Search

Diabetic kidney disease (DKD) is the chief cause of renal involvement in diabetic patients. It is primarily a clinical diagnosis. Non-diabetic kidney disease (NDKD) may be missed if they are not biopsied. In this study, we describe the spectrum of NDKD and evaluate the predictors considered for planning a biopsy in diabetic patients with kidney disease. In a retrospective cohort study, diabetic patients who underwent kidney biopsy at our centre between May 2006 and July 2019 were evaluated for NDKD. 321 diabetic patients who underwent kidney biopsy were analyzed. Mean age was 49.3 ± 12.4 years and 71% were males. 75.8% patients had hypertension and 25.2% had diabetic retinopathy. Based on the kidney biopsy, patients were classified as DKD-127 (39.6%), NDKD—179(55.8%) and combined DKD + NDKD—15(4.7%). Overall, the most commonly diagnosed pathology was membranous nephropathy-MN (17%), followed by IgA nephropathy (16.0%) and focal segmental glomerulosclerosis-FSGS (14.9%). In patients with DKD + NDKD, IgA nephropathy (53.3%) was predominant. 165 (51.4%) patients had a diagnosis potentially amenable to a specific therapy. On multivariate analysis, female gender [OR 2.07 (1.08–3.97), p = 0.02], absence of diabetic retinopathy [OR 7.47 (3.71–15), p

OBJECTIVES To evaluate the various quantitative parameters of Doppler ultrasound, contrast-enhanced ultrasound (CEUS), and shear wave elastography (SWE) of graft kidneys in the early postoperative period and to explore their utility in the diagnosis of parenchymal causes of graft dysfunction. METHODS In this ethically approved study, consecutive patients who underwent renal transplantation from March 2017 to August 2018 were recruited, and those with urologic or vascular complications and those who denied consent were excluded. All patients underwent ultrasound with Doppler, SWE, CEUS (using sulfur hexafluoride), and renal scintigraphic examinations 3 to 10 days after transplantation. A composite reference standard was used, including the clinical course, renal function test results, urine output, and histopathologic results for graft dysfunction. Cortical SWE values, quantitative CEUS parameters (generated from a time-intensity curve), and their ratios were analyzed to identify graft dysfunction and differentiate acute tubular necrosis (ATN) from acute rejection (AR). RESULTS Of the 105 patients included, 19 developed graft dysfunction (18.1%; 12 ATN, 5 AR, and 2 drug toxicity) in the early postoperative period. The peak systolic velocity in the interpolar artery showed a significant difference between control and graft dysfunction groups (P

Introduction The majority of primary membranous nephropathy (MN) cases are no longer considered idiopathic with the discovery of the podocytic autoantigens: phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain–containing 7A (THSD7A). Limited data on PLA2R-related MN in Indians exist in literature, and THSD7A-related MN remains undocumented in this population. We aimed to characterize the baseline PLA2R and THSD7A profile of adult and pediatric membranous nephropathy (MN) in a large Indian single-institution cohort. Methods A retrospective analysis of all cases of MN (primary and secondary) between 2014 and 2017 was performed with PLA2R direct immunofluorescence and THSD7A immunohistochemistry on the biopsies and anti-PLA2R enzyme-linked immunosorbent assay (ELISA) on baseline sera. Results MN constituted 10% of kidney biopsies received in the study period. A total of 216 cases with adequate tissue underwent PLA2R direct immunofluorescence, and 110 of them had available sera for PLA2R ELISA. Combining both testing methods, the prevalence of PLA2R-related primary MN was 72.8%, with moderate concordance between the 2 methods (kappa 0.61). PLA2R was also detected in 16.7% cases of secondary MN, most commonly lupus MN. THSD7A immunohistochemistry performed on 176 cases showed a prevalence of 3.4% in primary MN. One case of lupus MN was also positive for THSD7A. Dual positivity (PLA2R and THSD7A) was noted in 2 cases. The large pediatric cohort tested showed a prevalence of 44% of PLA2R based on tissue testing, whereas 1 case demonstrated THSD7A positivity. Conclusion This study in a large cohort of Indian patients demonstrates prevalence rates of PLA2R- and THSD7A-related MN similar to world literature, including the substantial cohort of pediatric MN. It also confirms variation in MN in the form of outliers within PLA2R (related to tissue and serum testing), dual positivity for PLA2R and THSD7A, and PLA2R/THSD7A-positive secondary MN., Graphical abstract

Purpose The microRNAs expression has emerged as a potential biomarker for the diagnosis and prognosis of prostate cancer. This study investigated the expression of miRNA-182 and miRNA-187 in prostate cancer patients and established a correlation between miRNA expression and staging of prostate cancer. Materials and Methods This prospective observational study involved patients undergoing transrectal ultrasound-guided biopsy for suspicion of prostate cancer. Pre-biopsy urine samples and prostatic core tissue samples of the patients were preserved and the miRNA-182 and miRNA-187 were studied. Results Sixty-three patients were included in this study, thirty-three patients were diagnosed with prostate cancer and thirty patients having benign histopathology were considered as controls. The expression of miRNA-182 was significantly increased (p=0.002) and miRNA-187 significantly decreased (p

Purpose: T-lymphocytes-infiltrating tumors (TILs) are white blood cells (CD3+) found within the tumor and are thought to indicate a T-cell-mediated specific immune response. The purpose was to evaluate the presence and the subtypes of TILs in Wilms tumor (WT) specimens. Materials and Methods: A prospective study was conducted, and consecutive cases of WT registered and treated at our center were included in the study. The resected tumor was processed by taking multiple sections from the tumor and the peritumoral area. The sections were then processed for evaluating TILs and their subtypes (CD4 + and CD8+). TILs were assessed as a percentage of the total mononuclear cell infiltration in both these areas in all specimens. Results: Twenty-four consecutive specimens of WT were studied. The mean TILs (CD3+) counts was significantly higher (P = 0.001) in the peritumoral area (22.64 ± 1.42; range 20.2%–25%) as compared to the tumor (21.08 ± 2.42; range 14.6%–23.1%). The mean T-Helper (CD4+) counts was also significantly higher (P < 0.001) in the peritumoral area (13.04 ± 1.79; range 10.5%–16.5%) than in the tumor (7.30 ± 1.81; range 4.2%–10.1%). The mean cytolytic T-lymphocytes (CTLs-CD8+) counts in peritumoral area were 6.64 ± 1.09 (range 4.2%–9.2%), while in the tumor, it was 11.96 ± 3.09 (range 3.6%–16.4%). Two patients died on follow-up due to recurrence. These patients showed a markedly lower CD8+ cell count and higher CD4+/CD8+ ratio in the tumor. Conclusion: T-cells infiltration takes place in WT, and most of the patients demonstrate a higher concentration of CTL (CD8+) in the tumor as compared to the peritumoral area.

Wilms tumor (WT) is the most common childhood tumor of the kidney, which histologically mimics various stages of nephrogenesis. Spectrum of chemotherapy induced histopathological changes has been described in literature, and is one of the most important predictors of disease outcome and survival rates. Extensive chondroid differentiation and absence of necrosis in a postchemotherapy nephrectomy specimen of a radiologically proven Wilms tumor is an unusual finding. Herein, we present the case of 6-year-old girl from South Africa who received a 10-week course of chemotherapy upon radiological diagnosis of WT, and post-surgery nephrectomy specimen revealed extensive mature cartilage island formation on histology raising diagnostic dilemma. Reporting of such cases is extremely important to recognize tumor morphological heterogeneity, particularly post- chemotherapy, and developing consensus for selecting further treatment and clinical follow-up.

Introduction: C4d, an early product in the classical/lectin complement pathway has shown potential in the evaluation of C3 glomerulopathy where its absence would support an alternative pathway abnormality. As autoimmune/genetic complement testing is not readily available to most parts of the world, glomerular C4d staining may serve as a useful additional step toward the diagnosis. Methods: To test this hypothesis, C4d staining was performed on a large cohort of C3 glomerulopathy. Archival cases from 2011 to 2017 were reviewed and immunohistochemistry for C4d was performed, scored (scale of 0 to 3+), and correlated with the immunofluorescence and ultrastructural findings. Paraffin immunofluorescence was performed in cases of “discordant C4d” to unmask Igs. Results: Twenty-seven cases of dense deposit disease (DDD) and 14 cases of C3 glomerulonephritis (C3GN) were retrieved. C4d demonstrated a range of staining intensities with negative/traces in only 22% of DDD and 64% of C3GN. Lower-intensity C4d staining (1 to 2+) was mostly concordant with similar amounts of Igs/C1q. Discordant 3+ staining was noted in approximately 50% of cases of DDD and 20% of cases of C3GN. Among them, paraffin immunofluorescence unmasked polyclonal Igs in 2 of 5 cases of DDD and 1 of 3 cases of C3GN. Conclusion: This observational study suggests that the presence of glomerular C4d should not exclude a C3 glomerulopathy. In lower intensities, it appears to represent overlying classical/lectin pathway activation with concordant Ig/C1q deposits. A subset of cases, however, displays intense and discordant C4d staining, which raises the possibility of an associated lectin pathway abnormality, a potential future area of study. Keywords: C3 glomerulonephritis, C3 glomerulopathy, C4d, dense deposit disease, lectin pathway

Objective To study the mRNA and protein expression of GRP78 in tumor and serum of the RCC patients and compare with the controls and to correlate the expression with the grade and stage of RCC. Materials and methods A prospective cohort study involving 60 patients planned for radical/partial nephrectomy for primary RCC between July 2017 to June 2019. The RCC and adjacent non-tumorous renal tissues (Control) along with serum samples of patients were collected. Control for the serum samples is from the patients undergoing simple nephrectomy for non-functioning kidney due to benign etiology. The GRP78 expression was studied using RT-PCR for mRNA expression, Western blot analysis and immunohistochemistry (IHC) for protein expression and using ELISA in serum for both the subjects and controls. Results Mean age of patients was 50.3 years. The mRNA and protein expression of GRP78 in tissue samples were significantly higher in RCC patients as compared to controls (p < 0.001). IHC also demonstrated significantly higher expression in tumour samples as compared to controls (p < 0.001). Circulatory levels of GRP78 in serum samples were also significantly increased (p < 0.0001) in RCC patients in comparison to control subjects. The expression of GRP78 in circulation significantly correlated with the pathological tumor stage (p = 0.03), grade of disease (p < 0.001). Conclusion The GRP78 in RCC is significantly upregulated both at molecular and protein level expression. The overexpression of GRP78 correlates with the stage and grade of disease, thereby, highlighting its prognostic ability., RCC; Glucose regulated protein 78; Endoplasmic reticulum chaperone protein; Binding immunoglobulin protein (BiP).

Introduction: Plasma cells (PCs) have conventionally been counted on the bone marrow aspirate, and small focal involvement may be missed even on bone marrow biopsy sections. Material and Methods: We aimed to study the role of CD138, CD56, anti-κ, and anti-λ immunohistochemistry (IHC) to separate PC myeloma from reactive plasmacytosis and to study the utility of these in cases suspected as myelomas and lacking >10% PCs on bone marrow aspirate. The study comprised 35 diagnosed myelomas, 20 reactive plasmacytosis, and 19 M-band positive suspected myelomas. CD138 IHC was performed on all cases along with CD56, anti-κ, and anti-λ IHC. PCs were counted on CD138-immunostained sections by manual count and by image analysis. In addition, CD56 expression was correlated with clinical features in diagnosed myeloma group. Results: In all cases, both manual counts and image analysis, PC counts were significantly higher on the CD138 stained sections than bone marrow aspirates. It was seen that the manual PC counts and image analysis counts were equivalent in diagnosed myeloma cases. CD56 expression was seen in ~62.85% diagnosed myeloma cases while it was negative in cases of reactive plasmacytosis. CD56 expression was significantly higher in patients with lytic lesions (78.26% vs. 21.74%). CD138, anti-κ, and anti-λ IHC also helped classify 11/19 (57.8%) cases correctly. Conclusion: The use of CD138 along with the light chain and CD56 IHC adds a high diagnostic value in myeloma patients and suspected myeloma cases. The PCs can be counted manually on the CD138-immunostained sections and correlate well with the counts obtained by image analysis.

To evaluate the incidence of flares and treatment resistance in children with lupus nephritis and their association with renal outcomes. We retrospectively reviewed the case records of 34 children treated for lupus nephritis (Class II-IV) at a single center. Patients were followed for a minimum of five years to evaluate treatment response, onset of flares, and renal survival. Regression analyses were performed to identify the factors associated with treatment refractoriness, incidence of flares and renal survival. The incidence of flares was 0.16 episodes/person/year. Eight patients (23.5%) were refractory to treatment. The five-year renal survival was 79%. Multiple episodes of flares (P=0.028) and therapy refractoriness (P=0.003) were associated with poor renal survival. Prevention and aggressive management of renal flares is expected to prevent progression to end stage renal disease in lupus nephritis.

Background Persistent significant proteinuria has been associated with increased risk of progression to end-stage kidney disease in patients with idiopathic membranous nephropathy (IMN). Rituximab (RTX) therapy has given encouraging results in IMN, but most of the studies have used a higher dose, which is limited by the high cost as well as a potential increased risk of infections. Our study aimed to assess the efficacy and safety of low-dose RTX in patients with immunosuppression-resistant IMN. Methods A total of 21 patients with treatment-resistant IMN treated with RTX from 2015 to 2016 at our center were included in the study. They received two doses of RTX (500 mg each) infusion 7 days apart. CD19 count was performed after 4 weeks. A single dose of RTX was repeated after 4–6 weeks if CD19 count was not depleted. Results The mean standard deviation age of patients was 33.3 ± 12.3 years and 33.3% were females. Mean proteinuria before RTX therapy was 6.2 ± 2.2 g/day, serum creatinine was 0.9 ± 0.3 mg/dL and estimated glomerular filtration rate (eGFR) was 95.8 ± 26.9 mL/min/1.73 m2. All the patients were non-responders to prior immunosuppressive treatment. Twenty (95.2%) patients achieved targeted CD19 depletion with two doses of RTX. One patient required one additional RTX dose due to inadequate B-cell suppression. A total of 13 (61.9%) patients achieved remission with RTX therapy: 4 (19.0%) complete and 9 (42.9%) partial remission. Patients who did not respond to RTX had a significantly lower baseline eGFR compared with those who achieved remission (P = 0.022). One patient developed respiratory tract infection following RTX during the follow-up, which responded to a course of oral antibiotics. During median follow-up of 13.1 (10–23.9) months, four (19%) patients had deterioration in renal function and one patient relapsed after achieving partial remission. Renal survival was significantly better in patients who responded to RTX therapy as compared with those who did not achieve remission (P = 0.0037). Conclusion Low-dose RTX therapy is effective and safe in immunosuppression-resistant IMN.

Diabetic nephropathy (DN), a microvascular complication of diabetes, has emerged as an important health problem worldwide. There is strong evidence to suggest that oxidative stress, inflammation, and fibrosis play a pivotal role in the progression of DN. Apigenin has been shown to possess antioxidant, anti-inflammatory, antiapoptotic, antifibrotic, as well as antidiabetic properties. Hence, we evaluated whether apigenin halts the development and progression of DN in streptozotocin (STZ)-induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, and apigenin treatment groups (5–20 mg/kg po, respectively), apigenin per se (20 mg/kg po), and ramipril treatment group (2 mg/kg po). A single injection of STZ (55 mg/kg ip) was administered to all of the groups except control and per se groups to induce type 1 diabetes mellitus. Rats with fasting blood glucose >250 mg/dl were included in the study and randomized to different groups. Thereafter, the protocol was continued for 8 mo in all of the groups. Apigenin (20 mg/kg) treatment attenuated renal dysfunction, oxidative stress, and fibrosis (decreased transforming growth factor-β1, fibronectin, and type IV collagen) in the diabetic rats. It also significantly prevented MAPK activation, which inhibited inflammation (reduced TNF-α, IL-6, and NF-κB expression) and apoptosis (increased expression of Bcl-2 and decreased Bax and caspase-3). Furthermore, histopathological examination demonstrated reduced inflammation, collagen deposition, and glomerulosclerosis in the renal tissue. In addition, all of these changes were comparable with those produced by ramipril. Hence, apigenin ameliorated renal damage due to DN by suppressing oxidative stress and fibrosis and by inhibiting MAPK pathway.

Studies of nephrotic syndrome show that substitution of calcineurin inhibitors by mycophenolate mofetil (MMF) enables sustained remission and corticosteroid sparing and avoids therapy associated adverse effects. However, controlled studies in patients with steroid resistance are lacking. Here we examined the effect of switching from therapy with tacrolimus to MMF on disease course in an open-label, one-to-one randomized, controlled trial on children (one to 18 years old), recently diagnosed with steroid-resistant nephrotic syndrome, at a referral center in India. Following six months of therapy with tacrolimus, patients with complete or partial remission were randomly assigned such that 29 received MMF while 31 received tacrolimus along with tapering prednisolone on alternate days for 12 months. On intention-to-treat analyses, the proportion of patients with a favorable outcome (sustained remission, infrequent relapses) at one year was significantly lower (44.8%) in the MMF group than in the tacrolimus group (90.3%). The incidence of relapses was significantly higher for patients treated with MMF than tacrolimus (mean difference: 1.05 relapses per person-year). While there was no difference in the proportion of patients with sustained remission, the risk of recurrence of steroid resistance was significantly higher for patients receiving MMF compared to tacrolimus (mean difference: 20.7%). Compared to tacrolimus, patients receiving MMF had a significantly (71%) lower likelihood of a favorable outcome and significantly increased risk of treatment failure (frequent relapses, steroid resistance). Thus, replacing tacrolimus with MMF after six months of tacrolimus therapy for steroid-resistant nephrotic syndrome in children is associated with significant risk of frequent relapses or recurrence of resistance. These findings have implications for guiding the duration of therapy with tacrolimus for steroid-resistant nephrotic syndrome.

To correlate expression of Glypican-3 in Wilms tumor with histopathology, stage, and outcome. Glypican-3 mRNA expression by real-time PCR on tumor and normal germline samples from 75 fresh nephrectomies for Wilms tumor with fold change after normalization against GAPDH was compared. Survival analysis for event-free and overall survival (EFS, OS) with 2-year follow-up for Glypican-3 overexpression (>1.5 times) and clinicopathological parameters was performed. Glypican-3 was overexpressed in 37/75 (49.3%). It was overexpressed in 77% (10/13) cases with blastema predominance or anaplastic histology, as compared to 44% of other histologies (27/62) (p = 0.03). OS was 73 and 93%, respectively (p = 0.016), for those with and without GPC-3 overexpression. EFS was not significantly different with Glypican-3 overexpression (p = 0.11). All 5 deaths among blastema predominant tumors and 4/5 deaths among triphasic tumors had overexpressed Glypican-3. Most deaths in Stage IV, Stage III, and Stage I + II (5/7, 3/3, 1/1) had GPC-3 overexpression. On multivariate analysis, only histology and stage were found to have independent prognostic value. Glypican-3 overexpression in Wilms tumor correlates with poor OS on univariate analysis. However, only histology and stage have independent prognostic value. Glypican-3 levels may help to stratify intermediate outcome histology (triphasic) and Stage III Wilms tumors.

Objective Acute kidney injury (AKI) is a frequent presentation in malaria infections. Several cases of AKI that are accompanied by clinical symptoms of malaria infection, such as fever, nausea, respiratory distress, and anemia remain undiagnosed due to challenges in accurate diagnosis using peripheral blood microscopy and rapid diagnostic tests that are currently used in clinical settings. This is particularly true for P. vivax and P. knowlesi infections. As a result, these patients are not able to receive anti-malarial therapy in a timely manner. The objective of the present study was to investigate if patients presenting with AKI harbored any of the five human Plasmodium species (P. falciparum, P. vivax, P. knowlesi, P. malariae, and P. ovale) within their renal tissues. Results We found that renal biopsies from malaria associated AKI patients harbor the human malaria parasites P. falciparum, P. vivax and P. knowlesi as mono- and mixed species infections. Presence of microvascular injury in a majority of the malaria associated AKI cases suggested vascular involvement of P. vivax and P. knowlesi. This research note also highlights P. knowlesi as an emerging pathogen in the Indian subcontinent.

Introduction BK polyomavirus is ubiquitous and remains dormant in the urothelial tract, reactivating and replicating in the immunocompromised state especially in the setting of post-renal transplantation where it is believed to be directly oncogenic based on recent reports. Its oncogenic role in the immunocompetent host is controversial. This study aimed to investigate the association of BK polyomavirus in Urothelial Carcinoma. Material and methods Patients with suspected urothelial carcinoma (UC) admitted under Department of Urology over a period of one year were recruited and transuretheral bladder tumor (TURBT) resection was performed, along with sampling of cystoscopically normal-appearing urothelium away from the tumor. In addition, cystectomy specimens with UC were included, with sampling of grossly normal-appearing urothelium away from the tumor. Immunohistochemistry (IHC) for SV40 T-Antigen and chromogenic in situ hybridization (CISH) using BK polyomavirus specific probe was performed on the paired samples (tumor and normal). Results Twenty-three TURBT and 14 cystectomy specimens were assessed. None of the cases showed evidence of BK polyomavirus infection in tumor or in surrounding mucosa by IHC. CISH performed in ten cases were also found to be negative. In comparison, one post-renal transplant urothelial carcinoma in our experience showed diffuse SV40 staining. Conclusions This study suggests that BK polyomavirus infection is not associated with urothelial malignancy in the immunocompetent setting unlike in the immunocompromised setting where it should always be investigated for.

This study investigated the effect of α-amyrin (a pentacyclic triterpene) on high-fructose diet (HFD)-induced metabolic syndrome in rats. Male Wistar rats were randomly distributed into different groups. The control group was fed normal rat chow diet. The HFD group was fed HFD (60%; w/w) for 42 days. Pioglitazone (10 mg/kg, orally, once daily) was used as a standard drug. α-Amyrin was administered in 3 doses (50, 100, and 200 mg/kg, orally, once daily along with HFD). Plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were estimated. Changes in blood pressure, oral glucose tolerance, and insulin tolerance were measured. Hepatic oxidative stress as well as messenger RNA (mRNA) and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) were analyzed. A significant increase in systolic blood pressure, plasma glucose, total cholesterol, and plasma triglycerides and a significant decrease in HDL-C were observed in HFD rats as compared with control rats. Glucose tolerance and insulin tolerance were also significantly impaired with HFD. α-Amyrin prevented these changes in a dose–dependent manner. Hepatic oxidative stress as well as micro- and macrovesicular fatty changes in hepatocytes caused by HFD were also attenuated by α-amyrin. α-Amyrin preserved the hepatic mRNA and protein levels of PPAR-α, which was reduced in HFD group. This study thus demonstrates that α-amyrin attenuates HFD-induced metabolic syndrome in rats.

Oxidative stress-induced PARP activation has been recognized to be a main factor in the pathogenesis of cisplatin-induced nephrotoxicity. Accumulating literature has revealed that ACE inhibitors may exert beneficial effect in several disease models via preventing PARP activation. Based on this hypothesis, we have evaluated the renoprotective effect of enalapril, an ACE inhibitor, and its underlying mechanism(s) in cisplatin-induced renal injury in rats. Male Albino Wistar rats were orally administered normal saline or enalapril (10, 20 and 40 mg/kg) for 10 days. Nephrotoxicity was induced by a single dose of cisplatin (8 mg/kg; i.p.) on the 7th day. The animals were thereafter sacrificed on the 11th day and both the kidneys were excised and processed for biochemical, histopathological, molecular, and immunohistochemical studies. Enalapril (40 mg/kg) significantly prevented cisplatin-induced renal dysfunction. In comparison to cisplatin-treated group, the elevation of BUN and creatinine levels was significantly less in this group. This improvement in kidney injury markers was well substantiated with reduced PARP expression along with phosphorylation of MAPKs including JNK/ERK/p38. Enalapril, in a dose-dependent fashion, attenuated cisplatin-induced oxidative stress as evidenced by augmented GSH, SOD and catalase activities, reduced TBARS and oxidative DNA damage (8-OHDG), and Nox-4 protein expression. Moreover, enalapril dose dependently inhibited cisplatin-induced inflammation (NF-κB/IKK-β/IL-6/Cox-2/TNF-α expressions), apoptosis (increased Bcl-2 and reduced p53, cytochrome c, Bax and caspase-3 expressions, and TUNEL/DAPI positivity) and preserved the structural integrity of the kidney. Thus, enalapril attenuated cisplatin-induced renal injury via inhibiting PARP activation and subsequent MAPKs/TNF-α/NF-κB mediated inflammatory and apoptotic response.

The beneficial effect of garlic on cardiovascular disease is well known. However, the use of raw garlic against cardiac hypertrophy is not established. In the present study we explored whether raw garlic and its compound, diallyl disulfide (DADS) could inhibit hypertrophy through H2S and/or mitochondrial biogenesis. Cardiac hypertrophy was induced in rat by giving isoproterenol at the dose of 5 mg/kg/day subcutaneously for 14 days through alzet minipump. Aqueous garlic homogenate, DADS and NaHS (liberate H2S) were fed to third, forth and fifth group of rats for 14 days at a dose of 250 mg/kg/day, 50 mg/kg/day, 14 µM/kg/day respectively. Garlic and DADS reduced cardiac hypertrophy markers and normalized mitochondrial ETC-complex activities, mitochondrial enzyme activites and mitochondrial biogenetic and apoptotic genes expression. Garlic and DADS enhanced eNOS and p-AKT level in rat heart along with increased NRF2 protein level and Tfam gene expression. However, normalization was not observed after administration of NaHS which generates H2S in-vivo. In conclusion, garlic and DADS induces mitochondrial biogenesis and ameliorates cardiac hypertrophy via activation of eNOS-Nrf2-Tfam pathway in rats., Graphical abstract fx1, Highlights • Garlic reduced cardiac hypertrophy in rats. • Garlic attenuated cardiac hypertrophy through induction of Na+/K+-ATPase. • Three active metabolites of garlic were identified. • Garlic metabolites increased Na+/K+-ATPase and reduced hypertrophy in H9C2 cells.

Aim Pattern of kidney diseases varies across geographies due to multiple factors. There is a paucity of information from South Asia due to the absence of nationwide/regional biopsy registries. This study aimed to delineate the spectrum of renal parenchymal diseases in our region. Methods Records of kidney biopsies done in our nephrology department between 2006 and 2016 were analysed. Clinico-pathological correlation was done from the available records. Results Of the 3275 biopsy evaluated, 61.9% were males, and mean age was 33.2 ± 14.2 years. 6.2% patients were elderly (age ≥ 60 years). Nephrotic syndrome (60.3%) was the commonest indication for biopsy. On histology, 73.0% patients had primary glomerulonephritis (GN), 15.5% secondary GN, 5.3% tubulo-interstitial and 3.7% vascular disease. Focal segmental glomerulosclerosis (FSGS) was the commonest primary GN accounting for 18.2% of all GNs, followed by minimal change disease (16.8%), membranous nephropathy (MN) (16.0%) and IgA nephropathy (10.4%). Lupus nephritis (10.6%) and amyloidosis (3.7%) were the commonest secondary GN. The commonest cause of nephrotic syndrome was minimal change disease (22.9%), acute nephritic syndrome was lupus nephritis (30.6%), rapidly progressive renal failure was pauci-immune crescentic GN (24.5%). IgA nephropathy was the commonest etiology of asymptomatic urinary abnormalities (26.3%) and gross haematuria (50%). About 60.9% patients of undetermined chronic kidney disease had glomerular diseases, and 13.6% had chronic tubulointerstitial nephritis. Lupus nephritis and acute cortical necrosis were significantly more common in females compared with males. Conclusion This is one of the largest cohorts of kidney biopsies from India, and it delineates the unique features and differences in the pattern of kidney disease in our population.

Objectives Acute kidney injury (AKI) is a frequent clinical manifestation of severe malaria. Although the pathogenesis of P. falciparum severity is attributed to cytoadherence, the pathogenesis due to P. vivax and P. knowlesi are not very well understood and their presence within the host tissue has not been demonstrated. Therefore, the objective of this study was to determine if P. vivax and P. knowlesi interact with host renal tissue in malarial AKI. Methods Archival FFPE renal biopsies from 16 patients having AKI with suspected or confirmed malaria diagnosis, and 5 patients with non-malarial AKI, were subjected to histopathological analysis and DNA extraction. The total DNA from these renal biopsies was used to investigate the presence of the 5 species of human malaria parasite: P. falciparum, P. vivax, P. knowlesi, P. malariae and, P. ovale. The results of histopathology and PCR analysis were analyzed to understand the pathogenesis of malaria associated AKI. Results Renal biopsies from malarial AKI patients were found to harbor DNA from P. vivax (14 of 16), the zoonotic monkey parasite P. knowlesi (7) and P. falciparum (5) in the form of mono-infections as well as mixed infections. Sanger sequencing was used to confirm species identity. Histopathological analysis revealed the presence of microvascular injury as a common feature of P. vivax and P. knowlesi related AKI. Hemozoin could be detected within the renal tissue, which indicated the presence of metabolically active parasites. Conclusions P. vivax and P. knowlesi associated AKI may involve interaction of the host renal tissue with parasite derived components such as Plasmodium DNA and hemozoin which may lead to innate immune activation and host tissue injury.

Paraffin immunofluorescence is a well established "salvage" technique in renal pathology when representative glomeruli are not found in the fresh frozen tissue sent for routine direct immunofluorescence studies. A step of enzymatic digestion of the formalin-fixed paraffin-embedded biopsy exposes the antigenic immune complexes and allows staining with fluorochrome-tagged antibodies. We explored the utility of the technique of paraffin immunofluorescence outside the kidney in certain specific scenarios including extra renal amyloid and duodenal macroglobulinemia.

An aging population is an important demographic issue in India. The knowledge base about kidney diseases among the elderly Indians is inadequate. We aim to delineate the clinical profile and spectrum of biopsy-proven kidney disease in elderly patients. Records of all elderly patients (≥60 years) who had undergone kidney biopsy in the nephrology department from January 2010 to December 2014 were reviewed. Their clinical details and laboratory investigations at the time of biopsy were noted. Details of kidney biopsy were recorded from their biopsy reports. In total, 1728 patients underwent kidney biopsy during this period and 124 were elderly (7.2 %). Their mean age was 64.9 ± 4.9 years, and they were predominantly males (63.7 %). Mean serum creatinine was 3.0 ± 2.8 mg/dl, proteinuria was 4.0 ± 2.7 g/day, and 39.5 % had microscopic hematuria. The most common indications for biopsy were nephrotic syndrome (NS)—39.5 % and acute kidney injury/rapidly progressive glomerulonephritis (AKI/RPGN)—24.2 %. Another 8.1 % patients had NS with AKI. MN (39.0 %) was the chief cause of NS, and pauci-immune crescentic glomerulonephritis (GN) (28.2 %) was the leading cause of AKI/RPGN. MN, pauci-immune crescentic GN and acute on chronic tubulointerstitial nephritis (A/CTIN) and acute tubular injury (ATI) were more common in the elderly, while MCD, FSGS, IgA nephropathy and lupus nephritis were more frequent in the younger patients. 68.5 % of the elderly patients biopsied were diagnosed with a renal disease which was potentially amenable to specific treatment. The spectrum of biopsy-proven kidney disease in the elderly Indians seen in our tertiary care hospital varies from the younger population. Kidney biopsy provides useful information with therapeutic and prognostic implications in these patients. The percentage of elderly patients among the total biopsied population is low in India, and these patients present late with renal dysfunction. Prospective studies are needed to assess the outcome of the commonly seen kidney diseases in elderly patients.

Objective p27 is a cell cycle-dependent kinase inhibitor whose presence in nucleus is associated with good prognosis. Recent studies propose that when localized to cytoplasm, it functions as an oncogene and confers a poorer prognosis. This study aimed at analysing the subcellular localization of p27 and its prognostic significance in oral squamous cell carcinomas (OSCCs). Methods Immunohistochemistry for p27 was carried out on 60 cases of OSCC (30 cases each of those with lymph node metastasis [LN+ve SCC] and without lymph node metastasis [LN−ve SCC]) and 30 normal mucosa. The relationship between p27 localization and prognosis was analysed statistically. Results Nuclear immunopositivity was seen in 15%, 23%, 7% and 60%, while cytoplasmic immunopositivity was seen in 80%, 63%, 97% and 43% of all SCC, LN+ve OSCC, LN−ve SCC cases and normal mucosa, respectively. There was a significant inverse correlation between nuclear and cytoplasmic p27 immunopositivity (P = 0.001). Nodal status and tumour stage were the only two parameters that correlated with disease-free survival (DFS) in OSCC cases. However, in LN+ve SCC, a significantly shortened DFS was seen in cases with cytoplasmic p27 expression compared to those without (P = 0.02). Conversely, LN+ve SCC with nuclear p27 had longer DFS on comparison with those without (P = 0.04). Conclusions To the best of our knowledge, this is the first study to analyse cytoplasmic localization of p27 in OSCC and correlate with prognosis. Cytoplasmic localization is associated with poor prognosis in OSCC with lymph node metastasis allowing the consideration of cytoplasmic p27 in predicting prognosis and targeted therapeutic approaches.

Tamoxifen is the most prescribed anticancer oral drug for increasing overall survival and decreasing recurrence and the risk of contralateral disease. However, some side effects, such as endometrial and liver tumors, thromboembolic disorders, and drug resistance, are associated with long-term tamoxifen treatment. We assessed the hematologic and organ toxicity after oral administration of three different doses of nanotamoxifen formulations. We also performed biodistribution studies of Technetium-99m (99mTc)-nanotamoxifen after intravenous administration. The results demonstrated that nanotamoxifen was well-tolerated, with no adverse effect on biochemical parameters of blood and at the cellular level. Nitric oxide (NO) levels indicated no free radical formation. Oral nanotamoxifen is well-tolerated, with no hepatic or renal toxicity. Intravenous nanotamoxifen has potential to escape the liver, and is known for producing the harmful metabolite 4-hydroxytamoxifen (4OH-tamoxifen), which can cause uterine cancer.

Posttransplant lymphoproliferative disorder (PTLD) is reported in 1%–3% among pediatric renal allograft recipients. We report the experience of PTLD among pediatric renal allograft recipients at a pediatric nephrology center in North India. Four cases of PTLD were identified from among records of 95 pediatric renal allograft recipients over a period of 21 years. Constitutional and localizing symptoms were present in three patients each. The diagnosis was suggested on positron emission tomography in three patients and confirmed by histopathology in all. Sites affected included tonsils, cervical lymph nodes, duodenum, and para-aortic lymph nodes in one patient each. The lymphocytic infiltrate was polymorphic in three patients and monomorphic in one. Immunostaining suggested B-cell origin in all patients. There was evidence of Epstein–Barr virus infection in only one patient. The patients were successfully managed with reduction of immunosuppression (in all), rituximab (in 3), and excision of affected tissue (in 1). Over a follow-up period of 30–88 months, there were no episodes of disease recurrence or allograft rejection, and renal function was preserved.

Background: Substantial number of patients with paucibacillary leprosy may still have active skin lesions at the end of MD treatment because of the continuing immune responses, though this does not denote failure of treatment. A clinical trial was conducted to compare efficacy of a homoeopathic medicine with MDT for the cure of leprosy. Aim: To compare the effect of a homoeopathic medicine - Sulphur with the Multi drug in the treatment of Paucibacillary leprosy according to WHO guidelines. Materials and Methods: Out of total 90 patients enlisted, 60 confirmed Borderline Tuberculoid (BT) leprosy patients of the age 14 years to less than 60 years were registered under this trial. All the patients were allotted a precoded number, randomly and equally divided in two groups. One group was treated with Sulphur in 200 potency in liquid orally once in week for two years and the other group received Paucibacillary (PB) regimen as recommended by WHO. At the end of two years findings were corroborated. Results: The study showed that MDT therapy (PB regimen) and homoeopathic medicine were found equally effective as histopathology of skin showed no granulomatous lesion. The most significant clinical sign observed in all cases treated with Sulphur was reappearance of normal skin colour and regain of loss of sensation of the skin lesion. Conclusions: MD therapy (PB regimen) and homoeopathic medicine were found equally effective. The patients of paucibacillary leprosy could get rid of the skin symptoms if treatment with Sulphur (is also given with MDT).

Background- Inflammation remains a crucial factor for progression of cardiac diseases and cardiac hypertrophy remains an important cause of cardiac failure over all age groups. As a key regulator of inflammation, toll like receptor 4 (TLR4) plays an important role in pathogenesis of cardiac diseases. Being an important regulator of innate immunity, the precise pathway of TLR4 mediated cardiac complications is yet to be established. Therefore, the primary objective of the present study was to find the role of TLR4 in cardiac hypertrophy and the molecular mechanism thereof. Methods- Cardiac hypertrophy was induced with administration of isoproterenol (5mg/kg/day, sc). TLR4 receptor inhibitor RS-LPS (lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides; 5 microgram/day) and agonist LPS (Lipopolysaccharide from Escherichia coli; 3.12 microgram/day) were administered through osmotic pump along with isoproterenol. Cardiac hypertrophy as well as oxidative stress and mitochondrial parameters were evaluated. Results- Cardiac hypertrophy was confirmed with increased heart weight/body weight ratio as well as assessment of hypertrophic markers in heart. There was a marked increase in the TLR4 expression and oxidative stress along with mitochondrial dysfunction in ISO group. TLR4 inhibition significantly decreased heart weight/body weight ratio and ANP, collagen and β-MHC expression and restored the disturbed cellular antioxidant flux. The mitochondrial perturbations that were observed in hypertrophy heart, was normalized after administration of TLR4 inhibitor but not with the agonist. TLR4 agonism further exaggerated the oxidative stress in heart and hence accelerated the disease development and progression. Conclusively- Our data shows that, increased TLR4 ligand pool in cardiac hypertrophy may exaggerate the disease progression. However, inhibition of TLR4 attenuated cardiac hypertrophy through reduced cardiac redox imbalance and mitochondrial dysfunction.

Introduction Duct ectasia (DE) and periductal mastitis (PDM) are the most common benign breast conditions seen in women. The etiopathogenesis of these entities is still not clear and most of the theories regarding the causation are based on the histological features as seen on light microscopy. The ultramicroscopic features associated with these conditions that may give more insight to the etiopathogenesis are unknown. Aim To study the ultrastructural changes occurring in mammary duct cones in patients with DE and PDM using Transmission Electron Microscopic (TEM). Method Major ducts removed by radical duct excision from 21 patients with final histopathological diagnosis of DE and PDM were subjected to TEM study with 2 normal duct samples as controls. Results The TEM features of DE were denudation of the epithelial cells with focal loss of microvilli, widening of the inter-epithelial junctions with focal disruption of the T bars, periductal collagenisation without inflammation, and features suggestive of Epithelial Mesenchymal Transition (EMT). PDM features are intact epithelial lining with proliferative epithelium and periductal collagenisation with inflammation. Conclusions Based on the TEM findings, we suggest that DE and PDM are two different entities. EMT a novel finding observed in DE in this study.

Background. Rituximab has emerged as an important medication for patients with steroid-dependent or steroid-resistant nephrotic syndrome. Patients. We report the efficacy and safety of therapy with intravenous rituximab, administered once weekly for 2–4 doses, in 193 patients (mean age 10.9, range 2.2–18.7 years) with difficult-to-treat steroid dependence (n = 101), calcineurin inhibitor (CNI)-dependent steroid resistance (n = 34) and CNI-resistant nephrotic syndrome (n = 58) managed at this center during 2006–13. Outcomes. Therapy in patients with steroid dependence and CNI-dependent steroid resistance led to significantly reduced relapse rates (respective mean difference 2.7 relapses/year and 2.2 relapses/year, corresponding to a decrease in relapses by 81.8 and 71.0%; both P < 0.0001). This resulted in a significant reduction in steroid requirement (mean difference 104.5 and 113.6 mg/kg/year, respectively; both P < 0.0001) and a trend to improved standard deviation scores for height (P = 0.069) and body mass index (P = 0.029). Remission was longer in patients with steroid dependence compared with CNI-dependent steroid resistance (median 16 versus 10 months; P < 0.0001). Prior response to cyclophosphamide predicted a lower risk of relapse in the former (hazard ratio, HR 0.56; P = 0.045); patients with initial resistance and CNI-dependent steroid resistance had increased risk of relapse (HR 2.66; P = 0.042). B-cell recovery, noted in 62.5% patients at 6 months, was not related to occurrence of relapse; redosing (n = 42 patients) was safe and effective. Response to therapy was unsatisfactory in patients with steroid- and CNI-resistant nephrotic syndrome, with remission in 29.3%. Focal segmental glomerulosclerosis was associated with higher odds of non-response (odds ratio 11.1; P = 0.028) and lack of response was associated with progressive chronic kidney disease (HR 9.97; P = 0.035). Therapy with rituximab was safe; adverse effects or infections were noted in 19 (9.8%) patients. Conclusions. Therapy with rituximab is effective and safe in reducing relapse rates and need for immunosuppressive medications in patients with steroid-dependent and CNI-dependent steroid-resistant nephrotic syndrome.

Atypical HUS associated with anti-CFH autoantibodies is an uncommon illness associated with high risk of progression to end-stage renal disease. Disease relapses after transplantation, observed in one-third cases, often lead to graft loss. We report four patients with anti-CFH antibody-associated HUS who underwent renal transplantation 16-62 months from initial presentation. Two patients each received organs from deceased and living-related donors. Anti-CFH antibody titers were monitored during the illness and following transplantation. All patients received two doses of IV rituximab before or after transplantation; three patient each received 1-2 g/kg of IV immunoglobulin or underwent 2-5 sessions of plasma exchanges. The use of therapeutic plasma exchange, IV immunoglobulin, and rituximab in two cases enabled two-third reduction in anti-CFH antibody titers before transplantation. At 5- to 26-month follow-up, all patients showed satisfactory graft function without recurrence of HUS. This is the first report of patients with anti-CFH antibody-associated HUS who underwent living-related renal transplantation. Clearance of anti-CFH antibody by therapeutic plasma exchange and adjuvant immunosuppression aimed at decreasing antibody levels may enable successful transplantation and recurrence-free survival.

Malignant melanoma of soft parts (MMSP), first described by Franz M. Enzinger, is a rare tumour of unknown cell origin. We describe a case of a 45-year-old male who presented with a one-year history of abdominal pain, weakness, and anaemia. Computerised tomography enteroclysis showed a mass in the jejunum that was suggestive of a gastrointestinal stromal tumour. An ulceroinfiltrative lesion measuring 6.5 x 4 x 2cm was identified. Microscopy revealed typical features of MMSP with numerous osteoclasts-like giant cells. The diverse histomorphology and immunohistochemical characteristics of this case involving a rare tumour at a rare site is presented.

In this prospective study, we measured serum levels of the soluble urokinase receptor (suPAR) in pediatric patients with nephrotic syndrome of various etiologies. Mean levels of suPAR were 3316pg/ml in 99 patients with steroid-resistant focal segmental glomerulosclerosis and 3253pg/ml in 117 patients with biopsy-proven minimal change disease, which were similar to that of 138 patients with steroid-sensitive nephrotic syndrome (3150pg/ml) and 83 healthy controls (3021pg/ml). Similar proportions of patients in each group had suPAR over 3000pg/ml. Compared with controls, suPAR levels were significantly higher in patients with focal segmental glomerulosclerosis (FSGS) and estimated glomerular filtration rate (eGFR) under 30ml/min per 1.73m 2 (6365pg/ml), congenital nephrotic syndrome (4398pg/ml), and other proteinuric diseases with or without eGFR under 30ml/min per 1.73m 2 (5052 and 3875pg/ml, respectively; both significant). There were no changes following therapy and during remission. Levels of suPAR significantly correlated in an inverse manner with eGFR ( r =-0.36) and directly with C-reactive protein ( r =0.20). The urinary suPAR-to-creatinine ratio significantly correlated with proteinuria ( r =0.25) in 151 patients and controls. Using generalized estimating equations approach, serum suPAR significantly correlated with eGFR (coefficient=-13.75), age at sampling (2.72), and C-reactive protein (39.85). Thus, serum suPAR levels in nephrotic syndrome are similar to controls, and do not discriminate between FSGS, minimal change disease, or steroid-responsive illness.

Collapsing glomerulopathy (CG) is a distinct clinicopathologic entity associated with various infections, medications and acute ischemia. There have been few scattered reports of CG from India. This study aimed at evaluating the clinicopathologic features of idiopathic CG in Indian patients with comparison between adult-onset and childhood CG. This study included all cases of idiopathic CG diagnosed over a period of 4 years (2006-2009). Appropriate clinical details and laboratory findings were retrieved. Renal biopsies were reviewed and detailed pathologic features assessed. Statistical analysis was performed to compare various features between adult-onset and childhood CG. Over these 4 years, 30 cases of idiopathic CG were diagnosed. Of these, 11 were children. Childhood CG cases had longer duration of symptoms and lower serum urea and creatinine levels compared with adult patients. In renal histology, tubular atrophy and interstitial fibrosis was frequent in our cases. Pediatric cases of CG showed a higher proportion of segmental glomerulosclerosis. On clinical follow-up, nine of the 30 patients progressed to end-stage renal disease and these included two pediatric patients. Idiopathic CG is a significant cause of renal dysfunction in both pediatric and adult patients. Childhood and adult-onset CG differ in few clinicopathologic features. Early and accurate diagnosis of CG is imperative for appropriate management of these patients.

A Borderline Lepromatous (BL) leprosy case was treated with Mercurius solubilis , a homoeopathic medicine for two years. The clinical, immunological and histological assessment of the patient before and after treatment was recorded. The patient showed appreciable improvement in clinical signs and symptoms. Lesions on the skin almost disappeared; no swelling of hand and feet was noted along with disappearance of infiltration on eye brows. Nodular lesions on both the ear lobes diminished remarkably. Regain of sensation to touch, pain and pressure were noted and their test responses were normal. Slit skin smears were negative from all sites with 0 Bacteriological Index [BI] which was positive for acid fast bacilli [AFB] with an average of 4+ BI before treatment. Histologic study revealed absence of granuloma in dermis except the presence of occasional clusters of lymphocytes. Lepromin reaction which was negative before treatment was positive with 14 mm after 2 years of treatment. Estimation of different cytokines after completion of treatment showed appreciable changes with remarkable reduction in the levels of proinflammatory cytokines (IFN and TNF).

Gain-of-function mutations in the calcium channel TRPC6 lead to autosomal dominant focal segmental glomerulosclerosis and podocyte expression of TRPC6 is increased in some acquired human glomerular diseases, particularly in membranous nephropathy. These observations led to the hypothesis that TRPC6 overactivation is deleterious to podocytes through pathological calcium signaling, both in genetic and acquired diseases. Here, we show that the effects of TRPC6 on podocyte function are context-dependent. Overexpression of TRPC6 alone did not directly affect podocyte morphology and cytoskeletal structure. Unexpectedly, however, overexpression of TRPC6 protected podocytes from complement-mediated injury, whereas genetic or pharmacological TRPC6 inactivation increased podocyte susceptibility to complement. Mechanistically, this effect was mediated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation. Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates. Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression. Together, these data suggest a dual and context dependent role of TRPC6 in podocytes where acute activation protects from complement-mediated damage, but chronic overactivation leads to focal segmental glomerulosclerosis.

Studying ultrastructural changes could reveal novel pathophysiology of obese-asthmatic condition as existing concepts in asthma pathogenesis are based on the histological changes of the diseased airway. While asthma is defined in functional terms, the potential of electron microscopy (EM) in providing cellular and subcellular detail is underutilized. With this view, we have performed transmission EM in the lungs from allergic mice that show key features of asthma and high-fat- or high-fructose-fed mice that mimicked metabolic syndrome to illustrate the ultrastructural changes. The primary focus was epithelial injury and metaplasia, which are cardinal features of asthma and initiate airway remodeling. EM findings of the allergically inflamed mouse lungs correlate with known features of human asthma such as increased mitochondria in airway smooth muscle, platelet activation and subepithelial myofibroblasts. Interestingly, we found a clear and unambiguous evidence to suggest that ciliated cells can become goblet cells using immunoelectron microscopy. Additionally, we show for the first time the stressed mitochondria in the bronchial epithelia of high-fat- or high-fructose-fed mice even without allergen exposure. These results may stimulate interest in using EM in understanding novel pathological mechanisms for different subtypes of asthma including obese asthma.

Growing interest in the application of nanotechnology to treat lymphatic filariasis (LF) implies that the imminent medical arsenal of this interesting technology is attractive for health authorities. Currently, they are completely dependent on friendly oral mass drug (anti-filarials) administration to eliminate this morbid disease and are now looking for new alternatives to bring about further improvements.A plethora of issues affecting the oral bioavailability of the mainstay human lymphatic filarial drugs, leading to meager pharmacokinetics and pharmacodynamics issues in anti-filarial chemotherapy are identified. Various important nanomedical drug delivery systems are highlighted and their solutions provided. A conceptual resolution to strictly arrest the transmission of LF in endemic areas is also presented.Unless the solutions for pharmacokinetic tribulations and the measurement of factual pharmacodynamic endpoints for the existing anti-filarial drugs are evaluated using relevant approaches, health authorities will not be able to devise optimal treatment regimens for affected patients. Contemporary therapeutic paradigms need to be shifted toward the upcoming schemes of nanopharmaceutical sciences, which have enormous potential to advance the community-directed management of this tropical disease by improving the pharmacokinetic and pharmacodynamic properties of the filaricidal agents.

Objectives To evaluate the ability of magnetic resonance spectroscopic imaging to improve prostate cancer detection rate. Methods A retrospective analysis was carried out of 278 men with prostate-specific antigen in the range of 4–10 ng/mL and normal digital rectal examination who underwent transrectal ultrasound-guided prostate biopsy. Outcomes were compared between men who had a standard biopsy versus those who also underwent a prebiopsy magnetic resonance spectroscopic imaging. Men with an abnormal voxel on magnetic resonance spectroscopic imaging had standard transrectal ultrasound biopsies plus biopsies directed to the abnormal voxels. Results The study group (n = 140) and control group (n = 138) were similar in baseline parameters, such as mean age, prostate size and mean prostate-specific antigen. The overall cancer detection in the magnetic resonance spectroscopic imaging positive group (24.4%) was more than double that of the control group (10.1%). On comparing the magnetic resonance spectroscopic imaging results with the transrectal ultrasound biopsy findings, magnetic resonance spectroscopic imaging had 95.6% sensitivity, 41.9% specificity, a positive predictive value of 24.4%, a negative predictive value of 98% and an accuracy of 51.4%. Conclusions Magnetic resonance spectroscopic imaging-directed transrectal ultrasound biopsy increases the cancer detection rate compared with standard transrectal ultrasound biopsy in patients with normal digital rectal examination and elevated prostate-specific antigen in the range of 4–10 ng/mL.

To determine the etiology, course and predictors of outcome in children with crescentic glomerulonephritis (GN).Retrospective, descriptive study.Pediatric Nephrology Clinic at a referral center in Northern India.Clinic records of patients aged18 year with crescentic GN diagnosed from 2001 - 2010 and followed at least 12 months were reviewed. Crescentic GN, defined as crescents in ≥50% glomeruli, was classified based on immunofluorescence findings and serology. Risk factors for renal loss (chronic kidney disease stage 4-5) were determined.Of 36 patients, (median age 10 yr) 17 had immune complex GN and 19 had pauci-immune crescentic GN. The etiologies of the former were lupus nephritis (n=4), postinfectious GN (3), and IgA nephropathy, Henoch Schonlein purpura and membranoproliferative GN type II (2 each). Three patients with pauciimmune GN showed antineutrophil cytoplasmic antibodies (ANCA). Rapidly progressive GN was present in 33 patients, and required dialysis in 12. At median 34 (19-72) months, 2 patients with immune complex GN and 8 with pauciimmune GN showed renal loss. Renal survival was 94.1% at 3 yr, and 75.3% at 8 yr in immune complex GN; in pauciimmune GN survival was 63.2% and 54.1%, respectively (P=0.054). Risk factors for renal loss were oliguria at presentation (hazards ratio, HR 10.50; P=0.037) and need for dialysis (HR 6.33; P=0.024); there was inverse association with proportion of normal glomeruli (HR 0.91; P=0.042).Pauci-immune GN constitutes one-half of patients with crescentic GN at this center. Patients with pauciimmune GN, chiefly ANCA negative, show higher risk of disease progression. Renal loss is related to severity of initial presentation and extent of glomerular involvement.

Background: Immunofluorescence (IFM) antigen mapping is the most commonly used technique to diagnose and differentiate epidermolysis bullosa (EB). In India, IFM is limited to few research laboratories and is not readily available, making the diagnosis largely clinical and often inaccurate. Ob jective of the Study: To examine the diagnostic usefulness of immunohistochemistry (IHC) as compared to IFM in resource-limited settings. Methods: Forty-four consecutive EB patients were included in this study. IHC and IFM were performed on 7-µm frozen tissue sections using standard laboratory protocols with a limited panel of antibodies. The kappa coefficient of agreement was calculated with genetic analysis as the gold standard. Results: IFM and IHC accurately identified the subtype of EB in 80.9% (p < 0.001) of the cases, when a clear blister cavity was evident on biopsy. The sensitivities and specificities of IHC and IFM for diagnosing EB simplex, junctional EB, and dystrophic EB were 100, 100, and 60% and 82.4, 100, and 100%, respectively. IHC was equally effective (p < 0.001) in establishing the type of EB as IFM. Conclusions: IHC staining and its interpretation were simple and comparable to IFM. IHC had an advantage of showing subtle changes in the epidermal architecture that could not be appreciated on IFM and hence can be considered useful in resource-limited settings.

11p13 and 11p15 loss of heterozygosity (LOH) in Wilms tumor (WT), the commonest molecular pathogenetic event in WT, shows variation in different parts of the world. The present study looked for the presence of 11p13 and 11p15 LOH as well as nephrogenic rests in WT occurring in India. Twenty-two cases of WT were subjected to thorough pathological examination for presence of nephrogenic rests. Fresh frozen tissue was evaluated for LOH at 11p13 and 11p15, using PCR for microsatellite markers. Among twenty-two consecutive cases of WT, 20 were unilateral and 2 were bilateral. 6/22 showed LOH at 11p13 (27.7 %) and 1/22 showed LOH at 11p15 (4.54 %). 2/22 cases showed presence of nephrogenic rests. One of the cases with LOH at 11p13 had intralobar nephrogenic rest in the adjacent kidney. One specimen had perilobar nephrogenic rest in the adjacent kidney but did not show LOH for either 11p13 or 11p15 in the tumor. LOH at 11p13 is seen in 27.27 % of WT in India, which is similar to reports in the English language literature. LOH at 11p15 was seen in 4.54 % of WT, which is lower than that reported from Western subjects.

A young adult was diagnosed to have acute lymphoblastic leukemia, T-cell immunophenotype and was initiated on chemotherapy. He presented with acute renal failure two days after the completion of his induction regimen. A renal biopsy showed features of necrotizing crescentic glomerulonephritis (GN). Serology for c-anti-neutrophil cytoplasmic antibody (ANCA) was positive and a final diagnosis of ANCA-associated necrotizing crescentic GN was made. Aggressive immunosuppression could not be used due to the presence of nosocomial pneumonia and the patient expired 26 days after the renal biopsy diagnosis. We report for the first time the association of acute lymphoblastic leukemia with crescentic GN and, hence, expand the list of malignancy-related ANCA-positive GN.

The aim of the study was to assess the impact of protocol biopsies in a live-related renal transplant program using tacrolimus-based immunosuppression in the short term. Eighty-three live-related transplant recipients were randomly allocated to protocol biopsy group (Group I, n = 40) and a control group (Group II, n = 43). Other immunosuppressants in these groups consisted of either mycophenolate mofetil or azathioprine and steroids. Protocol biopsies were conducted in biopsy group at 1, 6, and 12 months post-transplant. The non-biopsy group was followed by serial serum creatinine and biopsies in them were conducted as and when clinically indicated. Both groups were analyzed at 12 months with respect to graft function and survival. The two groups were similar with respect to age, number of dialysis pre-operatively, tacrolimus levels, induction therapy, donor age, and donor glomerular filtration rate. Forty protocol biopsies were conducted at 1 month, 31 at 6 months, and 26 at 12 months. The prevalence of sub-clinical rejection at 1, 6, and 12 months in these biopsies was 17.5%, 11.2%, and 10.3%, respectively. The prevalence of calcineurin inhibitor toxicity during same period was 15%, 15.5%, and 14.4%, respectively. The cumulative rejection rate in Group I and Group II at 12-month follow-up was 10.3% and 11.3% ( P = 0.78), respectively, and cumulative calcineurin inhibitor toxicity at 12 months was 14.4% and 9.3% ( P = 0.59), respectively, were not statistically significant. There was no difference in graft survival and function at 1 year. Protocol biopsies have a limited role in a well-matched renal transplant program with tacrolimus-based immunosuppression in the short term. However, the long-term impact of protocol biopsies needs further evaluation.

Tissue transglutaminase 2 enzyme plays a diverse role in intracellular and extracellular functioning. Aberrant expression of anti-TG2 antibody has recently been proposed for extraintestinal identification of celiac disease (CeD), but its utility is questionable. To examine whether anti-TG2 immunohistochemical (IHC) staining can be of diagnostic value in identifying extraintestinal involvement in CeD, tissue blocks of patients with IgA nephropathies (IgAN), minimal change disease, membranous glomerulonephritis, membrano-proliferative glomerulonephritis, normal kidney, intestinal biopsies from CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease; liver biopsies from patients with chronic hepatitis B and C, acute liver failure (ALF), and CeD-associated liver diseases were retrieved and subjected to IHC staining for anti-tissue transglutaminase 2 enzyme. H-score was calculated by multiplying the area of positivity and stain intensity. Anti-TG2 stain H-scores were almost similar in IgAN and non-IgANs (H-score 6.31±3 vs. 7.03±2.7); however, H-scores in both of these groups were significantly higher than in normal renal parenchyma (1.6±1.5). Only 6.2% patients with IgAN with anti-TG2 immunostain positivity showed a positive anti-tTG antibody serology and villous abnormalities, suggestive of CeD. Intestinal biopsies from patients with CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease also showed high anti-TG2 H-scores, with no statistically significant differences. Liver biopsies from patients with both ALF, as well as chronic liver diseases showed high anti-TG2 H-scores; with highest stain expression in ALF. In conclusion, IHC expression of anti-TG2 stain correlates with both acute and chronic tissue injuries, irrespective of etiology and organ involvement. It is not a reliable marker for diagnosis of CeD.

A 3-year-old girl presented with a non-healing ulcer, originating as a pustule over the right anterior chest wall of 1½ month duration associated with high fever. A subcutaneous nodule along with right apical and anterior axillary lymph nodes was palpable. Abdominal ultrasound and chest skiagram were normal. Fine needle aspiration cytology (FNAC) from the axillary lymph node was suggestive of embryonal rhabdomyosarcoma. Bone marrow aspirate was normal. The ulcer and subcutaneous nodule were excised completely with adequate margins. Histopathological examinations were compatible with malignancy of histiocytic origin with clear resected margins. The axillary nodes were free of tumour. Adjuvant chemotherapy was given for 13 months. The patient is doing well at 8 years follow-up.