Impact of 25-hydroxy vitamin D levels in severe acute respiratory syndrome coronavirus 2 patients with respect to clinical and biochemical profile: An experience from a tertiary care hospital.

INTRODUCTION: Among the many micronutrients, Vitamin D deficiency has been associated with the severity of Severe Acute Respiratory Syndrome Coronavirus 2 patients. DESIGN AND METHODS: A retrospective observational study was conducted on Severe acute respiratory syndrome coronavirus 2 patients admitted to a tertiary care hospital between April 5, 2021, and May 5, 2021. RESULTS: Among 285 patients,77.2 % of the patients who stayed for more than 14 days were either Vitamin D insufficient or deficient [P value < 0.05]. In our study, the mean oxygen saturation at admission was 85.7 % in the Vitamin D deficiency group compared to 95.6 % in Vitamin D sufficiency patients [P value < 0.05]. Mean serum ferritin was 398 ng/ml in the Vitamin D deficiency group compared to 393 ng/ml in Vitamin D sufficiency patients [P value > 0.05]. The mean C-reactive protein was 107.6 mg/ml in the Vitamin D deficiency group compared to 21.8 ng/ml in Vitamin D sufficiency patients [P value < 0.05]. The mean D-Dimer was 2268 ng/ml in the Vitamin D deficiency group compared to 781 ng/ml in Vitamin D sufficiency patients [P value < 0.05]. In the non-survivor group,97.4 % were Vitamin D deficient and insufficient. Only 2 % of the patients who survived were Vitamin D deficient [P value < 0.05]. CONCLUSION: We observed that low 25-hydroxy Vitamin D levels were associated with lower oxygen saturation and higher acute physiology and chronic health evaluation II scores, requiring a more extended stay in the hospital. C-reactive protein and D-dimers were significantly higher in Vitamin D deficient patients, suggesting severe disease. We did not find statistically significant findings in the case of the correlation of serum ferritin levels with Vitamin D status.

Analyzing the drivers of cancer relapse: hypocalcemia and iron absorption in hormone-dependent female cancers.

BACKGROUND: Alterations in the levels of nutrients like calcium, ferritin, and electrolytes play a pivotal role in human physiology and might serve as biomarkers. Ferritin, an iron storage protein is important in various metabolic reactions of both cancer and cancer stem cells (CSCs) and is found to regulate 'stemness' leading to cancer relapse. Interestingly, ferritin levels are found to be regulated by calcium uptake. Several studies have shown that high levels of calcium inhibit absorption of iron, thereby reducing ferritin levels. In the present study, we evaluated and correlated the serum ferritin and calcium levels in pre- and post-treated hormone-dependent female cancers and deciphered their role in tumor recurrence and relapse. MATERIALS AND METHODS: The present retrospective study was approved by the Institutional Ethical Committees (IEC) of GIMSR (No. GIMSR/Admn./Ethics/approval/IEC-3/2021), and Omega cancer hospitals (Reg No: ECR/1486/Inst/AP/2020). Serum from 197 clinical samples diagnosed with breast, cervical, and ovarian cancers (99 pre-and 98 post-treatment) and 10 blood samples were analyzed for ferritin and calcium using auto bioanalyzer and sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Ferritin levels were elevated in both pre- and post-treatment hormone-dependent female cancer patients while calcium levels showed gradual decrease. The mean ferritin value for pre-treatment was 0.0409 mg/dL while it was 0.0428 mg/dL for post-treatment hormone-dependent female cancer. CONCLUSION: Our results suggest that hypocalcaemia in post-treatment cancer patients leads to ferritin accumulation which might make these patients more prone to tumor recurrence and relapse.

Clinical and biochemical profile of COVID-19 patients admitted in a tertiary care hospital in Visakhapatnam, India during post unlock 2.0 - a retrospective study.

There have been more than 31378143 confirmed coronavirus disease 2019 (COVID-19) cases in India. It was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Because the risk of severe COVID-19 is not consistent across all individuals, uncertainty is linked to disease development. COVID-19 results have been related to systemic inflammation as a predictor. In COVID-19, increased levels of inflammatory markers have been associated with cytokine storm, coagulopathy, and endothelial dysfunction. A significant amount of research suggests that these results have a role in the cause of death in individuals suffering from a severe form of COVID-19. We aim to show our experience of COVID-19 at GITAM Institute of Medical Sciences and Research (GIMSR), Visakhapatnam. We analyzed data on 558 patients admitted to our dedicated COVID hospital during post unlock (UL) 2.0 in India from August 2 to August 31, 2020. The mean age was 43.65 years; 69% of them were male. Using MoHFW India severity guidelines, 68.10% were mild, 18.64% were moderate, and 13.26% were severe cases. Fatigue (66.13%) was the most common complaint, followed by anosmia (63.80%), fever (57.53%), diarrhea (56.09%), shortness of breath (22.40%), and others. The most common preexisting comorbidity seen in our patients was diabetes mellitus and hypertension, respectively. Laboratory parameters revealed mean hemoglobin of 13.04±1.91 gm/dl, mean total leukocyte count of 7378.49±3229 cells/cumm, mean platelet count of 2.3±0.8 lakhs/cumm, mean erythrocyte sediment rate of 40±30 mm/hr, mean ferritin level of 335.96 ng/ml, mean D-dimer level of 794.88 ng/ml and mean CRP of 23.27 mg/l. Severity was associated with higher age, symptomatic presentation, elevated leucocytes, and elevated inflammatory markers.

A preclinical study on the protective effect of melatonin against methotrexate-induced small intestinal damage: effect mediated by attenuation of nitrosative stress, protein tyrosine nitration, and PARP activation.

PURPOSE: One of the major toxic side effects of methotrexate (MTX) is enterocolitis. To date, there is no efficient standard treatment for this side effect. Nitrosative stress is reported to play a critical role in MTX-induced mucositis. The purpose of this study is to investigate whether pretreatment with melatonin, an inhibitor of nitro-oxidative stress, prevents MTX-induced mucositis in rats. METHODS: Rats were pretreated with melatonin (20 and 40 mg/kg body weight) i.p. daily 1 h before MTX (7 mg/kg body weight) administration for three consecutive days. After the final dose of MTX, the rats were killed and the small intestines were used for analysis. RESULTS: The small intestines of MTX-treated rats showed moderate to severe injury. The villi were distorted, blunted, and atrophied and focally absent in various segments of the small intestines. Crypt abscesses were also found, suggesting an inflammatory response. Pretreatment with melatonin had a dose-dependent protective effect on MTX-induced mucositis. Morphology was saved to a moderate extent with 20 mg melatonin pretreatment, and near-normal morphology was achieved with 40 mg melatonin pretreatment. Damage to the villi and crypt abscess was reduced. The villi/crypt ratio was almost restored. Melatonin pretreatment protected the small intestines from MTX-induced damage by attenuating nitrosative stress, protein tyrosine nitration and PARP expression. CONCLUSION: Because of its versatility in protecting against nitro-oxidative stress and reducing inflammation, we suggest that melatonin could be beneficial in ameliorating MTX-induced enteritis in humans.

Preclinical efficacy of melatonin to reduce methotrexate-induced oxidative stress and small intestinal damage in rats.

BACKGROUND: Methotrexate is widely used as a chemotherapeutic agent for leukemia and other malignancies. The efficacy of this drug is often limited by mucositis and intestinal injury, which are the major causes of morbidity in children and adults. AIM: The present study investigates whether melatonin, a powerful antioxidant, could have a protective effect. METHOD: Rats were pretreated with melatonin (20 and 40 mg/kg body weight) daily 1 h before methotrexate (7 mg/kg body weight) administration for three consecutive days. After the final dose of methotrexate, the rats were sacrificed and the small intestine was used for light microscopy and biochemical assays. Intestinal homogenates were used for assay of oxidative stress parameters malondialdehyde and protein carbonyl content, and myeloperoxidase activity, a marker of neutrophil infiltration as well as for the activities of the antioxidant enzymes. RESULT: Pretreatment with melatonin had a dose-dependent protective effect on methotrexate (MTX)-induced alterations in small intestinal morphology. Morphology was saved to some extent with 20 mg melatonin pretreatment and near normal morphology was achieved with 40 mg melatonin pretreatment. Biochemically, pretreatment with melatonin significantly attenuated MTX-induced oxidative stress (P < 0.01 for MDA, P < 0.001 for protein carbonyl content) and restored the activities of the antioxidant enzymes (glutathione reductase P < 0.05, superoxide dismutase P < 0.01). CONCLUSION: The results of the present study demonstrate that supplementation by exogenous melatonin significantly reduces MTX-induced small intestinal damage, indicating that it may be beneficial in ameliorating MTX-induced enteritis in humans.

Melatonin attenuates methotrexate-induced oxidative stress and renal damage in rats.

Nephrotoxicity is an adverse side effect of methotrexate (MTX) chemotherapy. The present study verifies whether melatonin, an endogenous antioxidant prevents MTX-induced renal damage. Adult rats were administered 7 mg/kg body weight MTX intraperitoneally for 3 days. In the melatonin pretreated rats, 40 mg/ kg body weight melatonin was administered daily intraperitoneally 1 h before the administration of MTX. The rats were killed 12 h after the final dose of MTX/vehicle. The kidneys were used for light microscopic and biochemical studies. The markers of oxidative stress were measured along with the activities of the antioxidant enzymes and myeloperoxidase activity in the kidney homogenates. Pretreatment with melatonin reduced MTX induced renal damage both histologically and biochemically as revealed by normal plasma creatinine levels. Melatonin pretreatment reduced MTX induced oxidative stress, alteration in the activity of antioxidant enzymes as well as elevation in myeloperoxidase activity. The results suggest that melatonin has the potential to reduce MTX induced oxidative stress, neutrophil infiltration as well as renal damage. As melatonin is an endogenous antioxidant and is non-toxic even in high doses it is suggested that melatonin may be beneficial in minimizing MTX induced renal damage in humans.

Neutrophil infiltration and oxidative stress may play a critical role in methotrexate-induced renal damage.

BACKGROUND: Nephrotoxicity is one of the adverse side effects of methotrexate (MTX) chemotherapy. The mechanism of renotoxicity of MTX is not fully understood. It is essential to understand the mechanism of nephrotoxicity of MTX in order to diminish the side effects and hence maximize the benefits of chemotherapy. OBJECTIVES: The aim of the study was to verify whether oxidative stress and neutrophil infiltration play a role in MTX-induced renal damage using a rat model. METHODS: Adult male rats were administered MTX at the dose of 7 mg/kg body weight intraperitoneally for 3 consecutive days and sacrificed 12 or 24 h after the last dose. Vehicle-treated rats served as controls. The kidneys were removed and used for light microscopic and biochemical studies. Myeloperoxidase activity, a marker of neutrophil infiltration was measured in kidney homogenates along with the markers of oxidative damage including protein carbonyl content, protein thiol and malondialdehyde. The activities of the antioxidant enzymes, namely glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase, were also assayed. RESULTS: MTX treatment induced damage to the glomeruli and tubules. Plasma creatinine levels in the MTX-treated rats were significantly elevated compared with controls. A significant increase in myeloperoxidase activity (p<0.05) was observed in the kidneys of MTX-treated rats. Protein carbonyl content and malondialdehyde, sensitive and reliable markers of oxidative damage to proteins and lipids, respectively, were significantly elevated (p<0.01) in the kidneys of MTX-treated rats compared with controls. The activities of the antioxidant enzymes, namely, superoxide dismutase and glutathione peroxidase, were significantly elevated (p<0.01 and p<0.05, respectively) in kidneys of rats following MTX treatment. CONCLUSION: The results of the present study provide evidence for the role of neutrophil infiltration and oxidative stress in MTX-induced renal damage. Administration of inhibitors of myeloperoxidase or scavenging hypochlorous acid, the product of myeloperoxidase, by supplementation with antioxidants as an adjuvant therapy may be promising in alleviating the renal side effect of MTX.

Methotrexate-induced nitrosative stress may play a critical role in small intestinal damage in the rat.

Methotrexate (MTX), a structural analogue of folic acid, is widely used as a chemotherapeutic agent for leukemia and other malignancies. One of the major toxic effects of MTX is intestinal injury and enterocolitis .The mechanism of gastrointestinal toxicity of methotrexate has not been investigated completely. Therefore cancer chemotherapy has to be accompanied by symptomatic therapy such as antibiotics and anti-diarrheal drugs. It is important to investigate the mechanism by which methotrexate induces intestinal damage in order to perform cancer chemotherapy effectively by preventing the side effects. This study aimed at investigating whether nitrosative stress plays a role in methotrexate induced small intestinal damage using a rat model. Adult male rats were administered methotrexate at the dose of 7 mg/kg body weight intraperitoneally for 3 consecutive days and sacrificed 12 or 24 h after the final dose of methotrexate. Vehicle treated rats served as control. The intestinal tissue was used for light microscopic studies and markers of nitrosative stress including tissue nitrite level and nitrotyrosine. Myeloperoxidase (MPO) activity, a marker of neutrophil infiltration was also measured in intestinal homogenates. The villi were damaged at 12 h and the damage progressed and became severe at 24 h after the final dose of MTX. Biochemically, tissue nitrate was elevated fivefold at 12 h and fourfold at 24 h after the final dose of MTX as compared with control. Nitrotyrosine, measured immunohistochemically was detected in all the parts of the small intestine. Duodenum stained the most for nitrotyrosine, followed by ileum and then jejunum. The staining for nitrotyrosine was more intense at 24 h as compared with 12 h after the final dose of methotrexate. There was marked neutrophil infiltration as evidenced by increase in MPO activity in the small intestines. In conclusion, the results of the present study reveal that nitrosative stress may play a critical role in methotrexate induced small intestinal damage. Intervention studies using nitric oxide synthase inhibitors is being carried out in order to confirm the role of nitrosative stress in methotrexate induced small intestinal damage.