patients often diagnosed late when limb threatening ischemia has already set in. Arterial colour doppler ultrasonography and ankle brachial pressure index are easy, non- invasive and often underutilised tools for diagnosis of PAD.Methods: In the present study, 100 diabetic patients were enrolled to study the comparison of Ankle Brachial Pressure Index to arterial doppler USG in diagnosis of peripheral artery disease.Results: Colour duplex ultrasonography (CDU) was taken as gold standard. Ankle brachial index (ABI) was compared with it. Sensitivity of ABI was 92.50%, Specificity was 88.33%, Positive Predictive Value was 84.09% and Negative Predictive Value was 94.64% respectively.Conclusions: Peripheral arterial disease (PAD) is very common in patients with diabetes. ABI is a simple and very sensitive test to detect PAD early in these patients.
Background: Little is known about outcomes of patients admitted to the ICU with severe sepsis and septic shock, despite the seriousness of sepsis as a public health problem in developing countries. Understanding sepsis outcome studies is hampered by lack of an agreed severity of illness scoring system for sepsis patients. The objective of the present study is to assess and compare the validity of 3 mortality prediction models SAPS 2, APACHE II and SOFA for prediction of mortality in patients of sepsis.Methods: One hundred patients of Sepsis were selected after applying the inclusion and exclusion criteria. Informed consent was taken from the patients or their relatives A careful and detailed history was recorded to assess the onset and duration of clinical events and the probable risk factors for the same; a detailed general physical examination was performed. Blood sampling for CBC, RFT, LFT and arterial blood gas analysis was done. SAPS 2, APACHE II and SOFA scores were calculated on the day of admission.Results: The ROC analysis shows that the best discrimination was provided by SAPS 2 score (AUROC=0.981), followed by APACHE II (AUROC=0.978) and SOFA (AUROC=0.911).Conclusions: SAPS 2 score was superior to the APACHE II and SOFA scores for predicting survival in patients with septic shock but a combination of factors must be taken in consideration to estimate the prognosis in the ICU.
Background: Microalbuminuria and left ventricular hypertrophy (LVH) have both been shown independently to be associated with increased cardiovascular (CVS) mortality in type 2 diabetes mellitus (DM) patients. This cross-sectional study was conducted to examine whether microalbuminuria is associated with LVH in non-hypertensive type 2 DM patients with early or no diabetic nephropathy.Methods: 100 patients of type 2 DM were studied. Patients with Hypertension (BP >140/90 mm hg or on anti-hypertensive medication), history of coronary artery disease or valvular heart disease, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, known thyroid disease or active urinary tract infection (UTI) were excluded from the study. All patients were subjected to spot urine test for microalbuminuria by urinary albumin creatinine ratio (UACR), 12 lead ECG to detect LVH, 2D echocardiography to calculate LV mass index (LVMI), anthropometry, urine routine examination, kidney function test, fasting lipid profile and HbA1c.Results: Of the 100 enrolled patients, 39 were found to have normoalbuminuria, 39 had microalbuminuria & 22 patients had macroalbuminuria. The correlation between increased albuminuria and LVMI was found to be statistically significant (P value < 0.001) and the LV mass significantly increased as albuminuria increased along the continuum of normoalbuminuria to macroalbuminuria. UACR showed a statistically significant correlation with age, eGFR, duration of diabetes (P value < 0.01) and HbA1c (P value < 0.05).Conclusions: Microalbuminuria is associated with LVH in non-hypertensive type 2 DM patients and thus may serve as an early marker of LVH and help identify patients at high CVS risk.
Background: Thyroid hormones play a very important role in regulating metabolism, development, protein synthesis, and influencing other hormone functions. CKD has been known to affect the pituitary-thyroid axis and the peripheral metabolism of thyroid hormones. We aimed to study the thyroid dysfunction in patients of chronic kidney disease for the prevalence of subclinical hypothyroidism.Methods: This cross-sectional study was conducted at Chhatrapati Shivaji Subharti Hospital and Medical College, Meerut, Uttar Pradesh, India, over a 2 year period. The study group comprised 100 patients with Chronic kidney disease. Free thyroxine (fT3, fT4) and thyroid-stimulating hormone (TSH) were measured. Patients with family history of thyroid disorder or past history of any medication for thyroid disease or history of any surgery or any radiological intervention to thyroid gland were excluded from the study.Results: Of 100 CKD patients, 25 were found to have subclinical hypothyroidism (SCH) and 75 were euthyroid. The mean age in patients with SCH was 47.72±10.09 and in euthyroid patients was 46.11±14.332. 12 males (48%) and 13 females (52%) patients were found to have subclinical hypothyroidism and 49 male (65%), 26 female (35%) patients were euthyroid. Prevalence of SCH was 25% with a mean TSH level of 8.68± 1.84.Conclusions: We observed a high prevalence of SCH in our CKD patients. SCH is an additional risk factor in CKD patients and the present study finds thyroid dysfunction being SCH to be very common in CKD patients and reveals significant association between CKD progression and thyroid dysfunction.
Background: Genetic changeability of hepatitis B virus (HBV) signifies a challenge for the sensitivity of immunologic and molecular diagnostics. Therefore, knowing the spread of HBV genotypes (GENs) and mutation has considerable impacts on treatment strategies, vaccination program, diagnosis, and prevention. The present study aimed to detect HBV GENs and mutants in HBsAg-positive patients. Methods: The study conducted on 4927 patients in Meerut, India, between March 2013 and April 2017. The blood specimens were analyzed for HBsAg using an ELISA kit, then the blood samples from HBsAg-positive patients were subjected to HBeAg assay and DNA isolation. Amplification of the HBV DNA of pre-S gene and pre-core or basal core promoter region were performed by RT-PCR and sequenced to analyze both GEN and mutation. Results: According to the results, 245 cases were positive for HBsAg, and 55 were HBeAg-positive. With regard to HBV DNA levels, 16 samples were found positive in PCR assay with 7 (43.8%) less than 2000 IU/mL, 4 (25%) between >2000 and 20,000 IU/mL, and 5 (3.25%) >20,000 IU/mL. No mutations were detected in GENs B and A. The prevalence of HBV GENs B and A were 68.8% (n = 11) and 31.25% (n = 6), respectively. Conclusion: GEN-B was more prevalent in comparison to GEN-A. The genetic diversity of HBV and distribution of its GENs and mutation improve the current knowledge of epidemiological, clinical and virological patterns of hepatitis B in this region, which help physicians to prescribe proper antiviral/interferon therapy according to current genotyping pattern.
Background: Metabolic Syndrome is a constellation of dyslipidemia (elevated triglycerides, low high-density lipoproteins (HDL)), elevation of arterial blood pressure (BP), dysregulated glucose homeostasis, and increased abdominal obesity.Methods: We studied the association of high sensitivity C-reactive protein with metabolic syndrome by case-control method in our tertiary care hospital in West U.P.Results: The mean age of cases and controls was 52.6 ± 7.7 and 51.4±7.0 years, respectively. There were 25 (50%) male and 25 (50%) female in case groups, and 27 (54%) males and 23 (46%) females in control group. Our analysis revelaed that there was a significant association between hs-CRP and the central obesity when compared in case-control group (3.57 vs 0.96 mg/L) (p value <0.001). There was no significant association between hs-CRP and high triglycerides, hypertension, diabetes, and reduced high density lipoprotein cholesterol.Conclusions: Raised hsCRP level can be considered as a surrogate marker of chronic inflammation in patients with metabolic syndrome.
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