Alcohol use and non‐adherence to antiretroviral therapy in HIV‐infected patients in West Africa

Aim To investigate the association between alcohol use and adherence to highly active antiretroviral treatment (HAART) among human immunodeficiency virus (HIV)‐infected patients in subSaharan Africa. Design and setting Cross‐sectional survey conducted in eight adult HIV treatment centres from Benin, Côte d'Ivoire and Mali. Participants and measurements During a 4‐week period, health workers administered the Alcohol Use Disorders Identification Test to HAART‐treated patients and assessed treatment adherence using the AIDS Clinical Trials Group follow‐up questionnaire. Findings A total of 2920 patients were enrolled with a median age of 38 years [interquartile range (IQR) 32–45 years] and a median duration on HAART of 3 years (IQR 1–4 years). Overall, 91.8% of patients were identified as adherent to HAART. Non‐adherence was associated with current drinking [odds ratio (OR) 1.4; 95% confidence interval (CI) 1.1–2.0], hazardous drinking (OR 4.7; 95% CI 2.6–8.6) and was associated inversely with a history of counselling on adherence (OR 0.7; 95% CI 0.5–0.9). Conclusions Alcohol consumption and hazardous drinking is associated with non‐adherence to HAART among HIV‐infected patients from West Africa. Adult HIV care programmes should integrate programmes to reduce hazardous and harmful drinking.     

Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study

BACKGROUND/AIMS: Weight loss is considered therapeutic for patients with NAFLD. However, there is no epidemiological evidence that dietary habits are associated with NAFLD. Dietary patterns associated with primary NAFLD were investigated. METHODS: A cross-sectional study of a sub-sample (n=375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for secondary NAFLD. Participants underwent an abdominal ultrasound, biochemical tests, dietary and anthropometric evaluations. A semi-quantitative food-frequency questionnaire was administered. RESULTS: After exclusion, 349 volunteers (52.7% male, mean age 50.7+/-10.4, 30.9% primary NAFLD) were included. The NAFLD group consumed almost twice the amount of soft drinks (P=0.03) and 27% more meat (P<0.001). In contrast, the NAFLD group consumed somewhat less fish rich in omega-3 (P=0.056). Adjusting for age, gender, BMI and total calories, intake of soft drinks and meat was significantly associated with an increased risk for NAFLD (OR=1.45, 1.13-1.85 95% CI and OR=1.37, 1.04-1.83 95% CI, respectively). CONCLUSIONS: NAFLD patients have a higher intake of soft drinks and meat and a tendency towards a lower intake of fish rich in omega-3. Moreover, a higher intake of soft drinks and meat is associated with an increased risk of NAFLD, independently of age, gender, BMI and total calories.     

In situ lipolytic regulation in subjects born small for gestational age

OBJECTIVE: Subjects born small for gestational age (SGA) who are prone to develop insulin resistance in adulthood display an abnormal development pattern of the adipose tissue during fetal and postnatal life. Since the lipolytic activity of the adipose tissue is critical in the development of insulin resistance, the purpose of this study was to investigate whether SGA itself might affect lipolysis regulation. STUDY DESIGN: We studied the effect of catecholamines, by local injection of isoproterenol, and the effect of insulin, using two-step infusion at 8 and 40 mU/m2/min, on the in situ lipolysis of the subcutaneous abdominal adipose tissue of 23 subjects born SGA and 23 born appropriate for gestational age (AGA), using the microdialysis technique. RESULTS: Under isoproterenol infusion, the increase in dialysate glycerol concentration was significantly 1.5-fold higher in the SGA than in the AGA group (P=0.02) and induced a 20% increase in the plasma FFA concentration (P=0.04), whereas no significant increase was observed in the AGA group. The antilipolytic action of insulin on dialysate glycerol concentration was similar in both groups throughout the insulin infusion. CONCLUSION: Subjects born SGA demonstrated a hyperlipolytic reactivity to catecholamines, which might be regarded as an additional deleterious component of the insulin resistance associated with SGA. In contrast, being born SGA does not directly affect the antilipolytic action of insulin, showing that it does not play a major role in causing the long-term metabolic complications associated with reduced fetal growth.     

Safe use of pegylated interferon/ribavirin in hepatitis C virus cirrhotic patients with hypersplenism after partial splenic embolization

BACKGROUND AND AIMS: Partial splenic embolization (PSE) is a non-surgical alternative for the treatment of hypersplenism. Thrombocytopenia precludes the use of pegylated interferon (peg-IFN) and ribavirin in cirrhotic patients with hepatitis C virus (HCV). We aimed to evaluate the role of PSE as a procedure allowing combined HCV therapy in this setting. METHODS: A retrospective analysis of the safety and rate of sustained virological response (SVR) after a full-dose course of peg-IFN plus ribavirin in eight HCV cirrhotic patients with severe hypersplenism undergoing PSE at a tertiary centre in Madrid, Spain, from May 2002 to August 2004. RESULTS: Six patients (75%) were in Child-Pugh class B (median score 7). PSE significantly improved the mean platelet (P = 0.012), leucocyte (P = 0.017) and haemoglobin (P = 0.035) levels, and prothrombin activity (P = 0.012). After a mean of 20 weeks after PSE all patients started weight-adjusted ribavirin plus peg-IFN-alpha2b (n = 6) or 180 microg/week of peg-IFN-alpha2a (n = 2). Six subjects (75%) completed therapy with no peg-IFN dose reductions; the dose of ribavirin was reduced in two patients reaching haemoglobin levels of less than 10 g/dl (one also received erythropoietin and granulocyte colony-stimulating factor because of neutrophil counts < 300 cells/microl). Three patients (38%) achieved SVR. Portal vein thrombosis was observed in 50% of patients, but did not preclude antiviral therapy. The pathogenic mechanism was multifactorial. It was successfully managed with anticoagulant therapy in two cases. CONCLUSIONS: PSE allowed the safe use of peg-IFN plus ribavirin in HCV cirrhotic patients with severe cytopenias who otherwise would never have been treated. The rate of SVR was 38%.     

Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy

BACKGROUND: Immune restoration following combination antiretroviral therapy (cART) questions the maintenance of prophylaxis among HIV-infected patients with cryptococcosis. OBJECTIVE: To describe the long-term outcome after the diagnosis of cryptococcosis at the cART era. DESIGN: Multicentre cohort of patients with a diagnosis of cryptococcosis between 1996 and 2000, follow-up until December 2002. Comparison with a historical cohort (1990-1994) for survival. SETTING: Eighty-four French AIDS clinical centres. PATIENTS: Two-hundred and forty HIV-infected adult patients at the cART era and 149 at the pre-cART era experiencing a first episode of culture-confirmed cryptococcosis. RESULTS: In the cART era, 82/189 patients surviving more than 3 months after initiation of antifungal therapy had their maintenance therapy interrupted with a subsequent median follow-up of 19 months. Their relapse rate per 100 person-years was 0.9 [95% confidence interval (CI),0.0-2.0]. When considering the whole cART cohort, probability of reaching negative serum cryptococcal antigen was 71% after 48 months of follow-up. A CD4 cell count < 100/microl [relative risk (RR), 5.5; 95% CI, 1.3-22.2], antifungal therapy < 3 months over the past 6 months [RR, 5.0; 95% CI, 1.1-22.3] and serum cryptococcal antigen titre > or = 1/512 [RR, 3.5; 95% CI, 1.1-10.8] were associated with a higher rate of cryptococcosis relapse. The mortality rate per 100 person-years was 15.3 [95% CI,12.2-18.4] in the cART era versus 63.8 [95% CI,53.0-74.9] in the pre-cART era although early mortality did not differ between the two periods. CONCLUSION: Overall survival after cryptococcosis has dramatically improved at the cART era. Immune restoration and low serum cryptococcal antigen titres are associated with lower cryptococcosis relapse rates.     

Somatostatin and dopamine-somatostatin multiple ligands directed towards somatostatin and dopamine receptors in pituitary adenomas

AIM: We report the comparative efficacy of octreotide, cabergoline and multiple ligands directed towards the different somatostatin subtypes (ssts), such as BIM-23A779 and SOM-230, and of chimeric analogs which bind both somatostatin and the dopamine D2 receptors (D2R), such as BIM-23A760 and BIM-23A781, in cell cultures from human growth hormone (GH)-secreting pituitary adenomas. PROCEDURES: RT-PCR analysis of the quantitative expression of the different ssts and D2R mRNAs was performed on tumor fragments of 22 GH-secreting adenomas collected after surgery. Pharmacological studies, using the different ligands, were performed on cell cultures of such tumors. RESULTS: sst2, sst5 and D2R were constantly coexpressed in all tumors, in variable amounts. The levels of expression of sst2 and D2R mRNAs were significantly correlated with the maximal GH suppression by either octreotide or cabergoline (p < 0.001). In each tumor tested, 3 patterns of response, in terms of GH suppression, were observed. GH secretion was preferentially inhibited by the sst2 preferential compound octreotide in 61% of the tumors. In 19% of the tumors, the maximal inhibition of GH release was achieved with the sst5 preferential compound BIM-23268. The dopamine analog cabergoline was the most effective inhibitor of GH secretion in 21% of cases. Among the compounds tested, the most potent inhibitors of GH secretion were the sst2, sst5, D2R chimeric compound BIM-23A760, followed by the sst universal ligand SOM-230. CONCLUSIONS: The variable patterns of response to sst2, sst5 and dopamine D2 analogs may explain the greater efficacy of drugs which bind to the 3 receptors in suppressing GH secretion. The biological potency (EC50) and efficacy of the chimeric compound BIM-23A760 on GH secretion can be partly explained by its high affinity for sst2. The effect of multiple receptor activation on the functions of other pituitary tumor types, such as prolactinomas and corticotropinomas, is not presently analyzed, and the efficacy of multireceptor ligands remains to be elucidated.     

Benefits of salmon eating on traditional and novel vascular risk factors in young, non-obese healthy subjects

AIM: The present clinical study tested the hypothesis that oil-rich fish consumption improves CHD risk factors. METHODS: Forty-eight (16 men) non-obese, healthy adults aged 20-55, consumed 125 g/day of salmon for a 4-week period followed by a 4-week period with no-fish (41 completers). Subjects were instructed to maintain dietary and physical activity patterns during the period of study. Blood pressure, anthropometric, body composition and dietary information with fasting blood samples to determine traditional and novel CHD risk markers and plasma fatty acids were obtained before and after each period. RESULTS: Compared to no-fish, eating salmon significantly decreased systolic, diastolic and mean arterial blood pressure by 4%, triglycerides by 15%, and LDL-cholesterol by 7%, and significantly increased HDL-cholesterol by 5% (P<0.05). The changes in blood pressure and lipids alone with salmon intake predict around a 25% reduction in CHD risk based on the PROCAM risk calculator. Plasma adiponectin demonstrated a trend towards improvement (8.39 micromol/L with salmon and 7.52 with no-fish; P=0.086) but no significant changes were found either in plasma leptin, glucose or insulin after salmon consumption. CONCLUSIONS: Daily consumption of salmon improves traditional risk predictors of CHD in non-obese subjects. Adiponectin may be involved but the impact on novel risk factors needs study in high-risk subjects.     

Low serum adiponectin levels in subjects born small for gestational age: impact on insulin sensitivity

OBJECTIVE: Increasing evidence point to the role of the adipose tissue on the insulin resistance associated with reduced fetal growth. Since adiponectin, exclusively produced by the adipose tissue, exerts an important insulin-sensitizing activity, it appears critical to investigate the effect of being born small for gestational age (SGA) on adiponectin production in adulthood and its relationship with insulin sensitivity. SUBJECTS AND METHODS: Serum adiponectin concentrations were measured in 486 young adults born SGA, precisely selected on birth data, who were compared to 573 age-matched subjects born appropriate for gestational age (AGA). The relationship between serum adiponectin levels and insulin-resistance indices measured under OGTT were tested and compared between the two groups. RESULTS: The SGA group demonstrated significantly reduced serum adiponectin levels than controls (12.6 +/- 6.9 vs 13.2 +/- 6.4 microg/ml, P = 0.02) and the difference remained significant when the key regulatory factors were taken into account (P = 0.008). In the AGA group, fasting I/G taken as an insulin-resistance index negatively correlated with serum adiponectin concentrations (P = 0.02), while the relationship followed a U-shape with increased fasting I/G ratio despite high concentrations of serum adiponectin in the SGA group (P = 0.12). CONCLUSION: Subjects born SGA demonstrated significantly reduced serum adiponectin levels, which were not related to insulin-resistance indices in comparison to what observed in age-matched subjects born AGA. Although this defect in adiponectin production and in its insulin-sensitizing action remains to be elucidated at the molecular level, it strengthens the critical contribution of the adipose tissue in the metabolic complications associated with reduced fetal growth.     

Intracellular Ca-carbonate biomineralization is widespread in cyanobacteria

Cyanobacteria have played a significant role in the formation of past and modern carbonate deposits at the surface of the Earth using a biomineralization process that has been almost systematically considered induced and extracellular. Recently, a deep-branching cyanobacterial species, Candidatus Gloeomargarita lithophora, was reported to form intracellular amorphous Ca-rich carbonates. However, the significance and diversity of the cyanobacteria in which intracellular biomineralization occurs remain unknown. Here, we searched for intracellular Ca-carbonate inclusions in 68 cyanobacterial strains distributed throughout the phylogenetic tree of cyanobacteria. We discovered that diverse unicellular cyanobacterial taxa form intracellular amorphous Ca-carbonates with at least two different distribution patterns, suggesting the existence of at least two distinct mechanisms of biomineralization: (i) one with Ca-carbonate inclusions scattered within the cell cytoplasm such as in Ca. G. lithophora, and (ii) another one observed in strains belonging to the Thermosynechococcus elongatus BP-1 lineage, in which Ca-carbonate inclusions lie at the cell poles. This pattern seems to be linked with the nucleation of the inclusions at the septum of the cells, showing an intricate and original connection between cell division and biomineralization. These findings indicate that intracellular Ca-carbonate biomineralization by cyanobacteria has been overlooked by past studies and open new perspectives on the mechanisms and the evolutionary history of intra- and extracellular Ca-carbonate biomineralization by cyanobacteria.Cyanobacteria are a phylogenetically and ecologically diverse phylum of Gram-negative bacteria that have impacted the global cycle of carbon on the Earth for billions of years and induced the oxygenation of the atmosphere (1–3). By performing oxygenic photosynthesis—a unique capability that appeared only once in evolution—in this particular group of bacteria, cyanobacteria have contributed significantly to the primary production on the past and present Earth (4). Moreover, cyanobacteria have received great attention from geologists as major players in the formation of carbonate sedimentary deposits such as stromatolites (5, 6), the oldest ones formed by cyanobacteria possibly as old as 2.98 billion years (Ga) (7). Fossils of Ca-carbonate–encrusted cyanobacterial cells (calcimicrobes) have been looked for extensively. The temporal distribution of calcimicrobes in the geological record dating back as far as the early Proterozoic (∼2.5–2.3 Ga) (8) has been interpreted as the result of paleoenvironmental and/or evolutionary changes (9, 10). Despite the importance of carbonate biomineralization by cyanobacteria in the formation of calcimicrobes and sedimentary deposits, the involved mechanisms are still poorly understood (11, 12). Some authors have proposed that cyanobacterial calcification might be promoted by CO₂-concentrating mechanisms (CCMs) that possibly developed in the late Proterozoic to accommodate photosynthetic carbon limitation under low CO₂ fugacity (10). This model states that bicarbonates are actively imported into the cells, transformed to CO₂ within carboxysomes for fixation by ribulose-1,5-bisphosphate carboxylase/oxygenase. The resulting alkalinity is transferred outside the cells, which raises the external pH and thus induces CaCO₃ precipitation (13). Other authors have stressed the importance of cell-surface properties of some cyanobacteria for the nucleation of CaCO₃ minerals and did not observe notable effects of photosynthesis on CaCO₃ precipitation (14). In any case, precipitation of CaCO₃ by cyanobacteria has been invariably considered a noncontrolled and extracellular process.This paradigm has been questioned recently by the discovery of a new deep-branching cyanobacterial species, Candidatus Gloeomargarita lithophora, enriched from the hyperalkaline Lake Alchichica (Mexico) and forming amorphous carbonates intracellularly (15). However, many studies characterized the ultrastructure of cyanobacteria (16, 17) and explored their impact on calcification (11, 18, 19), but none of them reported the presence of intracellular carbonates. Here, we investigated whether intracellular carbonate biomineralization is restricted to one particular species and/or specific environmental condition or whether it exists in other diverse cyanobacteria; this is essential to assess the evolution of intracellular carbonate biomineralization and its significance at geological timescales. For this purpose, we screened 68 cyanobacterial strains scattered throughout the phylogenetic tree of cyanobacteria (Fig. 1) to search for intracellular carbonates.Open in a separate windowFig. 1.Bayesian phylogenetic tree of 16S rRNA gene sequences of the cyanobacterial strains observed by electron microscopy. Strains forming intracellular Ca-carbonates are shown in color (green for those with Ca-carbonate inclusions at the cell poles and red for those with inclusions scattered in the cytoplasm). The tree is based on 1,292 conserved sites; numbers at branches are posterior probabilities (only those >0.75 are shown).