Water quality criteria assessment for chlorinated benzenes using the quantitative structure activity relation approach and porphyrogenic endpoint in rats

Sub‐chronic toxicity data on rats for various chlorobenzenes have been utilized to show a high correlation between log dose porphyria and log P, the log of the octanol:water partition coefficient. Various predictive equations were calculated as a function of log P (log P)² log P + (log P)² log 1/S_W and (log 1/S_w)². All have good correlations except for the case of (log 1/S_w)². The calculated log criterion values obtained from predicted dose for porphyria in rats were regressed against log P and the log of the bioconcentration factor (log B) and various single and multi‐parameter regression equations were found. Criteria predicted from log P values and sub‐chronic toxicity data tended to be between 10–100 times larger than criteria calculated by other means (chronic toxicity, carcinogenicity or organoleptic). This quantitative structure activity relation approach has the advantage of providing criteria for all congeners in a series, whether or not they have been tested for carcinogenicity.     

The genetic and non-genetic toxicity of the fungicide Vinclozolin

The mutagenic/cocarcinogenic, potential of the fungicide Vinclozolinwas assessed by a comprehensive examinationof toxicity mechanismsat both the genetic and the metabolic level. Vinclozolin didnot induce any significant increase inchromosomal aberrationsin human pheripheral blood lymphocytes cultured in vitro, bothin the presence and in the absence of metabolic activation.However, significant dose-related increases in micronucleatederythrocytes (up to 4-fold over the control) were found in thebone marrow cells of mice 24 h after treatment with the fungicideover a range of concentrations from 312.5 to 1250 mg/kg. Themorphology and the size of micronuclei induced was suggestiveof a predominantly clastogenic mode of action. Several cytochromeP450 (CYP)-dependent reactions have been monitored in liver,kidney and lung microsomes of male and female Swiss Albino CD1mice in order to ascertain certain toxic non-genetic properties(related to carcinogenesis) of Vinclozolin. It was found tobe a selective inducer towards CYP 3A (liver, kidney) and 2E1(liver), as exemplified by the significant increases of thedemethylation of aminopyrine (APND, up to 2.3-fold, female liver),and hydroxylation ofp-nitrophenol (pNPH, up to 5.6-fold, maleliver). In general, however, Vinclozolin has a complex patternof induction and suppression of CYP-dependent enzymes, as shownfrom the reduced expression of various monooxygenases dependingupon dose, sex or organ considered. For example, pNPH activitywas suppressed in kidney (up to 48% loss, averaged between maleand female), whereas ethoxycoumarin O-deethylase was reducedin lung up to 53% in male (at the highest dose). These datawere sustained by means of Western immunoblotting using rabbitpolyclonal antibodies anti-CYP 3A and 2E1. Northern blottinganalysis using CYP 3A1/2 and 2E1 cDNA biotinylated probes showedthat the expression of such isozymes is regulated at the mRNAlevel. Taken together, the findings indicate the clastogenicactivity and the possible cotoxic, cocarcinogenic and promotingpotential of Vinclozolin. ⁴To whom correspondence should be addressed at: Department of Pharmacology, University of Bologna, Via Imeno 48, 40126 Bologna, Italy     

Crystal and molecular structure of 1,4-bis(chloroacetyl)-trans-2,5-dimethylpiperazine,a model compound of poly(trans-2,5-dimethyl-1,4-piperazinediylfumaroyl)

The molecular and crystal structure of 1,4-bis(chloroacetyl)-trans-2,5-dimethylpiperazine synthesized by us, was determined from X-ray diffractometer data. The structure was solved by Patterson and Fourier methods and refined by least-squares techniques to R 0,065 for 1081 independent reflections. The crystals are monoclinic, space group P2₁/n, with Z = 2 in a unit cell of dimensions: a = 9,486 (6), b = 9,139 (6), c = 7,036 (5) Å, β = 95,73 (10)°, the numbers in parentheses being the estimated standard deviations refering to the last significant digit. The trans-2,5-dimethylpiperazine ring is in a flattened-chair conformation with the side methyl groups in axial position. The atoms of the amide are nearly coplanar. It seems to be proved that the structure of the trans-2,5-dimethylpiperazine ring in poly(trans-2,5-dimethyl-1,4-piperazinediylfumaroyl) is similar to that found for 1,4-bis(chloroacetyl)-trans-2,5-dimethylpiperazine.     

Fast and safe closing of urethra during laparoscopic radical cystectomy

PURPOSE: To present a simple alternative technique to close the membranous urethra during laparoscopic radical cystectomy. PATIENTS AND METHODS: A series of 18 laparoscopy-assisted cystectomies were performed in our institute from November 2002 to May 2005. In order to prevent neoplastic-cell spillage, in 14 of these patients, the membranous urethra was closed with Hem-o-lok clips after careful dissection of the urethra and withdrawal of the bladder catheter. RESULTS: In all cases, one or two Hem-o-lok clips were easily, safely, and quickly positioned. The remaining length of the membranous urethra was sufficient for anastomosis with the neobladder if appropriate. In follow-up (mean 14 months), no local recurrence has been recorded. CONCLUSION: The closing of the membranous urethra with Hem-o-lok clips during laparoscopy-assisted cystectomy is in our experience a simple, fast, safe, and effective alternative that should be considered when laparoscopic radical cystectomy is performed.     

Genetic instability in Drosophila melanogaster: putative multiple insertion mutants at the singed bristle locus.

A series of eleven independent mutants at the X chromosome singed bristle (sn) locus of Drosophila melanogaster is described. All mutants descend from flies caught in the wild and bred in the laboratory. On the basis of their inordinately high spontaneous mutation frequency, ten of the mutants are classified as putative insertion mutants. Reversions to wild type occur at frequencies of 10(-4)-10(-3). Some reversions appear to be losses of the inserted element, others appear (by analogy with prokaryotes) to be changes in the orientation of the inserted elements. Consistent with the insertion hypothesis, some sn mutants generate what are interpreted to be deletions at the sn locus. In their mutational properties, the sn mutants are analogous to insertion sequence (IS) elements and bacteriophage Mu of Escherichia coli, but the precise nature of the insertion remains unknown.     

Chemical and antibacterial evaluation of Hypericum triquetrifolium Turra

Five extracts and pure compounds from the aerial parts of Hypericum triquetrifolium were tested for their antibacterial activity against 31 gram-positive and gram-negative strains using the agar dilution method (Lorian). The ethyl acetate extract exhibited a weak antibacterial activity against Staphylococcus strains, and pure constituents such as quercetin and I3,II8-biapigenin were the active components of this extract.     

Streptococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 287 cases

Background

There has not been a comprehensive, multi-centre study of streptococcal peritonitis in patients on peritoneal dialysis (PD) to date.

Methods

The predictors, treatment and clinical outcomes of streptococcal peritonitis were examined by binary logistic regression and multilevel, multivariate poisson regression in all Australian PD patients involving 66 centres between 2003 and 2006.

Results

Two hundred and eighty-seven episodes of streptococcal peritonitis (4.6% of all peritonitis episodes) occurred in 256 individuals. Its occurrence was independently predicted by Aboriginal or Torres Strait Islander racial origin. Compared with other organisms, streptococcal peritonitis was associated with significantly lower risks of relapse (3% vs 15%), catheter removal (10% vs 23%) and permanent haemodialysis transfer (9% vs 18%), as well as a shorter duration of hospitalisation (5 vs 6 days). Overall, 249 (87%) patients were successfully treated with antibiotics without experiencing relapse, catheter removal or death. The majority of streptococcal peritonitis episodes were treated with either intraperitoneal vancomycin (most common) or first-generation cephalosporins for a median period of 13 days (interquartile range 8–18 days). Initial empiric antibiotic choice did not influence outcomes.

Conclusion

Streptococcal peritonitis is a not infrequent complication of PD, which is more common in indigenous patients. When treated with either first-generation cephalosporins or vancomycin for a period of 2 weeks, streptococcal peritonitis is associated with lower risks of relapse, catheter removal and permanent haemodialysis transfer than other forms of PD-associated peritonitis.