Comparison of immunoblot analysis of emergent multidrug-resistant Salmonella typhimurium definitive phage type 104 with a non-multidrug-resistant definitive phage type 104 strain.

BACKGROUND AND PURPOSE: The emergent multidrug-resistant (MDR) Salmonella typhimurium definitive phage type 104 (DT104) is a public and veterinary health problem not only due to its wide host range and potential for enhanced virulence, but also the difficulty associated with its control. There is thus a need to investigate possible antigens of MDR DT104. METHODS: Using standard protocols, whole cell lysates, outer membrane extracts and cell-free ultracentrifuge supernatants of selected isolates of MDR DT104 were prepared, electrophoretically separated and tested for their antigen-antibody reactivity in comparison with a non-MDR DT104 strain. RESULTS: Protein antigens of both strain types were recognized by antibodies in chick serum in a similar manner for all methods of antigen preparation used. CONCLUSIONS: This study did not find differences between the antibody recognition of MDR DT104 and that of the non-MDR DT104 strain tested. This observation should strengthen the quest for the possible use of vaccines to control this emergent strain in poultry.     

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.     

Memory impairment in patients with cirrhosis

BACKGROUND AND AIM: Subclinical hepatic encephalopathy (HE) in cirrhotic patients is usually characterized by memory impairment and psychomotor slowing. Our aim was to investigate memory status in cirrhotic patients with and without clinically overt HE. MATERIAL AND METHODS: Thirty-two cirrhotic patients (10 female and 22 male) aged 49 +/- 17 years and 20 healthy subjects (six female and 14 male) aged 46 +/- 12 years were included in the study. Memory status was defined by Wechsler Memory Scale, verbal memory process and complex memory process tests. RESULTS: Grade-1 HE was detected in 7 (22%) patients with cirrhosis. We detected 36 to 92% decrement in various memory tests in cirrhotic patients without HE as compared to healthy subjects. The scores for all psychometric testing results were significantly lower in cirrhotic patients without HE as compared to healthy subjects. We detected 42.9 to 100% decrement in various memory tests in cirrhotic patients with HE than cirrhotic patients without HE. However, there was no statistical significant difference between cirrhotic patients with and without HE. There was no statistical significant difference in cirrhotic patients with Child-Pugh A, B, and C. CONCLUSION: In conclusion, memory status was influenced in which patients with cirrhosis yet has a normal mental and neurological status to routine clinical examination (subclinical HE). Occasionally, decreased memory performance may adversely affect the satisfaction and lifestyle of these patients. Therefore, subclinical HE is an important social problem.     

Neuraminidase produces a decrease of adherence of slime-forming <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> to gelatin-impregnated polyester fiber graft fabric: an experimental study

Because slime-forming microorganisms are the major causative agents of graft infections, we aimed to investigate bacterial adherence in slime-forming and nonslime-forming Staphylococcus aureus and to determine the role of neuraminidase (NANase) on adherence to gelatin-impregnated polyester fiber graft fabric. An in vitro model was developed to quantitatively measure bacterial adherence to the surface of the graft. The grafts were divided into two groups – those colonized with slime-forming S. aureus and those colonized with nonslime-forming S. aureus. The grafts were put into sterile tubes and human plasma was instilled and incubated at 37°C to perform fibrin deposition on the grafts. After 48 h of incubation, grafts were drained and inoculated with slime-forming or nonslime-forming S. aureus in triptic soy broth in the presence or absence of NANase. Following 36 h of incubation at 36°C, grafts were vortexed and cultured to perform a colony count. Bacterial counts were expressed as total colony-forming units per square centimeter of graft. Slime-forming S. aureus had greater affinity with the graft compared with nonslime-forming S. aureus (P < 0.05). The adherence of slime-forming S. aureus was impaired by NANase treatment (P < 0.001) but NANase treatment of nonslime-forming S. aureus did not change the adherence to the graft (P > 0.05). These results show that slime plays an important role in the pathogenesis of vascular graft infection. Adherence of slime-forming S. aureus can be decreased by NANase treatment. This may have implications for the development of neuraminidase-embedded vascular grafts to diminish biomaterial-related infections.     

Critical stages of tumor growth regulation in transgenic mice harboring a hepatocellular carcinoma revealed by distinct patterns of tumor necrosis factor-alpha and transforming growth factor-beta mRNA production

There is now good evidence that cytokines contribute to the regulation of tumor growth. The cytokine-driven modulation of tumor growth was investigated during the progression of a hepatocellular carcinoma (HCC) in SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of liver growth correlated with increased transforming growth factor (TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis factor (TNF)-alpha mRNA were detected earlier during tumor development. Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2, IL-4 and IFN-gamma mRNA production could be reported. In vitro, hepatocyte-like tumor cell lines established at two stages, either before or after HCC differentiation, were characterized. The early-stage-derived cell line produced TNF-alpha mRNA, but had barely detectable expression of TGF-beta 1 mRNA, while later-stage- derived cell lines showed the reciprocal pattern. All cell lines displayed a lack of sensitivity to TNF-alpha, although some degree of sensitivity to TNF-alpha could be observed in the presence of actinomycin-D or after treatment with IFN-gamma. The early-stage- derived cell line was sensitive to the growth inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines displayed a loss of sensitivity to TGF-beta 1 which correlated with the increased expression of TGF-beta 1 mRNA. Altogether, this suggests that tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression patterns during HCC progression. This model of HCC could be of valuable interest to assess the impact of various immunotherapeutic strategies on modulation of tumor growth.      

Removal of hydrosalpinges increases endometrial leukaemia inhibitory factor (LIF) expression at the time of the implantation window

BACKGROUND: The presence of hydrosalpinges is associated with lower implantation and pregnancy rates in women undergoing IVF-embryo transfer, while salpingectomy improves these parameters. Although the mechanism by which hydrosalpinges affects fertility is not entirely understood, an adverse effect on endometrial receptivity has been postulated. In this study, we hypothesized that the adverse effects of hydrosalpinges on fertility may be in part mediated by inappropriate endometrial expression of leukaemia inhibitory factor (LIF), a cytokine implicated in implantation. METHODS: In order to test our hypothesis, we prospectively examined the expression of LIF during the window of implantation in the endometrium of infertile women (n = 10) with hydrosalpinges prior to and following salpingectomy and of fertile controls (n = 10) by Western blotting and immunohistochemistry. RESULTS: LIF expression was significantly lower in infertile women with hydrosalpinges compared with fertile controls (P < 0.05). Salpingectomy resulted in an increase in LIF expression in eight out of 10 women with hydrosalpinges. LIF levels were increased by 231 +/-49% (mean +/- SEM) following salpingectomy. Immunohistochemical analysis confirmed the Western blot findings. The increased LIF immunoreactivity was predominantly localized to luminal and glandular epithelial cells. CONCLUSIONS: Our findings suggest that observed benefit from salpingectomy in infertile women with hydrosalpinges may be in part mediated by the up-regulation of endometrial LIF expression.     

Dose-intensive therapy for extensive-stage small cell lung cancer and extrapulmonary small cell carcinoma: long-term outcome.

Treatment for extensive-stage small cell lung cancer (ES SCLC) or extrapulmonary small cell carcinoma (EPSC) is typically palliative. We set out to determine progression-free survival (PFS) and overall long-term survival of ES SCLC and EPSC patients, physiologically aged < or = 60 years, responding to first-line chemotherapy followed by high-dose combination alkylating agents with hematologic stem cell support. Patients in first-line chemotherapy response underwent stem cell collection (marrow, peripheral blood progenitor cells, or both) followed by high-dose therapy with 1 of 2 regimens: CBP (cyclophosphamide, cisplatin, and carmustine) or ICE (ifosfamide, carboplatin, and etoposide) with or without etanidazole. Involved-field radiotherapy was given to selected patients with oligometastatic disease distributed in sites allowing for reasonable radiation ports, and prophylactic cranial radiotherapy was given upon recovery to patients in complete response (CR) or near-CR. A total of 36 patients were treated. Of 29 patients with ES SCLC, 6 (21%) had achieved CR, 18 near-CR, and 5 partial response prior to high-dose therapy. Of 7 patients with EPSC, 3 (43%) had achieved CR, 3 had achieved near-CR, and 1 had progression of disease prior to high-dose therapy. Thirteen ES SCLC patients received high-dose CBP. Of the remaining 23 patients with SCLC or EPSC, 17 were treated with ICE and 6 with ICE plus etanidazole, a hypoxic cell sensitizer. Treatment-related mortality was 11% (4 of 36 patients). For all patients, the median event-free survival (EFS) was 5 months. The 2- and 5-year survivals after intensification were 12% (95% confidence interval [CI], 5%-31%) and 9% (95% CI, 3%-27%), respectively. Of the 30 patients in or near CR prior to high-dose therapy, 5 remain continuously progression-free (2 ES SCLC, 3 EPSC) for a median of 55 months (range, 1-96 months) after high-dose therapy. By multivariate analysis, factors associated with more favorable EFS were the use of a more aggressive induction regimen (ICE), and the EPSC histology. These factors were also associated with more favorable overall survival. Other factors associated with more favorable overall survival were the use of short induction therapy (< or = 4 cycles) and younger age (<50 years). Except for high-dose ICE with etanidazole, the use of high-dose systemic therapy in ES SCLC and EPSC was associated with low treatment-related morbidity and mortality over the past 5 years. Late complications were infrequent, and most patients returned to full-time work and activity, barring disease recurrence. Nonetheless, few patients with ES SCLC have progression-free long-term survival. We conclude that high-dose therapy is not indicated as an approach for ES SCLC, except as part of an investigative trial. Conversely, 3 of the 7 patients with EPSC remain relapse-free (range, 1-96 months), warranting further phase II evaluation of this approach in this population.     

Hypoglycaemic Activity of Nauclea Latifolia Sm. (Rubiaceae) in Experimental Animals

Aqueous, ethanolic and hexane extracts of the leaves of Nauclea latifolia (Rubiaceae) were assessed for their fasting blood glucose lowering effect in normoglycaemic and streptozotocin - diabetic rats. Wistar strain albino rats were given different doses of the extracts after 18 hrs fast and their blood glucose measured at 0,1,2,4 and 6 hours after treatment. The aqueous and ethanolic extracts significantly lowered the fasting blood glucose levels of the STZ-diabetic rats in a dose-dependent manner. The highest dose administered (400mg/kg) lowered the fasting blood glucose of the diabetic rats by 31.7% (aqueous) and 36.1% (ethanolic) extracts. The aqueous extract did not significantly lower the glucose levels of normoglycaemic rats (maximum 6.6%), nor was any significant decrease seen in the rats administered with the hexane (maximum of 4.0% for normoglycaemic and 2.4% for diabetics) extract. The hypoglycaemic and antihyperglycaemic potentials of the aqueous and ethanolic extracts were comparable to that of glibenclamide (1mg/kg).These results further support the traditional use of the plant in the treatment of diabetes mellitus.