Cyclosporine A inhibition of microcystin toxins

Cyclosporine A (CyA) given i.v. at a dose of 1.25 mg/mouse blocks a subsequent i.v. lethal dose (1.7-1.8 x LD50) of microcystin-LR for 24 hr, and is about 50% protective at 48 hr. Conversely, the fraction of mice that can be rescued by CyA (0.2 mg/mouse) after a lethal dose of microcystin-LR decreases rapidly with a pharmacodynamic half-time of only about 100 sec. The prophylactic action of CyA was tested against lethal doses of four microcystins. The acute lethality of 1.7-1.8 x LD50 dose of microcystin-LR, -RR, -LY, or -LA given 1 hr after administration of 0.2 mg of CyA is 0%, 0%, 58%, or 100%, respectively. Even a 0.6 mg/mouse dose of CyA is ineffective prophylaxis against a lethal dose of microcystin-LA. The inhibitory potency of CyA on microcystin toxicity can be completely reversed by the single L-amino acid substitution of alanine for arginine in the microcystin.     

Bile acid profile as early indicator of allograft function during orthotopic liver transplantation

Orthotopic liver transplantation was performed in 20 pigs. Serum total bile acids (STBA) were determined and their profile compared with standard early function parameters: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid. In phase I, the STBA level was 32.89 +/- 1.29 mumol/l. In phase II, STBA accumulated to 84.46 +/- 15.25 mumol/l (p less than 0.01), followed by hepatic clearance in phase III (63.61 +/- 9.71 mumol/1; NS). Between phase III and 6- and 12-hour samples, STBA decreased progressively, reaching values of 33.63 +/- 7.05 mumol/l at 24 h. AST was elevated in phases I, II, III, and at 6, 12 and 24 h (p less than 0.001), as was ALT (but with insignificant differences). Thus, STBA and their profile appear to be earlier and more specific indicators of early graft function than conventional parameters.     

Basic and clinical studies on norfloxacin in the pediatric field

Pharmacokinetic , bacteriological and clinical studies on norfloxacin (NFLX), a quinolone-carboxylic acid antibacterial agent, were conducted in the pediatric field. 1. Serum concentrations and urinary excretion of NFLX after single dose of 2.2 approximately 5.6 mg/kg (mean 4.4 +/- 1.2 mg/kg) were determined in 13 children with ages between 6 and 11 years. The mean peak serum concentration of the drug was 0.37 +/- 0.20 micrograms/ml at 2 hours after administration. The mean half-life of the drug in serum was 2.8 +/- 0.4 hours and the serum concentration at 8 hours was 0.11 +/- 0.06 micrograms/ml. The mean urinary concentration reached a maximum of 125.2 +2- 166.2 micrograms/ml in pooled urine from 0 to 2 hours and the mean urinary recovery rate in the first 8 hours after administration was 22.1 +/- 6.0%. A dose-response relationship was observed between doses/body weight and peak serum concentrations. 2. The clinical efficacy, bacteriological efficacy and the safety of NFLX were evaluated in 65 pediatric patients with ages between 2 years 10 months and 15 years 7 months with infections. In 62 assessable cases (acute purulent tonsillitis 9 cases, acute pneumonia 3 cases, chronic rhinitis 1 case, urinary tract infections 15 cases, and acute colitis 34 cases), clinical efficacies were excellent in 48 cases, good in 13 cases, and fair in 1 case with an overall efficacy rate of 98.4%. Staphylococcus aureus 1 strain, Staphylococcus epidermidis 1 strain, Escherichia coli 10 strains, Salmonella sp. 5 strains, Morganella morganii 1 strain, Pseudomonas aeruginosa 3 strains, Haemophilus parainfluenzae 1 strain and Campylobacter jejuni 12 strains were isolated from the patients as pathogens. Bacteriologically, all of these strains were eradicated except that 3 strains of C. jejuni only decreased. With regard to side effects, dizziness and nausea were observed in 1 case each but they were slight and the continuation of the treatment was possible. No abnormal laboratory test data were observed. From the above results, NFLX was considered to be a useful drug for the treatment of pediatric infections.     

Posterior urethral valves in patients with Down syndrome

Renal and urological anomalies in Down syndrome (DS) have received little attention compared with the nephrourological findings described in other chromosomal abnormalities. Renal hypoplasia, hydroureteronephrosis, ureterovesical and ureteropelvic junction obstruction, and vesicoureteral reflux, but not posterior urethral valves, have been associated with DS. We report the occurrence of posterior urethral valves in three male infants with DS at a single institution. All had multiple urological procedures for correction or palliation of obstruction. Children with DS may have an increased risk for developing posterior urethral valves and obstructive uropathy. Furthermore, they may also develop chronic renal failure secondary to posterior urethral valves. Therefore, we suggests that infants with DS be screened with ultrasonography for renal and urological abnormalities early in life and, if abnormal, a contrast voiding cystourethrogram be performed to rule out posterior urethral valves or other bladder or urethral abnormalities. A review of the renal and urological anomalies in DS reported in the literature since 1960 is presented.     

Separation of phagocytic leukocytes from the peripheral blood of chickens

Phagocytic leukocytes were separated from the peripheral blood of chickens using a one-step Percoll density gradient technique. Heterophils recovered from two fractions of the gradient were of 96.9 to 99.8% purity and were fully viable and functional, as demonstrated by their capacity to phagocytose latex beads and staphylococci. Adherent mononuclear cells were cultured from specific gradient fractions and shown to phagocytose staphylococci.