Glutathione-S-Transferase and Thiol Stress in patients with acute renal failure

Introduction: Tubular damage is common finding in acute renal failure (ARF). Various etiologies have been put forth to explain the tubular damage in ARF, one important mechanism among them is oxidative damage to renal tubules. Several biomolecules including low-molecular weight peptides and enzymes in urine have been proposed as early markers of renal failure. Current study has been undertaken to study the thiol stress and glutathione-S-transferase (GST) levels in ARF patients. Method: 58 ARF patients and 55 healthy controls were selected based on inclusion and exclusion criteria. Serum thiols, GST, malanoldehyde (MDA) and urine thiols were determined by spectrophotometer based methods. Results: Serum thiols and urine thiols were significantly decreased (p<0.0001), and serum GST and MDA levels were significantly increased (p<0.0001) in ARF patients compared to healthy controls. Serum GST and MDA correlated positively in ARF cases (r2 = 0.6938, p<0.0001). Conclusion: There is significant thiol stress and increased lipid peroxidation in ARF patients which leads to tubular cell membrane damage and release of GST into blood stream and into urine. This may be possible mechanism for the increased presence of GST in urine (enzymuria) found in other studie

Retro-trochanteric sciatica-like pain: current concept

The aim of this manuscript is to review the current knowledge in terms of retro-trochanteric pain syndrome, make recommendations for diagnosis and differential diagnosis and offer suggestions for treatment options. The terminology in the literature is confusing and these symptoms can be referred to as ‘greater trochanteric pain syndrome’, ‘trochanteric bursitis’ and ‘trochanteritis’, among other denominations. The authors focus on a special type of sciatica, i.e. retro-trochanteric pain radiating down to the lower extremity. The impact of different radiographic assessments is discussed. The authors recommend excluding pathology in the spine and pelvic area before following their suggested treatment algorithm for sciatica-like retro-trochanteric pain. Level of evidence II

Proteins, drug targets and the mechanisms they control : the simple truth about complex networks

Realizing the promise of molecularly targeted inhibitors for cancer therapy will require a new level of knowledge about how a drug target is wired into the control circuitry of a complex cellular network. Here we review general homeostatic principles of cellular networks that enable the cell to be resilient in the face of molecular perturbations, while at the same time being sensitive to subtle input signals. Insights into such mechanisms may facilitate the development of combination therapies that take advantage of the cellular control circuitry, with the aim of achieving higher efficacy at a lower drug dosage and with a reduced probability of drug-resistance development