Apoptosis as a mechanism of natural resistance to HIV-1 infection in an exposed but uninfected population.

BACKGROUND: Apoptosis, also known as programmed cell death, has been reported not only as a pathogenic mechanism, but also as a mechanism of resistance and control of a variety of infections. Particularly during HIV-1 infection, apoptosis is the main mechanism by which infected and uninfected CD4+ lymphocytes are eliminated. However, apoptosis as a mechanism of natural resistance to HIV infection has this far not been explored. OBJECTIVE: To determine whether apoptosis could explain, at least in part, the natural resistance to HIV infection observed in some exposed but uninfected individuals (ESN). RESULTS: Our data shows that peripheral blood monocytes in the ESN group has a predisposition to undergo spontaneous apoptosis, as well as apoptosis induced by HIV infection in vitro, compared with monocyte population from the control group at low risk of HIV infection. CONCLUSIONS: These findings suggest that, in some ESN individuals, monocytes could play an important role in the control of HIV infection by undergoing apoptosis. However, since the variability among individuals is large, studies with larger cohorts focusing in monocyte apoptosis as pathogenic mechanisms are required.     

Resistance of Helicobacter pylori to antimicrobial treatment in a Seville hospital catchment area.

AIM: To determine the sensitivity to metronidazol, clarithromycin, amoxicillin and tetracycline of strains of Helicobacter pylori isolated in a prospective series of patients referred to a university hospital in Seville for endoscopic examination. METHODS: During the period from March 1998 to July 1999 we studied 117 patients with ulcer. The diagnosis of bacterial infection was based on the rapid urease test, histological study, Gram staining or culture of gastric biopsy material (from the antrum and corpus) obtained during gastroscopy. Susceptibility studies were done with the diffusion method using E-test strips. RESULTS: Helicobacter pylori infection was found in 64 patients. A total of 58 strains were grown, 40 of which were from patients who had received no previous treatment to eradicate the infection (69%), and 18 of which were from patients who had failed one or more eradication therapies (31%). In the first group, metronidazol resistance was found in 42%, clarithromycin resistance in 13%, and resistance to both in 10% of the patients. In the second group these rates were 39%, 44% and 17% respectively, and one strain was found which was also resistant to tetracyclines (2%). No strains resistant to amoxicillin were found. CONCLUSIONS: We found high rates of resistance, especially to clarithromycin, and especially in patients who had received previous eradication therapy. Empirical treatments should use effective antimicrobials and avoid regimens based on a single antibiotic. Culture of gastric biopsy samples provides information on the resistance to antimicrobials in a given setting, and this information can be used to develop the most rational treatment for the infection.     

Characterization of mast cell subpopulations in lip cancer

BACKGROUND: Lip squamous cell carcinoma (SCC) is the most common form of oral cancer. Human mast cells (MCs), which are increased in lip SCC, are classified by their protease content in tryptase-positive (MC(T)) and tryptase/chymase-positive (MC(TC)). MC proteases are associated with tumor progression and angiogenesis. The aim of this study was to quantify and characterize MC subpopulations in lip SCC. METHODS: Serial sections from lip SCC (n = 21) and normal lip vermilion (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC subpopulation density and distribution. RESULTS: MC(T) and MC(TC) were increased in lip SCC when compared with normal lip (P < 0.0001), where MC(T) predominated over MC(TC) (P < 0.01). In lip SCC neither subpopulation predominated. Regarding distribution, MC(T) were higher than MC(TC) at the intratumoral stroma, whereas MC(TC) were higher than MC(T) at the peritumoral stroma (P < 0.01). CONCLUSIONS: The results suggest that MC subpopulations may contribute to lip SCC progression. While intratumoral MC(T) may stimulate angiogenesis, peritumoral MC(TC) may promote extracellular matrix degradation and tumor progression at the invasion front.     

Traumatic colonic perforation: Review of 16 years' experience

The surgical management of colon injuries in civilian practice requires individualization. Primary repair, either by debridement and suture or resection and anastomosis, is a safe method of management in selected cases and results in a shorter hospital stay, less morbidity and a complication rate that is no higher. In this series, over half of the colon injuries were managed in this way. Exteriorization and proximal colostomy are accepted methods of management, but possibly should be reserved for the more severely injured patient. The criteria for individualization are briefly summarized.     

Radioprotection of mouse skin by WR-2721 in single and fractionated treatments

The radioprotective action of WR-2721 on mouse skin has been studied using single doses, two and five fractions. Significant radioprotection was observed with 200-500 mg/kg, in animals breathing air or oxygen at the time of irradiation. The degree of radioprotection increased with increasing dose, and was significantly greater in air than in oxygen, especially at low drug doses. Cumulative drug toxicity limited the fractionated treatments to lower drug doses, but the protection observed was similar to that seen with single doses at the same drug levels. The protection factors observed are lower than many published values for skin, and we conclude that a single protection factor cannot yet be stated for any dose of WR-2721. Local tissue oxygenation may account for some of the discrepancies in different studies.     

Transgenic mice expressing cyan fluorescent protein as a reporter strain to detect the effects of rotenone toxicity on retinal ganglion cells

This is the first study using a reporter transgenic model to investigate the effects of an environmental toxin on the retina. Rotenone is a widely used pesticide that inhibits mitochondrial complex I and produces neurotoxicity. Previous studies demonstrated the time course and dose response of rotenone toxicity on retinal ganglion cells (RGC). However, previous analyses of rotenone-induced retinotoxicity provided little detail of the optic nerve axons and cellular pathology. These limitations were successfully surmounted by using a transgenic mouse line shown to express cyan fluorescent protein (CFP) in neurons, including RGC, under regulatory elements of the human the thy1.1 promoter (thy-CFP). Data showed that CFP expression is limited to RGC and their processes in the retina of thy-CFP mice. Eyes exposed to the pesticide rotenone displayed marked alterations in RGC morphology, inner plexiform layer, optic disc, and optic nerves. After 24 h, the number of CFP-labeled RGC was reduced 50%. Correlated with a loss of RGC bodies was an approximate 50% reduction in CFP fluorescence intensity at the optic disc. The findings showed that rotenone-induced degeneration of RGC and their processes can be visualized with exquisite detail in thy-CFP mice, and that this approach may provide a novel and effective way to monitor the association between environmental toxins and neurodegeneration in living animals.