The effect of granulocyte macrophage-colony stimulating factor on bacterial translocation after administration of 5-fluorouracil in rats

BACKGROUND: After surgical resection for colorectal carcinoma there is a high recurrence rate and, therefore, adjuvant chemotherapy may be useful in some patients. 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent in the management of patients with colorectal cancer. However, gastrointestinal injury induced by chemotherapeutic agents may result in bacterial translocation from the gut into the systemic circulation. Granulocyte macrophage-colony stimulating factor (GM-CSF) may be used to prevent this side effect by means of macrophage activity stimulation. MATERIALS AND METHODS: A total of 45 rats were divided into three groups. Control group received intraperitoneal saline solution, 5-FU and GM-CSF groups received 50 mg/kg/day 5-FU intravenous infusion and GM-CSF group also received 200 ng/day GM-CSF subcutaneously for 6 days. Intestinal tissue was also sampled for pathological examination at day 7. Plasma levels of tumor necrosis factor-alpha and interleukin-6 were determined, bacterial translocation was quantified by lymph node, liver and spleen culture, and plasma endotoxin content was measured. RESULTS: White blood cell counts of the 5-FU rats were significantly lower than in the control and GM-CSF groups (P < 0.01). The plasma endotoxin, tumor necrosis factor-alpha and interleukin-6 levels in the 5-FU and GM-CSF groups were significantly increased at day 7 compared with the control groups (P < 0.01), but these levels were significantly lower in the GM-CSF group compared to the 5-FU group (P < 0.01). 5-FU intervention caused significant increase in the frequencies of bacterial translocation at liver, spleen, mesenteric lymph node, and portal blood. Compared with 5-FU group, GM-CSF decreased the bacterial translocation (P < 0.01). CONCLUSIONS: This study observed that the administration of 5-FU resulted in bacterial translocation. Activation of inflammatory response with GM-CSF is highly effective in prevention of bacterial translocation in 5-FU interventions.     

Self-efficacy and its interrelation with family environment and metabolic control in Turkish adolescents with type 1 diabetes

To explore the relationship between self‐efficacy, family environment (cohesion and organization) and metabolic control. Research design and methods: A total of 100 adolescents with diabetes were assessed on a single occasion. Eligibility criteria were an age range of 11–18 yr, diagnosis of type 1 diabetes of at least 1 yr duration, and ability to complete the questionnaire unaided. Adolescents completed self‐efficacy and family environment questionnaires. Metabolic control was assessed by HbA1c. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) Version 10.0. Independent paired t‐tests and Pearson's correlation coefficient were used as test methods. Results: Boys and girls were comparable on self‐efficacy, and self‐efficacy scores were quite satisfactory for both boys and girls. There was a significant positive correlation between self‐efficacy and family cohesion in girls, but self‐efficacy was not related to the family environment (cohesion and organization) and metabolic control in the total sample. Conclusion: In the present study, there was no relationship between self‐efficacy, family environment, and metabolic control in the total sample, but in girls, self‐efficacy and family cohesion was positively correlated.     

p53 gene mutations are rare in human papillomavirus-associated colon cancer

Recent studies suggest that infection with high risk human papillomavirus (HPV) is a common event in colon tumors. Infection by oncogenic HPV may result in functional inactivation of the p53 protein in absence of mutations. Thus far no studies have been made to examine the frequency of p53 mutations in HPV-associated colon cancer. The purpose of this study was to investigate the interrelationship between p53 mutations and HPV infection. The 'hot-spot' region of the p53 gene for mutations was analyzed by PCR-SSCP and direct sequencing in HPV-positive tumor samples. Only 2 mutations were identified in 56 samples. This rate was much lower than reported for sporadic colon tumors. Our results indicate an inverse relationship between p53 mutations and HPV infection and suggest that p53 inactivation caused by HPV infection may play a role in the pathogenesis of colon cancer.     

A Case of Distal Vaginal Agenesis Presenting with Recurrent Urinary Tract Infection and Pyuria in a Prepubertal Girl

Background

Isolated distal vaginal agenesis is a rare anomaly and mostly becomes symptomatic after menarche. We describe an unusual presentation of this anomaly in a prepubertal girl.

The effect of the nitric oxide synthesis inhibitor L-NAME on amitriptyline-induced hypotension in rats

OBJECTIVE: Hypotension induced by tricyclic antidepressants is multifactorial. Previous animal experiments suggest a contribution from nitric oxide production. Our study aimed to evaluate the role of nitric oxide in amitriptyline-induced hypotension using N-nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, and 3-morpholino sydnonimine, a nitric oxide donor, in anesthetized rats. METHODS: Amitriptyline intoxication was induced by the continuous infusion of amitriptyline 0.625 mg/kg/min throughout the experiment in anesthetized rats. Fifteen and 25 minutes after amitriptyline infusion began, two bolus doses of 10 mg/kg of N-nitro-L-arginine methyl ester (n = 8) or an equivalent volume of 5% dextrose solution (n = 8) was administered to each rat (Protocol 1). To investigate whether the effect of N-nitro-L-arginine methyl ester on blood pressure is counteracted by 3-morpholino sydnonimine, after the same protocol of amitriptyline infusion and 5 minutes after an N-nitro-L-arginine methyl ester bolus, a bolus of 3000 nmol/kg of 3-morpholino sydnonimine was administered (n = 8) to each rat (Protocol 2). To investigate the effect of N-nitro-L-arginine methyl ester on 3-morpholino sydnonimine induced hypotension, a group of rats received a continuous infusion of 0.54 mg/kg/h of 3-morpholino sydnonimine until 50% reduction was observed in mean arterial blood pressure followed by a bolus dose of 10 mg/kg of N-nitro-L-arginine methyl ester (n = 6) or 5% dextrose solution (n = 6) (Protocol 3). Outcome measures included mean arterial blood pressure, heart rate, and QRS duration in electrocardiogram. Student's t test and survival analysis were used for selected comparisons. RESULTS: For all parameters, the treatment groups were similar at baseline and at postamitriptyline periods before therapy was rendered. Amitriptyline infusion significantly reduced mean arterial blood pressure by 50.8 +/- 2.2% and prolonged QRS by 23.9 +/- 7.2% after 15 minutes. In Protocol 1, N-nitro-L-arginine methyl ester significantly increased mean arterial blood pressure compared to dextrose-treated control animals within 30 minutes (77.9 +/- 8.5% vs. 49.7 +/- 5.0% mmHg, p < 0.01, 95% CI 57.1-98.7%). QRS duration progressively increased during the amitriptyline infusion; however, there was no significant difference in QRS width between N-nitro-L-arginine methyl ester and control groups at any time point. N-nitro-L-arginine methyl ester increased survival time compared to controls (33.4 +/- 4.1 vs. 19.9 +/- 2.7 minutes, p < 0.01, 95% CI 25.4-41.3) but did not affect mortality. In Protocol 2 of continuous infusion of amitriptyline, 3-morpholino sydnonimine counteracted the N-nitro-L-arginine methyl ester-induced increase in mean arterial blood pressure. In both protocols, heart rate decreased significantly during amitriptyline infusion but there was no difference between treatment and control groups. In Protocol 3, N-nitro-L-arginine methyl ester bolus reversed 3-morpholino sydnonimine-induced hypotension compared to dextrose bolus. (83.8 +/- 5.7% vs. 54.6 +/- 4.8%, p < 0.01, 95% CI 69.2-98.4). CONCLUSION: N-nitro-L-arginine methyl ester is found to be effective in temporarily improving hypotension and prolonging survival time but does not affect overall mortality. Because this effect was antagonized by 3-morpholino sydnonimine, nitric oxide production appears to contribute to the pathophysiology of amitriptyline-induced hypotension.