Dietary restriction interferes with oxidative status and intrinsic intestinal innervation in aging rats

ObjectivesTo evaluate the effects of dietary restriction on oxidative status, the HuC/D–neuronal nitric oxide synthase (nNOS) myenteric neuron population, HuC/D-S100 glial cells, and the morphometry of the small intestine in rats at various ages.MethodsFifteen Wistar rats were divided into 7-and 12-mo-old control groups and a 12-mo-old experimental group subjected to dietary restrictions (50% of normal ration) for 5 mo. At 7 and 12 mo of age, the animals were anesthetized, and blood was collected to assess the biochemical components and oxidative status. Ileum samples were subjected to double-marker (HuC/D-nNOS and HuC/D-S100) immunostaining and histologic processing to morphometrically analyze intestinal wall elements and determine the metaphase index and rate of caliciform cells. The data were subjected to analysis of variance and the Tukey post hoc test with a 5% significance level.ResultsAge affected the oxidative status by increasing lipid peroxidation, with no effect on blood components, intrinsic innervation, and intestinal wall elements. The animals subjected to dietary restriction showed improved levels of total cholesterol, triacylglycerols, and oxidative status, with no changes in the nNOS neuron population. However, the dietary restriction dramatically decreased the glial and HuC/D myenteric populations, led to atrophy of the neuronal cell body, induced glial hypertrophy, and decreased the thickness of the intestinal wall.ConclusionThe high oxidative status of the aging animals was reversed by dietary restriction, which also lowered cholesterol and triacylglycerol levels. The present dietary restriction elicited morpho-quantitative changes in the myenteric plexus and histology of the ileum, with likely effects on intestinal functions.     

Partnerships: survey respondents’ perceptions of inter-professional collaboration to address alcohol-related harms in England

Tackling alcohol-related harms crosses agency and professional boundaries, requiring collaboration between health, criminal justice, education and social welfare institutions. It is a key component of most multi-component programmes in the United States, Australia and Europe. Partnership working, already embedded in service delivery structures, is a core mechanism for delivery of the new UK Government Alcohol Strategy. This article reports findings from a study of alcohol partnerships across England. The findings are based on a mix of open discussion interviews with key informants and on semi-structured telephone interviews with 90 professionals with roles in local alcohol partnerships. Interviewees reported the challenges of working within a complex network of interlinked partnerships, often within hierarchies under an umbrella partnership, some of them having a formal duty of partnership. The new alcohol strategy has emerged at a time of extensive reorganisation within health, social care and criminal justice structures. Further development of a partnership model for policy implementation would benefit from consideration of the incompatibility arising from required collaboration and from tensions between institutional and professional cultures. A clearer analysis of which aspects of partnership working provide ‘added value’ is needed.     

Amphiphilic Antimony(V) Complexes for Oral Treatment of Visceral Leishmaniasis

The need for daily parenteral administration is an important limitation in the clinical use of pentavalent antimonial drugs against leishmaniasis. In this study, amphiphilic antimony(V) complexes were prepared from alkylmethylglucamides (L8 and L10, with carbon chain lengths of 8 and 10, respectively), and their potential for the oral treatment of visceral leishmaniasis (VL) was evaluated. Complexes of Sb and ligand at 1:3 (SbL8 and SbL10) were obtained from the reaction of antimony(V) with L8 and L10, as evidenced by elemental and electrospray ionization-tandem mass spectrometry (ESI-MS) analyses. Fluorescence probing of hydrophobic environment and negative-staining transmission electron microscopy showed that SbL8 forms kinetically stabilized nanoassemblies in water. Pharmacokinetic studies with mice in which the compound was administered by the oral route at 200 mg of Sb/kg of body weight indicated that the SbL8 complex promoted greater and more sustained Sb levels in serum and liver than the levels obtained for the conventional antimonial drug meglumine antimoniate (Glucantime [Glu]). The efficacy of SbL8 and SbL10 administered by the oral route was evaluated in BALB/c mice infected with Leishmania infantum after a daily dose of 200 mg of Sb/kg for 20 days. Both complexes promoted significant reduction in the liver and spleen parasite burdens in relation to those in the saline-treated control group. The extent of parasite suppression (>99.96%) was similar to that achieved after Glu given intraperitoneally at 80 mg of Sb/kg/day. As expected, there was no significant reduction in the parasitic load in the group treated orally with Glu at 200 mg of Sb/(kg day). In conclusion, amphiphilic antimony(V) complexes emerge as an innovative and promising strategy for the oral treatment of VL.     

Prognostic and biologic significance of chromosomal imbalances assessed by comparative genomic hybridization in multiple myeloma

Cytogenetic abnormalities, evaluated either by karyotype or by fluorescence in situ hybridization (FISH), are considered the most important prognostic factor in multiple myeloma (MM). However, there is no information about the prognostic impact of genomic changes detected by comparative genomic hybridization (CGH). We have analyzed the frequency and prognostic impact of genetic changes as detected by CGH and evaluated the relationship between these chromosomal imbalances and IGH translocation, analyzed by FISH, in 74 patients with newly diagnosed MM. Genomic changes were identified in 51 (69%) of the 74 MM patients. The most recurrent abnormalities among the cases with genomic changes were gains on chromosome regions 1q (45%), 5q (24%), 9q (24%), 11q (22%), 15q (22%), 3q (16%), and 7q (14%), while losses mainly involved chromosomes 13 (39%), 16q (18%), 6q (10%), and 8p (10%). Remarkably, the 6 patients with gains on 11q had IGH translocations. Multivariate analysis selected chromosomal losses, 11q gains, age, and type of treatment (conventional chemotherapy vs autologous transplantation) as independent parameters for predicting survival. Genomic losses retained the prognostic value irrespective of treatment approach. According to these results, losses of chromosomal material evaluated by CGH represent a powerful prognostic factor in MM patients.     

Longer Times of Receipt of Adjuvant Endocrine Therapy Correspond to Improved Functional Capacity and Lower Adiposity in Women Receiving Adjuvant Therapy

Purpose

To study the use of functional capacity (FC) level and duration of aromatase inhibitor (AI) therapy with adiposity parameters in women with breast cancer.

High Prevalence of Helicobacter pylori in Liver Cirrhosis (Relationship with Clinical and Endoscopic Features and the Risk of Peptic Ulcer)

In 153 consecutive patients with cirrhosis weassessed: (1) the prevalence of IgG to Helicobacterpylori and compared it with that found in 1010 blooddonors resident in the same area; and (2) therelationships of IgG to Helicobacter pylori with clinical andendoscopic features and with the risk of peptic ulcer.The IgG to Helicobacter pylori prevalence of cirrhoticswas significantly higher than in blood donors (76.5% vs 41.8%; P < 0.0005) and was notassociated with sex, cirrhosis etiology, Child class,gammaglobulins and hypertensive gastropathy. In bothgroups, the prevalence of IgG to Helicobacter pylori was significantly higher in subjects over 40. Amongpatients with cirrhosis a significantly higherprevalence of Helicobacter pylori was found in patientswith previous hospital admission (P = 0.02) and/or upper gastrointestinal endoscopy (P = 0.01) andpatients with peptic ulcer (P = 0.0004). Multivariateanalysis identified increasing age and male sex as riskfactors for a positive Helicobacter pylori serology and no independent risk factors for pepticulcer. The high prevalence of Helicobacterpylori-positive serology found in the present series isrelated to age and sex and might also be explained byprevious hospital admissions and/or uppergastrointestinal endoscopy. Our results do not confirmthe role of Helicobacter pylori as risk factor forpeptic ulcer in patients with liver cirrhosis.     

Hemorrhagic complications in patients treated with anticoagulant doses of a low molecular weight heparin (enoxaparin) in routine hospital practice.

Low molecular weight heparins (LMWHs) are a rapidly growing class of anticoagulant drug. Their efficacy has been demonstrated in several clinical settings where they are rapidly becoming the anticoagulant of choice. Controlled clinical studies in patients with deep vein thrombosis, pulmonary embolism, and unstable angina have documented that the frequency of major hemorrhage is 0.5-4%. The purpose of the study was to determine the frequency of minor and major hemorrhage occurring in patients receiving anticoagulant doses of an LMWH (enoxaparin) during routine clinical practice. A prospective, observational study of consecutive patients receiving enoxaparin 1 mg/kg twice daily for at least 24 hours in five internal medicine wards of a university teaching hospital was performed. Five hundred forty-nine patients were studied. The mean age was 67.5+/-15.5 years and the mean duration of enoxaparin therapy was 3.8+/-1.5 days. Hemorrhage was documented in a total of 94 patients (17.3%). Major hemorrhage occurred in 14 patients (2.6%), injection-site hemorrhage occurred in 55 patients (10%), and minor hemorrhage (noninjection site) was documented in 25 patients (4.7%). There were two deaths attributed to hemorrhage. Patients with major hemorrhage were older than patients with minor or no hemorrhage (75.5+/-10.4 versus 66.8+/-15.2 years; p=0.03) and occurred in patients receiving enoxaparin for a longer period (5.14+/-3.8 days) than those with minor (4+/-2.5 days) or no hemorrhage (2.9+/-2.1 days). Major hemorrhage was significantly associated with impaired renal function, chronic liver disease, and concomitant treatment with warfarin or a proton pump inhibitor. Enoxaparin used in anticoagulant doses in unselected medical patients is not associated with more major hemorrhagic complications than observed in controlled clinical trials. Major hemorrhage may be more likely in older patients, in patients with chronic liver disease and impaired renal function, in patients receiving prolonged enoxaparin therapy, and in patients receiving warfarin or proton pump inhibitors.