Oxadiazolyl thiazolidinedione as a non-adipogenic PPAR-γ partial agonist and its effect on glucose homeostasis in type 2 diabetes.

The familiar glitazone anti-diabetics are thiazolidinedione derivatives, known to elicit action through full agonistic activity on PPAR-γ receptors. Full agonists are known for the side effect of weight gain, while partial agonists are weak to non-adipogenic compounds possessing anti-diabetic property. This work identified a new synthetic oxadiazolyl thiazolidinedione (OXTZD) as a ligand for PPAR-γ receptor with partial agonist activity and less transactivation potential compared to rosiglitazone through in-vitro PPAR-γ competitive binding assay and PPAR-γ transactivation-based luciferase reporter assay, respectively. OXTZD did not induce significant lipid accumulation when compared to differentiation control which contained insulin in PPAR-γ-dependent adipogenesis assay. In-vivo studies have proved that OXTZD effectively reduced blood glucose level in type 2 diabetic rats and also improved glucose tolerance and insulin sensitivity. After 15 days of oral treatment with OXTZD, rats did not gain weight, suggesting that OXTZD was effective in suppressing the weight gain. Molecular docking of OXTZD to PPAR-γ, predicted hydrogen bonds with SER342, ARG288, and CYS285 residues in arm III of the ligand binding domain which are unique to the partial agonists. Results of in-vitro, in-vivo, and docking studies were in good correlation to the fact that OXTZD is a PPAR-γ partial agonist having glucose-lowering property and lacks the side effect of weight gain. In conclusion, OXTZD could be developed as a therapeutic agent for diabetes and/or serve as a lead compound for further drug design studies targeting PPAR-γ for effective management of type 2 diabetes without inducing weight gain.

Penile reconstruction in a newborn following complicated circumcision: A case report.

INTRODUCTION: Grade V post-circumcision penile injury is known as "total phallic loss". It is usually seen with the use of mono-polar electro-cautery for circumcision resulting in penile necrosis. We report on a newborn treated by release of the subcutaneous corporal remnant and explain why this option should be considered of choice in cautery-related Grade V injuries. REPORT OF A CASE: A 25-day old Saudi Arabian newborn with Grade V penile injury underwent reconstruction at our tertiary-care center. Upon exploration, the remnant part of the penis under the suprapubic skin was 2.6 cm. This included the root of the penis (estimated to be 1.8 cm long in the newborn) as well as an extra 0.8 cm of corporal length from the pendulous part of the penis which has retracted under the skin. Full release of the suspensory ligament was done. The result at 6 months was satisfactory both functionally and cosmetically. DISCUSSION: Options of management of Grade V injuries include sex-reassignment, phallic reconstruction using flaps, and release of the subcutaneous corporal remnant. We demonstrate that the latter option should be considered of choice in cautery-related Grade V injuries because there is usually preservation of the most proximal part of the corpora of the shaft which becomes retracted under the skin. Hence, the released remnant is of adequate length. CONCLUSION: Post-circumcision Grade V penile injuries of the newborn are best reconstructed with release of the subcutaneous corporal remnant. The neophallus is erectile and has an acceptable length and appearance.

Relapse of B-cell acute lymphoblastic leukaemia presenting as right aural polyp with facial and mandibular nerves palsy.

A patient presenting with an ear polyp is a common finding in otorhinolaryngology practice. The common causes include chronic otitis media and cholesteatoma. We report an adult female patient with a history of acute leukaemia presenting with chronic otitis media symptoms and right ear polyp. She was subsequently diagnosed as relapse of B-cell acute lymphoblastic leukaemia based on histopathological examination. The presentation may be similar to an inflammatory pathology of the middle ear, making it misleading.

Laparoscopic versus open orchiopexy in the management of peeping testis: a multi-institutional prospective randomized study.

OBJECTIVE: Peeping testis is an inconsistently palpable/seen undescended testis that migrates back and forth at the internal inguinal ring. Both open and laparoscopic orchiopexy are effective forms of management. The present study aimed to evaluate the efficacy and safety of both approaches. PATIENTS AND METHODS: Between September 2007 and January 2012, 46 peeping inguinal testes were randomly treated with either open (25 cases) or laparoscopic (21 cases) orchiopexy procedures. Spermatic vessels were preserved for all cases. Operative details, postoperative morbidity and final testicular site and size were recorded. RESULTS: The median age of the children was 2.5 years (range 0.5-12.0). The follow-up period ranged from 1.0 to 5.5 years. Of these testes, 20 in the open surgery group and 19 in the laparoscopic group maintained correct intrascrotal position (P = 0.428). Re-do orchiopexy was indicated for two cases in the surgical group (P = 0.493). No cases of testicular atrophy or hernia were encountered. CONCLUSION: Open and laparoscopic orchiopexy procedures for peeping testes are fairly comparable. However, laparoscopy is relatively more effective, as two re-do orchiopexies were required in the open surgical group.