bluuebunny/crossref_metadata_2025_split huggingface dataset:
The lipoprotein/lipid profile is modulated by a gene–diet interaction effect between polymorphisms in the liver X receptor-α and dietary cholesterol intake in French-Canadians
Authors: Robitaille Julie , Houde Alain , Lemieux Simone , Gaudet Daniel , Pérusse Louis , Vohl Marie-Claude 
Published: January 2007

Genetic and nutritional factors interact together and modulate the plasma lipid profile. We identified variations in the gene encoding the liver X receptor α (LXRα) and investigated their effects on the plasma lipoprotein/lipid profile. We also examined whether the association between cholesterol intake and plasma lipid profile was modulated by LXRα variants. The LXRα gene was sequenced in thirty-five French-Canadian men with high plasma total cholesterol (>5·0 mmol/l) and LDL-cholesterol (>3·5 mmol/l) concentrations. Dietary cholesterol was obtained from a food-frequency questionnaire. The LXRα c.-115G>A, c.-840C>A and c.-1830T>C genotypes were determined by direct sequencing in 732 subjects. Molecular screening of the LXRα gene revealed sixteen variants. Genotypes c.-115G>A, c.-840C>A and c.-1830T>C (rare allele frequency of 14·3 %, 14·2 % and 11·0 %, respectively) were analysed further. Plasma total cholesterol concentrations were higher in carriers of the -115A, -840A and -1830C allele, compared with the -115G/G, -840C/C and -1830T/T homozygotes (P ≤ 0·05). In a model including the c.-115G>A polymorphism, cholesterol intake, the interaction term c.-115G>A × cholesterol intake (mg/d) and covariates, LXRα-115G>A explained 1·8 % and 2·1 % of the variance in total cholesterol and LDL-cholesterol concentrations (P = 0·02 andP = 0·01), whereas the interaction term explained 2·9 % (P = 0·002) and 2·8 % (P = 0·005), respectively. When subjects were divided into four groups according to the median of cholesterol (290·8 mg) and -115G>A genotypes, high cholesterol intake was associated with higher cholesterol levels in -115A carriers. Similar results were observed for c.-840C>A and c.-1830T>C. These results suggest that cholesterol intake interacts with LXRα variants to modulate the plasma lipid profile.
The effects of changes in nutritional demand on gastrointestinal parasitism in lactating rats
Authors: Normanton Heidi , Houdijk Jos G. M. , Jessop Neil S. , Knox Dave P. , Kyriazakis Ilias 
Published: January 2007

Lactating rats experience a breakdown of immunity to parasites, i.e. they carry larger worm burdens after re-infection compared to their non-lactating counterparts. Feeding high-protein foods to lactating rats results in reduced worm burdens. This could be attributed to changes in gastrointestinal environment or to overcoming effects of nutrient scarcity on host immunity. The latter hypothesis was addressed through a manipulation of nutrient demand by manipulating litter size. Twenty-three rats were immunized prior to mating and re-infected on day 2 of lactation with 1600 infective Nippostrongylus brasiliensis larvae. From parturition onwards, rats received ad libitum a low-protein food (100 g crude protein/kg). Litter sizes were standardised to nine (LS9), six (LS6) or three (LS3) pups, by day 2 of lactation. After a further 10 d, LS9 and LS6 rats carried more worms than LS3 rats. However, feeding treatments did not affect concentrations of mucosal inflammatory cells. Achieved feed intake did not differ consistently between the treatment groups. However, LS9 and LS6 rats lost weight, whilst LS3 rats gained weight during lactation. The results support the view that resistance to N. brasiliensis is sensitive to changes in nutrient demand, and the improved resistance to N. brasiliensis is likely due to effects of overcoming nutrient scarcity on host immunity.
Main intestinal markers associated with the changes in gut architecture and function in piglets after weaning
Authors: Montagne Lucile , Boudry Gaëlle , Favier Christine , Huërou-Luron Isabelle Le , Lallès Jean-Paul , Sève Bernard 
Published: January 2007

We analysed the spatio-temporal sequence of events concerning the morphology, physiology and ecology of the gut of piglets during the 2 weeks following weaning, in order to provide a limited number of variables that could be relevant markers of the gut post-weaning changes. An experiment was conducted on sixty piglets fasted for 2 d, then administered a weaning diet with a moderate or a high content of wheat using controlled gastric feeding, and slaughtered at different time-points post-weaning. Sixty-nine variables were analysed by principal component analysis. The results showed that the temporal changes induced in the gut by weaning can be divided into two periods: an acute period happening immediately after weaning, followed after day 5 by a more progressive adaptative and maturational phase. The main factors of this adaptation were the refeeding process and the time, while the dietper sehad little influence. The villus length, lactase activity, macromolecule fluxes across the jejunum and the plasma cholecystokinin were proposed as markers of the acute phase. The mass of the jejunum, the weight of the pancreas, the content of stomach, the trypsin activity and the theophylline-induced secretion in jejunum were related to the re-feeding. Markers proposed to follow the gut maturation were the maltase activity, the glucose absorption and the basal resistance in the ileum, the lactobacilli and enterococci in the colon, and the pH of colonic and caecal contents. These markers might be helpful to design suitable diets to limit post-weaning gut disorders in pigs.
Short duration of breast-feeding as a risk-factor for β-cell autoantibodies in 5-year-old children from the general population
Authors: Holmberg Hanna , Wahlberg Jeanette , Vaarala Outi , Ludvigsson Johnny ,   for the ABIS study group
Published: January 2007

Breast-feeding has been suggested to have a protective effect against the development of type 1 diabetes. In the present study, we investigated the relation between duration of breast-feeding and β-cell autoantibodies in 5-year-old non-diabetic children who participated in a prospective population-based follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short duration of total breast-feeding was associated with an increased risk of GADA and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2·09, 95 % CI 1·45, 3·02; P < 0·000) as well as with an increased risk of IAA above the ninety-fifth percentile at this age (OR 2·89, 95 % CI 1·81, 4·62; P < 0·000). A short duration of exclusive breast-feeding was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2·01, 95 % CI 1·08, 3·73; P = 0·028) as well as with an increased risk of IA-2A above the ninety-ninth percentile (OR 3·50, 95 % CI 1·38, 8·92; P = 0·009) at 5 years of age. An early introduction of formula was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 1·84, 95 % CI 1·01, 3·37; P = 0·047) at 5 years of age. The positive association between a short duration of both total and exclusive breast-feeding, as well as an early introduction of formula, and positivity for β-cell autoantibodies in children from the general population suggests that breast-feeding modifies the risk of β-cell autoimmunity, even years after finishing breast-feeding
Determinants of childhood overweight and obesity in China
Authors: Li Y. , Zhai F. , Yang X. , Schouten E. G. , Hu X. , He Y. , Luan D. , Ma G. 
Published: January 2007

In order to investigate the determinants of childhood overweight and obesity in China, the prevalence of overweight (including obesity) was compared according to different dietary and physical activity patterns and parental body weight status. A total of 6826 children aged 7–17 years from the 2002 China National Nutrition and Health Survey were included in the study. Information for dietary intake was collected using three consecutive 24-h recalls by trained interviewers. The amounts of cooking oil and condiments consumed were weighed. An interview-administered 1-year physical activity questionnaire was used to collect physical activity information. The results showed that the heavier the parental body weight, the higher the overweight prevalence in children. The prevalence ratio increased if parent(s) were overweight and/or obese, up to 12·2 if both parents were obese. Overweight children consumed significantly more dietary energy, protein and fat, but less carbohydrate than their normal weight counterparts. On average, overweight children spent 0·5 h less on moderate/vigorous activities and 2·3 h more on low intensity activities per week. The following prevalence ratios were statistically significant: walking to and from school (0·6); moderate/vigorous activities ≥ 45 min/d (0·8); low intensity physical activities >2 h/d (1·3); the consumption of ≥ 25 g/d cooking oil (1·4); ≥ 200 g/d meat and meat products consumption (1·5); ≥ 100 g/d dairy products (1·8). After adjustment for parental body weight status and socioeconomic status, only cooking oil consumption and walking to and from school remained significantly related to child overweight. In conclusion, parental weight status is an important determinant. Fat intake, low intensity activities and active transport to/from school may be suitable entry points for overweight prevention among Chinese school children.
HIV epidemic trend and antiretroviral treatment need in Karonga District, Malawi
Authors: WHITE R. G. , VYNNYCKY E. , GLYNN J. R. , CRAMPIN A. C. , JAHN A. , MWAUNGULU F. , MWANYONGO O. , JABU H. , PHIRI H. , McGRATH N. , ZABA B. , FINE P. E. M. 
Published: January 2007

SUMMARYWe describe the development of the HIV epidemic in Karonga District, Malawi over 22 years using data from population surveys and community samples. These data are used to estimate the trend in HIV prevalence, incidence and need for antiretroviral treatment (ART) using a simple mathematical model. HIV prevalence rose quickly in the late 1980s and early 1990s, stabilizing at around 12% in the mid-1990s. Estimated annual HIV incidence rose quickly, peaking in the early 1990s at 2·2% among males and 3·1% among females, and then levelled off at 1·3% among males and 1·1% among females by the late 1990s. Assuming a 2-year eligibility period, both our model and the UNAIDS models predicted 2·1% of adults were in need of ART in 2005. This prediction was sensitive to the assumed eligibility period, ranging from 1·6% to 2·6% if the eligibility period was instead assumed to be 1·5 or 2·5 years, respectively.
HIV-1 and HIV-2 prevalence and associated risk factors among postnatal women in Harare, Zimbabwe
Authors: HUMPHREY J. H. , NATHOO K. J. , HARGROVE J. W. , ILIFF P. J. , MUTASA K. E. , MOULTON L. H. , CHIDAWANYIKA H. , MALABA L. C. , ZIJENAH L. S. , ZVANDASARA P. , NTOZINI R. , ZUNGUZA C. D. , WARD B. J. ,   and the ZVITAMBO Study Group
Published: January 2007

SUMMARYStudies of antenatal women form the predominant source of data on HIV-1 prevalence in Africa. Identifying factors associated with prevalent HIV is important in targeting diagnostic services and care. Between November 1997 and January 2000, 14 110 postnatal women from Harare, Zimbabwe were tested by ELISAs reactive to both HIV-1 and HIV-2; a subset of positive samples was confirmed with assays specific for HIV-1 and HIV-2. Baseline characteristics were elicited and modelled to identify risk factors for prevalent HIV infection. HIV-1 and HIV-2 prevalences were 32·0% (95% CI 31·2–32·8) and 1·3% (95% CI 1·1–1·5), respectively; 4% of HIV-1-positive and 99% of HIV-2-positive women were co-infected. HIV-1 prevalence increased from 0% among 14-year-olds to >45% among women aged 29–31 years, then fell to <20% among those aged >40 years. In multivariate analyses, prevalence increased with parity, was lower in married women than in single women, divorcees and widows, and higher in women with the lowest incomes and those professing no religion. Adjusted HIV-1 prevalence increased during 1998 and decreased during 1999. Age modified the effects of parity, home ownership and parental education. Among older women, prevalence was greater for women who were not homeowners. Among younger women, prevalence increased with parity and low parental education. None of these factors distinguished women co-infected with HIV-2 from those infected with HIV-1 alone. Prevalent HIV-1 infection is associated with financial insecurity and weak psychosocial support. The ZVITAMBO study apparently spanned the peak of the HIV-1 epidemic among reproductive women in Harare.
Comparison of smallpox outbreak control strategies using a spatial metapopulation model
Authors: HALL I. M. , EGAN J. R. , BARRASS I. , GANI R. , LEACH S. 
Published: January 2007

SUMMARYTo determine the potential benefits of regionally targeted mass vaccination as an adjunct to other smallpox control strategies we employed a spatial metapopulation patch model based on the administrative districts of Great Britain. We counted deaths due to smallpox and to vaccination to identify strategies that minimized total deaths. Results confirm that case isolation, and the tracing, vaccination and observation of case contacts can be optimal for control but only for optimistic assumptions concerning, for example, the basic reproduction number for smallpox (R0=3) and smaller numbers of index cases (∼10). For a wider range of scenarios, including larger numbers of index cases and higher reproduction numbers, the addition of mass vaccination targeted only to infected districts provided an appreciable benefit (5–80% fewer deaths depending on where the outbreak started with a trigger value of 1–10 isolated symptomatic individuals within a district).
The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males
Authors: Sargentini‐Maier Maria Laura , Rolan Paul , Connell John , Tytgat Dominique , Jacobs Tom , Pigeolet Etienne , Riethuisen Jean‐Michel , Stockis Armel 
Published: January 2007

What is already known about this subject • Brivaracetam is a new chemical entity structurally related to levetiracetam, displaying a markedly higher affinity for the binding site believed to be primarily involved in the antiepileptic effect of levetiracetam.• Studies to evaluate the pharmacological profile of brivaracetam demonstrate an approximately 10‐fold higher potency than levetiracetam as well as a higher efficacy in models of epilepsy.• If translated into therapeutic effects in humans, this would mean a greater decrease in seizure frequency and a higher number of responders and seizure‐free patients in refractory epileptic patients as seen with levetiracetam. What this study adds • This article reports the results of the first in human study with brivaracetam. Its pharmacokinetics and adverse events profile after single administration are evaluated, together with the effect of food on the former.AimsThe objective of the study was to evaluate the pharmacokinetics (and how they are affected by food), CNS pharmacodynamics and the adverse event profile of brivaracetam after single increasing doses.MethodsHealthy males (n = 27, divided into three alternating panels of nine subjects) received two different single oral doses of brivaracetam (10–1400 mg) and one dose of placebo during three periods of a randomized, double‐blind, placebo‐controlled study. The effect of food on its pharmacokinetics was assessed using a standard two‐way crossover design in a further eight subjects who received two single oral doses of brivaracetam (150 mg) in the fasting state and after a high fat meal.ResultsAdverse events, none of which were serious, were mostly CNS‐related and included somnolence, dizziness, and decreased attention, alertness, and motor control. Their incidence, severity and duration were dose‐related. The maximum tolerated dose was established to be 1000 mg. Severe somnolence lasting 1 day occurred in one subject following 1400 mg. Brivaracetam was rapidly absorbed under fasting conditions, with a median tmax of approximately 1 h. Cmax was dose‐proportional from 10 to1400 mg, whereas AUC deviated from dose linearity above 600 mg. A high‐fat meal had no effect on AUC (point estimate 0.99, 90%CI: 0.92–1.07) but delayed tmax (3 h) and decreased Cmax (point estimate 0.72, 90%CI: 0.66–0.79).ConclusionsBrivaracetam was well tolerated after increasing single doses that represent up to several times the expected therapeutic dose. Brivaracetam was found to have desirable pharmacokinetic properties. The most common adverse events were somnolence and dizziness.
Variability in non‐nucleoside reverse transcriptase and protease inhibitors concentrations among HIV‐infected adults in routine clinical practice
Authors: Moltó José , Blanco Asunción , Miranda Cristina , Miranda José , Puig Jordi , Valle Marta , DelaVarga Meritxell , Fumaz Carmina R. , Barbanoj Manuel José , Clotet Bonaventura 
Published: January 2007

AimsThe objective of this study was to assess interindividual variability in plasma trough concentrations of non‐nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) among HIV‐infected adults in an outpatient routine clinical practice setting.MethodsThe study included 117 patients who attended our clinic for routine outpatient blood tests and who were receiving antiretroviral therapy which included NNRTI or PI. Patients were not informed that drug concentrations were going to be assessed until blood sampling. The time of the last antiretroviral treatment intake and blood sampling were recorded. Drug concentrations were considered optimal if they were above the proposed minimum effective concentration. In addition, efavirenz, nevirapine and atazanavir concentrations were considered potentially toxic if they were higher than 4.0 mg l−1, 6.0 mg l−1, and 0.85 mg l−1, respectively.ResultsOverall, interindividual variability in NNRTI and PI plasma concentrations was approximately 50%, and only 68.4% of the patients had drug concentrations within the proposed therapeutic range. Inappropriate adherence only explained 35% of subtherapeutic drug concentrations.ConclusionInterindividual variability in trough concentrations of NNRTI and PI among HIV‐infected adults is large in routine clinical practice, with drug concentrations being outside the therapeutic window in a significant proportion of patients. Therapeutic drug monitoring may be useful to guide antiretroviral therapy in clinical practice.
Effects of clarithromycin and grapefruit juice on the pharmacokinetics of glibenclamide
Authors: Lilja Jari J. , Niemi Mikko , Fredrikson Hanna , Neuvonen Pertti J. 
Published: January 2007

What is already known about this subject • Severe hypoglycaemia has been reported after concomitant use of clarithromycin and glibenclamide.• Glibenclamide is a substrate for the transporters P‐glycoprotein and OATP2B1.• Clarithromycin inhibits P‐glycoprotein and grapefruit juice inhibits OATP2B1. What this study adds • Clarithromycin increases the plasma concentration of glibenclamide.• A pharmacokinetic interaction may explain reported hypoglycaemia during simultaneous administration of clarithromycin and glibenclamide.• Grapefruit juice has no effect on the pharmacokinetics of glibenclamide.AimsCase reports suggest that clarithromycin can increase the glucose‐lowering effect of glibenclamide which is metabolized mainly by CYP2C9 and is a substrate for P‐glycoprotein and OATP2B1. Our objective was to evaluate whether the P‐glycoprotein inhibitor, clarithromycin, increases and the putative OATP2B1 inhibitor, grapefruit juice, decreases plasma concentrations of glibenclamide.MethodsIn a randomized three‐phase crossover study, 12 subjects ingested 250 mg clarithromycin or placebo twice daily or 200 ml grapefruit juice three times daily for 2 days. On day 3, they ingested 0.875 mg glibenclamide with sugar water or grapefruit juice. Concentrations of glibenclamide and clarithromycin in plasma, glucose in blood, and excretion of hydroxyglibenclamide into urine were measured up to 12 h.ResultsClarithromycin increased the peak concentration (Cmax) of glibenclamide to 1.25‐fold (95% confidence interval (CI) 1.12, 1.40; P < 0.01) and the area under the plasma concentration‐time curve to 1.35‐fold (95% CI 1.21, 1.50; P < 0.01) compared with the placebo phase. The time to Cmax, the half‐life of glibenclamide, and the amount of hydroxyglibenclamide excreted into urine remained unaltered. Grapefruit juice did not change the pharmacokinetics of glibenclamide. Clarithromycin concentrations implied a good compliance. Blood glucose did not deviate between the phases.ConclusionsClarithromycin increased plasma concentrations of glibenclamide, possibly by inhibiting P‐glycoprotein in the intestinal wall. Although not seen with the present study design, clarithromycin may enhance the effect of glibenclamide by increasing plasma glibenclamide concentrations, which warrants close monitoring of blood glucose during their co‐administration. Grapefruit juice had no effect on glibenclamide pharmacokinetics.
Detection and follow‐up of fibroblast growth factor receptor 3 expression on bone marrow and circulating plasma cells by flow cytometry in patients with t(4;14) multiple myeloma
Authors: Chandesris M. O. , Soulier J. , Labaume S. , Crinquette A. , Repellini L. , Chemin K. , Malphettes M. , Fieschi C. , Asli B. , Uzunhan Y. , Fermand J. P. , Bories J. C. , Arnulf B. 
Published: January 2007

SummaryThe t(4;14)(p16;q32) translocation, found in 15% of multiple myeloma (MM) cases, indicates a poor prognosis. Plasma cells (PC) with t(4;14) ectopically express the fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase receptor, which has potential transforming activity and may represent a therapeutic target. To detect FGFR3 protein expression, bone marrow (BM) aspirate from 200 consecutive newly diagnosed (n = 116) or relapsing (n = 74) MM patients was studied by flow cytometry (FC) using anti‐CD138 and anti‐FGFR3 antibodies. FC data was compared to real time quantitative‐polymerase chain reaction (RQ‐PCR) of the IGH‐MMSET and FGFR3 transcripts. An IGH‐MMSET transcript was found in 24/200 patients (12%). In 20 of these, FC detected CD138+/FGFR3+ cells. No expression of FGFR3 was detected in the 4 FGFR3− cases by RQ‐PCR. FGFR3 was never expressed on PC without t(4;14). Circulating PC (CPC) were detected in patients with (11/11) and patients without (13/41) t(4;14). In 2/8 t(4;14) cases studied longitudinally, coexisting FGFR3+ and FGFR3− CPC were observed. Fluorescent in situ hybridisation (FISH) analysis of the FGFR3− subclones showed deletion of the der(14) in one patient. In conclusion, as a supplemental method to RQ‐PCR or FISH, FC analysis of FGFR3 expression is a reliable and routinely available method for the detection and management of new therapeutic approaches of t(4;14) MM.