In vivo microdialysis of 2-deoxyglucose 6-phosphate into brain: a novel method for the measurement of interstitial pH using 31P-NMR

A unique method for simultaneously measuring interstitial (pHe) as well as intracellular (pHi) pH in the brains of lightly anesthetized rats is described. A 4-mm microdialysis probe was inserted acutely into the right frontal lobe in the center of the area sampled by a surface coil tuned for the collection of 31P-NMR spectra. 2-Deoxyglucose 6-phosphate (2-DG-6-P) was microdialyzed into the rat until a single NMR peak was detected in the phosphomonoester region of the 31P spectrum. pHe and pHi values were calculated from the chemical shift of 2-DG-6-P and inorganic phosphate, respectively, relative to the phosphocreatine peak. The average in vivo pHe was 7.24+/-0.01, whereas the average pHi was 7.05+/-0.01 (n = 7). The average pHe value and the average CSF bicarbonate value (23.5+/-0.1 mEq/L) were used to calculate an interstitial Pco2 of 55 mm Hg. Rats were then subjected to a 15-min period of either hypercapnia, by addition of CO2 (2.5, 5, or 10%) to the ventilator gases, or hypocapnia (PCO2 < 30 mm Hg), by increasing the ventilation rate and volume. pHe responded inversely to arterial Pco2 and was well described (r2 = 0.91) by the Henderson-Hasselbalch equation, assuming a pKa for the bicarbonate buffer system of 6.1 and a solubility coefficient for CO2 of 0.031. This confirms the view that the bicarbonate buffer system is dominant in the interstitial space. pHi responded inversely and linearly to arterial PCO2. The intracellular effect was muted as compared with pHe (slope = -0.0025, r2 = 0.60). pHe and pHi values were also monitored during the first 12 min of ischemia produced by cardiac arrest. pHe decreases more rapidly than pHi during the first 5 min of ischemia. After 12 min of ischemia, pHe and pHi values were not significantly different (6.44+/-0.02 and 6.44+/-0.03, respectively). The limitations, advantages, and future uses of the combined microdialysis/31P-NMR method for measurement of pHe and pHi are discussed.     

Molecular alterations in early gastric carcinomas. No apparent correlation with Helicobacter pylori status

The effect of nitric oxide (NO) donors on high-voltage-activated Ca2+ channels in insulin-secreting RINm5F cells was investigated using the patch-clamp technique in the whole-cell configuration. Sodium nitroprusside (SNP, 2-400 microM) induced a dose-dependent reduction in Ba2+ currents with maximal inhibition of 58%. The IC50 for SNP was 45 microM. A different NO donor, (+/-)S-nitroso-N-acetylpenicillamine (SNAP, 500 microM), also produced a 50% decrease in current amplitude. When 200 microM SNP was administered together with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidozoline-1-oxyl-3-oxide (carboxy-PTIO, 300 microM), the Ba2+ current inhibition was lowered to 7%. Administration of 500 microM 8-bromoguanosine 3':5'-cyclic monophosphate sodium salt (8-Br-cGMP) mimicked the effects of SNP, causing a comparable decrease (56%) in peak-current amplitude. When soluble guanylyl cyclase was blocked by 10 microM 1H-[1,2, 4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), the inhibitory effect of 200 microM SNP was reduced from 39% to 15%. The SNP-induced current decrease was 36% of controls after the blockade of L-type Ca2+ channels and 30% in the presence of 2.5 microM omega-conotoxin-MVIIC. These data indicate that NO inhibits both L-type and P/Q-type Ca2+ channels in RINm5F cells, probably by an increase in the intracellular levels of cGMP. NO may then significantly influence the Ca2+-dependent release of hormones from secretory cells as well as that of neurotransmitters from nerve terminals.     

CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2

RASGRP2 encodes the calcium and diacylglycerol (DAG)-regulated guanine nucleotide exchange factor I (CalDAG-GEFI) identified as a Rap1-activating molecule. Pathogenic variants previously identified in RASGRP2 allowed the characterization of CalDAG-GEFI deficiency as a non-syndromic, autosomal recessive platelet function disease. We report on the clinical manifestations and laboratory features of a Portuguese family with a likely pathogenic variant in RASGRP2 (c.999G>C leading to a p.Lys333Asn change in the CDC25 catalytic domain of CalDAG-GEFI) and discuss the contribution of this variant to the disease manifestations. Based on the study of this family with one homozygous patient and five heterozygous carriers and on a critical analysis of the literature, we challenge previous knowledge that CalDAG-GEFI deficiency only manifests in homozygous patients. Our data suggest that at least for the RASGRP2 variant reported herein, there is a phenotypic expression, albeit milder, in heterozygous carriers.     

Essential Oils from Annonaceae Species from Brazil: A Systematic Review of Their Phytochemistry,and Biological Activities

The present work involves a systematic review of the chemical composition and biological effects of essential oils from the Annonaceae species collected in Brazil from 2011 to 2021. Annonaceae is one of the most important botanical families in Brazil, as some species have economic value in the market as local and international fruit. In addition, the species have useful applications in several areas—for instance, as raw materials for use in cosmetics and perfumery and as medicinal plants. In folk medicine, species such as Annona glabra L. and Xylopia sericea A. St.-Hil. are used to treat diseases such as rheumatism and malaria. The species of Annonaceae are an important source of essential oils and are rich in compounds belonging to the classes of mono and sesquiterpenes; of these compounds, α-pinene, β-pinene, limonene, (E)-caryophyllene, bicyclogermacrene, caryophyllene oxide, germacrene D, spathulenol, and β-elemene are the most abundant. The antimicrobial, anti-inflammatory, antileishmania, antioxidant, antiproliferative, cytotoxic, larvicidal, trypanocidal, and antimalarial activities of essential oils from the Annonaceae species in Brazil have been described in previous research, with the most studies on this topic being related to their antiproliferative or cytotoxic activities. In some studies, it was observed that the biological activity reported for these essential oils was superior to that of drugs available on the market, as is the case of the essential oil of the species Guatteria punctata (Aubl.) R. A. Howard., which showed a trypanocidal effect that was 34 times stronger than that of the reference drug benznidazol.     

Influence of freezing process on free sugars content of papaya and banana fruits

Changes in individual sugar content (fructose, glucose and sucrose) during freezing and frozen storage have been evaluated by HPLC on papaya (Carica papaya grupo Solo var Sunrise), fruits proceedings from female and hermaphrodite flowers, and banana (Musa cavendishii var enana). Effects of thermal treatments, such as blanching and microwaving, prior to freezing banana fruit were examined. Both an increase in total sugar levels of papaya samples during freezing and a decrease in sucrose, by invertase, were found followed by an increase in fructose and glucose. A slight decrease in total sugars of banana samples during freezing and storage has been observed, with no significant differences between the pretreatments applied. © 1998 SCI.     

Dual Modification of Banana Starch: Partial Characterization

Banana starch was double modified by cross‐linking and substitution, using two different cross‐linking agents, i.e. phosphorus oxychloride (POCl₃) and a mixture of sodium trimetaphosphate/sodium tripolyphosphate. The morphological and physicochemical properties and the absorption capacity for heavy metals of the modified starches were assessed. Double modified starch granules (cross‐linked carboxymethyl starches CCSA and CCSB) presented changes in the surfaces. These starches had a bigger average particle size than unmodified starch due to the swelling of the granules during the chemical modification, also aggregates were formed. The double modified banana starches presented an A‐type X‐ray diffraction pattern with slightly decreased crystallinity compared with the unmodified counterparts. The double modification of banana starch decreases the temperature and enthalpy of gelatinization and the decomposition temperature. These results are related to partial disorganization during the chemical treatment. The double modified banana starch possess sorption capacity for heavy metal ions in the order Cd²⁺ >Pb²⁺>Cu²⁺>Hg²⁺. Due to their physicochemical characteristics and absorption capacity, the double modified banana starches can be used in diverse applications.     

燃料液滴云雾爆轰特性研究

借助立式爆轰管对燃料液滴云雾的爆轰参数进行实验测定,分析影响爆轰性能的因素.研究结果表明,燃料C5H8.68和环氧丙烷(PO)液滴云雾的临界当量起爆能与当量浓度比的关系为"U"型曲线,C5H8.68和PO在当量浓度比分别为1.17和1.05时,云雾的临界起爆能最小,在富燃料一侧,当量浓度比在一定范围内,C5H8.68和PO云雾爆轰力分别为2.6 Mpa和1.76 Mpa,用C5H8.68代替PO可以相应增加燃料空气炸药的威力.     

Phenotypic and genetic heterogeneity of lactic acid bacteria isolated from “Alheira”, a traditional fermented sausage produced in Portugal

The aim of this study was to evaluate the phenotypic and genetic heterogeneity of lactic acid bacteria (LAB) isolated from “Alheira”, a fermented sausage produced in Portugal.     

Neuropsychological effects of antiepileptic drugs: a current perspective

Epilepsy has widespread direct and indirect effects on the patient's quality of life. These patients generally have neuropsychological impairments that lower their educational and occupational levels of achievement, and many have additional emotional and/or behavioral disorders. Multiple factors underlie the cognitive changes associated with epilepsy, including the effect of antiepileptic drug (AED) therapy itself. Although it is recognized that the beneficial results of reduced seizure frequency may compensate at least in part for detrimental cognitive AED side effects, polypharmacy and higher AED blood levels can shift this balance. Further, there is much debate concerning the existence and clinical importance of differential AED cognitive side effects. While all the major AEDs can produce cognitive side effects, more recent research indicates that the magnitude of these effects may not be clinically significant with monotherapy within standard therapeutic range. The impact of AED differential cognitive side effects on the patient's quality of life is only beginning to be appreciated as research focuses on this important aspect of patient management. The information gained from such investigations will influence not only current therapeutic decisions, but also the development of future anticonvulsants.