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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.

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. With the rising prevalence of obesity in children, studies examining how obesity contributes to the early development of proteinuria and renal injury in children are lacking. Recently, we observed that the early progression of proteinuria in the obese SS LepR mutant rats was associated with the increased renal infiltration of stimulatory dendritic cells (sDCs). Previous studies have demonstrated that sDCs interact with and activate T-cells to elicit a pro-inflammatory response. Therefore, the current study examined whether chronic treatment with abatacept will reduce proteinuria in SS LepR mutant rats prior to puberty by interfering with sDC-T-cell crosstalk. Four-week-old SS and SS LepR mutant rats were treated with either vehicle (PBS) or abatacept (1 mg/kg, i.p. every alternate day) for 4 weeks. We observed no significant differences in blood glucose levels and mean arterial pressure between vehicle- and abatacept-treated SS and SS LepR mutant rats. While proteinuria only rose from 9±3 to 48±28 mg/day in SS rats, proteinuria markedly increased from 40±13 to 638±73 mg/day in SS LepR mutant rats. Chronic treatment with abatacept significantly decreased the progression of proteinuria by almost 50% in SS LepR mutant rats (350±15 mg/day; pLepR mutant rats) without having any effect in SS rats (29±11 mg/day). We observed a significant increase in the renal infiltration of sDCs and cytotoxic T-cells in SS LepR mutant rats in comparison to their lean SS counterparts, and chronic treatment with abatacept reduced the infiltration of sDCs and cytotoxic T-cells only in the SS LepR mutant rats. These data indicate that targeting sDC/T-cell interaction pathways could offer novel therapeutic insights in the early management of proteinuria and renal injury associated with PPO.

Diabetes and hypertension are the major causes of chronic kidney disease (CKD). Epidemiological studies within the last few decades have revealed that obesity-associated renal disease is an emerging epidemic and that the increasing prevalence of obesity parallels the increased rate of CKD. This has led to the inclusion of obesity as an independent risk factor for CKD. A major complication when studying the relationship between obesity and renal injury is that cardiovascular and metabolic disorders that may result from obesity including hyperglycemia, hypertension, and dyslipidemia, or the cluster of these disorders [defined as the metabolic syndrome, (MetS)] also contribute to the development and progression of renal disease. The associations between hyperglycemia and hypertension with renal disease have been reported extensively in patients suffering from obesity. Currently, there are several obese rodent models (high-fat diet-induced obesity and leptin signaling dysfunction) that exhibit characteristics of MetS. However, the available obese rodent models currently have not been used to investigate the impact of obesity alone on the development of renal injury before hypertension and/or hyperglycemia. Therefore, the aim of this review is to describe the incidence and severity of renal disease in these rodent models of obesity and determine which models are suitable to study the independent effects obesity on the development and progression of renal disease.

Recently, we reported that the early progression of proteinuria in the obese Dahl salt-sensitive (SS LepR mutant) strain was associated with increased renal macrophage infiltration in the absence of hyperglycemia and elevations in arterial pressure. Macrophages (MØ) can be divided into two distinct phenotypes: M1-macrophages (classical; pro-inflammatory), and M2-macrophages (alternative; anti-inflammatory). 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 MØ and M1 macrophages into M2 macrophages. Therefore, the objective of the current study was to examine whether treatment with IL-25 would reduce the early progression of proteinuria in SS LepR mutant rats by increasing renal M2 macrophages. Four week-old SS LepR mutant rats were separated into two groups (n=5/group): (1) vehicle (PBS) and (2) IL-25 (1μg/day, i.p.) for the first 10 days of the study. At baseline, proteinuria was similar in vehicle and IL-25 treated rats (81±18 vs. 66±8 mg/day, respectively). After 2 weeks, proteinuria was markedly reduced in the IL-25-treated group compared to the values measured in the vehicle treated rats (191±37 vs. 365±55 mg/day respectively; pLepR mutant strain is associated with renal macrophage infiltration and also suggest that IL-25 may be considered a therapeutic target for renal disease associated with obesity. This study was supported by DK109133. Key Words: Obesity, Renal Disease, Macrophages, IL-25

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.

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 SSWTrats (192 ± 4 and 149 ± 6 mmHg, respectively). At baseline, proteinuria was fourfold higher in SSLepRmutant than SSWTrats 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 SSWTrats. Kidneys from the SSLepRmutant strain displayed more glomerulosclerosis and glomerular lipid accumulation than SSWTrats. 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 SSWTrats 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.

Background: Hand hygiene has been identified as the single most important factor in minimising hospital acquired infections. However, compliance of handwashing guidelines has remained low. The aim of this study was to study the handwashing practices in the Paediatric and Neonatal intensive care units and Neonatal nurseries in Patan Hospital, and secondly to re-evaluate the improvement on compliance of handwashing guidelines after intervention.Methods: Pre-intervention study was conducted by covertly observing the handwashing practices by the healthcare workers. The healthcare workers were then shown the video demonstrating correct methods of handwashing as recommended by World health organization. The cycle was completed by discretely re-observing the handwashing practices following intervention.Results: Sixty five samples were collected initially. Only 6 (9.2%) had completed all steps of handwashing correctly. Post- intervention, 51 samples were collected, out of which 35 (68.6%) had correctly completed all the steps. Following audio-visual demonstration, 100% correctly completed 8/10 steps of handwashing with soap and water. 8 (16%) failed to dry hands using a single use towel and 14 (28%) failed to turn off the tap using elbow. Postintervention, 100% correctly completed 4/7 steps of handwashing using chlorhexidine. Four (15%) still failed to rub backs of fingers to opposite palm, eight (30%) failed to palm to palm with fingers interlaced, and rub thumb to opposite palm.Conclusions: Compliance in hand hygiene is low despite the known fact that it reduces nosocomial infections. However, a simple intervention like video demonstration can improve the compliance among healthcare workers.

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.

Type 1 diabetes (T1D) is an autoimmune disease that results from the activation of immune cells destroying the insulin-producing pancreatic β-cells. T1D accounts for nearly 90% of childhood-onset diabetes and 10% for adult-onset diabetes. The cause of T1D involves both genetic and environmental factors interacting to produce susceptibility to this disease. Like any other autoimmune disease, the pathogenesis of T1D occurs when there is an immune imbalance between pro-inflammatory T-helper 1 (Th1) cells versus antiinflammatory T-helper 2 (Th2) cells. Moreover, it has been suggested that sex hormones influence the predisposition for T1D diabetes. While most autoimmune diseases usually affect females, T1D affects males as well. However, the prevalence of T1D is higher in prepubertal females compared to same age males. After puberty, several studies demonstrate that the development of T1D occurs twice as much in males as in females. Similar results are observed in animal models of T1D. This indicates that there are sex differences in T1D and that sex hormones are major contributors to sexual dimorphism in the onset and progression of autoimmune T1D. Moreover, there are immunological differences that effect β-cell function between females and males at the initial diagnosis of T1D, and these differences become markedly evident in females when they reach puberty, which occurs earlier than males. The purpose of this chapter is to discuss sex differences in T1D and how sex hormones impact the immune balance during the development and/or progression of autoimmunity T1D.

Hypertension and diabetes are the major causes of chronic kidney disease (CKD). However, epidemiological studies within the last few decades have revealed obesity as an independent risk factor for CKD. Recently, we reported that the obese Dahl salt-sensitive leptin receptor mutant (SS LepR mutant) strain displays proteinuria and podocyte injury by 6 weeks of age independent of hyperglycemia and elevations in arterial pressure. The current study examined whether the development of renal injury in the SS LepR mutant strain is associated with elevations in glomerular filtration rate (GFR). During the study, the SS LepR mutant strain developed hyperinsulinemia and dyslipidemia but not hyperglycemia. Baseline MAP (via carotid catheter) at 6 weeks of age was similar between SS WT (n=8) and SS LepR mutant (n=8) rats and averaged 124 mmHg. However, by 18 weeks of age, MAP increased significantly in the SS LepR mutant strain compared to the values measured in SS WT rats (192±4 vs 149±6 mmHg, respectively). At baseline, protein excretion was 4-fold higher in the SS LepR mutant strain compared to SS WT rats and remained elevated over the course of the study (778±96 vs 137±25 mg/day, respectively). At 6 weeks of age, GFR was 34% higher in the SS LepR mutant strain compared to age-matched SS WT rats indicating renal hyperfiltration (2.92±0.23 vs 2.18±0.25 mL/min/kwt, respectively). While we observed only a 40% reduction in GFR in SS WT rats (1.30±0.07 mL/min/kwt), GFR markedly decreased by 70% in the SS LepR mutant strain (0.87±0.08 mL/min/kwt). Over time, kidneys from the SS LepR mutant strain displayed more glomerulosclerosis, mesangial expansion, and renal fibrosis in comparison to SS WT rats. Glomeruli were isolated from the renal cortex of both strains at 6 and 18 weeks of age and RNA sequencing was performed to identify genes and pathways driving glomerular injury. The major, most consistent signaling pathways that changed at 6 and 18 weeks of age were involved in leukocyte extravasation. In conclusion, these data provide evidence that renal hyperfiltration may contribute to glomerular capillary leukocyte extravasation leading to the early development of proteinuria during obesity in the absence of hypertension and hyperglycemia.

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 ETAblockade 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.

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 Conclusions The mean serum uric acid levels and number of hyperuricemic subjects were found to be significantly higher in cases when compared to controls.

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.

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 1 st January, 2009 and 31 st 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.

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

Background: Serum alkaline phosphatase (ALP) is a member of a family of zinc metalloprotein enzymes and is secreted mainly by the liver, bone, mucosal epithelia of small intestine, proximal convoluted tubule of kidney and placenta. High mitochondrial aspartate transaminase (AST) is seen in extensive tissue necrosis during myocardial infarction and also in chronic liver diseases like liver tissue deterioration and necrosis. Marked elevations of alanine transaminase (ALT) levels are observed with diseases that involve primarily hepatocytes such as viral hepatitis, ischemic liver injury (shock liver) and toxin-induced liver damage. Serum gamma –glutamyl transferase (?-GT) activity is mainly attributed to the hepatobiliary system and most commonly raised in alcoholic liver disease. The objective of this study is to diagnose hepotobiliary and bone diseases with the facilitation of various biochemical markers as single enzyme lacks the specificity.Materials and methods: It was a hospital based case control study carried out in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between 1st January 2010 and 31st July, 2011. The variables collected were age, gender, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma–glutamyl transferase (?-GT). The One way ANOVA was used to examine the statistical significant difference between groups. Post Hoc test LSD used for the comparison of means of control versus case groups. A p-value of

Background: Chronic Kidney Disease (CKD) is a worldwide growing issue and a public health problem. It is associated with significant morbidity and mortality. The prevalence of CKD has been described in several studies. High prevalence of CKD has also reported in the different studies from different part of world. The prevalence of reduced glomerular filtration rate (GFR) in Australia was 11.2%. Singapore, a South-East Asian country, reported a CKD prevalence of 10.1%, while the prevalence of CKD in Japanese general population was reported to be 18.7%. Reduced kidney function is associated with a variety of biochemical abnormalities such as electrolytes. However, the extent of the changes and their magnitude in relation to different stages of CKD is not well defined especially in the early stages of CKD. Thus, the main objective of our study was to assess the variations in the serum levels of sodium, potassium, calcium and phosphorus in different stages of CKD. Materials and methods: It was a hospital based cross-sectional study conducted in the Department of Clinical Biochemistry in collaboration with the Department of Internal Medicine (nephrology unit), Kathmandu, Nepal between 1st February, 2008 to 1st January, 2010. CKD was defined as per National Kidney Foundation Guidelines. The variables collected were age, gender, blood pressure, serum level of urea, creatinine , sodium, potassium, calcium, phosphorus, urinary albumin, urinary total protein (UTP), urinary protein creatinine ratio (PCR). The One way ANOVA was used to examine the statistical significant difference between groups. Correlation of different parameters with markers of CKD was done by Pearson‘s correlation for quantitative data. A p-value of

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 1 st July 2012 and 31 st 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: 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 1 st January 2010 and 31 st 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 (≥40MAU/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: 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 1 st January 2008 and 31 st 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.

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.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.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 levels5 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 CEA20 ng/ml(47%).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.

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.

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 1st 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: 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 1 st January 2010 and 31 st 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: 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 1 st January, 2009 and 28 th 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: 2 years. Similarly, BMI (kg/m 2 ) was categorized into three groups: 25 kg/m 2 . 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.

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 1 st January, 2007 and 28 th 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.