The role of N-acetylcysteine (NAC), a glutathione (GSH) precursor, was investigated in protection against isoniazid-(INH) and rifampicin-(RIF) induced oxidative hepatic injury in young Wistar rats. The hepatotoxic dose of INH and RIF was 50 mg kg-1 day-1 each and the hepatoprotective dose of NAC was 100 mg kgday-. All drugs were administered intraperitoneally (i.p.) in sterile water (4.0 ml kg-1 day-1) over a period of 3 weeks. Status of oxidative/antioxidative profiles was the mechanistic approach to assess the hepatotoxicity and/or hepatoprotection. The oxidative injury in INH-RIF co-exposed animals was closely associated with significant decline of GSH and related thiols, as well as with compromised antioxidant enzyme system. The oxidative stress was further supported by increased lipid peroxidation observed in these animals. The co-administration of NAC prevented the induction of oxidative stress in INH-RIF co-exposed animals. The amelioration of oxidative stress by NAC was faithfully reflected as normal morphology in these animals, except the presence of mild degree of portal triaditis in one animal co-exposed to INH-RIF and NAC. In contrast, the animals co-exposed to INH-RIF alone showed histological lesions which ranged from intralobular inflammation to patchy necrosis. These results suggest that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by NAC.

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Introduction: The treatment of large complete staghorn calculi requires a sandwich combination of percutaneous nephrolithotomy (PCNL) and shockwave lithotripsy (SWL) or sometimes open surgery. Many urologists hesitate to place more than 2–3 tracts during PCNL because of the belief that this may increase complications. We present data to support multi-tract PCNL for large (surface area >3,000 mm²) complete staghorn calculi. Patients and Methods: From July 1998 to October 2003, 121 renal units (103 patients) with large complete staghorn renal calculi were treated with PCNL. All procedures were performed in the prone position after retrograde ureteral catheterization. Fluoroscopy-guided punctures were made by the urologist followed by track dilation to 34 french. When multiple tracts were anticipated all punctures were usually made at the outset and preplaced wires were put into the collecting system or down the ureter. Stones were fragmented and removed using a combination of pneumatic lithotripsy and suction. Postoperative stone clearance was documented on X-ray KUB. Results: 121 renal units of 103 patients (15 women and 88 men, mean age 43 years) were treated. Six patients had associated bladder calculi that were treated simultaneously. The stone surface area was 3,089–6,012 (mean 4,800) mm². 10 patients (9.7%) had renal insufficiency with a mean (range) serum creatinine of 3.0 (1.5–5.5) mg/dl. The number of tracts required per patient were 2 tracts in 11, 3 tracts in 68, 4 tracts in 39, and 5 tracts in 3, giving a total of 397 tracts in 121 renal units, over a total of 140 procedures (including second-look procedures in 19 renal units). The points of entry of these tracts were 121 upper calyx (30.4%), 178 middle calyx (44.8%), and 98 lower calyx (24.6%). All 121 units had one upper polar access tract of which 92 (76%) were supracostal. Complications were blood transfusion (n = 18), pseudoaneurysm (n = 2), fever (n = 22), septic shock (n = 1) and hydrothorax (n = 3). PCNL monotherapy achieved an 84% complete clearance rate that improved to 94% with SWL in 8 renal units with small residual fragments. Stone compositions were calcium oxalate (91%), uric acid (2%) and mixed (7%). Conclusion: Aggressive PCNL monotherapy using multiple tracts is safe and effective, and should be the first option for massive renal staghorn calculi.

OBJECTIVESTo assess the efficacy of superior pole access for complex lower pole calyceal calculi. PATIENTS AND METHODSIn all, 102 patients with complex inferior calyceal calculi were included in a prospective unrandomized study. Complex inferior calyceal calculi were defined as multiple calculi in two or more inferior calyces of the lower polar group, with each calyx draining through a separate infundibulum and at an acute angle to each other. In 33 patients (32%; group 1) an inferior calyceal puncture was made and in 69 (68%; group 2) access was obtained through a superior calyceal puncture. The stone-free rates, decrease in haemoglobin, operative duration, requirement for additional tracts and second procedures in the two groups were compared. RESULTSStone clearance rates and blood loss values were better in group 2, although they were not significantly different. The mean operative duration, number of tracts required and the re-look procedure rate was significantly less in group 2. Two patients (3%) in group 2 had hydrothorax related to supracostal puncture and required chest tube insertion. CONCLUSIONSSuperior calyceal puncture (supracostal or infracostal) affords optimum access to complex inferior calyceal stones, providing faster and better clearance with a single puncture, and less requirement for secondlook procedures.

1. 4-Nitrophenyl 4'-(3-aza-2-oxoheptyl)phenyl carbonate (I), an amide conjugate (XI) involving the carboxy group of 4-nitrophenyl 4'-carboxymethylphenyl phosphate and an amino group of keyhole-limpet haemocyanin, and a fluorescein derivative (XVII) were synthesized. 2. The conjugate (XI) was used as an immunogen with which to raise polyclonal antibodies in multigeneration cross-bred sheep; the fluorescent derivative (XVII) was used for the initial assessment of the antisera via binding assays monitored by fluorescence polarization; the carbonate ester (I) was used as a chromogenic substrate for the investigation of catalytic activity. 3. The IgG from the antiserum of sheep no. 270 was isolated by Na2SO4 precipitation and chromatography on Protein G-Sepharose. 4. This preparation of IgG catalysed the hydrolysis of the carbonate ester (I); the catalysis at pH 8.0 and 25 degrees C obeyed Michaelis-Menten kinetics with at least 25 turnovers, Km = 3.34 microM, and lower limits for kcat. of 0.029 s-1 and for kcat./Km of 8.77 x 10(3) M-1.S-1, on the unlikely assumption that the concentration of catalytic antibody is provided by twice the total IgG concentration (two sites per molecule); probable estimates of the fraction of the total IgG that is anti-haptenic IgG and of the fraction of this that is catalytically active suggest that the values of kcat./Km are actually very much larger than these lower limits. 5. The failure of the antibody preparation to catalyse the hydrolysis of the isomeric 2-nitrophenyl carbonate (II), which differs from compound (I) only in the position of the nitro substituent in the leaving group, compels the view that catalytic activity is due to antibody rather than contaminant enzyme; this conclusion is supported by (a) the failure of the following to discriminate effectively between the isomeric substrates (I) and (II): pig liver carboxylesterase, rabbit liver carboxylesterase (collectively EC 3.1.1.1), whole serum from a non-immunized sheep and whole serum from a sheep immunized with a derivative of 3-O-methylnoradrenaline and (b) the lack of catalytic activity in IgG preparations from sheep immunized with sulphoxide or sulphone analogues of immunogen (XI). 6. The various parameters used for the comparison of the kinetic characteristics of hydrolytic catalytic antibodies are discussed. 7. The characteristics of hydrolysis of compound (I) catalysed by the present polyclonal antibody preparation are shown to be substantially better in most respects than those of analogous reactions of two other carbonate esters catalysed by monoclonal antibodies.