Effect of diet on plasma acid-base composition in normal humans

AbstractEffect of diet on plasma acid-base composition in normal humans. Steady-state plasma and urine acid-base composition was assessed in 19 studies of 16 normal subjects who ingested constant amounts of one of three diets that resulted in different rates of endogenous noncarbonic acid production (EAP) within the normal range. Renal net acid excretion (NAE) was used to quantify EAP since the two variables are positively correlated in normal subjects. A significant positive correlation was observed between plasma [H+] and plasma PCO2, and between plasma [HCO3-] and plasma PCO2, among the subjects. Multiple correlation analysis revealed a significant interrelationship among plasma [H+], plasma PCO2, and NAE (r = 0.71, P < 0.001), and among plasma [HCO3-], plasma PCO2, and NAE (r = 0.77, P < 0.001). The partial correlation coefficients indicated a significant positive correlation between plasma [H+] and NAE, and a significant negative correlation between plasma [HCO3-] and NAE, when plasma PCO2 was held constant. These findings indicate that two factors influence the level at which plasma [H+] is maintained in normal subjects: (1) the steadystate rate of endogenous noncarbonic acid production, and (2) the setpoint at which plasma PCO2 is regulated by the respiratory system. Plasma [HCO3-] is also co-determined by these two factors. In disease states, therefore, both factors must be known before a disturbance in acid-base homeostasis can be excluded.Effet du régime sur la composition acido-basique plasmatique chez des sujets humains normaux. La composition acido-basique plasmatique et urinaire à l'équilibre a été déterminée dans 19 études de 16 sujets normaux qui ingéraient des quantités constantes de l'un de trois régimes aboutissant à différents taux de production endogène d'acides non carboniques (EAP) à l'intérieur de la normale. L'excrétion rénale nette d'acides (NAE) a été utilisée pour quantifier l'EAP puisque les deux variables sont positivement corrélées chez des sujets normaux. Une corrélation significative positive a été observée entre le [H+] plasmatique et la PCO2 plasmatique, et entre le [HCO3-] plasmatique et PCO2 plasmatique, parmi ces sujets. Une analyse par corrélations multiples a révélé une interrelation significative entre [H+] plasmatique, PCO2 plasmatique et NAE (r = 0,71, P < 0,001), et entre [HCO3-] plasmatique, PCO2 plasmatique et NAE (r = 0,77, P < 0,001). Les coefficients de corrélation partielle ont indiqué une corrélation significative positive entre [H+] plasmatique et NAE, et une corrélation significative négative entre [HCO3-] plasmatique et NAE, lorsque PCO2 plasmatique était maintenue constante. Ces résultats indiquent que deux facteurs influencent le niveau auqeal [H+] plasmatique est maintenu chez des sujets normaux: (1) le taux de production à l'équilibre d'acides non carboniques endogènes, et (2) le point d'équilibre auquel PCO2 plasmatique est régulée par le système respiratoire. [HCO3-] plasmatique est également codéterminé par ces deux facteurs. Ainsi, dans les états pathologiques, les deux facteurs doivent être connus avant de pouvoir exclure une perturbation de l'homéostasie acido-basique

Uma maneira prática de distinguir abelhas africanizadas (Apis mellifera L.) de abelhas européias usando o estado excitatório central, a mobilidade dos membros e viabilidade do ferrão

A key to understanding the expansion of Africanized honey bees (Apis mellifera) is distinguishing this aggressive form from its European relative. Current identification techniques have a degree of success, but each has its own set of problems, prohibiting wide-spread adoption and use. This study examined aspects of central excitatory state, persistence of mobile appendages, and a viable sting after decapitation for their use in distinguishing between these two races. Central excitatory state was not useful in distinguishing the Africanized honey bee from the European honey bee; however, appendage mobility and sting viability were significantly different between the two subspecies. Appendage mobility and sting viability are useful techniques for distinguishing the two subspecies, and alleviate the issues of expense, application, and accuracy.Uma chave para o entendimento da expansão da abelha africanizada (Apis mellifera) é distinguir esta abelha agressiva de sua equivalente européia. Técnicas de identificação atual têm um grau de sucesso, mas cada método tem seu próprio conjunto de problemas, tornando-se proibitivo sua adoção e uso em larga escala. Este estudo examinou aspectos do estado excitatório central, persistência de mobilidade de apêndices e viabilidade da ferroada após decapitação como ferramenta na distinção entre essas duas raças. O estado excitatório central não foi útil na distinção entre a abelha africanizada e a européia; todavia, a mobilidade de apêndices e a viabilidade do ferrão foram significativamente diferentes entre essas duas raças. A mobilidade de apêndices e a viabilidade do ferrão são técnicas úteis na distinção das duas raças e atenua os aspectos relacionados a gastos, aplicação e precisão

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

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2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant)

Since the 1995 publication of its Core Cardiovascular Training Statement (COCATS),1 the American College of Cardiology (ACC) has played a central role in defining the knowledge, experiences, skills, and behaviors expected of all clinical cardiologists upon completion of training. Subsequent updates have incorporated major advances and revisions—both in content and structure—including, most recently,

The coding and long noncoding single-cell atlas of the developing human fetal striatum.

Deciphering how the human striatum develops is necessary for understanding the diseases that affect this region. To decode the transcriptional modules that regulate this structure during development, we compiled a catalog of 1116 long intergenic noncoding RNAs (lincRNAs) identified de novo and then profiled 96,789 single cells from the early human fetal striatum. We found that D1 and D2 medium spiny neurons (D1- and D2-MSNs) arise from a common progenitor and that lineage commitment is established during the postmitotic transition, across a pre-MSN phase that exhibits a continuous spectrum of fate determinants. We then uncovered cell type-specific gene regulatory networks that we validated through in silico perturbation. Finally, we identified human-specific lincRNAs that contribute to the phylogenetic divergence of this structure in humans. This work delineates the cellular hierarchies governing MSN lineage commitment

The lipid phosphatase LPP3 regulates extra-embryonic vasculogenesis and axis patterning

Bioactive phospholipids, which include sphingosine-1-phosphate, lysophosphatidic acid, ceramide and their derivatives regulate a wide variety of cellular functions in culture such as proliferation, apoptosis and differentiation. The availability of these lipids and their products is regulated by the lipid phosphate phosphatases (LPPs). Here we show that mouse embryos deficient fo

Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks

In mammalian cells, DNA double-strand breaks (DSBs) are repaired by three pathways, nonhomologous end-joining (NHEJ), gene conversion (GC) and single-strand annealing (SSA). These pathways are distinct with regard to repair efficiency and mutagenic potential and must be tightly controlled to preserve viability and genomic stability. Here, we employed chromosomal reporter constructs to characterize the hierarchy of NHEJ, GC and SSA at a single I-SceI-induced DSB in Chinese hamster ovary cells. We discovered that the use of GC and SSA was increased by 6- to 8-fold upon loss of Ku80 function, suggesting that NHEJ is dominant over the other two pathways. However, NHEJ efficiency was not altered if GC was impaired by Rad51 knockdown. Interestingly, when SSA was made available as an alternative mode for DSB repair, loss of Rad51 function led to an increase in SSA activity at the expense of NHEJ, implying that Rad51 may indirectly promote NHEJ by limiting SSA. We conclude that a repair hierarchy exists to limit the access of the most mutagenic mechanism, SSA, to the break site. Furthermore, the cellular choice of repair pathways is reversible and can be influenced at the level of effector proteins such as Ku80 or Rad51

A fibril-specific, conformation-dependent antibody recognizes a subset of Aβ plaques in Alzheimer disease, Down syndrome and Tg2576 transgenic mouse brain

Beta-amyloid (Aβ) is thought to be a key contributor to the pathogenesis of Alzheimer disease (AD) in the general population and in adults with Down syndrome (DS). Different assembly states of Aβ have been identified that may be neurotoxic. Aβ oligomers can assemble into soluble prefibrillar oligomers, soluble fibrillar oligomers and insoluble fibrils. Using a novel antibody, OC, recognizing fibrils and soluble fibrillar oligomers, we characterized fibrillar Aβ deposits in AD and DS cases. We further compared human specimens to those obtained from the Tg2576 mouse model of AD. Our results show that accumulation of fibrillar immunoreactivity is significantly increased in AD relative to nondemented aged subjects and those with select cognitive impairments (p < 0.0001). Further, there was a significant correlation between the extent of frontal cortex fibrillar deposit accumulation and dementia severity (MMSE r = −0.72). In DS, we observe an early age of onset and age-dependent accumulation of fibrillar OC immunoreactivity with little pathology in similarly aged non-DS individuals. Tg2576 mice show fibrillar accumulation that can be detected as young as 6 months. Interestingly, fibril-specific immunoreactivity was observed in diffuse, thioflavine S-negative Aβ deposits in addition to more mature neuritic plaques. These results suggest that fibrillar deposits are associated with disease in both AD and in adults with DS and their distribution within early Aβ pathology associated with diffuse plaques and correlation with MMSE suggest that these deposits may not be as benign as previously thought

Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: The randomized PILLAR study

The phase IIb, double-blind, placebo-controlled PILLAR trial investigated the efficacy and safety of two different simeprevir (SMV) doses administered once-daily (QD) with pegylated interferon (Peg-IFN)-α-2a and ribavirin (RBV) in treatment-naïve patients with HCV genotype 1 infection. Patients were randomized to one of five treatments: SMV (75 or 150 mg QD) for 12 or 24 weeks or placebo, plus Peg-IFN and RBV. Patients in the SMV arms stopped all treatment at week 24 if response-guided therapy (RGT) criteria were met; patients not meeting RGT continued with Peg-IFN and RBV until week 48, as did patients in the placebo control group. Sustained virologic response (SVR) rates measured 24 weeks after the planned end of treatment (SVR24) were 74.7%-86.1% in the SMV groups versus 64.9% in the control group (P < 0.05 for all comparisons [SMV versus placebo], except SMV 75 mg for 24 weeks). Rapid virologic response (HCV RNA <25 IU/mL undetectable at week 4) was achieved by 68.0%-75.6% of SMV-treated and 5.2% of placebo control patients. According to RGT criteria, 79.2%-86.1% of SMV-treated patients completed treatment by week 24; 85.2%-95.6% of these subsequently achieved SVR24. The adverse event profile was generally similar across the SMV and placebo control groups, with the exception of mild reversible hyperbilirubinemia, without serum aminotransferase abnormalities, associated with higher doses of SMV