Increasing amounts of dietary myristic acid modify the plasma cholesterol level and hepatic mass of scavenger receptor BI without affecting bile acid biosynthesis in hamsters

The purpose of this study was to analyze the effects of increasing amounts of dietary myristic acid (0.03 to 4.2% of the total dietary energy) on the plasma and hepatic cholesterol metabolism. Six groups of hamsters received semi-purified diets containing 0.05% cholesterol and 12.5% lipids and differing only by the nature of the triglycerides (Safflower oil, lard, lard/coconut oil (1:1), milk fat, milk fat/coconut oil (1:1), coconut oil) for 3 weeks. A positive regression between the plasma cholesterol level and the dietary myristic acid level was observed (r = 0.60, P < 0.0001). However, it is noteworthy that the increase in plasma total cholesterol only reflects an increase in the level of HDL-cholesterol. In parallel, the mass SR-BI decreased linearly with the increased level of myristic acid in the diet, whereas the LDL-R did not change. This study shows that increasing amounts of myristic acid (0.03 to 4.2%) do not alter the cholesterol or bile acid metabolism and increase only the HDL-C.     

Is caseinomacropeptide from milk proteins,an inhibitor of gastric secretion?

The aim of this work was to study, in vivo, the effect of the ingestion of not glycosylated caseinomacropeptide (CMP) on gastric secretion. In Experiments #1 and #2, 7 calves fitted with a gastric pouch received either a diet without CMP (C diet) or C diet in which CMP was introduced (equal to and 5 folds that of CMP quantity contained in cow milk, diets CMP1 and CMP5, respectively). In Experiment #3, 2 calves (with gastric pouch) were fed C diet followed by an “iv perfusion” of CMP. In Experiment #4, 25 calves fed either C, CMP1 or CMP5 diets were fitted with a blood catheter for sample collections. The quantities of daily gastric secretions seemed few modified by CMP ingestion but the profile of these secretions was changed along the day. The most important result is that CMP can inhibit gastric secretions (mainly hydrochloric acid) stimulated by the meal, but there was no dose-dependent response. No similar observations were obtained after perfusion of CMP in jugular vein. CMP was not detected in blood. Results obtained in our experiments are not in favor of its significant intestinal absorption. Gastrin, somatostatin and VIP could be implicated in the mechanisms of regulation.     

Partially randomized, non-blinded trial of DNA and MVA therapeutic vaccines based on hepatitis B virus surface protein for chronic HBV infection

Background

Chronic HBV infects 350 million people causing cancer and liver failure. We aimed to assess the safety and efficacy of plasmid DNA (pSG2.HBs) vaccine, followed by recombinant modified vaccinia virus Ankara (MVA.HBs), encoding the surface antigen of HBV as therapy for chronic HBV. A secondary goal was to characterize the immune responses.

Methods

Firstly 32 HBV e antigen negative (eAg^–) participants were randomly assigned to one of four groups: to receive vaccines alone, lamivudine (3TC) alone, both, or neither. Later 16 eAg⁺ volunteers in two groups received either 3TC alone or both 3TC and vaccines. Finally, 12 eAg^– and 12 eAg⁺ subjects were enrolled into higher-dose treatment groups. Healthy but chronically HBV-infected males between the ages of 15 – 25 who lived in the western part of The Gambia were eligible. Participants in some groups received 1 mg or 2 mg of pSG2.HBs intramuscularly twice followed by 5×10⁷ pfu or 1.5×10⁸ pfu of MVA.HBs intradermally at 3-weekly intervals with or without concomitant 3TC for 11–14 weeks. Intradermal rabies vaccine was administered to a negative control group. Safety was assessed clinically and biochemically. The primary measure of efficacy was a quantitative PCR assay of plasma HBV. Immunity was assessed by IFN-γ ELISpot and intracellular cytokine staining.

Results

Mild local and systemic adverse events were observed following the vaccines. A small shiny scar was observed in some cases after MVA.HBs. There were no significant changes in AST or ALT. HBeAg was lost in one participant in the higher-dose group. As expected, the 3TC therapy reduced viraemia levels during therapy, but the prime-boost vaccine regimen did not reduce the viraemia. The immune responses were variable. The majority of IFN-γ was made by antigen non-specific CD16⁺ cells (both CD3⁺ and CD3^–).

Conclusions

The vaccines were well tolerated but did not control HBV infection.

Trial Registration

ISRCTN ISRCTN67270384     

The ligase chain reaction distinguishes hepatitis B virus S-gene variants

Abstract The functional significance of charged amino acids of the anion-selective porin Omp34 from Acidovorax delafieldii was investigated by means of conductance measurements. Chemical modification of Lys and Arg as well as titration of charges by adjusting the pH value revealed that positively charged amino acid residues determine the major functional properties of the porin. Positive charges are involved in creating the protein surface potential, the selectivity filter inside the channels, and the voltage-sensing and/or gating mechanisms.     

GABAA Receptors Containing ρ1 Subunits Contribute to In Vivo Effects of Ethanol in Mice

GABA_A receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR), and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABA_A receptor subunits. (S)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ1” antagonist), when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests), but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ2” antagonist) did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting) ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABA_A receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo.     

The Association between Individual and Combined Components of Metabolic Syndrome and Chronic Kidney Disease among African Americans: The Jackson Heart Study

Introduction

Approximately 26.3 million people in the United States have chronic kidney disease and many more are at risk of developing the condition. The association between specific metabolic syndrome components and chronic kidney disease in African American individuals is uncertain.

Methods

Baseline data from 4,933 participants of the Jackson Heart Study were analyzed. Logistic regression models were used to estimate the odds and 95% confidence intervals of chronic kidney disease associated with individual components, metabolic syndrome, the number of components, and specific combinations of metabolic syndrome components.

Results

Metabolic syndrome was common with a prevalence of 42.0%. Chronic kidney disease was present in 19.4% of participants. The prevalence of metabolic components was high: elevated blood pressure (71.8%), abdominal obesity (65.8%), low fasting high density lipoprotein cholesterol (37.3%), elevated fasting glucose (32.2%) and elevated triglycerides (16.2%). Elevated blood pressure, triglycerides, fasting blood glucose, and abdominal obesity were significantly associated with increased odds of chronic kidney disease. Participants with metabolic syndrome had a 2.22-fold (adjusted odds ratio (AOR) 2.22; 95% CI, 1.78–2.78) increase in the odds of chronic kidney disease compared to participants without metabolic syndrome. The combination of elevated fasting glucose, elevated triglycerides, and abdominal obesity was associated with the highest odds for chronic kidney disease (AOR 25.11; 95% CI, 6.94–90.90).

Conclusion

Metabolic syndrome as well as individual or combinations of metabolic syndrome components are independently associated with chronic kidney disease in African American adults.     

Pyrrolooxygenases from Argentine wheat varieties

Pyrrolooxygenase activities were examined in different varieties of Argentine wheat (Triticum aestivum) which included the traditional Klein varieties and the new mixed Mexican and traditional varieties (DeKalb and Cargill). The enzymatic activities were variety-dependent and were more inhibited in some varieties than in others, while some (Cargill) were devoid of the proteic inhibitor. The enzymes were isolated from the flours as two isoenzymes of different charge whose relative proportions were dependent on the variety of wheat used. The more cationic isoenzymes were eluted with 10 mM Tris-HCl buffer (pH 7.6 from DEAE-cellulose and the less cationic were eluted with 50 mM NACl in the same buffer. The protein inhibitor, when present, was associated with the more cationic isoenzymes. Porphobilinogen oxygenase and skatole pyrrolooxygenase activities were higher in the endosperm, while tryptophan pyrrolooxygenase activity was higher in the embryo. The proteic inhibitors were mainly concentrated in the embryo.     

Describing the current status of Plasmodium falciparum population structure and drug resistance within mainland Tanzania using molecular inversion probes

High‐throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programmes, and to monitor the spread of mutations associated with drug resistance. An up‐to‐date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high‐burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania countrywide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome‐wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, approximately separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from nearby districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts (including two infections carrying pfk13‐R561H), and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region‐level complexity‐of‐infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared.     

Increase in female liver cancer in the Gambia, West Africa: evidence from 19 years of population-based cancer registration (1988-2006)

Background

Hepatocellular Carcinoma (HCC) is a common malignancy worldwide with a high burden in West Africa. Male to female ratios show consistent bias toward males, the biological bases and variations of which are not well understood. We have used data from the Gambian National Cancer Registry to compare trends in incidence of HCC in both genders.

Methods and Findings

Two periods were compared, 1988–1997 (early) and 1998–2006 (recent). In addition, the regression program joinpoint was used to assess trends over 19 years. Differences with self-reported ethnicity were assessed for the recent period using population data from 2003 census. Male to female ratio showed a significant decrease between the two periods from 3.28∶1 (95% CI, [2.93–3.65]) to 2.2∶1 (95% CI, [1.99–2.43]). Although rates in males were relatively stable (38.36 and 32.84 for, respectively, early and recent periods), they increased from 11.71 to 14.9 in females with a significant Annual Percentage Change of 3.01 [0.3–5.8] over 19 years and an increase in number of cases of 80.28% (compared to 26% in males). Significant variations in HCC risk, but not in gender ratio were observed in relation with ethnicity.

Conclusion

This analysis of the only national, population-based cancer registry in West Africa shows a significant increase in HCC in females over recent years. This increase may be the consequence of major changes in lifestyle or viral risk factors, in particular obesity and hepatitis C, which have both been documented to increase in West Africa during recent years.