RESUMEN
COVID-19 is a disease caused by a coronavirus named as SARS-CoV-2. It has become pandemic due to its contagious nature. Majority of the patients are asymptomatic or having mild flu like symptoms. Few need hospitalisation due to severe acute respiratory infection (SARI). Co-morbidity like diabetes, hypertension, renal failure etc. are associated with severe COVID-19 that often causes death. There have been only two published case reports of monoclonal gammopathy of unknown significance (MGUS) in patients with COVID-19 disease. Cytokine storm is often observed in severe COVID-19 and various cytokines including IL-6 that activates plasma cells are increased in blood in this condition. Here we present a case of severe COVID-19 patient with bioclonal gammopathy. He was known diabetic and hypertensive on treatment. He developed SARI, cytokines storm and septicaemia, treated with antibiotics, enoxaparin, hydroxychloroquine, insulin, anti-hypertensives, put on ventilator, subsequently developed septicaemia, multi-organ failure and died. Two M-bands on serum capillary electrophoresis with presence IgG-κ on both the M-bands indicates a biclonal gammopathy of unknown significance in this patient. We conclude that like MGUS, early stage biclonal gammopathy, although rare, gets manifested with M-bands on plasma protein electrophoresis. It is probably due to high level of IL-6 associated with cytokine storm in severe COVID-19 that stimulate early stage dyscratic plasma cells. Such biclonal gammopathy might be a risk factor for severe COVID-19 and associated mortality.
Asunto(s)
COVID-19/sangre , COVID-19/diagnóstico , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , SARS-CoV-2 , Índice de Severidad de la Enfermedad , COVID-19/complicaciones , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/complicaciones , Síndrome de Liberación de Citoquinas/diagnóstico , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/complicacionesRESUMEN
Biochemical basis of Malathion exposure-induced diabetes mellitus is not known. Hence, effects of its sub-toxic exposure on redox sensitive kinases (RSKs), insulin signaling and insulin-induced glucose uptake were assessed in rat muscle cell line. In this in vitro study, rat myoblast (L6) cells were differentiated to myotubes and were exposed to sub-toxic concentrations (10 mg/l and 20 mg/l) of Malathion for 18 hours. Total antioxidant level and insulin-stimulated glucose uptake by myotubes were assayed. Activation of JNK, NFκB, p38MAPK and insulin signaling from tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt were assessed in myotubes after Malathion exposure by western blot and was compared with those in controls. Paraoxonase (PON) activity was measured in cell lysate using p-nitrophenyl acetate as substrate. PON1 and PON2 expression in myotubes were assessed by PCR. The glucose uptake and total antioxidant level in L6-derived myotubes after sub-toxic exposure to Malathion were decreased in a dose-dependent manner. Phosphorylation levels of RSKs (JNK, p38MAPK and IκBα component of NFκB) were increased and that of IRS-1 and Akt on insulin stimulation was decreased following Malathion exposure as compared to those in controls. PON1 and PON2 genes were expressed in myotubes with and without Malathion exposure. Significant PON activity was present in cell lysate. We conclude that sub-toxic Malathion exposure induces oxidative stress in muscle cells activating RSKs that impairs insulin signaling and thereby insulin-stimulated glucose uptake in muscle cells. This probably explains the biochemical basis of Malathion-induced insulin resistance state and diabetes mellitus.
Asunto(s)
Glucosa/metabolismo , Insecticidas/toxicidad , Insulina/farmacología , Malatión/toxicidad , Fibras Musculares Esqueléticas/efectos de los fármacos , Mioblastos Esqueléticos/efectos de los fármacos , Animales , Línea Celular , Fibras Musculares Esqueléticas/metabolismo , Mioblastos Esqueléticos/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosforilación , Proteínas Quinasas/metabolismo , Ratas , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: The study was conducted to assess biochemical profiles in premenopausal and postmenopausal women having breast cancer. MATERIALS AND METHODS: A hospital based case control study was carried out at Manipal Teaching Hospital (MTH), Pokhara, Nepal. The analysed variables were age, metabolic profile including total cholesterol, triglycerides, HDL-C, LDL-C, blood sugar, insulin concentration, C-peptide, HbA1c and selenium. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. RESULTS: In premenopausal women, significant differences were noted for total cholesterol (P value <0.001), triglycerides (P value 0.002), HbA1c level (P value <0.001), insulin concentration (P value 0.030), C-peptide concentration (P value 0.001), and selenium (P value <0.001) between cases and controls. Insignificant results were found for HDL-C (P value 0.749), LDL-C (P value 0.933), blood sugar (P value 0.59) and BMI (P value 0.746). Similarly, significant difference in total cholesterol (P value <0.001), triglycerides (P value 0.001), LDL-C (P value <0.001), HDL-C (P value 0.025), blood sugar (P value <0.001), insulin concentration (P value <0.001), c-peptide concentration (P value <0.001), HbA1c level (P value <0.001) and selenium (P value <0.001) were observed for postmenopausal patients and controls. CONCLUSIONS: Assessing metabolic changes and their management may be important for control of breast cancer and increased survival.
Asunto(s)
Neoplasias de la Mama/metabolismo , Posmenopausia/metabolismo , Premenopausia/metabolismo , Adulto , Anciano , Glucemia/metabolismo , Neoplasias de la Mama/sangre , Péptido C/sangre , Péptido C/metabolismo , Estudios de Casos y Controles , HDL-Colesterol/sangre , HDL-Colesterol/metabolismo , LDL-Colesterol/sangre , LDL-Colesterol/metabolismo , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Insulina/sangre , Insulina/metabolismo , Persona de Mediana Edad , Posmenopausia/sangre , Premenopausia/sangre , Selenio/sangre , Selenio/metabolismo , Triglicéridos/sangre , Triglicéridos/metabolismoRESUMEN
BACKGROUND: Glycated hemoglobin (HbA1C) levels are enhanced by elevated glucose concentrations. Glycation of hemoglobin is also modulated by lipid peroxides, ascorbic acid and reduced glutathione (GSH). We determined the strength of the relationships among these variables in a group of hyperthyroid patients. METHODS: Twenty-two untreated hyperthyroid patients and 17 healthy controls were recruited for the study. Whole blood GSH, HbA1C, plasma lipid peroxides, ascorbic acid and fasting glucose were analyzed in both the groups. Direct and partial correlation analysis was performed to explore the possible relationships between these variables. RESULTS: In hyperthyroid patients, HbA1C and lipid peroxides levels were found to be significantly increased than the controls. Ascorbic acid and GSH were decreased significantly in the test group when compared with the healthy control group. With partial correlation analysis, fasting glucose and lipid peroxides were found to have a significant positive correlation with HbA1C. Ascorbic acid and GSH showed no significant association with HbA1C levels. CONCLUSION: These data suggest that HbA1C levels are closely associated with fasting glucose and lipid peroxides in hyperthyroid patients. Therefore, serum lipid peroxides level should be kept in mind while interpreting HbA1C as a long-term glycemic index in hyperthyroid cases.