硝苯地平对抗吗啡戒断所致焦虑作用研究

目的··：评价钙拮抗剂硝苯地平对戒断后期焦虑症状及复吸的治疗作用。方法··：大鼠自然戒断后，采用Ｖｏｇｅｌ＇ｓ饮水冲突模型（简称Ｖｏｇｅｌ冲突模型）观察吗啡依赖大鼠的焦虑情绪与硝苯地平的作用。结果··：２０，３０，５０ｍｇ·ｋｇ－１的硝苯地平能明显增加大鼠的舔水次数和被电击次数，并呈剂量相关性，以３０ｍｇ·ｋｇ－１作用最为明显。结论··：钙离子拮抗剂可治疗吗啡戒断所致的焦虑症状，可能与５－ＨＴ等神经递质的释放或与ＧＡＢＡ能神经有关     

Sensitivity of effect variables in rheumatoid arthritis: A meta-analysis of 130 placebo controlled NSAID trials controlled NSAID trials

In a meta-analysis of placebo controlled NSAID trials, the sensitivity of the effect variables was calculated as the correlation coefficient and as the difference between drug and placebo, divided by the placebo group standard deviation. The patient's global evaluation was the most sensitive variable overall. Pain was more sensitive than Ritchie's index. Several variables may be omitted from clinical trials, especially if two active drugs are being compared. For example, the best maximum estimate for the difference in ESR between NSAADs and placebo was 1.0 mm/hr (95% confidence interval −1.5 to 3.4 mm/hr), and for joint size 0.44% (−1.0 to 1.9%), corresponding to a quarter of a millimeter for each of the 10 joints usually measured. It is suggested to record only the patient's global evaluation, pain, and morning stiffness.     

酶活性法测定GAD抗体及其初步临床应用

目的建立测定谷氨酸脱羧酶（ＧＡＤ）抗体的方法，以探讨该抗体对胰岛素依赖型糖尿病（ＩＤＤＭ）的预测、早期诊断及其发病机制研究的意义。方法用专用酶反应试管建立放射性同位素底物测定ＧＡＤ活性的分析方法。结果底物浓度为４ｍｍｏｌ／ｍｌ（３７ｋＢｑ）时，酶活性测定在一定浓度范围内剂量效应呈直线关系（ｒ＝０９８９）。结合免疫沉淀与酶活性分析，建立了免疫沉淀酶活性分析测定ＧＡＤ抗体的方法，２份ＩＤＤＭ患者ＧＡＤ抗体阳性血清与酶活性免疫沉淀指数存在剂量效应关系。用免疫沉淀酶法测定１５例正常人及２０例病程１年以内的ＩＤＤＭ患者血清，两组酶活性免疫沉淀指数分别为０１９３±００８７和０３８１±０１２１，差异有显著性（Ｐ＜００１）。按照超过正常人组免疫沉淀指数ｘ＋２ｓ为阳性区分，２０例ＩＤＤＭ患者血清中ＧＡＤ抗体阳性９例，占４５％。结论该方法简单，能直接反映酶活性的改变，无需高纯度的ＧＡＤ，特别适用于刚开始从事ＧＡＤ抗体研究的实验室及阳性血清筛查。     

基于两样本孟德尔随机化方法探讨睡眠与痛风的关联

[目的] 通过两样本孟德尔随机化设计,探讨睡眠与痛风之间的关联。[方法] 从一项包含763 813名参与者的全基因组关联研究(genome-wide association study,GWAS)中获取痛风遗传关联数据。以与打鼾、睡眠时间、睡眠类型、失眠及白日困倦程度等睡眠表型相关的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,采用逆方差加权(inverse variance weighted,IVW)评估遗传学预测的不同睡眠表型与痛风发生风险的关系。采用MR-Egger回归和孟德尔随机多态性残差和离群值(MR pleiotropy residual sum and outlier,MR-PRESSO)检验进行敏感性分析,以评估工具变量的多效性。进一步采用加权中位数法、简单中位数法、最大似然比法等分析方法检验结果的稳健性与可靠性。[结果] IVW结果显示,遗传学预测的打鼾[优势比(odds ratio,OR)=3.12,95%置信区间(confidence interval,CI)(1.21～8.05),PFDR=0.045]和失眠[OR=1.09,95%CI(1.04～1.15),PFDR=0.005]与痛风发生风险呈正相关,而睡眠时间、睡眠类型及白日困倦程度与痛风发生之间不存在统计学关联。MR-Egger回归提示上述因果关联未受到水平多效性影响,加权中位数法、简单中位数法、最大似然比法得出与IVW相似的结果。[结论] 打鼾、失眠与痛风发生风险呈正相关,纠正打鼾和失眠可能对痛风有一定的预防作用。     

The depressing effect of tetracaine and ryanodine on the slow outward current correlated with that of contraction in voltage-clamped frog muscle fibres

The effects of tetracaine (10–50 M) and ryanodine (0.1–10 M) were tested on the slow outward K⁺ current (I _so) and the mechanical tension of isolated frog muscle fibres in a voltage-clamp device (double mannitol-gap) connected to a mechanoelectric transducer. In the concentration range tested, both drugs induced a simultaneous inhibition of tension and current. In all cases the effect on tension was twice that on current. The tetracaine-induced current and tension blocks were fully reversible and dose-dependent. In contrast the ryanodine effects on current and tension were not reversible and did not exhibit a dose dependence except for the delay before the onset of the response, which was shortened when the concentration was raised. Linear regression analysis of the time-dependent and dose-dependent effects of both drugs indicated a strong correlation between the decreases in tension and current. It is concluded that the slow outward current is partly under the control of the Ca²⁺ release from sarcoplasmic reticulum during contraction.     

Molecular epidemiology of norovirus variants detected in children under five years of age in Hyderabad,India

PurposeNoroviruses are common viral agents in acute diarrhea in all age groups worldwide. Norovirus has been classified into 10 genogroups, GI to GX with over 48 genotypes among them the GII.4 genotype has evolved over time with a clear pattern of periodic variant replacement. Immunity is strain or genotype specific with little or no protection conferred across genogroups. The present study was aimed to determine the epidemiology, prevalent genotypes of norovirus in children below five years of age in the Hyderabad region, India.MethodsThe stool samples and clinical data were collected from 458 children below 5 years of age comprising of cases with acute gastroenteritis (n ?= ?366) and a control group (n ?= ?92) admitted to the pediatric ward. All the samples were tested for Norovirus by ELISA and RT-PCR. Sequencing was done for predominant strains.Results10.3% (n ?= ?38) of cases and 3.2% (n ?= ?3) of the control group were found to be Norovirus positive. Predominant genotypes were GII-82.5% followed by GI-12.5%.ConclusionSequencing and Phylogenetic analyses of 20 GII.4 strains was done. All of the isolates are clustered away from published the GII.4 variants thus suggesting the appearance of a new variant.     

Studies on the Level of Natural Antibodies Reactive with Various Tumor Cells during Urethane Carcinogenesis in BALB/c Mice

Serum from young normal BALB/c mice was found to contain IgM antibodies able tomediate complement-dependent lysis of certain syngeneic or allogeneic tumor target cells. The titer of such naturally occurring antitumor antibodies (NATA) was found to increase with aging.A longitudinal serological study comparing the cytotoxicity potential of NATA fromnormal and from urethan-treated BALB/c mice was performed. It was found that urethan-treated mice that did not develop primary lung-adenomas within the duration of the experi-ment had significantly lower NATA titers, against one out of 4 target cells assayed, than urethan-treated animals that developed lung adenomas. This difference was evident in two independent experiments. The results suggested that the lower NATA activity of the urethan-treated mice that did not develop tumors existed even before exposure to the carcinogenic insult. This raises the possibility that certain populations could be segregated according to their natural antibody profile into those individuals which will develop primary tumors within a certain period if exposed to a subthreshold amount of carcinogen, and those which will not.     

Large Family With Maturity-Onset Diabetes of the Young and a Novel V121I Mutation in HNF4A

Maturity-onset diabetes of the young (MODY) is a subtype of early-onset diabetes mellitus which is characterized by autosomal dominant inheritance. Several genes are known to induce MODY : HNF4A/MODY1, GCK/MODY2, TCF1/MODY3, IPF1/MODY4, TCF2/MODY5 and NEUROD1/MODY6. We studied a Swiss family with 13 diabetic patients over 3 generations. The average age at diagnosis was 35 +/- 15 years (7 subjects before 30). In addition, 2 individuals had an abnormal oral glucose tolerance. The mutation present in this family was located in the DNA binding domain of HNF4A, a strongly conserved region across almost all species, and segregated in all the MODY patients. Identification of this missense mutation allowed for presymptomatic diagnosis in the younger generations and will improve medical follow-up of the predisposed individuals.     

The concentrative nucleoside transporter family,SLC28

The SLC28 family consists of three subtypes of sodium-dependent, concentrative nucleoside transporters, CNT1, CNT2, and CNT3 (SLC28A1, SLC28A2, and SLC28A3, respectively), that transport both naturally occurring nucleosides and synthetic nucleoside analogs used in the treatment of various diseases. These subtypes differ in their substrate specificities: CNT1 is pyrimidine-nucleoside preferring, CNT2 is purine-nucleoside preferring, and CNT3 transports both pyrimidine and purine nucleosides. Recent studies have identified key amino acid residues that are determinants of pyrimidine and purine specificity of CNT1 and CNT2. The tissue distributions of the CNTs vary: CNT1 is localized primarily in epithelia, whereas CNT2 and CNT3 have more generalized distributions. Nucleoside transporters in the SLC28 and SLC29 families play critical roles in nucleoside salvage pathways where they mediate the first step of nucleotide biosynthesis. In addition, these transporters work in concert to terminate adenosine signaling. SLC28 family members are crucial determinants of response to a variety of anticancer and antiviral nucleoside analogs, as they modulate the entry of these analogs into target tissues. Further, this family is involved in the absorption and disposition of many nucleoside analogs. Several CNT single nucleoside polymorphisms (SNPs) have been identified, but have yet to be characterized.     

Advanced 1H Solid‐State NMR Spectroscopy on Hydrogels, 1

Summary: The nature of the pH dependent collapse of poly(methacrylic acid) (PMAA) hydrogels is investigated using recent ¹H solid‐state NMR methods. In aqueous solution, PMAA changes from an expanded conformation at high pHs to a compact contracted form at low pHs, where hydrogen bonds play a central role. In solid‐state ¹H NMR spectra, recorded under fast magic angle spinning (MAS), dried PMAA samples previously collapsed at low pHs show characteristic signals in the spectral region of the carboxylic acid protons. With the aid of 2D ¹H‐¹H double‐quantum (DQ) MAS NMR spectra, three signals can be distinguished at 8, 10.5 and 12.5 ppm, which are attributed to free carboxylic groups and two different types of hydrogen bonded forms, respectively. The 12.5 ppm signal arises from the hydrogen bond with the shortest H? H distance, corresponding to the form that is most stable with respect to increasing temperature and pH. The weaker hydrogen‐bonded form (with a signal at 10.5 ppm) requires a slightly lower pH, while the free acid signal (at 8 ppm) emerges under the most acidic medium. Moreover, the stabilities of the hydrogen‐bonded carboxylic acid dimers can be inferred from the proton‐proton distances within the dimers, i.e. (275 ± 5) pm and (295 ± 15) pm for the protons at 12.5 and 10.5 ppm, respectively, which are determined by means of DQ MAS sideband patterns. Both the stability of the hydrogen bonds and the acidity of the protons may be related to the stereochemistry and the conformation of the PMAA chains.