Role of noradrenergic hyperactivity in neonatal opiate abstinence

Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the α2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.     

Juvenile Rheumatoid Arthritis: Benefits from Massage Theraphy

Studied children with mild to moderate juvenile rheumatoid arthritiswho were massaged by their parents 15 minutes a day for 30 days(and a control group engaged in relaxation therapy). The children'sanxiety and stress hormone (cortisol) levels were immediatelydecreased by the massage, and over the 30-day period their paindecreased on self-reports, parent reports, and their physician'sassessment of pain (both the incidence and severity) and pain-limitingactivities     

Knowledge, attitudes and beliefs about AIDS in township school students in Cape Town

Students (N = 377) from four Cape Town township high schools were surveyed to obtain information on their knowledge of and attitudes towards the acquired immunodeficiency syndrome (AIDS), and on their sexual behaviour. The study was undertaken to provide information for planning an AIDS education intervention. Three-quarters of students reported that they had had sexual intercourse. Most students had heard of AIDS, and the majority of these knew that it was infectious. More than half of the students were confused or lacked knowledge about the modes of transmission. Two-thirds of the students believed AIDS could be prevented, but knowledge of prevention strategies was superficial. Of the sexually active students only 11.4% had ever used a condom, and of all students 39.6% stated that they would use a condom in the future. Two-thirds of the students were not aware that there is no cure for AIDS. Students did not acknowledge that AIDS could affect them directly, and attributed the problem to prostitutes and 'promiscuous' people in 36.4% of responses, and to 'white' people in 23.8% of responses. Students expressed intolerance, fear and rejection of people with AIDS, and only 6.4% would accept an affected person into their class. Almost all the students wanted AIDS education at school, and most of these requested that the school nurse facilitate this education. It is concluded that appropriate AIDS prevention education is urgently required for both high school and junior school students.     

A natural musaceas plant extract inhibits proteasome activity and induces apoptosis selectively in human tumor and transformed, but not normal and non-transformed, cells

Animal studies have demonstrated that a dietary polyphenol known as tannic acid (TA) exhibits anticarcinogenic activity in chemically induced cancers. Most recently, we have reported that TA and ester-bond containing green tea polyphenols are potent proteasome inhibitors in vitro and in vivo. We hypothesize that CellQuest, a patented formula which contains high level of TA obtained from a musaceas (plantain) plant extract, will inhibit the tumor cell proteasome activity. Here, we report that a partially purified CellQuest fraction, S3, potently inhibits the proteasomal chymotrypsin-like activity of Jurkat T cell extracts in a concentration-dependent manner. Inhibition of the proteasome by S3 in leukemia Jurkat T, simian virus 40-transformed and prostate cancer LNCaP cells results in accumulation of ubiquitinated proteins and the natural proteasome substrate p27Kip1, followed by induction of apoptosis. In contrast, non-transformed, immortalized human natural killer cells and normal human fibroblasts are resistant to S3-mediated proteasome inhibition and apoptosis induction. Our present study suggests that CellQuest targets and inhibits the proteasome selectively in tumor cells, which may contribute to the claimed anticancer activity.     

Modellmyotonie nach 2,4-Dichlorphenoxyacetat (2,4-D) bei der Ratte

Zusammenfassung 1. 2,4-D in einer Dosis, die in vivo Myotonie hervorruft, steigert in vitro am Zwerchfellpräparat die Atmung und die Lactatproduktion, sowohl in einem K- wie auch in einem Nareichen Inkubationsmedium.2. In vivo wurden nach 2,4-D in myotonieerzeugender Dosis G-6-P, F-6-P, FDP, DAP, -GP, Pyruvat und Lactat vermehrt im ruhenden Skeletmuskel (Bauchmuskulatur) gefunden, woraus auf eine gesteigerte Glykolyse geschlossen wurde.3. Kreatinphosphat nahm unter den gleichen Bedingungen wie unter 2. ab. ATP und ADP blieben praktisch unverändert.4. Die unter 1., 2. und 3. erwähnten Befunde werden hypothetisch entweder mit Entkoppelung der oxydativen Phosphorylierung oder einem induzierten bzw. gesteigerten energieverbrauchenden Prozeß in Zusammenhang gebracht. Dabei wäre auch die Kombination dieser beiden energiereduzierenden Prozesse möglich.

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Summary 1. A dose of 2,4-D (which brings about myotonia in vivo), increases O₂-consumption in vitro and increases the production of lactate in potassium as well as sodium rich incubating media.2. In vivo, after a dose of 2,4-D which brought about myotonia, an increase of G-6-P, F-6-P, FDP, DAP, -GP, pyruvate, and lactate was found in the abdominal skeletal muscles at rest. This finding indicated an increase in glycolysis.3. Under the same conditions as in paragraph 2 creatine-phosphate was decreased. ATP and ADP practically unchanged.4. There is a hypothetical connection between the findings mentioned in paragraphs 1, 2 and 3 either in the view of uncoupling of the oxydative phosphorylation or in the view of a process involving an increase in energy consumption. With that, a combination of both energy reducing processes would also be possible.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Construction and characterization of Listeria monocytogenes mutants with in-frame deletions in the response regulator genes identified in the genome sequence

Two-component systems are widely distributed in prokaryotes where they control gene expression in response to diverse stimuli. To study the role of the sixteen putative two-component systems of Listeria monocytogenes systematically, in frame deletions were introduced into 15 out of the 16 response regulator genes and the resulting mutants were characterized. With one exception the deletion of the individual response regulator genes has only minor effects on in vitro and in vivo growth of the bacteria. The mutant carrying a deletion in the ortholog of the Bacillus subtilis response regulator gene degU showed a clearly reduced virulence in mice, indicating that DegU is involved in the regulation of virulence-associated genes.     

川芎嗪诱导大鼠骨髓间质干细胞分化为神经元样细胞的研究

目的用川芎嗪(ligustrazin hydrochloride)在体外定向诱导SD青年鼠骨髓间质干细胞(mesenchymal stem cells，rMSCs)分化为神经元样细胞。方法用低糖DMEM冲洗骨髓腔，收集骨髓细胞悬液，接种在塑料培养瓶中。经体外扩增、纯化，选用第5代后的骨髓间质干细胞进行诱导分化。用10μg／LbFcF预诱导24h，更换成含川芎嗪的无血清培养基DMEM诱导间质干细胞分化为神经元样细胞。用免疫组织化学SABC法鉴定神经丝蛋白(NF—M)、神经元特异性烯醇化酶(NSE)、巢蛋白(nestin)、微管联合蛋白-2(MAP-2)、生长相关蛋白-43(GAP-43)、胶质纤维酸性蛋白(GFAP)的表达。结果第5代间质干细胞形态达到均一，呈梭形。用川芎嗪诱导15min到3h，间质干细胞胞体逐渐增大，并伸出细长突起形似神经元样细胞。免疫组织化学显示NF-M、NSE、nestin、MAP-2和GAP-43表达阳性，而GFAP阴性。对照组上述染色均为阴性。结论川芎嗪可诱导骨髓间质干细胞分化为神经元样细胞。     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

17-Ketosteroide und ihre Fraktionen bei myotonischer Dystrophie

Zusammenfassung Bei 15 Patienten mit myotonischer Dystrophie (10 männliche und 5 weibliche) haben wir die 17-Ketosteroide im Urin untersucht. Sie lagen in der Regel im unteren Normbereich oder waren gering vermindert.Die Fraktionen der 17-Ketosteroide konnten wir bei 6 männlichen und 2 weiblichen Patienten aus dieser Untersuchungsreihe bestimmen. Dabei zeigte sich, daß zwar entsprechend der herabgesetzten Ausscheidung der 17-Ketosteroide anteilig auch die Fraktionen vermindert sind, von ihnen aber keine fehlt. Auch für eine erhebliche Verschiebung innerhalb der 17-Ketosteroide zugunsten oder zuungunsten einer Fraktion findet sich bei unseren 8 Patienten kein Anhalt.     

Randomized controlled trial assessing the effect of vitamin A supplementation on maternal morbidity during pregnancy and postpartum among HIV-infected women

OBJECTIVE: To determine whether low-cost treatment of HIV using vitamin A would be beneficial, we examined the effect of vitamin A supplementation on morbidity of HIV-1 infected women. METHODS: We conducted a randomized, double blind placebo-controlled trial at King Edward VIII Hospital, in Durban, South Africa. In total, 312 HIV-seropositive pregnant women between 28 and 32 weeks' gestation were recruited into this trial. Patients were randomized to receive placebo or 5,000 IU retinyl palmitate and 30 mg beta-carotene daily. At delivery of their children, patients received placebo or 200,000 IU retinyl palmitate. The main outcome measures were pre- and postnatal report of HIV-related symptoms. RESULTS: Vitamin A did not confer any significant beneficial effect on the report of either HIV or pregnancy-related symptoms during the pre- or postnatal period. CONCLUSION: In this study of HIV-infected pregnant women, vitamin A supplementation given in doses designed to decrease mother-to-infant transmission did not result in significant beneficial effect on reported symptoms pre- or postnatally. Further investigation with larger number of participants, tailoring supplementation for specific clinical conditions, outside the context of pregnancy, is required to help clarify the possible clinical benefits of vitamin A.