Evaluation of the mutagenic and cytotoxic effects of mercurous chloride by the micronuclei technique in golden Syrian hamsters

The aims of this study were to evaluate the mutagenic and cytotoxic activity of mercurous chloride by the micronucleus technique in vivo on the bone marrow of golden Syrian hamsters after a single i.p. drug administration. Forty male golden Syrian hamsters were classified into eight groups: negative control, positive control and six groups treated with different doses of mercurous chloride (1.25, 2.5, 5, 10, 20 and 40 mg/kg). The negative control was injected with physiological saline i.p. and the positive control with cyclophosphamide at a dose of 80 mg/kg i.p. With respect to mutagenic effect, the average number of micronucleated polychromatic erythrocytes (MPE) in hamsters treated with different doses of mercurous chloride was not significant compared with the negative control. With respect to cytotoxic effect, the average polychromatic erythrocyte/red blood cell ratio showed a significant decrease when the doses were higher than the 2.5 mg/kg dose compared with the negative control. In conclusion, this preliminary study shows a cytotoxic effect but not a mutagenic effect of calomel in vivo at one time point (24 h).     

Epitope mapping of the Brucella melitensis BP26 immunogenic protein: usefulness for diagnosis of sheep brucellosis

Sequencing of bp26, the gene encoding the Brucella sp. immunogenic BP26 periplasmic protein, was performed in the reference strains of Brucella abortus, B. suis, and B. ovis. The three bp26 sequences were almost identical to that published for B. melitensis 16M bp26, and only minor nucleotide substitutions, without modifying the amino acid sequence, were observed between species. The bp26 genes of the seven B. abortus biovar reference strains and B. abortus S19 and RB51 vaccine strains were also sequenced. Again, only minor differences were found. Surprisingly, the bp26 nucleotide sequence for B. abortus S19 was almost identical to that found for B. melitensis 16M and differed from the sequence described previously by others (O. L. Rossetti, A. I. Arese, M. L. Boschiroli, and S. L. Cravero, J. Clin. Microbiol. 34:165-169, 1996) for the same B. abortus strain. The epitope mapping of BP26, performed by using a panel of monoclonal antibodies and recombinant DNA techniques, allowed the identification of an immunodominant region of the protein interesting for the diagnosis of B. melitensis and B. ovis infection in sheep. A recombinant fusion protein containing this region of BP26 reacted indeed, in Western blotting, as the entire recombinant BP26 against sera from B. melitensis- or B. ovis-infected sheep while it avoided false-positive reactions observed with sera from Brucella-free sheep when using the entire recombinant BP26. Thus, use of this recombinant fusion protein instead the entire recombinant BP26 could improve the specific serological diagnosis of B. melitensis or B. ovis infection in sheep.     

Hyperthermia and maximal oxygen uptake in men and women

To compare the effect of hyperthermia on maximal oxygen uptake (O_2max) in men and women, O_2max was measured in 11 male and 11 female runners under seven conditions involving various ambient temperatures (T_a at 50% RH) and preheating designed to manipulate the esophageal (T_es) and mean skin temperatures at O_2max. The conditions were: 25°C, no preheating (control); 25, 35, 40, and 45°C, with exercise-induced preheating by a 20-min walk at ~33% of control O_2max; 45°C, no preheating; and 45°C, with passive preheating during which T_es and were increased to the same degree as at the end of the 20-min walk at 45°C. Compared to O_2max (l·min^–1) in the control condition (4.52±0.46 in men, 3.01±0.45 in women), O_2max in men and women was reduced with exercise-induced or passive preheating and increased T_a, ~4% at 35°C, ~9% at 40°C and ~18% at 45°C. Percentage reductions (7–36%) in physical performance (treadmill test time to exhaustion) were strongly related to reductions in O_2max (r=0.82–0.84). The effects of hyperthermia on O_2max and physical performance in men and women were almost identical. We conclude that men and women do not differ in their thermal responses to maximal exercise, or in the relationship of hyperthermia to reductions in O_2max and physical performance at high temperature. Data are reported as mean (SD) unless otherwise stated.     

Coordinated multivesicular release at a mammalian ribbon synapse

Traditional models of synaptic transmission hold that release sites within an active zone operate independently. Although the release of multiple vesicles (multivesicular release; MVR) from single active zones occurs at some central synapses, MVR is not thought to require coordination among release sites. Ribbon synapses seem to be optimized to release many vesicles over an extended period, but the dynamics of MVR at ribbon synapses is unknown. We examined MVR at a ribbon synapse in a retinal slice preparation using paired recordings from presynaptic rod bipolar and postsynaptic AII amacrine cells. When evoked release was highly desynchronized, discrete postsynaptic events were larger than quantal miniature excitatory postsynaptic currents (mEPSCs) but had the same time course. The amplitude of these multiquantal mEPSCs, which seem to arise from the essentially simultaneous release of multiple vesicles, was reduced by lowering release probability. The release synchrony reflected in these multivesicular events suggests that release within an active zone is coordinated during MVR.     

Use of UroLume as an alternative to the treatment of recurrent stenosis of bulbar urethra and obstructive prostatic hyperplasia in patients with high surgical risk

This device consists of a woven in a form of a tubular mesh, made up for the use in the urethra. We report the clinical and uroflujometric results in 10 patients with urethral stricture and 4 with obstructive prostatic hyperplasia. The study includes a 7 year period since October of 1993 up until June 2000. All patients were evaluated pre and post stent insertion with periodic follow ups to assess the prostatic symptoms score, quality of life assessment, peak urinary flow rate, mean flow rate and post-void residual urine volume. The results were the following: For the group with urethral stricture the I-PSS decreased from 26.8 to 5.4 points, the peak flow rate increased from 8.24 to 16.12 mL/sec and the post-void residual urine volume decreased from 42.7 to 31.6 mL. By 12-month follow-up most endoprostheses were 90% covered with urothelium, only one of these patients required stent extraction with no sphincter lesion. For the prosthatic hyperplasia group the I-PSS decreased from 20.2 to 8 points. The peak flow rate increased from 6.95 to 14.5 mL/sec and the post-void residual urine volume decreased from 49 to 18.3 mL. By 12-month follow-up two patients were 95% covered with epithelium, and the other two were 70%. There have not been significant problems related to infections, migration, incontinence or erectile disfunction. An 80% of patients have shown some irritative symptoms (urgency, frequency or dysuria) at least during the first month after stent insertion. These 7 year results suggest that Urolume urethral endoprostheses can be a long-term effective treatment alternative to these patients.     

Bruton tyrosine kinase gene mutations in Argentina

The block in differentiation from pro-B to pre-B cells results in a selective defect in the humoral immune response characteristic of human X-linked agammaglobulinemia (XLA). Mutations of Bruton tyrosine kinase (BTK) gene have been identified as the cause of XLA. Mutation detection is the most reliable method for making a definitive diagnosis, except when clinical and laboratory findings are distinctive and coupled with history of X-linked inheritance. To provide a definitive diagnosis to 40 families incorporated in the Argentinian Primary Immunodeficiencies Registry we analysed the BTK gene by SSCP analysis as screening method for XLA, followed by direct sequencing. The molecular defect was localized in 45 patients from 34 unrelated families. From the 34 independent mutations identified, 16 were previously undescribed, 31 were unique mutations, 22 were exonic single nucleotide changes (16 missense and 6 nonsense) and four intronic mutations. Because five families had clinical, immunological and inheritance data sufficient for a definitive diagnosis, our study allowed 37 patients from 29 families previously categorized probable/ possible XLA, have now definitive diagnosis leading to appropriate genetic counseling.     

Renal dysfunction after chronic blockade of nitric oxide synthesis

The effects of the chronic inhibition of nitric oxide (NO) on renal hemodynamics and tubular function were studied in rats treated for 8 weeks with the NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg/day). In addition, the effect of L-NAME administration on vasoactive systems (renin-angiotensin system, aldosterone, catecholamines, endothelin, and thromboxane A(2)) was evaluated. Chronic inhibition of NO significantly elevated blood pressure, reduced glomerular filtration rate and renal blood flow, blunted the pressure-diuresis-natriuresis response, and increased protein urine excretion. All these changes were associated with blunted nitrite production in response to acetylcholine in glomeruli. No changes were observed in the plasma levels of either renin activity, aldosterone, or endothelin in L-NAME-treated rats. Similarly, no differences were observed in the urinary excretion of thromboxane B(2) between both group of animals. By contrast, plasma concentrations of both epinephrine and norepinephrine were elevated in rats treated with L-NAME. In summary, the results show that chronic blockade of NO produced not only alterations in renal function, but also renal damage, suggesting an important renoprotective role of NO. An activation of sympathoadrenal system could participate in these renal alterations.     

Heat-shock protein (HSP70-2) allelic frequencies in three distinct Mexican populations

The major histocompatibility complex (MHC) genes are highly polymorphic and therefore have been useful in population genetics and disease association studies. We analyzed restriction fragment length polymorphism of HSP70-2 alleles in healthy unrelated Mestizo, Mazatecan and Nahua populations. Both Indian groups, Mazatecans and Nahuas, were in Hardy-Weinberg equilibrium, while Mestizos were in disequilibrium (chi 2 = 0.399; P < 0.05). The Mazatecan Indians presented a high frequency of BB homozygosity (17.35%) compared to Mestizos (5%) (P = 0.01). Mexican ethnic groups present differences in distribution of BB genotype. The low frequency of BB genotype in Mestizos may be the result of a negative selection process.     

Urothelial signet-ring cell carcinoma of the renal pelvis with collagenous spherulosis: a case report

We present a unique case of urothelial carcinoma of the right renal pelvis. It occurred in a 58-year-old woman. The tumor was located in the renal pelvis with extension into the adjacent renal medulla and cortex. Two years after surgical excision the patient is free of recurrence and metastasis. The tumor was well demarcated, without capsule, firm, solid, and whitish on the cut surface. It was 3x4 cm in largest diameter and without signs of necroses and hemorrhages. The tumor did not infiltrate the ureter. Histologically the predominant pattern of the tumor was adenocarcinomatous differentiation, and only very rare foci of urothelial carcinoma composed of typical transitional cells were found. No signs of intestinal type of metaplasia and adenocarcinoma, changes similar to the cystitis cystica or cystitis glandularis, were found in the tumor or in its vicinity. Most of the tumor looked like solid nests composed of cells with intracytoplasmic lumens. The resulting appearance was that of typical signet-ring cell change. These solid nests were usually surrounded by columnar epithelium, which in many areas formed papillary structures. A very striking feature was formation of collagen spherules. Small collagen spherules were often surrounded by a layer of the neoplastic cells so that collagenous rosettes were formed. In some areas these collagenous spherules clustered together so that they formed areas of collagenous spherulosis. The collagen in the spherules reacted positively with collagen IV. Ultrastructurally these spherules were formed by basal membrane-like material. Intracytoplasmic lumens of the signet-ring cell change were endowed by slender microvilli at ultrastructural level.