Different SNP combinations in the GCH1 gene and use of labor analgesia

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate if there is an association between different SNP combinations in the guanosine triphosphate cyclohydrolase (GCH1) gene and a number of pain behavior related outcomes during labor. A population-based sample of pregnant women (n = 814) was recruited at gestational week 18. A plasma sample was collected from each subject. Genotyping was performed and three single nucleotide polymorphisms (SNP) previously defined as a pain-protective SNP combination of GCH1 were used.</p> <p>Results</p> <p>Homozygous carriers of the pain-protective SNP combination of GCH1 arrived to the delivery ward with a more advanced stage of cervical dilation compared to heterozygous carriers and non-carriers. However, homozygous carriers more often used second line labor analgesia compared to the others.</p> <p>Conclusion</p> <p>The pain-protective SNP combination of GCH1 may be of importance in the limited number of homozygous carriers during the initial dilation of cervix but upon arrival at the delivery unit these women are more inclined to use second line labor analgesia.</p

Validation of serum IGF-I as a biomarker to monitor the bioactivity of exogenous growth hormone agonists and antagonists in rabbits

The development of new growth hormone (GH) agonists and growth hormone antagonists (GHAs) requires animal models for pre-clinical testing. Ideally, the effects of treatment are monitored using the same pharmacodynamic marker that is later used in clinical practice. However, intact rodents are of limited value for this purpose because serum IGF-I, the most sensitive pharmacodynamic marker for the action of GH in humans, shows no response to treatment with recombinant human GH and there is little evidence for the effects of GHAs, except when administered at very high doses or when overexpressed. As an alternative, more suitable model, we explored pharmacodynamic markers of GH action in intact rabbits. We performed the first validation of an IGF-I assay for the analysis of rabbit serum and tested precision, sensitivity, linearity and recovery using an automated human IGF-I assay (IDS-iSYS). Furthermore, IGF-I was measured in rabbits of different strains, age groups and sexes, and we monitored IGF-I response to treatment with recombinant human GH or the GHA Pegvisomant. For a subset of samples, we used LC-MS/MS to measure IGF-I, and quantitative western ligand blot to analyze IGF-binding proteins (IGFBPs). Although recovery of recombinant rabbit IGF-I was only 50% in the human IGF-I assay, our results show that the sensitivity, precision (1.7–3.3% coefficient of variation) and linearity (90.4–105.6%) were excellent in rabbit samples. As expected, sex, age and genetic background were major determinants of IGF-I concentration in rabbits. IGF-I and IGFBP-2 levels increased after single and multiple injections of recombinant human GH (IGF-I: 286±22 versus 434±26 ng/ml; P<0.01) and were highly correlated (P<0.0001). Treatment with the GHA lowered IGF-I levels from the fourth injection onwards (P<0.01). In summary, we demonstrated that the IDS-iSYS IGF-I immunoassay can be used in rabbits. Similar to rodents, rabbits display variations in IGF-I depending on sex, age and genetic background. Unlike in rodents, the IGF-I response to treatment with recombinant human GH or a GHA closely mimics the pharmacodynamics seen in humans, suggesting that rabbits are a suitable new model to test human GH agonists and antagonists

Effectiveness and Cost Effectiveness of Expanding Harm Reduction and Antiretroviral Therapy in a Mixed HIV Epidemic: A Modeling Analysis for Ukraine

A cost-effectiveness study by Sabina Alistar and colleagues evaluates the effectiveness and cost effectiveness of different levels of investment in methadone, ART, or both, in the mixed HIV epidemic in Ukraine

Growth Hormone and Anabolic Androgenic Steroids : Effects on Neurochemistry and Cognition

Growth hormone (GH) stimulates growth and metabolism but also displays profound effects on the central nervous system (CNS). GH affects neurogenesis and neuroprotection, and has been shown to counteract drug-induced apoptosis in the brain. Anabolic androgenic steroids (AAS), mainly abused for their anabolic and performance-enhancing properties, can cause several adverse effects, such as cardiovascular complications, sterility, depression, and aggression. GH and AAS are both believed to interact with several signaling systems in the CNS. The aim of this thesis was to further investigate the impact of GH and AAS on neurochemistry and cognitive functions. Recombinant human GH (rhGH) and the steroid nandrolone decanoate (ND) were administered, separately and in combination with each other, to male rats. The results demonstrated that administration of GH improved spatial memory, assessed in a water maze test. Furthermore, GH induced alterations of the GABAB receptor mRNA expression, density, and functionality in the brain, for example in regions associated with cognition. GH also altered the mu opioid peptide (MOP) receptor, but not the delta opioid peptide (DOP) receptor functionality in the brain. Thus, some of the GH effects on cognition may involve effects on the GABAB receptors and MOP receptors. ND, on the contrary, seemed to induce impairments of memory and also altered the GABAB receptor mRNA expression in the brain. Furthermore, ND lowered the IGF-1 plasma concentrations and attenuated the IGF-1, IGF-2, and GHR mRNA expression in the pituitary. In addition, significant effects of GH and ND were found on plasma steroid concentrations, organ weight, as well as body weight. In conclusion, this thesis contributes with further knowledge on the cognitive and neurochemical consequences of GH and ND use. The findings regarding ND are worrying considering the common use of AAS among adolescents. GH improves memory functions and affects signaling systems in the brain associated with cognition, hence the hypothesis that GH can reverse drug-induced impairments is further strengthened

Growth Hormone and Anabolic Androgenic Steroids : Effects on Neurochemistry and Cognition

Growth hormone (GH) stimulates growth and metabolism but also displays profound effects on the central nervous system (CNS). GH affects neurogenesis and neuroprotection, and has been shown to counteract drug-induced apoptosis in the brain. Anabolic androgenic steroids (AAS), mainly abused for their anabolic and performance-enhancing properties, can cause several adverse effects, such as cardiovascular complications, sterility, depression, and aggression. GH and AAS are both believed to interact with several signaling systems in the CNS. The aim of this thesis was to further investigate the impact of GH and AAS on neurochemistry and cognitive functions. Recombinant human GH (rhGH) and the steroid nandrolone decanoate (ND) were administered, separately and in combination with each other, to male rats. The results demonstrated that administration of GH improved spatial memory, assessed in a water maze test. Furthermore, GH induced alterations of the GABAB receptor mRNA expression, density, and functionality in the brain, for example in regions associated with cognition. GH also altered the mu opioid peptide (MOP) receptor, but not the delta opioid peptide (DOP) receptor functionality in the brain. Thus, some of the GH effects on cognition may involve effects on the GABAB receptors and MOP receptors. ND, on the contrary, seemed to induce impairments of memory and also altered the GABAB receptor mRNA expression in the brain. Furthermore, ND lowered the IGF-1 plasma concentrations and attenuated the IGF-1, IGF-2, and GHR mRNA expression in the pituitary. In addition, significant effects of GH and ND were found on plasma steroid concentrations, organ weight, as well as body weight. In conclusion, this thesis contributes with further knowledge on the cognitive and neurochemical consequences of GH and ND use. The findings regarding ND are worrying considering the common use of AAS among adolescents. GH improves memory functions and affects signaling systems in the brain associated with cognition, hence the hypothesis that GH can reverse drug-induced impairments is further strengthened

A National Swedish Methadone Program 1966-1989

Methadone Maintenance treatment of compulsive opioid addiction was started by the study of Dole and Nyswander (1965) and has subsequently been replicated in programs throughout the world. Methadone treatment has become the most effective modality for the treatment of chronic heroin addiction. In 1966 a Swedish National methadone maintenance program was opened at the Psychiatric Research Center, Ulleråker hospital at Uppsala. The aim of this thesis was to study the outcome of methadone treatment along various lines: • An open randomised controlled study comparing the efficacy of methadone treatment and drug free treatment in 34 heroin addicts, 20-24 years of age. • Before/after comparisons of rehabilitation among 345 heroin addicts admitted during the 23 years when this was a centralised National program. • Retention in treatment. Study subjects, methods and treatment goals: Subjects underwent an admission procedure when background data was collected through hospital records, and personal interviews. Therapeutic efforts focused on vocational rehabilitation, i.e. a return to full-time work or studies, hoping to make patients abandon their drug addict’s life-style and make them socially accepted and self-supporting. Results: Thirty-four heroin addicts with a history of 4-8 years of heroin use were randomly assigned either to methadone treatment (17) or an untreated control group (17). The controls could not apply for methadone treatment until two years later. Outcome after six years observation showed that 81% became free of drug abuse, while the corresponding figure for the controls was only 1/17 (6%). The mean yearly death rate for the controls was 7.2%. Likewise, among the total material of 345 heroin addicts, 70-80% of the patients became engaged in work or studies, a significant increase compared with the situation before treatment (1.7%). The program was an effective reducer of illicit heroin use and criminality among its patients and prevented the occurrence of HIV infection among patients in long-term methadone treatment. The average one-year retention during 1967-1989 was 90% and cumulative retention showed that 29% were still in treatment 10 years after admission. Conclusion: The present results emphasise the importance of vocational rehabilitation and support in a treatment strategy based on long-term maintenance therapy

Att bli bemött och att bemöta : En studie om meritering i tillsättning av lektorat vid Uppsala universitet

The general purpose of this thesis is to contribute to further understanding of the academic appointment process explored and defined as participation in a collegial educational process. The appointment process for academic positions has historically been regulated by state authorities ever since the first university was established in Sweden and has continuously been questioned for necessity, procedure etc. The object of study is the appointment process focusing the consideration of teaching skill in appointing academic teachers. A theoretical construction is used as a method in order to grasp what the experts and applicants consider. The thesis draws theoretical inspiration from the French sociologist Pierre Bourdieu especially his work on social practice and his explanations within praxeological knowledge. In this thesis cultural capital, habitus and doxa are used as concepts for constructing a social practice. Inspired by Bourdieu’s concepts, the appointment process is made visible grounded on documentation: judgments of qualifications written by external experts and the applicants’ documentation in their applications. The empirical material on merits is analyzed according to Bourdieu’s indicators on symbolic capacities. The disposition of habitus (as an inner organizing principle) is limited to cultural capital and background demographic data. The indicators on scientific skill are also transmitted into symbolic capacities on teaching skill. Three appointments as assistant professors are analyzed, framed by information on advertisement, description of documentation, time lapse and final decision in appointment committees. The main conclusions are that the experts select whom to appoint using their practical sense unaware of the driving forces, explained as social practice. The experts act in line with the purpose of the assignment and they follow all the rules and instructions. Teaching skill is focused by the applicants and experts as practical mastery in the subject field (pedagogical authority). Selection is explained by the concept of habitus. Another conclusion is the tendency to “nuanced” co-optation similar to when appointments were made by self selection and teaching ability was important in early 19th century. A final conclusion is that in positioning of arguments in shared beliefs (doxa) in questioning the appointment process, researchers in the early years of this century represent heterodox opinions