Patterns and outcomes of late onset thyroid disturbances after COVID-19 vaccination: A report of 75 cases.

Isolated cases of subacute thyroiditis exist in the early period of COVID-19 vaccination, largely after mRNA vaccines. Here we report late onset thyroid disturbances and persistent health issues in patients of thyroid disorders after COVID-19 vaccination. Seventy-five patients with post COVID-19 vaccination thyroid disturbances were identified. Among these, 41 had flare of underlying thyroid illness, majority occurring at a median time lag of 28.4 weeks since 2nd dose. Thirty-one cases of new onset hypothyroidism and three of new onset hyperthyroidism were reported, with a median time lag respectively of 17.2 and 22.6 weeks since 2nd dose. Most cases occurred after ChAdOx1-nCoV-19, which was the commonest vaccine employed in mass roll out in India. Significant improvement was observed in majority, after a median follow up of 22-26 weeks. New onset health issues persisting for ≥4 weeks were reported in 37.3% and were common in individuals with history of COVID-19 before vaccine. New onset metabolic, musculoskeletal, and reproductive disorders were the common health complaints. Active monitoring is warranted for late onset adverse events after COVID-19 vaccines of all types. Larger studies with involvement of unvaccinated individuals are required to understand the incidence and causality of late onset thyroid disturbances after COVID-19 vaccines.

Genome-wide differential methylation analyses identifies methylation signatures of male infertility.

STUDY QUESTION: Do methylation changes in sperm DNA correlate with infertility? STUDY ANSWER: Loss of spermatogenesis and fertility was correlated with 1680 differentially-methylated CpGs (DMCs) across 1052 genes. WHAT IS KNOWN ALREADY: Methylation changes in a number of genes have been correlated with reduced sperm count and motility. STUDY DESIGN, SIZE, DURATION: This case-control study used spermatozoal DNA from 38 oligo-/oligoastheno-zoospermic infertile patients and 26 normozoospermic fertile men. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Genome-wide methylation analysis was undertaken using 450 K BeadChip on spermatozoal DNA from six infertile and six fertile men to identify DMCs. This was followed by deep sequencing of spermatozoal DNA from 32 infertile patients and 20 fertile controls. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1680 DMCs were identified, out of which 1436 were hypermethylated and 244 were hypomethylated. Classification of DMCs according to the genes identified BCAN, CTNNA3, DLGAP2, GATA3, MAGI2 and TP73 among imprinted genes, SPATA5, SPATA7, SPATA16 and SPATA22 among spermatogenesis-associated genes, KDM4C and JMJD1C, EZH2 and HDAC4 among genes which regulate methylation and gene expression, HLA-C, HLA-DRB6 and HLA-DQA1 among complementation and immune response genes, and CRISPLD1, LPHN3 and CPEB2 among other genes. Genes showing significant differential methylation in deep sequencing, i.e. HOXB1, GATA3, EBF3, BCAN and TCERG1L, are strong candidates for further investigations. The role of chance was ruled out by deep sequencing of select genes. LARGE-SCALE DATA: N/A. LIMITATIONS, REASON FOR CAUTION: Genome-wide analyses are fairly accurate, but may not be exactly validated in replication studies across all DMCs. We used the 't' test in the genome-wide methylation analysis, whereas other tests could provide a more robust and powerful analysis. WIDER IMPLICATIONS OF THE FINDINGS: DMCs can serve as markers for inclusion in infertility screening panels, particularly those in the genes showing differential methylation consistent with previous studies. The genes validated by deep sequencing are strong candidates for investigations of their roles in spermatogenesis. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Council of Scientific and Industrial Research (CSIR), Govt. of India with grant number BSC0101 awarded to Rajender Singh. None of the authors has any competing interest to declare.

Congenital adrenal hyperplasia complicated by gonadotropin-dependent precocious puberty.

Precocious puberty, characterised by the early appearance of secondary sexual characteristics, poses challenges in diagnosis and management. Here, we describe a case of precocious puberty diagnosed in a boy in middle childhood, who presented with progressive phallus enlargement, pubic hair development and increased aggressive behaviour. Hormonal evaluation confirmed the diagnosis of congenital adrenal hyperplasia (CAH), complicated by gonadotropin-dependent precocious puberty. The case highlights the importance of assessment of testicular volume in a patient presenting with precocious puberty. Symmetrical testicular enlargement in a patient with CAH suggests premature activation of the hypothalamic-pituitary-gonadal axis. The patient received glucocorticoid therapy to suppress androgen production related to CAH and gonadotropin-releasing hormone analogue therapy to control premature activation of the hypothalamic-pituitary-gonadal axis. Follow-up visits showed regression of secondary sexual characteristics and improved growth velocity.

Integrated use of contrast-enhanced and grey-scale ultrasound in assigning American College of Radiology Thyroid Imaging-Reporting and Data System scores for characterisation of thyroid nodules: A prospective observational study.

Background: The advent and increased use of high-resolution ultrasonography has resulted in improved detection of thyroid nodules. Even with the use of various Thyroid Imaging-Reporting and Data System, accurate imaging diagnosis of malignant thyroid nodules has been suboptimal, which necessitated use of newer modalities like contrast-enhanced ultrasonography alone and in combination for this purpose. Although the combined use of various Thyroid Imaging-Reporting and Data System and contrast-enhanced ultrasonography has turned out to be accurate in many studies, the ideal way to integrate contrast-enhanced ultrasonography into the Thyroid Imaging-Reporting and Data System algorithm is under-investigated. Purpose: To estimate and compare the diagnostic accuracy of American College of Radiology Thyroid Imaging-Reporting and Data System and contrast-enhanced ultrasonography in differentiating benign and malignant nodules alone and in combination. To estimate the diagnostic accuracy of contrast-enhanced ultrasonography in re-categorisation of Thyroid Imaging-Reporting and Data System 3 and Thyroid Imaging-Reporting and Data System 4 thyroid nodules. Materials and methods: This was a prospective cohort study performed in a tertiary care university-based hospital for 3 years. Adult patients with clinical or previous sonographic diagnosis of thyroid nodules were selected. Each of the nodules were assessed using ultrasonography and categorised using American College of Radiology Thyroid Imaging-Reporting and Data System criteria. The lesion was then assessed for contrast-enhanced ultrasonography features. The final diagnosis of the nodules was made using fine needle aspiration cytology. The diagnostic accuracy in diagnosis of malignant thyroid nodules for each of the American College of Radiology Thyroid Imaging-Reporting and Data System and contrast-enhanced ultrasonography alone and in combination was assessed. The diagnostic accuracy of contrast-enhanced ultrasonography in diagnosis of malignant thyroid nodules categorised as Thyroid Imaging-Reporting and Data System 3 and Thyroid Imaging-Reporting and Data System 4 was also assessed. Results: American College of Radiology Thyroid Imaging-Reporting and Data System had a sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 86.6%, 54.5%, 17.4%, 97.3% and 57.7%, respectively, in diagnosis of malignant thyroid nodules. Contrast-enhanced ultrasonography had a sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 86.6%, 95.4%, 67.9%, 98.4% and 94.4%, respectively, in diagnosis of malignant thyroid nodules. Contrast-enhanced ultrasonography had sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 93.3%, 100.0%, 100.0%, 99.2% and 99.3%, respectively, in re-categorisation of Thyroid Imaging-Reporting and Data System 3 and Thyroid Imaging-Reporting and Data System 4 nodules. Conclusion: Contrast-enhanced ultrasonography can play a key role in diagnosis of malignant thyroid nodules which are categorised as indeterminate on grey-scale ultrasound.

Molecular study of the KCNJ11 gene and its correlation with Prakriti to preventing and managing type 2 diabetes.

In Ayurveda, every individual is believed to possess a unique entity known as Prakriti, which distinguishes them from others physically, physiologically, and psychologically. This entity also determines an individual's response to a particular stimulus, and it is believed that such responses are not solely determined by genetics. The present research aims to validate the Ayurvedic concept of Prakriti from a modern molecular perspective to strengthen the personalized and precise treatment approach. A study was conducted to investigate the role of the KCNJ11gene in the susceptibility of individuals to type 2 diabetes mellitus (T2DM) with their metabolic status. The research involved allele mining on three major Prakriti groups - Vata, Pitta, and Kapha - in 112 patients with T2DM and 112 healthy individuals. The KCNJ11 gene, responsible for insulin secretion membrane pore formation, was analyzed to determine the susceptibility of different Prakriti types to T2DM. The MutPred tool predicted the molecular cause of disease-related amino acid substitution. According to the study, only Pitta and Kapha Prakriti were diagnosed with diabetes, while all three Prakriti types were present in the control group of healthy individuals. A protein model was prepared, and the changes resulting from mutations were observed for each group in their protein sequence, both as synonymous and non-synonymous mutations. Ultimately, these changes contributed to the manifestation of T2DM. Based on the findings, it appears that Prakriti groups may experience changes in protein function due to nonsynonymous mutations and differences in amino acids at the protein level.

Association of Variant rs7903146(c/t) Single Nucleotide Polymorphism of Transcription Factor 7-like 2 Gene with Newly Detected Hyperglycemia in Pregnancy.

Background: Transcription factor 7-like 2 (TCF7L2) gene has a significant role in hyperglycemia in pregnancy (HIP) risk. The current study was planned with the aim to evaluate the association of single nucleotide polymorphism (SNP) rs7903146 in patients of newly detected HIP among Indian population of northern region. Methods: This study was an observational case control study done among newly detected HIP (The World Health Organization (WHO) criteria, 2013) and healthy pregnant females without diabetes. Participants from both the group were genotyped for rs7903146 (C/T) variant of TCF7L2 gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: A total of 71 cases of newly detected HIP were included in the study, out of which 25 (35.2%) of them were of first-time detected diabetes mellitus in pregnancy (DIP) and 46 (64.7%) were of gestational diabetes (GDM) and 100 were pregnant females without diabetes in third trimester were enrolled as controls. Average age of participants in the case group was 28.7 ± 4.0 years and the control group were 26.5 ± 3.6 years (P value 0.09). The wild homozygous CC genotype, heterozygous CT genotype and homozygous TT genotype were present in 39.4%, 53.5%, 7.1% of case group vs 53%, 43% and 4% of control group, respectively. No significant association of rs7903146(C/T) SNP of TCF7L2 gene in HIP (CC/CT, CC/TT P value 0.15, 0.38, respectively) in our population was found. There was no significant difference in the distribution of genotypes between DIP and GDM. Conclusion: This study shows no evidence of association of rs7903146(C/T) SNP of TCF7L2 gene with newly detected HIP in our population.

Clinical Prediction of Type 2 Diabetes Mellitus (T2DM) via Anthropometric and Biochemical Variations in Prakriti.

Type 2 Diabetes Mellitus (T2DM) is a complicated multifactorial illness involving hereditary and external environmental variables. The symptoms typically appear gradually over a number of years without realizing it. This viewpoint is further supported by the Ayurvedic constitution concept (Prakriti). Prakriti explains the biological variability that is observed in different individuals. This study was conducted a retrospective investigation to examine if there was a link between type 2 diabetes and an individual's constitution based on anthropometric and biochemical characteristics. Physical and mental characteristics and anthropometric and biochemical markers were used to determine reported cases' prevailing Dosha Prakriti (constitution). Based on biochemical and anthropometric data, significant differences in Prakriti were found between the case (T2DM patients) and control (person without diabetes) groups. The incidence of numerous secondary problems linked with T2DM patients was also evaluated according to their Prakriti types, which revealed a positive relationship. The three primary contributing parameters, such as waist-hip ratio, postprandial blood sugar, and serum creatinine, were correctly classified all person with or without diabetes subjects to 90.6% of the time, whereas the constitution-wise study classified person with diabetes and without diabetes individuals of Pitta and Kapha Prakriti to 94.3% and 90%, respectively. A discriminant function was created to predict a person with diabetes and without diabetes based on these three contributing factors. The primary contributing biochemical parameters discovered by Prakriti in the current study could be used as a biochemical disease diagnostic for predicting type 2 diabetes susceptibility.

COVID-19-associated Mucormycosis: A clinico-epidemiological study.

BACKGROUND: There was an unprecedented increase in COVID-19-associated-Mucormycosis (CAM) cases during the second pandemic wave in India. METHODS: This observational study was done to know the epidemiological profile of CAM cases andincluded all patients admitted with mucormycosis between May 2021 and July 2021. RESULTS: Out of the enrolled 208 CAM cases (either SARS-CoV-2 RT-PCR or serology positive), 204, three and one had rhino-orbital-cerebral, pulmonary and gastrointestinal mucormycosis, respectively. 95.7 % of the patients had diabetes, out of which 42.3 % were recently diagnosed. Mean HbA1c was 10.16 ± 2.56 %. 82.5 % of the patients were unvaccinated. During their COVID-19 illness, 86.5 % were prescribed antibiotics, 84.6 % zinc preparations, 76.4 % ivermectin, and 64.9 % steroids, while only 39.5 % required oxygen therapy. The frequency of blood groups A, B, O and AB in our CAM patients was 29.5 %, 18.9 %, 38.9 % &12.6 %, respectively. At three months follow up, 60 (28.8 %) patients died, four (1.9 %) stopped antifungal treatment, and 144(69.23 %) were on antifungal treatment. 55 % (n = 33) of deaths occurred within 15 days of admission. Mortality was significantly associated with higher age, RT-PCR positive for SARS-CoV-2, raised serum creatinine and alkaline phosphatase during treatment. At 6 months follow-up, eight more patients died, three due to chronic kidney disease, four patients who had stopped treatment and one patient who was on a ventilator due to COVID-19 associated pneumonia and the rest 140(67.3 %) survived. CONCLUSION: Uncontrolled hyperglycemia, SARS-CoV-2 infection, rampant use of antibiotics, zinc supplementation and steroids were some of the risk factors for mucormycosis. Despite the overwhelming number of patients with an uncommon disease like mucormycosis, the six months mortality was much lower than expected.

Early detection of cutaneous complications of insulin therapy in type 1 and type 2 diabetes mellitus.

BACKGROUND: Subcutaneous insulin therapy is associated with important injection site complications, which can influence insulin pharmacokinetics resulting in glycemic fluctuations above and below target levels for blood glucose. OBJECTIVE: Our objective was to assess the prevalence and risk factors of cutaneous complications including insulin derived amyloidosis in insulin-injecting diabetes patients and to study the role of ultrasonography (in comparison to gel-assisted palpation) in early diagnosis of lipohypertrophy (LH). METHODS: This was a cross-sectional study conducted at a tertiary care center in India, wherein 500 patients injecting insulin for ≥2 years were randomly enrolled and evaluated for the presence of cutaneous complications of insulin therapy through clinical examination, ultrasonography and punch biopsy of skin. RESULTS: Clinical examination detected LH in 44.6% of patients. Ultrasonography diagnosed additional 13.4% of patients with LH which were missed on clinical examination. Incorrect rotation of sites (P < 0.001) and insulin syringe reusage for more than five times (P < 0.001) significantly increased the risk of LH. Skin biopsy was performed in 100 cases, out of which two patients showed apple green birefringence and its association with insulin was confirmed by positive staining with anti insulin antibody in these two patients. CONCLUSION: Improper rotation of sites and reuse of needles were the leading causes of LH in Indian diabetic patients. Ultrasonography is more objective and reliable method of detecting LH. Insulin-derived amyloidosis may be a more common complication of insulin therapy than previously thought.

Diabetes and rhino-orbito-cerebral mucormycosis - A deadly duo.

BACKGROUND: Rhino-orbito-cerebral mucormycosis(ROCM) is an uncommon yet potentially fatal fungal infection predominantly seen in immunocompromised individuals. However, there is very limited data available from India regarding outcome of patients with ROCM and diabetes mellitus. OBJECTIVE: To ascertain clinical parameters and factors in the final outcome of patients with diabetes mellitus and ROCM. MATERIALS AND METHODS: This series included retrospective analysis of medical records of 91 patients with diabetes mellitus who were diagnosed with ROCM from january 2007 to june 2019 at a tertiary care hospital in Punjab. RESULTS: The mean age of patients was 52.6 years (range 18-82 years), with men constituting the majority (71.4 %). Ophthalmoplegia was the most frequent presenting feature seen in 77 % of patients followed by proptosis (71 %). Intracranial involvement was seen in 20 % of the patients and cavernous sinus thrombosis was diagnosed in 9(10 %) patients. Out of 91 patients, 81 patients were subjected to appropriate surgical procedure depending upon site and extent of involvement by mucorales. A total of 53 (58.2 %) patients survived while 38(41.8 %) patients succumbed. Delay in presentation to hospital, intracranial extension and loss of vision at presentation adversely affected the outcome (p < 0.05). Aggressive surgical management in the form of multiple debridements was superior to single debridement (p < 0.05). Diabetic ketoacidosis did not significantly affect the outcome (p = 0.359). CONCLUSIONS: ROCM in patients with diabetes mellitus, is a rapidly progressive disease with a high fatality rate and grave outcome unless diagnosed early and managed aggressively.

Does using a high sun protection factor sunscreen on face, along with physical photoprotection advice, in patients with melasma, change serum vitamin D concentration in Indian conditions? A pragmatic pretest-posttest study.

BACKGROUND: Use of sunscreens on the face is becoming popular, and patients with melasma are prescribed sunscreen for use on the face. Results of a few Western studies on the effect of sunscreen use on serum vitamin D concentration are not applicable to Indian conditions. AIMS: To examine the effect of use of a high sun protection factor (SPF 50+, PA++++) sunscreen on face in patients with melasma on serum concentration of 25-hydroxyvitamin D. METHODS: Forty-five Indian patients (Fitzpatrick skin types III and IV) with melasma were advised to use a sunscreen with SPF 50 + for 3 months, 43 (33 female, 10 male; age 32.9 ± 8 years) completed the study. Patients staying outdoor for <4 hours applied sunscreen once daily after bath. Patients staying outdoors for >4 hours reapplied sunscreen 4 hours after first application. Patients were provided a container to measure the amount of sunscreen for use, which was approximately equal to recommended thickness. Compliance was tested by weighing the used tubes and tubes in use during monthly visits. Serum concentration of 25-hydroxyvitamin D was tested before and after the study period. RESULTS: Amount of sunscreen advised (100.5 ± 29.2 ml) and the actual amount used (96.6 ± 27.9 ml) were similar (P = 0.53, t-test). The difference between serum concentrations of 25-hydroxyvitamin D at the baseline (19.20 ± 9.06 ng/ml) and at 3 months (18.91 ± 8.39 ng/ml) was not significant (P = 0.87, paired t-test, 95% confidence interval of difference -3.33 to 3.92). No correlation was found between the amount of sunscreen used and the percentage change in serum 25-hydroxyvitamin D concentration at 3 months (rho = 0.099, P = 0.528, Spearman's rank correlation). LIMITATIONS: Longer duration of application and a larger sample size may detect minor differences in vitamin D concentration. CONCLUSION: Using a high SPF sunscreen on the face, along with physical photoprotection advice, in patients with melasma for 3 months does not influence serum 25-hydroxyvitamin D concentration in Indian conditions.

Association of Kaphaja and Kapha-Pittaja Prakriti and methylenetetrahydrofolate reductase C677T allele with type 2 diabetes.

BACKGROUND AND OBJECTIVES: Type 2 diabetes is a multifactorial disorder that results from the interaction between genetic predisposition and environmental factors. Different Prakriti (body constitution) individuals have different susceptibility for the diseases, and this Prakriti is determined by both genetic and environmental factor. This study was undertaken to determine the association status of Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C with type 2 diabetes and Prakriti. MATERIALS AND METHODS: After informed consent, 54 patients with type 2 diabetes and 56 individuals as normal controls were analyzed. Their constitution and pathological data were collected and MTHFR C677T and A1298C genotypes were determined. RESULTS: Kapha/Kapha-Pittaja Prakriti were associated and found to be strong risk factors (Chi-square test = 39.67, P < 0.00001, odds ratio [OR] = 16.133, 95% confidence interval [CI] = 6.32-41.20) for type 2 diabetes. MTHFR C677T was associated (Chi-square test = 7.743, P = 0.02) with type 2 diabetes where the major CC genotype was found to be a risk for type 2 diabetes (OR = 3.78, 95% CI = 1.14-12.45). A1298C was not associated with type 2 diabetes (Chi-square test = 2.264, P = 0.322). None of the Prakriti was associated with C677T and A1298C variants. INTERPRETATION AND CONCLUSION: In the present study, an extremely strong association between Prakriti (Kaphaja/Kapha-Pittaja) and type 2 diabetes (P < 0.00001) was detected. The present study gives a strong clue for the association of Prakriti (body constitutional) and clinical phenotype.

Outcome of Diabetic Pregnancies in a Tertiary Referral Centre, Varanasi.

AIM: The study was done to determine the maternal and fetal outcome of pregnancies complicated by maternal diabetes either Gestational Diabetes Mellitus (GDM) or preexisting (type 1 or type 2) diabetes over a period from March 2011 to Feb 2013 in a tertiary care hospital, Varanasi. METHODS: This is a retrospective audit of the maternal and fetal outcome of women who presented to the Sir Sundar Lal Hospital, Department of Obstetrics and Gynaecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India from March 2011 to Feb 2013, with GDM or pre-existing type 1 or type 2 Diabetes with pregnancy. The audit group comprised 65 pregnancies (67 babies), of whom 27 had preexisting diabetes and 38 cases developed gestational diabetes. Pregnant women who were found to be diabetic preconceptionally or in the first trimester were classified as 'pre-existing diabetes'. RESULTS: There were total of 65 diabetic women in this retrospective study, 39 women were GDM (60 %) while 26 women (40 %) were having pre-existing diabetes (24 type 1 diabetes and 2 women were in type 2 diabetes group). There were 35 multigravid women (53.85 %) and 30 primigravid women (46.15 %). There were 39 (60 %) women on Insulin. There were 42 Lower Segment Caesarean Section (64.62 %) and 23 Spontaneous Vaginal Delivery (35.38 %). In fetal and neonatal complications, there were three still births, one case of intrapartum death, and one case of shoulder dystocia. Fetal anomalies were less frequent, one case of Gastroschisis with Hydrocephalus associated with Menigomyelocoele, there was one case of isolated Hydrocephalus, and there was also one case of Truncus arteriosus. CONCLUSIONS: The study analyses maternal and fetal complication in the GDM group and also preexisting diabetes group. In our centre, the 60 % women were GDM while 40 % were having pre-existing diabetes. Total rate of fetal/neonatal complication rate was 7.69 % and of congenital anomaly rate it was 9.23 %. Proportion of still birth, Intrauterine death, and congenital malformations was higher in the pre-existing diabetes group although the data are not large enough to draw a statistically significant conclusion. LSCS rate was little higher in the GDM group (69.23 %) in comparison to the preexisting diabetes group where it was 57.69 %. SVD (Spontaneous Vaginal Delivery) rate was 30.77 % in GDM and 42.31 % in the pre-existing diabetes group. HbA1c was within normal range 84.62 % of GDM group while in 15.38 % it was raised >6 %. In the pre-existing diabetes group, only 19.23 % of women had HbA1c within acceptable range and 80.77 % had it >6. The aim of St Vincent Declaration is to 'achieve pregnancy outcome in the diabetic woman that is similar to that of the non-diabetic woman.' But, so far we have not been able to achieve this. Our HbA1c level is remarkably high in the pre-existing diabetes group. Only 3 out of 65 patients' women took Folic Acid periconceptionally. We need to work to achieve it our best. It is well known that insulin treatment during pregnancy results in reduction in the rate of macrosomia, fetal/neonatal, and maternal complications. Therefore, we need to use insulin judiciously and advocate its usage in the situations where it is needed.

Melatonin alleviates hyperthyroidism induced oxidative stress and neuronal cell death in hippocampus of aged female golden hamster, Mesocricetus auratus.

Oxidative stress is a well known phenomenon under hyperthyroid condition that induces various physiological and neural problems with a higher prevalence in females. We, therefore investigated the antioxidant potential of melatonin (Mel) on hyperthyroidism-induced oxidative stress and neuronal cell death in the hippocampus region of brain (cognition and memory centre) of aged female golden hamster, Mesocricetus auratus. Aged female hamsters were randomly divided into four experimental groups (n=7); group-I: control, group-II: Melatonin (5mgkg(-1)day(-1), i.p., for one week), group-III: Hyperthyroid (100µg kg(-1)day(-1), i.p., for two weeks) and group-IV- Hyper+Mel. Hormonal profiles (thyroid and melatonin), activity of antioxidant enzymes (SOD, CAT and GPX), lipid peroxidation level (TBARS) and the specific apoptotic markers (Bax/Bcl-2 ratio and Caspase-3) expression were evaluated. A significant increase in the profile of total thyroid hormone (tT3 and tT4) in hyperthyroidic group as compared to control while tT3 significantly decreased in melatonin treated hyperthyroidic group. However, Mel level significantly decreased in hyperthyroidic group but increased in melatonin treated hyperthyroidic group. Further, the number of immune-positive cells for thyroid hormone receptor-alpha (TR-α) decreased in the hippocampus of hyperthyroidic group and increased in melatonin treated hyperthyroidic group. Profiles of antioxidant enzymes showed a significant decrease in hyperthyroidic group with a simultaneous increase in lipid peroxidation (TBARS). Melatonin treatment to hyperthyroidic group lead to decreased TBARS level with a concomitant increase in antioxidant enzyme activity. Moreover, increased expression of Bax/Bcl-2 ratio and Caspase-3, in hyperthyroidic group had elevated neuronal cell death in hippocampal area and melatonin treatment reduced its expression in hyperthyroidic group. Our findings thus indicate that melatonin reduced the hyperthyroidism-induced oxidative stress and neuronal cell death in the hippocampus region of brain, suggesting a novel therapeutic approach of melatonin for management of cognition and memory function in females under hyperthyroid condition.

Prevalence of Autoantibodies and HLA DR, DQ in Type 1 Diabetes Mellitus.

INTRODUCTION: Type I diabetes Mellitus (T1DM) is caused by autoimmune destruction of ß-cells of pancreas. Two forms of T1DM are known called as 1A (autoimmune) and 1B (idiopathic). AIM: Aim was to study the prevalence of Anti-TTG IgA, Anti-TPO, GADA, ZnT8 and IA-2 autoantibodies and HLA DR and DQ genes and its diagnostic value in T1DM. MATERIALS AND METHODS: Thirty four T1DM patients, 59 type 2 diabetes mellitus (T2DM) patients and 28 healthy controls were included in study. Antibodies levels were estimated by ELISA and HLA typing was performed by SSP-PCR method. RESULT: The prevalence of various autoantibodies in T1DM were Anti-TTG 14.7%, Anti-TPO 17.65%, GADA 38.23%, ZnT8 11.76% and IA-2 5.88%. Only GADA and ZnT8 were significantly positive in T1DM. GADA (66.67%) and ZnT8 (33.33%) positivity was more in patients below 15 years age while levels of other antibodies were higher after 15 years age. All autoantibodies were detected in higher frequency in T1DM than in T2DM and controls. HLA DR and DQ typing showed highly significant increase in DRB1*0301 (61.76%, p=0.00) and DQB1*0201 (64.71%, p=0.00) in T1DM. Subjects with HLA DRB1*0301 and DQB1*0201 had 80-100% positive prevalence of GADA, ZnT8, IA-2, Anti-TTG and Anti-TPO autoantibodies. CONCLUSION: Combination of GADA antibody with DRB1 and DQB1 estimation improved diagnosis of T1A than insulin antigen specific antibodies alone.

Targeting inflammation in diabetes: Newer therapeutic options.

Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resistance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflammation.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. Interleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce inflammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabetes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory markers. Retinopathy drugs are used to target vascular endothelial growth factor, angiopoietin-2, various proteinases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapamycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, peroxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory therapies represent a potential approach for the therapy of diabetes and its complications.

Prevalence of osteoporosis in otherwise healthy Indian males aged 50 years and above.

UNLABELLED: Bone mineral density was studied in 200 healthy Indian men above 50 years age, without fractures or osteoporosis. Mean vitamin D was 18.96 ng/ml; other biochemical evaluations were normal. Bone density (femur neck) decreased with age; there was osteoporosis in 8.5 %, osteopenia in 42 %, while 49.5 % were normal. Vitamin D deficiency may have caused osteoporosis. PURPOSE: Osteoporosis is recognized as the disease of females; however, males are also affected and have serious consequences thereof. The present study aimed at studying the prevalence of osteoporosis in otherwise healthy Indian males aged 50 years or more and studying the factors affecting bone mineral density (BMD). METHODS: With informed consent, 200 healthy males aged 50 years or more without the history of fractures or diseases affecting the BMD were evaluated clinically (including anthropometry) and biochemically (serum calcium, phosphate, alkaline phosphatase, creatinine, albumin, 25-OH Vitamin D, intact parathyroid hormone (iPTH), and testosterone). The BMD was measured by single observer on Lunar DPX-NT at right proximal femur for least effects of artifacts. Calculation of T score and categorization as osteoporosis, osteopenia, and normal BMD was done as per WHO classification. RESULTS: The mean age was 62.61 ± 7.64 years, and BMI was 23.90 ± 3.73 kg/m(2). The testosterone levels were normal in 84 % subjects. The mean 25-OH vitamin D level was 18.96 ± 10.23 ng/ml; only 13.5 % subjects had normal levels. The mean iPTH level was 72.60 ± 43.77 pg/ml; 57 % subjects had normal iPTH (12-72 pg/ml). The other parameters studied were normal. The osteoporosis and osteopenia were more prevalent when BMD was evaluated at neck of femur (osteoporosis 8.5 vs 8 % at trochanter and 7.5 % at total right hip; osteopenia 42 vs 37 % at trochanter and 41 % at total right hip). The BMD deteriorated with age. CONCLUSION: The osteoporosis affects 8.5 % of otherwise healthy males aged 50 years and above. Vitamin D deficiency is common in such group and maybe responsible for osteoporosis.