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Mineralocorticoid excess commonly leads to hypertension (HTN) and kidney disease. In our study, we used single- cell expression and chromatin accessibility tools to characterize the mineralocorticoid target genes and cell types. We demonstrated that mineralocorticoid effects were established through open chromatin and target gene expression, primarily in principal and connecting tubule cells and, to a lesser extent, in segments of the distal convoluted tubule cells. We examined the kidney-protective effects of steroidal and nonsteroidal mineralocorticoid antagonists (MRAs), as well as of amiloride, an epithelial sodium channel inhibitor, in a rat model of deoxycorticosterone acetate, unilateral nephrectomy, and high-salt consumption-induced HTN and cardiorenal damage. All antihypertensive therapies protected against cardiorenal damage. However, finerenone was particularly effective in reducing albuminuria and improving gene expression changes in podocytes and proximal tubule cells, even with an equivalent reduction in blood pressure. We noted a strong correlation between the accumulation of injured/profibrotic tubule cells expressing secreted posphoprotein 1 (Spp1), Il34, and platelet-derived growth factor subunit b (Pdgfb) and the degree of fibrosis in rat kidneys. This gene signature also showed a potential for classifying human kidney samples. Our multiomics approach provides fresh insights into the possible mechanisms underlying HTN-associated kidney disease, the target cell types, the protective effects of steroidal and nonsteroidal MRAs, and amiloride., Introduction Chronic kidney disease (CKD) is a serious and growing public health issue, affecting approximately 14% of the population in the United States (1). It is the ninth leading cause [...]

As the metal additive manufacturing (AM) field evolves with an increasing demand for highly complex and customizable products, there is a critical need to close the gap in productivity between metal AM and traditional manufacturing (TM) processes such as continuous casting, machining, etc., designed for mass production. This paper presents the development of the scalable and expeditious additive manufacturing (SEAM) process, which hybridizes binder jet printing and stereolithography principles, and capitalizes on their advantages to improve productivity. The proposed SEAM process was applied to stainless steel 420 (SS420) and the processing conditions (green part printing, debinding, and sintering) were optimized. Finally, an SS420 turbine fabricated using these conditions successfully reached a relative density of 99.7%. The SEAM process is not only suitable for a high-volume production environment but is also capable of fabricating components with excellent accuracy and resolution. Once fully developed, the process is well-suited to bridge the productivity gap between metal AM and TM processes, making it an attractive candidate for further development and future commercialization as a feasible solution to high-volume production AM. [ABSTRACT FROM AUTHOR]

Recently, we have reported that the early progression of proteinuria in the obese Dahl salt-sensitive (SS) leptin receptor mutant (SSLepRmutant) strain was associated with increased renal macrophage infiltration before puberty. Macrophages can be divided into two distinct phenotypes: M1 (proinflammatory) and M2 (anti-inflammatory). Moreover, previous studies have demonstrated that interleukin (IL)-25 converts resting macrophages and M1 into M2. Therefore, the present study examined whether treatment with IL-25 would reduce the early progression of renal injury in SSLepRmutant rats by increasing renal M2. We also investigated the impact of IL-25 on M2 subtypes: M2a (wound healing/anti-inflammatory), M2b (immune mediated/proinflammatory), M2c (regulatory/anti-inflammatory), and M2d (tumor associated/proangiogenic). Four-wk-old SS and SSLepRmutant rats were treated with either control (IgG) or IL-25 (1 lg/day ip every other day) for 4 wk. The kidneys from SSLepRmutant rats displayed progressive proteinuria and renal histopathology versus SS rats. IL-25 treatment had no effect on these parameters in SS rats. However, in the SSLepRmutant strain, proteinuria was markedly reduced after IL-25 treatment. Chronic treatment with IL-25 significantly decreased glomerular and tubular injury and renal fibrosis in the SSLepRmutant strain. Although the administration of IL-25 did not change total renal macrophage infiltration in both SS and SSLepRmutant rats, IL-25 increased M2a by >50% and reduced M1 by 60% in the kidneys of SSLepRmutant rats. Overall, these data indicate that IL-25 reduces the early progression of renal injury in SSLepRmutant rats by inducing M2a and suppressing M1 and suggest that IL-25 may be a therapeutic target for renal disease associated with obesity. [ABSTRACT FROM AUTHOR]

The performance of a magnetic-field-assisted finishing (MAF) process, an advanced surface finishing process, is severely affected by the rheological properties of an MAF brush. The yield stress and viscosity of the MAF brush, comprising iron particles and abrasives mixed in a liquid carrier medium, change depending on the brush's constituents and the applied magnetic field, which in turn affect the material removal mechanism and the corresponding final surface roughness after the MAF. A series of experiments was conducted to delineate the effect of MAF processing conditions on the yield stress of the MAF brush. The experimental data were fitted into commonly used rheology models. The Herschel–Bulkley (HB) model was found to be the most suitable fit (lowest sum of square errors (SSE)) for the shear stress–shear rate data obtained from the rheology tests and used to calculate the yield stress of the MAF brush. Processing parameters, such as magnetic flux density, weight ratio of iron and abrasives, and abrasive (black ceramic in this study) size, with p-values of 0.031, 0.001 and 0.037, respectively, (each of them lower than the significance level of 0.05), were all found to be statistically significant parameters that affected the yield stress of the MAF brush. Yield stress increased with magnetic flux density and the weight ratio of iron to abrasives in MAF brush and decreased with abrasive size. A new process model, a rheology-integrated model (RM), was formulated using the yield stress data from HB model to determine the indentation depth of individual abrasives in the workpiece during the MAF process. The calculated indentation depth enabled us to predict the material removal rate (MRR) and the instantaneous surface roughness. The predicted MRR and surface roughness from the RM model were found to be a better fit with the experimental data than the pre-existing contact mechanics model (CMM) and wear model (WM) with a R2 of 0.91 for RM as compared to 0.76 and 0.78 for CMM and WM. Finally, the RM, under parametric variations, showed that MRR increases and roughness decreases as magnetic flux density, rotational speed, weight ratio of iron to abrasive particles in MAF brush, and initial roughness increase, and abrasive size decreases. [ABSTRACT FROM AUTHOR]

Pediatric intussusception is the leading cause of bowel obstruction in children under 2 years of age. Concurrent intussusception and appendicitis, known as "appendi-sception" is exceptionally rare in the pediatric population. A 37-month-old boy presented with periumbilical abdominal pain, vomiting, and red currant jelly stool for two weeks. Clinical examination and ultrasonography confirmed intussusception. Hydroreduction was attempted twice but failed, necessitating surgical intervention. During exploratory laparotomy, ileocolic intussusception and an inflamed appendix were discovered for which an appendectomy was performed. The postoperative course was uneventful, and histopathology confirmed suppurative appendicitis. The patient had no difficulty at the one-year follow-up. Intussusception with appendicitis as a lead point is rare and often challenging to diagnose preoperatively. The literature review revealed 11 pediatric cases, with concomitant intussusception and appendicitis highlighting diagnostic challenges due to symptom overlap. The overlap in symptoms between intussusception and appendicitis complicates diagnosis. Hydroreduction failure should prompt consideration of secondary causes, including appendicitis. Considering secondary causes in intussusception is crucial, especially when initial management fails. CT scans should be considered in such cases. Appendectomy and manual reduction can effectively manage concurrent intussusception and appendicitis. This case underscores the importance of considering multiple diagnoses in complex pediatric abdominal presentations. • Concurrent Intussusception and appendicitis is an uncommon condition with an estimated incidence of 0.01%. • Intussusception and acute appendicitis often present with similar symptoms, including vomiting, abdominal pain, and irritability. • Secondary causes, such as appendicitis, should be considered when initial treatments like hydroreduction fail. [ABSTRACT FROM AUTHOR]

Prepubertal obesity (PPO) has emerged as a major health problem over the past few decades and is a risk factor for the development of proteinuria. The current study investigated whether the development of renal injury in the obese SSLepR mutant strain occurs before puberty. When determining the temporal changes in serum sex hormones in female and male SS and SSLepR mutant rats between 4 and 10 wk of age, we only observed significant increases in estradiol and testosterone levels in female and male SS rats at 10 wk of age than at 4 wk of age. The results suggest that studying both strains between 4 and 8 wk of age is appropriate to study the effects of PPO on renal injury in this model. Proteinuria was significantly higher in SSLepR mutant rats as opposed to the values observed in SS rats at 8 wk of age, and we did not observe any sex differences in proteinuria in either strain. The kidneys from the SSLepR mutant rats displayed significant glomerular and tubular injury and renal fibrosis versus the values measured in SS rats without any sex differences. Overall, we observed increased immune cell infiltration in the kidneys from SSLepR mutant rats compared with SS rats. Interestingly, female SSLepR mutant rats displayed significant increases in not only M1 macrophages (proinflammatory) but also M2 macrophages (anti-inflammatory) versus male SSLepR mutant rats. These results suggest the SSLepR mutant rat may be a useful model to study early progression of obesity-related renal injury before the onset of puberty. [ABSTRACT FROM AUTHOR]

Recently, we reported that obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats develop glomerular injury and progressive proteinuria prior to puberty. Moreover, this early progression of proteinuria was associated with elevations in GFR. Therefore, the current study examined whether treatment with lisinopril to reduce GFR slows the early progression of proteinuria in SSLepRmutant rats prior to puberty. Experiments were performed on 4-week-old SS and SSLepRmutant rats that were either treated with vehicle or lisinopril (20 mg/kg/day, drinking water) for 4 weeks. We did not observe any differences in MAP between SS and SSLepRmutant rats treated with vehicle (148 ± 5 vs. 163 ± 6 mmHg, respectively). Interestingly, chronic treatment with lisinopril markedly reduced MAP in SS rats (111 ± 3 mmHg) but had no effect on MAP in SSLepRmutant rats (155 ± 4 mmHg). Treatment with lisinopril significantly reduced proteinuria in SS and SSLepRmutant rats compared to their vehicle counterparts (19 ± 5 and 258 ± 34 vs. 71 ± 12 and 498 ± 66 mg/day, respectively). Additionally, nephrin excretion was significantly elevated in SSLepRmutant rats versus SS rats, and lisinopril reduced nephrin excretion in both strains. GFR was significantly elevated in SSLepRmutant rats compared to SS rats, and lisinopril treatment reduced GFR in SSLepRmutant rats by 30%. The kidneys from SSLepRmutant rats displayed glomerular injury with increased mesangial expansion and renal inflammation versus SS rats. Chronic treatment with lisinopril significantly decreased glomerular injury and renal inflammation in the SSLepRmutant rats. Overall, these data indicate that inhibiting renal hyperfiltration associated with obesity is beneficial in slowing the early development of glomerular injury and renal inflammation. [ABSTRACT FROM AUTHOR]

Recently, we reported that Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats exhibit dyslipidemia and renal lipid accumulation independent of hyperglycemia that progresses to chronic kidney disease (CKD). Therefore, in the current study, we examined the effects of gemfibrozil, a lipid-lowering drug (200 mg/kg/day, orally), on the progression of renal injury in SS and SSLepRmutant rats for 4 weeks starting at 12 weeks of age. Plasma triglyceride levels were markedly elevated in the SSLepRmutant strain compared to SS rats (1193 ± 243 and 98 ± 16 mg/day, respectively). Gemfibrozil treatment only reduced plasma triglycerides in the SSLepRmutant strain (410 ± 79 mg/dL). MAP was significantly higher in the SSLepRmutant strain vs. SS rats at the end of the study (198 ± 7 vs. 165 ± 7 mmHg, respectively). Administration of gemfibrozil only lowered MAP in SSLepRmutant rats (163 ± 8 mmHg). During the course of the study, proteinuria increased to 125 ± 22 mg/day in SS rats. However, proteinuria did not change in the SSLepRmutant strain and remained near baseline (693 ± 58 mg/day). Interestingly, treatment with gemfibrozil increased the progression of proteinuria by 77% in the SSLepRmutant strain without affecting proteinuria in SS rats. The renal injury in the SSLepRmutant strain progressed to CKD. Moreover, the kidneys from SSLepRmutant rats displayed significant glomerular injury with mesangial expansion and increased renal lipid accumulation and fibrosis compared to SS rats. Treatment with gemfibrozil significantly reduced glomerular injury and lipid accumulation and improved renal function. These data indicate that reducing plasma triglyceride levels with gemfibrozil inhibits hypertension and CKD associated with obesity in SSLepRmutant rats. [ABSTRACT FROM AUTHOR]

Recently, we reported that obese Dahl salt-sensitive (SS) leptin receptor mutant (SSLepRmutant) rats display progressive renal injury. The present study demonstrated that the early development of renal injury in the SSLepRmutant strain is associated with an increase in the renal infiltration of macrophages compared with lean SS rats. We also examined whether depletion of macrophages with clodronate would reduce the early progression of renal injury in the SSLepRmutant strain. Four-week-old SS and SSLepRmutant rats were treated with either vehicle (PBS) or clodronate (50 mg/kg ip, 2 times/wk) for 4 wk. While the administration of clodronate did not reduce renal macrophage infiltration in SS rats, clodronate decreased macrophages in the kidneys of SSLepRmutant rats by >50%. Interestingly, clodronate significantly reduced plasma glucose, insulin, and triglyceride levels and markedly improved glucose tolerance in SSLepRmutant rats. Treatment with clodronate had no effect on the progression of proteinuria or renal histopathology in SS rats. In the SSLepRmutant strain, proteinuria was markedly reduced during the first 2 wk of treatment (159 ± 32 vs. 303 ± 52 mg/day, respectively). However, after 4 wk of treatment, the effect of clodronate was no longer observed in the SSLepRmutant strain (346 ± 195 vs. 399 ± 50 mg/day, respectively). The kidneys from SSLepRmutant rats displayed glomerular injury with increased mesangial expansion and renal fibrosis versus SS rats. Treatment with clodronate significantly decreased glomerular injury and renal fibrosis in the SSLepRmutant strain. Overall, these data indicate that the depletion of macrophages improves metabolic disease and slows the early progression of renal injury in SSLepRmutant rats. [ABSTRACT FROM AUTHOR]

The present study examined whether development of renal injury in the nondiabetic obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) strain is associated with elevations in glomerular filtration rate and renal lipid accumulation. Baseline mean arterial pressure at 6 wk of age was similar between Dahl salt-sensitive wild-type (SSWT) and SSLepRmutant rats. However, by 18 wk of age, the SSLepRmutant strain developed hypertension, while the elevation in mean arterial pressure was not as severe in SSWT rats (192 ± 4 and 149 ± 6 mmHg, respectively). At baseline, proteinuria was fourfold higher in SSLepRmutant than SSWT rats and remained elevated throughout the study. The early development of progressive proteinuria was associated with renal hyperfiltration followed by a decline in renal function over the course of study in the SSLepRmutant compared with SSWT rats. Kidneys from the SSLepRmutant strain displayed more glomerulosclerosis and glomerular lipid accumulation than SSWT rats. Glomeruli were isolated from the renal cortex of both strains at 6 and 18 wk of age, and RNA sequencing was performed to identify genes and pathways driving glomerular injury. We observed significant increases in expression of the influx lipid transporters, chemokine (C-X-C motif) ligand 16 (Cxcl16) and scavenger receptor and fatty acid translocase (Cd36), respectively, and a significant decrease in expression of the efflux lipid transporter, ATP-binding cassette subfamily A member 2 (Abca2; cholesterol efflux regulatory protein 2), in SSLepRmutant compared with SSWT rats at 6 and 18 wk of age, which were validated by RT-PCR analysis. These data suggest an association between glomerular hyperfiltration and glomerular lipid accumulation during the early development of proteinuria associated with obesity. [ABSTRACT FROM AUTHOR]

The endothelin (ET) system has emerged as a therapeutic target for the treatment of diabetic nephropathy (DN). The present study examined whether chronic endothelin A (ETA) receptor blockade with atrasentan prevents the progression of renal injury in two models of DN with preexisting renal disease that exhibit an increased renal ET-1 system compared with nondiabetic rats: streptozotocin-treated Dahl salt-sensitive (STZ-SS) and type 2 diabetic nephropathy (T2DN) rats. Nine week-old SS rats were treated with (STZ; 50 mg/kg ip) to induce diabetes. After 3 wk of diabetes, proteinuria increased to 353 ± 34 mg/day. The rats were then separated into two groups: 1) vehicle and 2) atrasentan (5 mg·kg-1·day-1) via drinking water. After 6 wk of treatment with atrasentan, mean arterial pressure (MAP) and proteinuria decreased by 12 and 40%, respectively, in STZ-SS rats. The degree of glomerulosclerosis and renal fibrosis was significantly reduced in the kidneys of atrasentan-treated STZ-SS rats compared with vehicle STZ-SS rats. Interestingly, treatment with atrasentan did not affect GFR but significantly increased renal blood flow by 33% and prevented the elevations in filtration fraction and renal vascular resistance by 23 and 20%, respectively, in STZ-SS rats. In contrast to the STZ-SS study, atrasentan had no effect on MAP or proteinuria in T2DN rats. However, treatment with atrasentan significantly decreased glomerular injury and renal fibrosis and prevented the decline in renal function in T2DN rats. These data indicate that chronic ETA blockade produces advantageous changes in renal hemodynamics that slow the progression of renal disease and also reduces renal histopathology in the absence of reducing arterial pressure and proteinuria. [ABSTRACT FROM AUTHOR]

Background: In future, increase in the number of healthcare professionals is dependent on the career interest among present undergraduate medical students. Based on their interest to pursue their specialty, the availability of medical doctors in each specialty could be done. Aims: This study was to find out future career interest and factors that influence undergraduate medical students to choose their future specialization. Materials and Methods: The study was carried out among first-year medical students from five countries. The students were asked to complete an 8-item questionnaire. Two thousand one hundred fifty three participants were enrolled in the study. Data were analyzed in Microsoft-Excel and Statistical Package for the Social Sciences. Results: Of the 2153 participants, only 1470 responded. Among the 1470 participants, 169 participants were excluded due to the ambiguity in responses, finally making it to 1301participants. Among them, Anatomy (49.3%) followed by Biochemistry (26.7%) and Physiology (24%) were the most preferred subjects. Conclusions: Anatomy was the most preferred basic science subject among the other subjects and the students were interested to pursuing surgery in future. Furthermore, the most preferred future specialties were surgery, internal medicine and pediatrics with gender variations; males preferring surgery and females in obstetrics and gynecology. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To develop the missing link between hyperuricemia and hypertension. Methods: The study was conducted in Department of Biochemistry in collaboration with Nephrology Unit of Internal Medicine Department. Hypertension was defined according to blood pressure readings by definitions of the Seventh Report of the Joint National Committee. Totally 205 newly diagnosed and untreated essential hypertensive cases and age-sex matched normotensive controls were enrolled in the study. The potential confounding factors of hyperuricemia and hypertension in both cases and controls were controlled. Uric acid levels in all participants were analyzed. Results: Renal function between newly diagnosed hypertensive cases and normotensive healthy controls were adjusted. The mean serum uric acid observed in newly diagnosed hypertensive cases and in normotensive healthy controls were (290.05±87.05) μmol/L and (245.24±99.38) μmol/L respectively. A total of 59 (28.8%) participants of cases and 28 (13.7%) participants of controls had hyperuricemia (odds ratio 2.555 (95% CI: 1.549–4.213), P<0.001). Conclusions: The mean serum uric acid levels and number of hyperuricemic subjects were found to be significantly higher in cases when compared to controls. [Copyright &y& Elsevier]

L7674 --> 968.3 --> Hypertension affects 108 million in the United States, which is more common in African American (AA) population (54%). Several Genome‐Wide Association Studies (GWAS) showed a strong association between the apolipoprotein1 (apol1) gene and hypertension in AA adults. Nearly 45% of AAs carry a coding variant of the APOL1 gene either G1APOL1 or G2APOL1. The disease phenotypes associated with APOL1 RV are dependent on the cell type‐specific expression and toxicity of APOL1. Recently, we have reported that APOL1 is highly expressed in endothelial cells (EC) of the human kidneys using single‐cell analysis, single nuclei analysis, and in‐situ hybridization. People who carry G1 or G2 APOL1 RV have a high risk of chronic kidney disease and hypertensive kidney disease. However, the direct role of APOL1 in the development of hypertension and hypertensive kidney disease is clear. Therefore, the objective of the current study was to examine the role of endothelial‐specific inducible G2APOL1 risk variants in the development of hypertension and hypertensive kidney disease. To understand the role of APOL1 in endothelial cells, we generated mice with endothelial‐specific inducible expression of APOL1 (EC/G2‐APOL1) by crossing the TRE‐G2APOL1 mice with the Cdh5tTA animals. Cadherin 5 (VE‐cadherin or endothelial cadherin) is an endothelial‐specific gene, removal of doxycycline from the diet led to a significant expression of APOL1 in different vascular beds such as the lung, heart, and kidney, which was confirmed both by in situ hybridization and qRT‐PCR. After collecting the baseline data, we performed UNX surgery on both WT control and Cdh5tTA/TRE‐G2APOL1 five‐week‐old mice and kept them in 4% salt diet for 12 weeks after UNX surgery. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (measured by tail‐cuff method) were significantly higher in Cdh5tTA/TRE‐G2APOL1 mice compared to control WT mice after 6 weeks of UNX surgery on a high salt diet. The significantly higher blood pressure in Cdh5tTA/TRE‐G2APOL1 mice was further associated with the increased urinary albumin/creatinine ratio and renal fibrosis. Interestingly, the blood pressure parameters SBP, DBP, and MAP were significantly reduced on STING, NLRP3, and gasdermin knock‐out mice on Cdh5tTA/TRE‐G2APOL1 background compared to Cdh5tTA/TRE‐G2APOL1 mice upon UNX‐surgery and 4% salt diet. Furthermore, the expression of the transcript of the mitochondrial gene including COX1, COX2, ATP6, and ND6 in the cytoplasm from kidney tissue obtained from Cdh5tTA/TRE‐G2APOL1 mice was significantly higher compared to control‐WT, which indicate that mitochondrial damage and leakage of the mitochondrial gene into the cytoplasm take place in the Cdh5tTA/TRE‐G2APOL1 mice upon UNX‐surgery and 4% salt‐diet. Therefore, EC specific apol1 gene induces mitochondrial damage, upregulates inflammasome and cGAS‐STING pathway to develop hypertension leading to hypertensive kidney disease. This project was supported by DK105821. [ABSTRACT FROM AUTHOR]

Background: Microalbuminuria in hypertension has been described as an early sign of kidney damage and a predictor for end stage renal disease and cardiovascular disease. Thus, it is of great importance to study urinary albumin creatinine ratio and progression of kidney disease in hypertensive patients. Aims: The present study was undertaken to find out the prevalence and association of microalbuminuria in newly diagnosed essential hypertension. Materials and Methods: Newly diagnosed essential hypertensive cases (n = 106) and normotensive controls (n = 106) were enrolled. Hypertension was defined according to Joint national committee-VII definitions. Microalbuminuria was measured using an U-Albumin (NycoCard, Norway) and adjusted for urine creatinine. Descriptive statistics and testing of hypothesis were used for the analysis using SPSS 16 software. Results: 51.88% of hypertension cases and 13.2% of normotensive controls had microalbuminuria in total population (odds ratio 7.086, P-value <0.001). 46.67% of cases and 12.08% of controls had microalbuminuria in male population (odds ratio 6.375, P-value <0.001). Similarly, 58.7% of cases and 14.58% of controls had microalbuminuria in female population (odds ratio 8.32, P-value <0.001). Conclusions: By showing strong association between microalbuminuria and hypertension, our findings suggest that microalbuminuria could be a useful marker to assess risk management of cardiovascular disease and renal disease. [ABSTRACT FROM AUTHOR]

R2070 --> Recent studies show that prepubertal obesity is associated with increased risk of hypertension in children. Moreover, previous reports have demonstrated that there is a link between the renin‐angiotensin system and obesity‐related hypertension via angiotensin II (Ang II) metabolism. However, to our knowledge, studies examining AngII metabolism during the development of hypertension associated with prepubertal obesity are limited. Therefore, the current study examined whether there are sex differences in arterial pressure and AngII metabolism in lean Dahl salt‐sensitive (SS) and obese SS leptin receptor mutant (SSLepRmutant) rats. Four week‐old female and male lean SS and obese SSLepRmutant rats (n=5 rats per group) were implanted with telemetry transmitters to measure MAP until the rats reached 8 weeks of age. Over the course of the study, we did not detect any differences MAP between female and male SS rats (115±2 and 120±2 mmHg, respectively). MAP was similar in male SSLepRmutant rats compared to their wild‐type littermates (118±6 mmHg). However, we observed a marked increase in MAP in female SSLepRmutant rats compared to the other groups (144±7 mmHg; p<0.05 vs. all groups). At the end of the study, plasma was collected and analyzed for AngII metabolites (AngII, Ang(1‐7), AngIII, AngIV, Ang(1‐5) and Ang(1‐9); via mass spectrometry). Interestingly, we did not observe any sex or strain differences in plasma AngII levels between lean SS and obese SSLepRmutant rats. Additionally, similar results were seen when measuring the plasma levels of Ang(1‐7), AngIV, and Ang(1‐5). However, AngIII and Ang(1‐9) levels were more than two‐fold higher in female obese SSLepRmutant rats versus their lean SS littermates and male obese SSLepRmutant counterparts (p<0.05 vs. all groups). Overall, these data indicate that the elevations in arterial pressure in female obese SSLepRmutant rats is associated with alterations in angiotensin metabolism with increases in plasma levels of AngIII and Ang(1‐9). Additionally, further studies are needed to investigate the roles of AngIII and Ang(1‐9) and their signaling pathways in the early development of hypertension in female obese SSLepRmutant rats prior to puberty. [ABSTRACT FROM AUTHOR]

R2057 --> Childhood/prepubertal (PPO) obesity has emerged as an epidemic and major health problem over the last few decades and is a risk factor for the development of proteinuria. Recently, we reported that the development of progressive renal injury in obese female and male Dahl salt‐sensitive leptin receptor mutant (SSLepRmutant) rats was associated with increased renal macrophage infiltration as early as 8 weeks of age. The current study investigated whether there are differences in the polarization of infiltrating macrophages in female and male SSLepRmutant rats during the early progression of renal injury (M1; pro‐inflammatory and M2; anti‐inflammatory). Sex hormones were also monitored to determine if the development of renal injury in SSLepRmutant strain occurs prior to puberty. Female and male lean SS and obese SSLepRmutant rats were studied biweekly from 4 to 10 weeks of age monitoring serum sex hormones and renal injury. Estradiol and testosterone levels were similar in all groups at 4 weeks of age and averaged 11±1 and 0.44±0.15 ng/mL, respectively. The levels of estradiol only significantly increased in female SS rats at 10 weeks of age (24±7 ng/mL; p<0.05 vs 4 weeks of age) and remain unchanged in all other groups. When examining the levels of testosterone in male rats, we observed a marked increase in male SS rats only at 10 weeks of age (2.53±0.69 ng/mL; p<0.05 vs 4 weeks of age), and we did not detect any differences from baseline in the other groups. Proteinuria was significantly higher in female and male SSLepRmutant rats as opposed to the values observed in SS rats at 4 weeks of age (56±7 and 60±13 vs 12±4 and 9±3 mg/day, respectively, n=6). While we observed minimal increases in proteinuria in SS rats at 8 weeks of age, proteinuria increased to 288±45 and 376±44 mg/day in female and male SSLepRmutant rats, respectively. We observed no sex differences in proteinuria in either the SSLepRmutant or SS rats. In support of our previous work, renal macrophage (CD68+) infiltration was significantly higher in the SSLepRmutant rats when compared to their lean counterparts. Interestingly, the female SSLepRmutant rats displayed significantly higher macrophage (CD68+) infiltration than their male counterparts. Moreover, female SSLepRmutant rats displayed significant increases in both macrophage subtypes M1 (CD68+/iNOS+) and M2 (CD68+/CD163+) versus male SSLepRmutant rats as well as SS rats. The male SSLepRmutant rats only displayed significant increases in M1 macrophages (CD68+/iNOS+) compared to male SS rats. The kidneys from the SSLepRmutant rats displayed significant glomerular injury and marked renal fibrosis versus the values measured in SS rats without any sex differences. These data indicate that the SSLepRmutant strain displays sex differences in renal macrophage polarization and develops renal injury prior to the onset of puberty. The SSLepRmutant strain may be considered a useful model to study the early development of renal injury associated with PPO and to understand the underlying mechanisms that contribute to future risk of obesity‐related CKD. [ABSTRACT FROM AUTHOR]

R2488 --> Recently, we reported that the early progression of proteinuria in the obese Dahl salt‐sensitive (SSLepRmutant) strain was associated with increased renal macrophage infiltration in the absence of hyperglycemia and elevations in arterial pressure. Macrophages (CD68+) can be divided into two distinct phenotypes: M1‐macrophages (pro‐inflammatory; CD68+/iNOS+), and M2‐macrophages (anti‐inflammatory; CD68+/CD163+). M1‐macrophages induce renal inflammation and fibrosis, whereas M2‐macrophages reduce renal inflammation and fibrosis. Moreover, previous studies have demonstrated that interlukin‐25 (IL‐25) converts resting macrophages and M1‐macrophages into M2‐macrophagess. Therefore, the objective of the current study was to examine whether treatment with IL‐25 would reduce the early progression of renal injury in SSLepRmutant rats by increasing renal M2‐macrophages. We also investigated the impact of IL‐25 on M2‐macrophage subtypes: M2a (wound healing/anti‐inflammatory; CD68+/CD163+/TLR1‐), M2b (immune mediated/pro‐inflammatory; CD68+/iNOS‐/CD86+), M2c (Regulatory/anti‐inflammatory; CD68+/CD163+/TLR1+), and M2d (tumor associated macrophage/pro‐angiogenic; CD68+/VEGF+). Four week‐old SSWT and SSLepRmutant rats were treated with either vehicle (PBS) or IL‐25 (1µg/day, i.p., every other day) for 4 weeks. While the administration of IL‐25 did not change total renal macrophage infiltration in both SSWT and SSLepRmutant rats, IL‐25 increased M2a‐macrophages by >50% and reduced M1‐macrophage by 60% in the kidneys of SSLepRmutant rats. Interestingly, IL‐25 significantly increased the insulin sensitivity without changing plasma glucose, triglyceride and total cholesterol levels in SSLepRmutant rats. IL‐25 administration had no effect on the progression of proteinuria or renal histopathology in SSWT rats. However, in the SSLepRmutant strain, proteinuria was markedly reduced during the first 2 weeks of treatment (105±13 vs. 295±45 mg/day, respectively), which was further consistent after 4 weeks of treatment (314±57 vs. 467±55 mg/day, respectively). The kidneys from SSLepRmutant rats displayed glomerular injury with increased mesangial expansion and renal fibrosis versus SSWT rats. Chronic treatment with IL‐25 significantly decreased glomerular injury and renal fibrosis in the SSLepRmutant strain. Overall, these data indicate that IL‐25 reduces the early progression of renal injury in SSLepRmutant rats by inducing M2a‐macrophages and suppressing M1‐macrophages. Therefore, IL‐25 may be considered a therapeutic target for renal disease associated with obesity. [ABSTRACT FROM AUTHOR]

R2451 --> Recently, we reported the early development of renal injury was associated with renal hyperfiltration along with increased renal macrophage infiltration and macrophage inflammatory protein alpha (MIP3α; inflammatory chemoattractant cytokine) expression in obese SSLepRmutant rats prior to puberty. MIP3α signals through the CCR6 receptor to recruit stimulatory dendritic cells (sDCs), which have been shown to play a pivotal role in cardiorenal injury by increasing pro‐inflammatory T‐helper 17 cells (Th17s). Therefore, the present study examined whether chronic blockade of MIP3α signaling would reduce the renal infiltration of sDCs and Th17s and slow the early progression of proteinuria in obese SSLepRmutant rats prior to puberty. Four‐week‐old SS and SSLepRmutant rats were separated into four groups (n=5/group): (1) SS and (2) SSLepRmutant rats treated with vehicle‐PBS and (3) SS and (4) SSLepRmutant rats treated with MIP3α neutralizing antibody (MNA; 100 µg/kg, i.p., every other day) for 4 weeks. We found a significant increase in the infiltration of sDCs and Th17s in the kidneys from vehicle‐SSLepRmutant rats compared to their lean vehicle‐SS counterparts. Chronic treatment with MNA only significantly reduced renal sDCs and Th17s in SSLepRmutant rats. While treatment with MNA did not have an effect on blood glucose and plasma triglyceride and cholesterol levels, MNA markedly reduced plasma insulin levels in SSLepRmutant rats (9.7±2.3 vs. 3.5±0.7 ng/ml respectively; p<0.05). MAP was significantly higher in vehicle‐SSLepRmutant rats compared to values measured in vehicle‐SS rats (160±10 vs. 127±7 mmHg, respectively p<0.05). However, chronic treatment with MNA had no effect on MAP in the SSLepRmutant rats in comparison to the vehicle‐ SSLepRmutant rats (150±3 mmHg). At baseline, proteinuria was not markedly elevated in SSLepRmutant rats compared to SS rats (31±15 vs. 10±3 mg/day, respectively). However, proteinuria markedly increased in SSLepRmutant rats versus SS rats over the course of the study (446±54 vs. 51±16 mg/day, respectively; p<0.05). Chronic treatment with MNA significantly decreased proteinuria in SSLepRmutant rats (149±19 mg/day; p<0.05 vs. vehicle‐SSLepRmutant rats) while not having any effect in SS rats (41±12 mg/day). Overall, these data indicate MIP3α plays a major role in the recruitment of sDCs and Th17s during the early progression of proteinuria in obese SSLepRmutant rats prior to puberty. These results also suggest that MIP3α may be a novel therapeutic target to inhibit insulin resistance and prevent progressive proteinuria in obese children. [ABSTRACT FROM AUTHOR]

Sepsis is a complex syndrome characterized by organ dysfunction and a dysregulated immune host response to infection. There is currently no effective treatment for sepsis, but platelets have been proposed as a potential therapeutic target for the treatment of sepsis. We hypothesized that the NLRP3 inflammasome is activated in platelets during sepsis and may be associated with multiorgan injury in response to polymicrobial sepsis. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in 12‐ to 13‐week‐old male Sprague–Dawley rats. The necrotic cecum was removed at 24 h post‐CLP. At 72 h post‐CLP, activated platelets were significantly increased in CLP versus Sham rats. Colocalization of NLRP3 inflammasome components was observed in platelets from CLP rats at 72 h post‐CLP. Plasma, pulmonary, and renal levels of IL‐1β and IL‐18 were significantly higher in CLP rats compared to Sham controls. Soluble markers of endothelial permeability were increased in CLP versus Sham. Renal and pulmonary histopathology were markedly elevated in CLP rats compared to Sham controls. NLRP3 is activated in platelets in response to CLP and is associated with inflammation, endothelial permeability and multiorgan injury. Our results indicate that activated platelets may play a role to cause multiorgan injury in sepsis and may have therapeutic potential for the treatment of sepsis multiorgan injury. [ABSTRACT FROM AUTHOR]

A correction to the article "A Prevalence of Thyroid Disorder in Western Part of Nepal" that was published in the February 2013 issue is presented.

Cysticercosis, a major health issue in developing countries, is caused by the larval stage of Taenia solium . Disseminated cysticercosis (DCC), which is characterized by widespread cysticerci in various tissues, is rare and often asymptomatic. Here, we report the case of a 50-year-old man from rural Nepal with distal cholangiocarcinoma and DCC involving the skin, brain, orbit, tongue, soft palate, heart, and abdominal organs. Despite the presence of abdominal pain, obstructive jaundice, anemia, and significant weight loss-symptoms indicative of biliary malignancy-there were no symptoms typical of DCC. Diagnostic imaging confirmed DCC and stomach-preserving pancreaticoduodenectomy was performed. Histopathological examination of the periampullary mass revealed distal cholangiocarcinoma. Postsurgical treatment for DCC included steroids, carbamazepine, and antiparasitic therapy with albendazole. The coexistence of cysticercosis and neoplasia, though uncommon, necessitates thorough diagnostic evaluation. This case underscores the clinical complexity and highlights the need for comprehensive management of concurrent conditions., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Recently, we reported that the early progression of renal injury in obese Dahl salt-sensitive leptin receptor mutant (SS LepR mutant) rats was associated with increased macrophage inflammatory protein 3- α (MIP3 α ) expression prior to puberty. Therefore, this study tested the hypothesis that MIP3 α plays a role in recruiting immune cells, thereby triggering renal inflammation and early progressive renal injury in SS LepR mutant rats prior to puberty. Four-week-old Dahl salt-sensitive (SS) and SS LepR mutant rats either served as control (IgG; intraperitoneal, every other day) or received MIP3 α -neutralizing antibody (MNA; 100 µg/kg) for 4 weeks. MNA reduced circulating and renal MIP3 α levels and proinflammatory immune cells by 50%. Although MNA treatment did not affect blood glucose and plasma cholesterol levels, MNA markedly decreased insulin resistance and triglyceride levels in SS LepR mutant rats. We observed no differences in mean arterial pressure (MAP) between SS and SS LepR mutant rats, and MNA had no effect on MAP in either strain. Proteinuria was significantly increased in SS LepR mutant rats versus SS rats over the course of the study. Treatment with MNA markedly decreased proteinuria in SS LepR mutant rats while not affecting SS rats. Also, MNA decreased glomerular and tubular injury and renal fibrosis in SS LepR mutant rats while not affecting SS rats. Overall, these data indicate that MIP3 α plays an important role in renal inflammation during the early progression of renal injury in obese SS LepR mutant rats prior to puberty. These data also suggest that MIP3 α may be a novel therapeutic target to inhibit insulin resistance and prevent progressive proteinuria in obese children. SIGNIFICANCE STATEMENT: Childhood obesity is increasing at an alarming rate and is now being associated with renal disease. Although most studies have focused on the mechanisms of renal injury associated with adult obesity, few studies have examined the mechanisms of renal injury involved during childhood obesity. In the current study, we observed that the progression of renal injury in obese Dahl salt-sensitive leptin receptor mutant rats was associated with an increase in MIP3 α , a chemokine, before puberty, and inhibition of MIP3 α markedly reduced renal injury., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Coding variants (named G1 and G2) in Apolipoprotein L1 (APOL1) can explain most excess risk of kidney disease observed in African American individuals. It has been proposed that risk variant APOL1 dose, such as increased risk variant APOL1 level serves as a trigger (second hit) for disease development. The goal of this study was to determine whether lowering risk variant APOL1 levels protects from disease development in a podocyte-specific transgenic mouse disease model. We administered antisense oligonucleotides (ASO) targeting APOL1 to podocyte-specific G2APOL1 mice and observed efficient reduction of APOL1 levels. APOL1 ASO1, which more efficiently lowered APOL1 transcript levels, protected mice from albuminuria, glomerulosclerosis, tubulointerstitial fibrosis, and renal failure. Administration of APOL1 ASO1 was effective even for established disease in the NEFTA-rtTA/TRE-G2APOL1 (NEFTA/G2APOL1) mice. We observed a strong correlation between APOL1 transcript level and disease severity. We concluded that APOL1 ASO1 may be an effective therapeutic approach for APOL1-associated glomerular disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The American Society of Gene and Cell Therapy. All rights reserved.)

Prepubertal obesity (PPO) has emerged as a major health problem over the past few decades and is a risk factor for the development of proteinuria. The current study investigated whether the development of renal injury in the obese SS LepR mutant strain occurs before puberty. When determining the temporal changes in serum sex hormones in female and male SS and SS LepR mutant rats between 4 and 10 wk of age, we only observed significant increases in estradiol and testosterone levels in female and male SS rats at 10 wk of age than at 4 wk of age. The results suggest that studying both strains between 4 and 8 wk of age is appropriate to study the effects of PPO on renal injury in this model. Proteinuria was significantly higher in SS LepR mutant rats as opposed to the values observed in SS rats at 8 wk of age, and we did not observe any sex differences in proteinuria in either strain. The kidneys from the SS LepR mutant rats displayed significant glomerular and tubular injury and renal fibrosis versus the values measured in SS rats without any sex differences. Overall, we observed increased immune cell infiltration in the kidneys from SS LepR mutant rats compared with SS rats. Interestingly, female SS LepR mutant rats displayed significant increases in not only M1 macrophages (proinflammatory) but also M2 macrophages (anti-inflammatory) versus male SS LepR mutant rats. These results suggest the SS LepR mutant rat may be a useful model to study early progression of obesity-related renal injury before the onset of puberty.

Background: Nepal is an endemic area with regards to iodine deficiency, as well as a nutritional iodine deficiency is thought to be prevalent in all the Himalayan, sub-Himalayan and the Terai regions of Nepal. Thyroid dysfunction is a major public health problem among the Nepalese population., Objectives: The objective of this study was to find out the prevalence of thyroid dysfunction among the patients who attended the Charak Hospital, Pokhara, Nepal., Materials and Methods: A hospital based study was undertaken by using the data which was retrieved from the thyroid function tests, which included free T3, free T4 and TSH, from the register which was maintained in the Department of Biochemistry of the Charak Hospital, Pokhara, Nepal, from 1(st) January, 2011 to 30th December, 2012. Descriptive statistics and testing of the hypothesis were used for the analysis by using the EPI INFO and the SPSS version 16 softwares., Results: The total number of cases was 1504, which included 23.20% males and 76.80% females. The prevalence of thyroid dysfunction was 17.42%. Females had more thyroid dysfunction than the males. Hypothyroidism (2.26%) and subclinical hypothyroidism (10.50%) had higher prevalences as compared to hyperthyroidism (1.59%) and subclinical hyperthyroidism (3.05%) in the western region of Nepal. A higher prevalence of the thyroid dysfunction was observed in the subjects who ages were above 41-50 years., Conclusion: Females and people of advanced ages were more vulnerable to thyroid dysfunction in the population. Hypothyroidism and subclinical hypothyroidism were preponderant, followed by subclinical hyperthyroidism.

Background: To obtain the maximum additional information about the prognosis of gastric cancer, we compared CA-50 with other previously defined markers., Materials and Methods: This hospital based study was carried out in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between 1st July 2012 and 31st December 2012. The variables collected were age, gender, AFP, CEA, CA19-9, and CA50, assayed with ELISA reader for all cases. The cut off values for serum AFP, CEA, CA19-9, and CA-50 were 10 μg/l, 10 μg/l, 37 U/ml, and 20 U/ml, respectively according to the manufacturer's instructions. Approval for the study was obtained from the institutional research ethical committee., Results: Of the 40 examined patients, 13 patients had tumors located in the upper third of the stomach, 6 patients had tumors in the middle third, 16 patients had tumors in the lower third, and 5 patients had tumors occupying two-thirds of the stomach or more. The distribution of lymph node staging of the patients was as follows: 7 patients belonged to N0, 9 patients to N1 stage, 10 patients to N2 stage, and 14 patients to N3 stage. The statistical method of Cox proportional hazards using multivariate analysis also illustrated that tumor markers including CEA (2.802), CA19-9 (2.690), CA50 (2.101), were independent prognostic factors, as tumor size (1.603), and lymph node stage (1.614)., Conclusions: The tumour markers now available, like CEA, CA 19-9 and CA 50, chiefly perceive advanced gastric cancer. The preoperative rise in those tumour marker level have a prognostic significance and may be clinically helpful in choosing patients for adjuvant management.

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.

Objective: This study was to assess liver involvement in multiple myeloma with the aid of liver function tests., Materials and Methods: A hospital based retrospective study was undertaken using data retrieved of multiple myeloma from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2007 and 28th February, 2012. We collected biomarkers of liver profiles including bilirubin (Total, Direct and Indirect), total protein, albumin, AG ratio, SGOT, SGPT, ALP, γGT, LDH, ferritin, renal profile and hematological profile. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software., Results: Out of 37 cases of multiple myeloma, serum level of AST, ALT, ALP, γGT and LDH were increased above the cut-off point in 22 (59.5%), 24 (64.86%), 13 (35.13%), 9 (24.3%) and 11 (29.7%) respectively. The mean values of AST (65.5±28.18 U/L), ALT (68.37±29.74 U/L), ALP (328.0±148.4 U/L), γGT (44.5±29.6 U/L) and LDH (361.7±116.5 U/L), total protein (9.79±1.03 gm/ dl) were significantly increased when compared with controls. In contrast, albumin (3.68±0.43 gm/dl) and the AG ratio (0.62±0.15) were significantly decreased. Similarly, anemia, hyperuricemia, azotemia, hypercalcaemia and Bence Jones proteinuria were found in 30 (78.9%), 27 (71.1%), 19 (51.5%), 15 (39.5%) and 16 (42.1%) respectively, in cases of multiple myeloma., Conclusions: While clinical manifestation of liver disease among the multiple myeloma was not common, abnormalities in liver function were characteristic.

Objective: To assess the diagnostic and prognostic value of AFP and des-gamma-carboxyprothrombin (DCP) in combination and alone for hepatocellular carcinoma., Materials and Methods: A case control study carried out in the Department of Biochemistry of Manipal College of Medical Sciences, Pokhara, Nepal between 1st January 2010 and 31st December 2011. The variables collected were age, gender, BMI, total proteins, albumin, AST, ALT, total bilirubin, DCP, AFP. Approval for the study was obtained from the institutional research ethical committee. Estimation of AFP was performed by ELISA reader for all cases. Analysis was done using descriptive statistics and confidence interval (CI). The data was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version., Results: The mean age of HCC cases was 53.6±14.93 yrs. The percentage of females was less than males in both cases (23%) and controls (29%). The specificity of DCP reached 100% when its values was equal or greater than 150 (MAU/ml) for 0, 3, 6, 9, 12 months preceding the diagnosis of HCC. Similarly, the specificity for AFP was also nearly 100% when its value was equal or greater than 200 ng/ml 0, 3, 6, 9, 12 months earlier to the finding of HCC. The specificity of DCP (≥40 MAU/mL) and AFP(≥20 ng/mL) in combination was 93%, 97%, 95%, 96%, 97% in respect to 0, 3, 6, 9, 12 months prior to the diagnosis of HCC., Conclusion: The combination of both DCP and AFP will improve the finding of initial HCC and the sensitivity of these markers was utmost at the time of HCC identification and noticeably lesser at former time points.

Objective: This study was performed to assess prostate biomarkers with reference to body mass index and duration of prostate cancer., Materials and Methods: A hospital based retrospective study was undertaken using data retrieved from the register maintained in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2009 and 28th February, 2012. Biomarkers studied were prostate specific antigen (PSA), acid phosphatase (ACP) and prostatic acid phosphatase (PAP), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γGT). Demographic data including age, duration of disease, body weight, height and body mass index (BMI) were also collected. Duration of disease was categorized into three groups: <1 year, 1-2 years and >2 years. Similarly, BMI (kg/m2) was categorized into three groups: <23 kg/m2, 23-25 kg/ m2 and >25 kg/m2. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software., Results: Out of 57 prostate cancers, serum level of PSA, ACP and PAP were increased above the cut-off point in 50 (87.5%), 30 (52.63%) and 40 (70.18%) respectively. Serum levels of PSA, ACP and PAP significantly declined with the duration of disease after diagnosis. We observed significant and inverse relation between PSA and BMI. Similar non-signficiant tendencies were apparent for ACP and PAP., Conclusions: Decreasing levels of prostate biomarkers were found with the duration of prostate cancer and with increased BMI. Out of prostate biomarkers, PSA was found to be significantly decreased with the duration of disease and BMI.

Background: Pancreatic cancer is a distressing disease with a miserable prospects and early recognition remains a challenge due to ubiquitous symptomatic presentation, deep anatomical location, and aggressive etiology. False positives and problems in distinguishing pancreatitis from adenocarcinoma limit the use of CA 19-9 as both disorders can present with similar symptoms and share radiographic physiognomies. This study aimed to assess the relative increase in accuracy of diagnosing the patients with chronic pancreatitis, benign neoplasm of pancreas and adenocarcinomas with CA 19-9, haptoglobin, and serum amyloid A in comparison to CA 19-9 alone., Materials and Methods: This hospital based case control study was carried out in the Departments of Medicine and Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal, between 1st January 2010 and 31st December 2011. The variables assessed were age, gender, serum CA19-9, serum haptoglobulin, serum Amyloid A. The data were analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version., Results: Out of 197 cases of pancreatic disease, maximum number of assumed cases were of adenocarcinoma of pancreas (95). Number of males (59) were more than females (36) in assumed cases of adenocarcinoma of pancreas. The mean values of CA19-9 raised considerably in cases of chronic pancreatitis, benign neoplasm and adenocarcinoma of pancreas when compared to controls. The highest augmention in CA19-9 values were in cases of adenocarcinoma of pancreas. The p-value indicates that in cases of chronic pancreatitis, there was not significant increase in precision of diagnosis., Conclusions: These statistics established that haptoglobin and SAA are useful in discriminating cancer from benign conditions as well as healthy controls.

Objective: The objective of our present study was to assess the role of serum amyloid A (SAA) in stages and prognosis of renal cell carcinoma., Material and Methods: It was a hospital based retrospective study carried out in the Department of Medicine and Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between 1st January 2008 and 31st December 2011. The variables collected were SAA, CRP. Approval for the study was obtained from the institutional research ethical committee. Quantitative analysis of human SAA and C-reactive protein (CRP) was performed by radial immune diffusion (RID) assay for all cases., Results: Of the 422 total cases of renal cell carcinoma, 218 patients had normal and 204 abnormal SAA. SAA levels were grossly elevated in T3 stage (122.3±SD35.7) when compared to the mean for the T2 stage (84.2±SD24.4) (p value: 0.0001). Similarly, SAA levels were grossly elevated in M1 stage (190.0±SD12.7) when compared to the M0 stage (160.9±SD24.8) (p: 0.0001). There was no significant association with elevated CRP levels (209.1±SD22.7, normal 199.0±SD19.5) ., Conclusion: The validity of SAA in serum as being of independent prognostic significance in RCC was demonstrated with higher levels in advanced stage disease.

Objective: The objective of our present study was to assess the efficacy of carcinoembryonic antigen (CEA) for differentiating and diagnosis of pancreatic and liver diseases in Pokhara valley., Materials and Methods: A hospital based retrospective study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2011 and 31st October, 2011. Estimation of CEA was performed by ELISA reader for all cases. Approval for the study was obtained from the institutional research ethical committee., Results: Of the 771 subjects, 208 (27%), 60(7.8%), 240(31.1%), 54(7.0%) , 75(9.7%), 59(7.7%), 75(9.7%) cases were of active chronic hepatitis , cryptogenic cirrhosis, alcoholic cirrhosis, primary biliary cirrhosis, hepatoma, acute or chronic pancreatitis, carcinoma of pancreas respectively. The majority of cases (104) of active chronic hepatitis had CEA levels <5 ng/ml(50%). CEA levels were found to be increased in cases of alcoholic cirrhosis with maximum number of cases (106) in range of 10 to 20 ng/ml (44%). There were no cases having more than 20 ng/ml of CEA in primary biliary cirrhosis and acute or chronic pancreatitis. In cases of pancreatic cancer, maximum number of cases (35) were having CEA >20 ng/ml(47%)., Conclusion: High levels of CEA are associated with advanced stage of disease. CEA can thus provide an important improvement in the diagnosis by differentiating pancreatic cancer especially from chronic pancreatitis when there is a high suspicion of malignancy. Increased CEA levels may also signify progression from benign to malignant transformation in the liver.

Objective: To evaluate several metabolic changes in patients with differentiated thyroid carcinoma (DTC ) which enhance cardiovascular risk in the western region of Nepal., Materials and Methods: This hospital based case control study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2009 and 31st December, 2011. The variables collected were age, gender, BMI, glucose, insulin, HbA1C, CRP, fibrinogen, total cholesterol, triglycerides, HDL, LDL, VLDL, f-T3, f-T4, TSH. One way ANOVA was used to examine statistical significance of differences between groups, along with the Post Hoc test LSD for comparison of means., Results: fT3 values were markedly raised in DTC cases (5.7±SD1.4) when compared to controls (2.2±SD0.9). Similarly, fT4 values were also moderately raised in cases of DTC (4.9±SD1.3 and 1.7 ±SD0.9). In contrast, TSH values were lowered in DTC cases (0.39±SD0.4) when compared to controls (4.2 ±SD 1.4). Mean blood glucose levels were decreased while insulin was increased and HDL reduced (39.5±SD4.7 as compared to the control 43.1±SD2.2)., Conclusion: Cardiovascular risk may be aggravated by insulin resistance, a hypercoagulable state, and an atherogenic lipid profile in patients with differentiated thyroid cancer.

Various synthetic progestogens that are used as contraceptives have been reported to influence lipid and lipoprotein fractions differently. Depo-medroxyprogesterone acetate (DMPA), a synthetic progestogen, is used by Nepalese women as a contraceptive agent. Our study aims to determine the effects of long-term use of DMPA on lipid metabolism. We performed this study on 60 healthy Nepalese women who had been using DMPA for more than 2 yr and age- and weight-matched control subjects who were not using hormonal contraceptives. Fasting blood samples were collected from the subjects for the estimation of total cholesterol (TC) and triglyceride (TG) levels, and the levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were estimated using the Friedewald's equation. TC and LDL-C levels in DMPA users were significantly higher than those in non-users. Our study concluded that DMPA use induces lipid metabolism changes that can increase the risk of cardiovascular diseases.