Experimentally Induced Hyperglycemia in Prepubertal Phase Impairs Oocyte Quality and Functionality in Adult Mice.

Reproductive abnormalities in women with a history of childhood diabetes are believed to be partially attributed to hyperglycemia. Prolonged hyperglycemia can negatively affect ovarian function and fertility during reproductive life. To address this in an experimental setting, the present study used streptozotocin-induced hyperglycemic prepubertal mouse model. The impact of prolonged hyperglycemic exposure during prepubertal life on ovarian function, oocyte quality, and functional competence was assessed in adult mice. The ovarian reserve was not significantly altered; however, the in vitro maturation potential (P < 0.001), mitochondrial integrity (P < 0.01), and meiotic spindle assembly (P < 0.05-0.001) in oocytes were significantly affected in hyperglycemic animals in comparison to control groups. The results from the study suggest that prepubertal hyperglycemia can have adverse effects on the oocyte functional competence and spindle integrity during the reproductive phase of life. Because these changes can have a significant impact on the genetic integrity and developmental potential of the embryos and fetus, the observation warrants further research both in experimental and clinical settings.

Bilateral massive nephromegaly-A rare presentation of t-cell acute lymphoblastic leukemia.

INTRODUCTION: Renal infiltration by leukemia causing massive bilateral nephromegaly is an extremely rare presentation of T-cell acute lymphoblastic leukemia(T-ALL). CASE REPORT: 18-month-old female toddler presented with fever and progressive abdominal distension of 4-6 weeks duration. Imaging revealed bilateral massively enlarged kidneys with normal excretion. Peripheral blood counts and smear examination was unremarkable and immunophenotypic evaluation of marrow was consistent with T-ALL. Chest imaging was unremarkable. She was started on modified Indian Childhood Collaborative Leukemia Group (ICiCLe) ALL protocol. Even with the best anti-tumor lysis syndrome (TLS) prophylaxis the child required two sessions of hemodialysis. An end-induction morphological remission & end-consolidation negative minimal residual disease (MRD) could be achieved. CONCLUSION: Bilateral massive nephromegaly is an extremely rare presentation of T-ALL. This case emphasizes the unusual presentation, need for prompt remediation of TLS, and most importantly the use of early intensification with four drug anthracycline & dexamethasone-based therapy for the treatment of T-ALL in children.

Impact of Temperature and Time Interval Prior to Immature Testicular-Tissue Organotypic Culture on Cellular Niche.

Cryopreservation of immature-testicular-tissue (ITT) prior to gonadotoxic treatment, while experimental, is the only recommended option for fertility preservation in prepubertal boys. The handling and manipulation of ITT before cryopreservation could influence the functionality of cells during fertility restoration, which this study explored by evaluating cellular niche and quality of mouse ITT subjected to various temperatures and time durations in vitro. ITT from 6-day-old mice were handled at ultraprofound-hypothermic, profound-hypothermic, and mild-warm-ischemic temperatures for varying time periods prior to 14-day organotypic culture. Viability, functionality, synaptonemal complex and chromatin remodeling markers were assessed. Results have shown that cell viability, testosterone level, and in vitro proliferation ability did not change when ITT were held at ultraprofound-hypothermic-temperature up to 24 h, whereas cell viability was significantly reduced (P < 0.01), when held at profound-hypothermic-temperature for 24 h before culture. Further, cell viability and testosterone levels in cultured cells from profound-hypothermic group were comparable to corresponding ultraprofound-hypothermic group but with moderate reduction in postmeiotic cells (P < 0.01). In conclusion, holding ITT at ultraprofound-hypothermic-temperature is most suitable for organotypic culture, whereas short-term exposure at profound-hypothermic-temperature may compromise postmeiotic germ cell yield post in vitro culture. This data, albeit in mouse model, will have immense value in human prepubertal fertility restoration research.

Hemosiderin tubulopathy-induced acute kidney injury - A rare initial manifestation of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by episodes of intravascular hemolysis, infections, and thromboembolic complications. Renal abnormalities are rare which occur either due to hemolytic crisis or repeated thrombotic episodes involving small venules. Acute kidney injury (AKI) requiring hemodialysis due to toxic effects of hemoglobinuria, with a stable disease is exceptional. We describe a case of an elderly gentleman presenting with features of severe AKI requiring hemodialysis due to hemosiderin tubulotoxicity as the first manifestation of PNH. The diagnosis was challenging because of the rarity and unfamiliarity with this entity. The outcome was complete recovery of renal function with hemodialysis.

Clinicopathological Characteristics and Outcomes of Diffuse Crescentic Glomerulonephritis - A Single Center Experience from Southern India.

INTRODUCTION: Diffuse Crescentic glomerulonephritis (CrGN) is characterized by rapidly progressive renal failure and has grave prognosis. There is significant regional and temporal variation in aetiology, prevalence and prognosis of diffuse crescentic glomerulonephritis (CrGN) with limited data available in adult Indian population. AIM: This study aims to identify the aetiology, clinico-pathological features and outcomes of diffuse CrGN in south Indian population. MATERIALS AND METHODS: In this retrospective study, clinical records of all adults (>18 years) over a 5-year period (2010-2014) with a histopathological diagnosis of diffuse CrGN (>50% crescents) were reviewed. Clinical, serological, biochemical and histopathological data were collected. Follow-up data at six months including renal outcome and mortality were studied. Data was analysed using SPSS version 15. RESULTS: There were 29 cases of diffuse CrGN accounting for an incidence of 2.9% among 1016 non-transplant kidney biopsies. The most common cause was pauci-immune crescentic GN. The median creatinine at admission was 7.2 mg/dl {(interquartile range (IR) 3.3 - 10.4)} and 75.9% of patients required haemodialysis at admission. Complete/partial recovery was seen in 34.5%. At the end of six months 31% were dialysis dependent and the mortality was 27.6%. On univariate analysis, the significant predictors of renal loss and mortality were oliguria (p=0.02), requirement of haemodialysis and serum creatinine (p=0.001) at admission (>5.5mg/dl) (p=0.003). Histopathological features did not influence the outcome in our study. CONCLUSION: In our cohort, the most common cause for diffuse CrGN is pauci-immune CrGN. Diffuse CrGN carries a poor prognosis. Patients with pauci-immune and AntiGBM disease have worst prognosis compared to immune complex CrGN. The presence of oliguria, high serum creatinine and requirement of haemodialysis at admission are associated with poor outcomes.