Characterization of palmitic acid toxicity induced insulin resistance in HepG2 cells.

BACKGROUND: An etiology of palmitic acid (PA) induced insulin resistance (IR) is complex for which two mechanisms are proposed namely ROS induced JNK activation and lipid induced protein kinase-C (PKCε) activation. However, whether these mechanisms act alone or in consortium is not clear. METHODS AND RESULTS: In this study, we have characterized PA induced IR in liver cells. These cells were treated with different concentrations of PA for either 8 or 16 h. Insulin responsiveness of cells treated with PA for 8 h was found to be same as that of control. However, cells treated with PA for 16 h, showed increased glucose output both in the presence and in absence of insulin only at higher concentrations, indicating development of IR. In these, both JNK and PKCε were activated in response to increased ROS and lipid accumulation, respectively. Activated JNK and PKCε phosphorylated IRS1 at Ser-307 resulting in inhibition of AKT which in turn inactivated GSK3ß, leading to reduced glycogen synthase activity. Inhibition of AKT also reduced insulin suppression of hepatic gluconeogenesis by activating Forkhead box protein O1 (FOXO1) and increased expression of the gluconeogenic enzymes and their transcription factors. CONCLUSION: Thus, our data clearly demonstrate that both these mechanisms work simultaneously and more importantly, identified a threshold of HepG2 cells, which when crossed led to the pathological state of IR in response to PA.

Mini-PCNL - a boon for CKD patients with nephrolithiasis.

Purpose: The prevalence of urinary stone disease in ESRD is 3.2%, leading to renal damage due to obstructive uropathy, infection, and frequent surgical intervention. PCNL, the gold standard for complex renal stone disease, has evolved with smaller access sheaths (14-20 F), improved optics, and fluoroscopic equipments. This study aims to assess the safety and feasibility of mini- PCNL in CKD patients with respect to postoperative outcome and its effect on stage of CKD. Patients and methods: This prospective study was conducted in the Department of Urology, Sher-I-Kashmir Institute of Medical Sciences, from January 2022 to October 2022. This study included adult patients with nephrolithiasis at CKD stage 3 or higher. The primary objective of this research was to assess the impact of mini-PCNL on renal function, specifically measuring changes in estimated glomerular filtration rate (eGFR) from baseline to a 6-month follow-up. The secondary objective was to evaluate the feasibility of mini-PCNL in CKD patients in terms of complications, stone clearance rate, and duration of hospital stay. Four variable Modification of Diet in Renal Diseases(MDRD) equation was used to calculate the estimated GFR(eGFR) of each patient and NKF/KDOQI classification system to classify the stage of CKD. Results: A total of 46 patients were included in the study. We found that for management of nephrolithiasis in CKD patients, mini-PCNL leads to significant improvement in eGFR at 6 months follow-up (mean difference = 14.25 ml/min/1.73 m2; p-value <0.01) with high stone-free rates (89.5%). The complication rates were comparable to standard PCNL. Conclusions: mini-PCNL is a bonanza for management of CKD patients with nephrolithiasis.

Comparison between peak systolic velocity of the inferior thyroid artery and technetium-99m pertechnetate thyroid uptake in differentiating Graves' disease from thyroiditis

ABSTRACT Objectives The differentiation between the various etiologies of thyrotoxicosis, including those with hyperthyroidism (especially Graves' disease [GD], the most common cause of hyperthyroidism) and without hyperthyroidism (like thyroiditis), is an important step in planning specific therapy. Technetium-99m (99mTc) pertechnetate thyroid scanning is the gold standard in differentiating GD from thyroiditis. However, this technique has limited availability, is contraindicated in pregnancy and lactation, and is not helpful in cases with history of recent exposure to excess iodine. The aim of this study was to identify the diagnostic value of the peak systolic velocity of the inferior thyroid artery (PSV-ITA) assessed by color-flow Doppler ultrasound (CFDU) and compare the sensitivity and specificity of this method versus 99mTc pertechnetate thyroid uptake. Subjects and methods We prospectively analyzed 65 patients (46 with GD and 19 with thyroiditis). All patients were evaluated with clinical history and physical examination and underwent 99mTc pertechnetate scanning and measurement of TRAb levels and PSV-ITA values by CFDU. The diagnosis was based on findings from signs and symptoms, physical examination, and 99mTc pertechnetate uptake. Results Patients with GD had significantly higher mean PSV-ITA values than those with thyroiditis. At a mean PSV-ITA cutoff value of 30 cm/sec, PSV-ITA discriminated GD from thyroiditis with a sensitivity of 91% and specificity of 89%. Conclusion Measurement of PSV-ITA by CFDU is a good diagnostic approach to discriminate between GD and thyroiditis, with sensitivity and specificity values comparable to those of 99mTc pertechnetate thyroid uptake.