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

The effects of intrathecal midazolam on the duration of analgesia in patients undergoing knee arthroscopy

Background: Spinal anaesthesia is a common anaesthetic technique for lower limb surgery. Many adjuvants have been tried to prolong the duration of analgesia provided by local anaesthetics when administered intrathecally. Midazolam has been shown to prolong the duration of analgesia when used as an adjuvant, providing the added advantages of mild sedation and amnesia, while being devoid of neurotoxicity, and the adverse effects of opioids. This study was designed to evaluate the effect of 2 mg preservative-free intrathecal midazolam added to spinal bupivacaine during postoperative analgesia, and the incidence of adverse effects, if any, in patients undergoing knee arthroscopies. Method: Fifty consenting American Society of Anesthesiologists (ASA) physical status I or II patients of either gender (men = 19, women = 31), aged between 18-56 years, were randomly allocated to two groups (25 each). Group M received 0.5% hyperbaric bupivacaine with preservative-free midazolam 2 mg intrathecally, and Group S received 0.5% hyperbaric bupivacaine with saline intrathecally. Peak sensory level, total duration of analgesia, duration of motor blockade, pain score using the Visual Analogue Scale, and sedation score using the Observer Assessment Score of Sedation were assessed, along with vital parameters, namely heart rate and systolic, diastolic and mean blood pressure. Results: The total duration of analgesia observed was significantly higher in Group M (399 &plusmn; 88.11 minutes) vs. Group S (301.60 &plusmn; 110.14 minutes), and the pain score was lower in Group M (33.6 &plusmn; 4.68 mm) vs. Group S (56.6 &plusmn; 8.64 mm). Conclusion: The addition of preservative-free midazolam 2 mg to intrathecal 0.5% hyperbaric bupivacaine prolongs the duration of analgesia without any observed adverse effects in patients undergoing knee arthroscopies.Keywords: intrathecal midazolam, spinal anaesthesi

Irreversible renal damage after transient renin-angiotensin system stimulation:involvement of an AT1-receptor mediated immune response

Transient activation of the renin-angiotensin system (RAS) induces irreversible renal damage causing sustained elevation in blood pressure (BP) in Cyp1a1-Ren2 transgenic rats. In our current study we hypothesized that activation of the AT1-receptor (AT1R) leads to a T-cell response causing irreversible impairment of renal function and hypertension. Cyp1a1-Ren2 rats harbor a construct for activation of the RAS by indole-3-carbinol (I3C). Rats were fed a I3C diet between 4-8 weeks of age to induce hypertension. Next, I3C was withdrawn and rats were followed-up for another 12 weeks. Additional groups received losartan (20 mg/kg/day) or hydralazine (100 mg/kg/day) treatment between 4-8 weeks. Rats were placed for 24h in metabolic cages before determining BP at week 8, 12 and 20. At these ages, subsets of animals were sacrificed and the presence of kidney T-cell subpopulations was investigated by immunohistochemistry and molecular marker analysis. The development of sustained hypertension was completely prevented by losartan, whereas hydralazine only caused a partial decrease in BP. Markers of renal damage: KIM-1 and osteopontin were highly expressed in urine and kidney samples of I3C-treated rats, even until 20 weeks of age. Additionally, renal expression of regulatory-T cells (Tregs) was highly increased in I3C-treated rats, whereas the expression of T-helper 1 (Th1) cells demonstrated a strong decrease. Losartan prevented these effects completely, whereas hydralazine was unable to affect these changes. In young Cyp1a1-Ren2 rats AT1R activation leads to induction of an immune response, causing a shift from Th1-cells to Tregs, contributing to the development of irreversible renal damage and hypertension

Bearing capacity improvement using micropiles a case study

Micropiles have been used effectively in many applications of ground improvement to increase the bearing capacity and reduce the settlements particularly in strengthening the existing foundations. Frictional resistance between the surface of the pile and soil and the associated group/network effects of micropiles are considered as the possible mechanism for improvement. This paper deals with a case study in which micropiles of 100 mm diameter and 4 m long have been used to improve the bearing capacity of foundation soil and in the rehabilitation of the total building foundation system. The micropiles were inserted around the individual footings at inclination of 70 degrees with the horizontal. The actual design for retrofitting was based on the assumption that the vertical component of the frictional force between the soil and the micropile resists the additional load coming from the structure over and above the bearing capacity. The technique was successful and the structure did not show any signs of distress later. Detailed finite element analysis conducted validated the suggested treatment. The paper describes the case study, the method of treatment adopted in the field and the results of numerical analysis