13C/31P NMR studies of glucose transport in human skeletal muscle

The muscle intracellular (IC) free glucose concentration and the rate of muscle glycogen synthesis were measured by using in vivo ¹³C and ³¹P NMR spectroscopy in normal volunteers under hyperinsulinemic (≈300 pM) clamp conditions at the following three plasma glucose levels: euglycemia (≈6 mM), mild (≈10 mM), and high (≈16 mM) hyperglycemia. In keeping with biopsy studies, muscle IC free glucose concentration at euglycemia (−0.03 ± 0.03 mmol/kg of muscle, mean ± SEM, n = 10) was not statistically different from zero. A small but statistically significant amount of IC free glucose was observed during mild and high hyperglycemia: 0.15 ± 0.08 (n = 5) and 0.43 ± 0.20 mmol/kg of muscle (n = 5), respectively. Muscle glycogen synthesis rate, in mmol per kg of muscle per min, was 111 ± 11 at euglycemia (n = 10), 263 ± 29 during mild hyperglycemia (n = 5), and 338 ± 42 during high hyperglycemia (n = 5), these three rates being significantly different from each other. As previous in vitro and in vivo studies, these rates suggest a K_m (concentration at which unidirectional glucose transport reaches half-maximal rate) of the muscle glucose transport system in the 15–25 mM range under hyperinsulinemic conditions. The low concentrations of muscle IC free glucose observed under hyperinsulinemic conditions were interpreted, with this estimate and in the framework of metabolic control theory, as glucose transport being the predominant step controlling muscle glucose flux not only at euglycemia but also during hyperglycemia.     

Modeling Chagas Disease at Population Level to Explain Venezuela's Real Data

Objectives

In this paper we present an age-structured epidemiological model for Chagas disease. This model includes the interactions between human and vector populations that transmit Chagas disease.

Methods

The human population is divided into age groups since the proportion of infected individuals in this population changes with age as shown by real prevalence data. Moreover, the age-structured model allows more accurate information regarding the prevalence, which can help to design more specific control programs. We apply this proposed model to data from the country of Venezuela for two periods, 1961–1971, and 1961–1991 taking into account real demographic data for these periods.

Results

Numerical computer simulations are presented to show the suitability of the age-structured model to explain the real data regarding prevalence of Chagas disease in each of the age groups. In addition, a numerical simulation varying the death rate of the vector is done to illustrate prevention and control strategies against Chagas disease.

Conclusion

The proposed model can be used to determine the effect of control strategies in different age groups.     

Cardiovascular Interactions of Desipramine,Fluoxetine, and Cocaine in Cocaine-Dependent Outpatients

The authors investigated the subacute cardiovascular effects of cocaine use alone and with antidepressants. At study entry, 55 cocaine-dependent (DSM-III-R) patients with cocaine-positive urines had slightly higher resting heart rates and blood pressures than 36 patients with cocaine-negative urines, which achieved significance (P < 0.05) for three of eleven parameters. A repeated-measures analysis of medication-compliant patients found no significant cardiovascular differences between cocaine-positive and cocaine-negative urine conditions for either desipramine (n = 10) or fluoxetine (n = 20). Cocaine use appears to produce minimal subacute cardiovascular effects, which are not accentuated by desipramine or fluoxetine, in physically healthy cocaine-dependent patients. (American Journal on Addictions 1996; 5:321–326)     

Chagasic meningoencephalitis: case report of a recently included AIDS-defining illness in Brazil

Recently, reactivation of Chagas disease (meningoencephalitis and/or myocarditis) was included in the list of AIDS-defining illnesses in Brazil. We report a case of a 52-year-old patient with no history of previous disease who presented acute meningoencephalitis. Direct examination of blood and cerebrospinal fluid (CSF) showed Trypanosoma cruzi. CSF culture confirmed the diagnosis. Serological assays for T. cruzi and human immunodeficiency virus (HIV) were positive. Despite treatment with benznidazol and supportive measures, the patient died 24 hours after hospital admission. In endemic areas, reactivation of Chagas disease should always be considered in the differential diagnosis of meningoencephalitis among HIV-infected patients, and its presence is indicative of AIDS.     

Redo pouches: Salvaging of failed ileal pouch-anal anastomoses

From October 1, 1984 to December 31, 1991 at the Clinica Chirurgica II of the University of Bologna, 140 patients submitted to ileal pouch-anal anastomosis for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Nineteen patients (13.5 percent) developed septic complications. Of these, 11 patients (7.8 percent) had pelvic sepsis. Eight patients required further surgical intervention. Five patients underwent the redo pouch procedure. Another redo pouch was performed in a patient who had previously, in another hospital, had an ileal pouch-anal anastomosis placed and then removed because of ischemic necrosis of the reservoir. No deaths are reported in the reoperated patients. Currently, five of the six patients who underwent the redo pouch procedure have a well-functioning ileoanal anastomosis. The redo pouch procedure should always be attempted prior to the establishment of pelvic fibrosis.     

Effectiveness of pirmenol hydrochloride in suppressing high frequency ventricular ectopy: a placebo-controlled, double-blind, multicenter study

An 8-center European clinical trial has established that pirmenol in dosages up to 400 mg daily is effective and safe for treating stable, high frequency, ventricular ectopy. At dosages of 300 mg and 400 mg of pirmenol a day, the average frequency of ectopy/hour decreased markedly compared with baseline values. The percentage of responders (premature ventricular contraction suppression of 70% compared with baseline) among the patients receiving 300 mg or 400 mg of pirmenol/day was significantly higher than in the placebo group. Observation of the frequency of reported adverse experiences, clinical laboratory tests and electrocardiographic tracings shows that dosages of pirmenol up to 400 mg daily were well tolerated.     

Favorable early and long-term prognosis following coronary bypass surgery therapy for myocardial infarction: results of a multicenter trial. TAMI Study Group

Coronary bypass surgery was performed before hospital discharge on 82 (21%) of 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trial of intravenous tissue plasminogen activator and coronary angioplasty for acute myocardial infarction. Time from infarct symptom onset to coronary bypass surgery was 7.3 +/- 1.9 hours for 24 patients operated upon on an emergency basis and 9.3 +/- 5.2 days for 58 patients having late in-hospital surgery. There were no operative deaths and five in-hospital deaths in the surgical group, all of which occurred in patients with preoperative cardiogenic shock. Although patients in the surgical group were older (59.7 +/- 10.4 years versus 54.9 +/- 10.2 years; p = 0.03), had more extensive coronary artery disease (42% three-vessel disease versus 11%; p = 0.001), and had a higher incidence of anterior wall myocardial infarction (48% versus 39%; p = 0.02), in-hospital mortality for the surgical group (6%) was similar to that in 301 patients not undergoing surgery (7%) in this trial. For patients discharged from the hospital, mortality at 1 year was 2.5% in the surgical group and 1.8% in patients not having coronary bypass surgery before hospital discharge. At a 1 year follow-up, there were no significant differences in the frequency of cardiac or noncardiac-related hospitalizations or in event-free survival between surgical and nonsurgical groups. The majority of patients in both groups considered themselves to be in excellent or good condition. Coronary bypass surgery can be performed with low morbidity and mortality rates in close temporal association to acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a treatment adherence enhancement program on health literacy, patient-provider relationships, and adherence to HAART among low-income HIV-positive Spanish-speaking Latinos

The impact of an adherence enhancement program for low income HIV-infected Spanish-speaking Latinos on health literacy, patient-provider relationships, and adherence to HAART was examined. Evaluations were conducted at baseline, 6 weeks, and 6 months for participants (n = 85) randomly assigned to either the intervention group or a comparison group; 69 (81%) remained in the study for the entire 6-month duration. The intervention group scored significantly better than the comparison group on 3 of 5 measures of HIV health literacy at 6 weeks and on 2 of 5 measures, at 6 months. While there was a weak trend for the intervention group to report an increase in self-efficacy of medication adherence management, baseline to 6 weeks, no other changes were significant. Perceptions of the quality of relationship and communications with their HIV-treating physicians improved both at 6 weeks (p = 0.04) and at 6 months (p < 0.001). The comparison group showed little change baseline to 6 weeks and baseline to 6 months. While there was a trend for the pilot group to report better medication adherence, these differences were not statistically significant. Further evaluation of the impact of this adherence enhancement program is needed.     

Loss of miR‐101 expression promotes Wnt/β‐catenin signalling pathway activation and malignancy in colon cancer cells

Colorectal cancer (CRC) is the second leading cause of cancer‐related mortality in Western countries. Although the aberrant expression of several microRNAs (oncomiRs) is associated with CRC progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that miR‐101 expression is differentially impaired in CRC specimens, depending on tumour grade. miR‐101 re‐expression suppresses cell growth in 3D, hypoxic survival and invasive potential in CRC cells showing low levels of miR‐101. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between miR‐101 expression and important CRC pro‐malignant features, such as inflammation, activation of the Wnt/β‐catenin signalling pathway and epithelial–mesenchymal transition (EMT). We then propose that up‐regulated miR‐101 may function as a tumour suppressor in CRC and that its pharmacological restoration might hamper the aggressive behaviour of CRC in vivo. MiR‐101 expression may also represent a cancer biomarker for CRC diagnosis and prognosis. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Genetic polymorphisms of interleukin 20 (IL-20) in patients with ulcerative colitis

Interleukin (IL)-20 belongs to the IL-10 family and is a potent immunomodulatory cytokine with implications for pathogenesis in the inflammatory bowel disease (IBD). The interleukin 20 gene is located within a 200 kb region of q31-32 locus of chromosome 1. No previous studies have reported this novel association between ulcerative colitis (UC) and IL-20 polymorphisms. In the present work, we evaluated the role of IL-20 gene polymorphisms as susceptibility markers for UC. Three polymorphisms of IL-20 gene (rs2981573, rs2232360, rs1518108) were genotyped by 5′ exonuclease TaqMan genotyping assays on an ABI Prism 7900 HT Fast Real-Time PCR system in a group of 198 Mexican Mestizo patients with UC and 698 ethnically matched healthy unrelated individuals with no family history of UC. We found significant decreased frequencies of two IL-20 genotypes: GG (rs2981573) [10.6% vs. 17.6%, p = 0.017, OR = 0.55, 95% CI: 0.33–0.93] and GG (rs2232360) [10.6% vs. 17.6%, p = 0.017, OR = 0.55, 95% CI: 0.33–0.93] in UC patients as compared to healthy controls. No significant differences of gene frequencies were found between UC patients and healthy controls in the rs1518108 polymorphism. In the subgroup analysis, no differences were found between the IL-20 genotypes and the clinical characteristics of UC. The results suggest that the GG genotypes of the IL-20 polymorphisms (rs2981573 and rs2232360) might have an important role in the development of UC in the Mexican population.