Volume 44, Issue 1

Objectives It is well recognized that overt thyroid dysfunction is associated with changes in body mass index (BMI). However, there is ongoing debate regarding the influence of thyroid stimulating hormone (TSH) on BMI, in euthyroid subjects. The aim of this study is to examine the association of TSH with BMI in an outpatient population without evidence of thyroid disease. Methods Cross-sectional study conducted in an Endocrinology Department. We identified the latest TSH and BMI measurements in 923 patients from the reference euthyroid population. All patients with positive thyroid autoimmunity and nodules were excluded. We performed a linear regression analysis using SPSSv.025. Results 923 adult patients were evaluated. 79.4% were males, with a mean age of 67.6 years old. Mean TSH level was 1.78 mIU/L and mean BMI was 29.2 kg/m 2 . A significant negative correlation between serum TSH concentration and BMI was evident (p=0.04; r=−0.067). Statistical significance was lost when performing subgroup analysis, for males and females (p=0.19 and p=0.075), elderly (≥65 years) and non-elderly (p = 0.55 and p = 0.32) and also obese (BMI ≥30 kg/m 2 ) and non-obese (p=0.39 and p=0.13) . Conclusions The relationship between BMI and TSH is not consensual in the literature. This study included a large cohort sample of euthyroid patients, majority men and with negative autoimmunity. Our results support the hypothesis that variation in thyroid status within the normal range, could have a negative effect on BMI, contrary to most published studies.

Objectives Glucose oxidase is an enzyme that is widely used in biosensors, especially kits for measuring blood sugar. Many diabetics use this type of kit to determine their blood sugar level. Aspergillus niger is the most important source of glucose oxidase for use in biosensors. Diabetes causes secondary diseases in patients for which medications are prescribed to improve them. Dexamethasone, a corticosteroid, is one of the drugs prescribed to diabetics to cure some secondary diseases. In this study, the effect of this drug on glucose oxidase was investigated from a kinetic and molecular point of view. Methods In this study, the kinetics of drug binding to the enzyme was measured and the type of inhibition was determined by Lineweaver-Burk plot. The Ki value of the drug was determined by drawing the secondary curve. Using fluorescence spectrophotometry and molecular docking, the binding of the drug to the enzyme was confirmed. Results The results showed that the drug inhibits the enzyme non-competitively. Determining the kinetics parameters of the drug-enzyme interaction showed that the drug acts as a potent inhibitor. Study at the molecular level by fluorescence spectrophotometer showed that the drug attachment alters the enzyme conformation to more compaction. In silico results showed that the drug is placed between two helices that are outside the active site and binds to the enzyme by three hydrogen bonds. Conclusions The result of this study is useful because it suggests that in diabetic patients taking dexamethasone, the amount of glucose declared by the kit may not be real due to the inhibition of glucose oxidase.

Objectives Leptin polymorphism (LEP) has been associated with coronary heart disease (CAD), obesity, and high body mass index (BMI). However, we performed a systematic review and meta-analysis to discover the association because previous studies reached different conclusions. Methods Review Manager, version 5.3.5, and Stata, version 15.0, were used for statistical analysis. We calculated the effect size of the studies using the OR with the corresponding 95% CI, and two-sided (bilateral) p-values of 0.05 were considered significant. To determine heterogeneity among the selected studies, the Q test and I2 statistics were used. Meta-regression was used to examine the disease (heart disease, obesity, and high BMI) and heterogeneity between these subgroups. Results Eleven studies with 18,984 subjects were included in this study. The G-2548A (rs12112075), rs7799039, and A19G (rs2167270) polymorphisms of the leptin gene (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Our pooled analysis revealed an association between the G-2548A (rs12112075) polymorphism and heart disease, high BMI, and obesity. This indicates that individuals carrying the AA allele are at an increased risk for heart disease, high BMI, and obesity. People with heart failure and coronary artery disease did not have the rs7799039 polymorphism or its alleles linked to them. Conclusions Combined analysis of data from current and published research suggests that the leptin gene polymorphisms G-2548A (rs12112075), rs7799039, and A19G (rs2167270) (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Further research is needed to understand this association.

Objectives Secreted by white adipose tissue, asprosin is a newly recognized adipokine whose physiological function is not well comprehended. This study intended to determine the effect of spinning and stationary cycling on serum asprosin levels in overweight women. Methods Forty-five overweight women with BMI>25 kg/m 2 in the age range of 30–40 years were assigned randomly to three groups of 15 participants: control, spinning (group cycling with music), and stationary bike (individual pedaling on a stationary bike). The participants performed the exercises three sessions per week for six weeks. Lipid profile and asprosin levels were measured by enzymatic and ELISA methods, respectively. Moreover, the paired t-test and one-way ANOVA were employed to make within-group and between-group comparisons, respectively. Results The stationary cycling and spinning exercise groups experienced significant reductions in weight, BMI, serum triglyceride, and asprosin levels from the pretest to the posttest. The control group showed no statistically significant differences. Serum concentrations of total cholesterol and low-density lipoprotein only declined in the spinning group. In this regard, neither the control group nor the stationary bicycle exhibited no significant change over time. The spinning group demonstrated a significant rise in high-density lipoprotein levels, which was not observed in the control group. In addition, there was no significant difference in WHR index between the intervention groups. Conclusions By lowering the serum asprosin level, a spinning exercise program appears to be effective in reducing disorders linked to metabolic diseases in overweight women.

Objectives Despite remarkable development of new therapeutic strategies to improve survival rates and treatment of patients with cancer, there are still many limitations in management of patients with distant metastasis breast cancer. Therefore, the aim of this study was to investigate a novel method to enhance therapeutic efficacy of Apatinib (as a chemotherapeutic agent) by co‐administration of Curcumin (as a bioactive herbal compound) in breast cancer treatment. Methods Effects of Apatinib, Curcumin, and their combinations (Apa‐Cur) was evaluated on viability and proliferation of breast cell line (MCF7) by MTT assay. Moreover, effects of Apatinib, Curcumin, and Apa‐Cur was investigated on apoptosis rate in the cancer cells. Expression levels of apoptosis-related genes ( BAX , SMAC , BCL2 , and SURVIVIN ) in treated cancer cells and untreated controls were evaluated using the Real-Time PCR method. Results The obtained results showed that all treatments of Apatinib, Curcumin, and Apa‐Cur significantly decreased viability and proliferation of the breast cancer cells in a concentration‐ and time‐dependent manner. However, anti-proliferation activity of Apa‐Cur combination was significantly higher than Apatinib and Curcumin treatment alone. In addition, Apatinib, Curcumin, and Apa‐Cur increased apoptosis percentage in the treated cancer cells through regulation of apoptosis-related genes expression. Conclusions In general, Apa‐Cur combination therapy exerts more profound anti-proliferation effects on breast cancer cell than Apatinib or Curcumin monotherapy. However, further studies are required to identify other possible signaling pathways and mechanisms involved in the anticancer effects of Apatinib, Curcumin, and Apa‐Cur.

Objectives Tuberculosis is an infectious airborne disease caused by Mycobacterium tuberculosis . Pulmonary tuberculosis is the ninth most frequent complication of diabetes mellitus. The co-existence of TB and DM in patient causes severe TB symptoms, modify radiological findings, slower response to treatment outcomes and prognosis. IFN-γ is the key cytokine which play role in the protective immune response against mycobacterium infection. The main function of IFN-γ is macrophage activation which is able to exert its microbicidal functions. Estimation and comparison of pre and post treatment serum IFN-γ among pulmonary tuberculosis among diabetic and non-diabetic patients. Methods The study was conducted in the Departments of Biochemistry and Pulmonary Medicine, FMHS, SGT University, Budhera, Gurugram and District TB Centre, Gurugram, Haryana, India. In this study, 100 newly diagnosed PTB patients without diabetes mellitus and 100 newly diagnosed PTB patients with diabetes mellitus (PTB-DM) above 15 years of age were included after obtaining written consent. 5 mL venous blood was collected from patients of pre and post anti-tubercular treatment. The level of IFN-γ was measured by ELISA method. Results The circulating level of IFN-γ in PTB patients was significantly decreased in post-treatment (25.53 ± 6.12 pg/mL) compared to pre-treatment (58.76 ± 16.02 pg/mL) with t-value 32.03 and p-value <0.001. The circulating level of IFN-γ in PTB-DM patients was significantly decreased in post treatment (29.11 ± 7.41 pg/mL) compared to pre-treatment (44.14 ± 10.85 pg/mL) with t-value 31.35 and p-value <0.001. In the present study, level of IFN-γ in pre-treatment PTB patients (58.76 ± 16.02 pg/mL) was significantly raised compared to PTB-DM patients (44.14 ± 10.85 pg/mL) with t-value 7.55 and p-value <0.001. However, level of IFN-γ in post-treatment PTB patients (25.53 ± 6.12 pg/mL) was significantly low compared to PTB-DM patients (29.11 ± 7.41 pg/mL) with t-value 3.71 and p-value <0.001. Conclusions The decreased level of IFN-γ in post-treatment compared to pre-treatment in both PTB and PTB-DM patients had shown efficacy of anti-tubercular treatment. However, the post treatment level of IFN-γ was high in PTB-DM patients compared to PTB patients which verified that effect of ATT was low in PTB-DM.

Objectives Preeclampsia is a multisystem illness that manifests in the third trimester of pregnancy after 20 weeks of gestation and is marked by proteinuria and hypertension (PE). Changes in lifestyle, such as eating a high-calorie diet and delaying delivery, have raised the likelihood of developing PE. Eclampsia, abrupt renal failure, thromboembolic episodes leading to cardiac and brain problems, pulmonary embolism, and coagulopathy associated with HELLP syndrome are a few of the complications that might follow preeclampsia in pregnant moms. The objects of this study is to estimate and correlate the levels of NGAL (neutrophil gelatinase associated lipocalin), IMA (ischemia modified albumin) and Uric acid in prreclampsia. Methods 40 diagnosed cases of preeclampsia and 40 healthy age and gestational age matched healthy controls were included in the study. Blood samples were collected from them and serum NGAL, IMA and Uric acid levels were estimated. Estimation of NGAL (neutrophil gelatinase associated lipocalin), IMA (ischemia modified albumin) was done by commercially available ELISA kits standard spectrophotometry methods in autoanalyzer Mind ray BS300 using commercially available kits. Results The parameters of NGAL and IMA were significantly increased in patients with PE (p<0.001) when compared with the healthy control subjects. γ-glutamyl transferases and OPN were found in patients with ALD (p<0.001) when compared with the control subjects. OPN showed significant positive correlations with AST (r=0.76, p<0.001), ALT (r=0.64 p<0.001), ALP (r=0.68, p<0.001), and GGT (r=0.61, p<0.001). Conclusions The current study focuses on the roles of NGAL and IMA, two sensitive markers of kidney injury that are particularly useful in identifying widespread endothelial dysfunction. As a result, the pattern of elevated NGAL and IMA levels can be useful for diagnosis.

Objectives Immobility and its physiological and psychological consequences are common problems in patients with multiple sclerosis. The aim of this study was to investigate the effect of 8 weeks of combined training on Adipsin and lipid profile and the possible relationship between these indicators and psychological function in women with multiple sclerosis. Methods In this quasi-experimental study, 40 women with multiple sclerosis were selected by purposeful sampling method and randomly divided into two equal control and exercise groups (n=20). Exercise was performed for 8 weeks (two resistance sessions and one endurance session per week). Before and after the intervention, blood samples were taken and the DASS-21 questionnaire was completed to assess anxiety, depression and stress. Data were analyzed using analysis of covariance, t-test, Bonferroni post hoc test and Pearson correlation test at a significance level of p≤0.05. Results In the exercise group, levels of Adipsin, total cholesterol, LDL, TG, weight, fat percentage, WHR, BMI, depression, anxiety and stress were significantly reduced and HDL levels were significantly increased after 8 weeks of combined exercise (p≤0.05). Also, BMI (p=0.01), fat percentage (p=0.01) and WHR (p=0.01) levels had significant positive correlation with Adipsin. There was a significant positive relationship between Total cholesterol level with depression index (p=0.04). Conclusions Performing combination exercises through improving body composition can increase the risk of obesity and cardiovascular risk factors and improve the psychological function of patients with multiple sclerosis. Specialists can use these exercises as an adjunct to drug therapy for MS patients.

Background There has been several discussion and debates regarding the possible setremental influence of elevated serum progesterone (SP) on the day of human chorionic gonadotropin (hCG) administration. Our study aims to assess progestron to oocyte rates for assessing CPR and live birth rate (LBR) in IVF cycles and review previous articles. Methods In this prospective cohort study, women under ovulation induction through IVF-ICSI using the GnRH-antagonist protocol were studied. Five specific indicators were considered to assess pregnancy outcome. The statistical analysis was done using SPSS software. Results In the present research, 78 patients underwent IVF. The cut-off points for each of the three parameters were 1.2 (with a sensitivity of 65.4% and a specificity of 54%), 6.5 (with a sensitivity of 73.1% and a specificity of 56%), and 0.16 (with a sensitivity of 65.4% and a specificity of 60%, respectively). Only the number of oocytes (area below the curve of 0.64) was able to predict clinical pregnancy. The cut-off point for this parameter was 6.5 (with a sensitivity of 74.1% and a specificity of 66%). On the other hand, none of the parameters were able to predict live birth. Conclusions The findings of this study should assist in the clinical management of patients with high SP on the day of HCG administration. We recommend, that the ratio of SP to oocyte is a useful parameter for refining the criteria of patients who have had embryo freezing of all embryos (by selective freezing) and subsequent transfer of frozen embryos.

Objectives The objective of this study is to estimate lipid parameters in subclinical hypothyroidism and correlate it with TSH. Methods Forty newly diagnosed cases of subclinical hypothyroidism and Forty age and gender-matched healthy controls were recruited for the study. Blood samples were collected from them and serum lipid profile (i.e. HDL, LDL, TG, serum total cholesterol) of the subjects was estimated by standard photometric methods in a fully auto-analyzer (MINDRAY BS-300) using commercially available kits and VLDL cholesterol was calculated using the Friedewald’s formula. While serum Ox-LDL, Lipoprotein A, Apolipoprotein A1 and Apo B were estimated by using commercial kit based on enzyme-linked immmunosorbent assay. Results The parameters such as Oxidized low-density lipoprotein (Ox-LDL), lipoprotein (a), apolipoprotein A1, apolipoprotein B and small dense lipoprotein (sd LDL) were significantly increased in subclinical hypothyroid cases when compared with the control subjects (p<0.0001). In present study results showed significant positive correlations of serum thyroid stimulating hormone (TSH) with Ox-LDL (r=0.85, p<0.01), sd LDL (r=0.71, p<0.01). Conclusions The present study focuses on the role of Ox-LDL, sd-LDL Lipoprotein A, Apolipoprotein A1 and Apo B that are sensitive indicators of atherogenic dyslipidemia in subclinical hypothyroidism and can serve as a better & novel risk factor for CAD.

Objectives To report a rare case of a metastatic adrenocortical carcinoma (ACC) that achieve a complete and a long-term remission. Case presentation AAC is a rare and aggressive tumor, with a high risk of recurrence and that present metastases in 21% of cases at diagnosis. Treatment of advanced ACC is challenging, mitotane is the only available adrenolytic treatment, with modest and unpredictable responses. Response rates to systemic chemotherapy are not encouraging. We describe the case of a 39-year-old woman with a metastatic ACC, that achieve a complete and long-term remission after chemotherapy, mitotane treatment and surgery of primary tumor and liver metastases. Conclusions A complete remission of a metastatic adrenocortical carcinoma is possible in some rare cases after a multimodal treatment.

On November 24th, 2021 a case of a new viral variant of SARS-CoV-2 was reported by South Africa and Botswana to WHO, which later was designated as the variant of concern on 26th November 2021. It has around 60 mutations (50 non synonymous, 8 synonymous, and 2 non coding) as compared to the original parent strain of Wuhan. Different hypotheses have been put forward as an explanation for the origin like reverse zoonosis i.e. animal to human transmission, origin from an immune compromised patient or use of highly mutagenic drug like molnupiravir as treatment. A huge spike in cases around the globe is suggestive of a high rate of infectivity and transmissivity as compared to the previous known variants. With whatever cases have been documented so far, it is said that omicron causes mostly mild clinical illnesses and there is a less chance of hospitalization according to the clinicians. Among the reported cases, there were already vaccinated patients also. So there is a possibility that omicron might be able to evade the vaccine induced immunity due to a huge number of mutations (especially in the spike protein sequences). Until new vaccines specific to the pathogen are being developed, the coverage of the currently acceptable vaccines should be increased so that none is deprived of the mandatory doses and a third booster dose might help to reduce the chances of serious complications of this new strain beforehand. So an equal focus on the host and environment is required along with the pathogen.

Objectives Patients with type 1 diabetes mellitus have been reported to have elevated prolactin levels and a possible relationship between prolactin levels and the development of the disease has been proposed. However, some studies show that prolactin mediates beneficial functions in beta cells. Therefore, we review information on the roles of prolactin in type 1 diabetes mellitus. Content Here we summarize the functions of prolactin in the immune system and in pancreatic beta cells, in addition, we describe studies related to PRL levels, its regulation and alterations of secretion in patients with type 1 diabetes mellitus. Summary Studies in murine models have shown that prolactin protects beta cells from apoptosis, stimulates their proliferation and promotes pancreatic islet revascularization. In addition, some studies in patients with type 1 diabetes mellitus have shown that elevated prolactin levels correlate with better disease control. Outlook Prolactin treatment appears to be a promising strategy to improve beta-cell vascularization and proliferation in transplantation and immunotherapies. Highlights – Prolactin is involved in several processes related to the etiology of type 1 diabetes mellitus, such as activation of the immune system, angiogenesis, and beta-cell survival and proliferation. – Observational studies evaluating prolactin levels in patients with type 1 diabetes mellitus are not consistent. – Studies in murine models have shown that prolactin enhances vascularization and proliferation in pancreatic islets. – Further studies are required to assess the positive and negative aspects of prolactin-based therapies.

COVID-19 emerged in Wuhan, China, but was caused by the original coronavirus, severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV2). In early 2020, there was a widespread breakout of cases well over world, resulting in an epidemic that rapidly escalated to become a pandemic. This abruptly shook the global healthcare system. The emergence of the alpha, beta, and delta SARS-CoV-2 were associated with new waves of infections, sometimes across the entire world but until this month i.e., between Nov-Dec, 2021, Delta variant reigned supreme until the emergence of a newer variant i.e., Omicron (B.1.1.529) of SARS-CoV-2. Delta had 13 mutations. Of these, nine are in the spike protein, the protrusion on the surface of the virus that helps it latch onto human cells. Specifically, two are in a molecular hook, called the “receptor-binding domain”. Omicron, a creation caused by monstrous mutations. At least 32 mutations are in the spike protein and 10 in the receptor-binding domain. was designated a COVID-19 variant of concern (VoC) by the World Health Organization (WHO) on 26th November 2021. Structurally, the omicron variant has shown too mutated at antibody binding sites which would leverage them for escaping the possible immune response by the body. We don’t yet know much about the other alterations and how they might affect the virus’s behavior. Omicron COVID-19 strain after identifying individuals with symptoms that were not the same as those seen in the Delta form. People with night sweats have also been reported. The new omicron variant has more mutations than the prevailing rampant delta virus. This makes the newer variant more transmissible, better able to evade itself from various vaccines readily available in the current scenario. These overall increases in the percentage changes in a single day cases of COVID-19 reported cases can be attributed to the beginning of third wave or can be speculated as newer surge of omicron variant cases. Yet another new variant has been detected in France with 46 mutations and 37 deletions in its genetic code, many affecting the spike protein. ‘B.1.640.2’ is the current nomenclature for this variation.

Coronaviruses as such are known since last century. The name is derived from their shape which has crown (corona) like radiating spikes. The recent one however is a different one from the Coronavirus involved in SARS (2002–2004) and MERS (2012) in being highly infectious. Initially COVID 19 had a high case fatality rate which has now decreased to a significant extent. Many cases of COVID 19 are asymptomatic with a significant number of positive cases developing a triad of fever, breathlessness and GI symptoms. Recent travel increases the probability of infection. The pathogenesis involves ACE 2 receptors. So, it has been found that there are more cases and mortality among hypertensive individuals. Even higher among the people who use ACE inhibitor in comparison to those who use other anti-hypertensive drugs. Treatment is usually symptomatic. Antiviral drugs and vaccines against COVID-19 are being used. Deranged liver enzymes are common in COVID-19, however, serious liver injury is not much documented. Liver injury is either due to disease itself or due to antiviral drugs. Extra care like strict social distancing, avoiding unnecessary contact is needed for those with autoimmune hepatitis, liver cancer and those who are in immunosuppression because of a scheduled or already liver transplant. Further research is definitely needed in this field. The upcoming researches should also focus on liver injuries associated with disease course and derangements arising as side effects of treatment of COVID-19.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects million women worldwide, presenting a complex pathophysiology that has not been fully elucidated yet. Recently, it has been suggested that PCOS triggers the endoplasmic reticulum (ER) stress, thus being associated with unfolded protein response (UPR) activation. Indeed, the UPR response has been associated with several pathological conditions, including in the reproductive system. Several studies demonstrated that ovarian UPR markers are upregulated in PCOS, being associated with worst ovarian outcomes, and this was ameliorated by ER stress inhibition. In this review, we aim to summarize the main findings from previous studies covering this topic, in an attempt to clarify the potential role of ER stress and the UPR response in the pathophysiology of PCOS.