The reinforcing properties of nicotine depend partly on cholinergic projections from the pedunculopontine tegmental (PPTg) and laterodorsal tegmental (LDTg) nuclei to midbrain dopamine neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Neuronal activation was investigated using Fos expression in these areas following acute (0, 0.1, 0.4, 0.8mg/kg) or chronic systemic nicotine (0, 0.1, 0.4, 0.8, 1.0mg/kg given once per day for 5 days). We also examined co-localization of Fos expression in bNOS and TH positive neurons to determine what populations of neurons were activated by nicotine. Acute nicotine resulted in dose related Fos expression, with the biggest increase seen after 0.4mg/kg nicotine, but no co-localization occurred with bNOS in the PPTg/LDTg. Surprisingly, nicotine also failed to activate midbrain dopamine neurons. After animals were sensitized to nicotine there was a similar dose response curve in Fos expression, but the biggest increase was seen after 0.8mg/kg nicotine. Chronic nicotine, like acute, also preferentially activated non-cholinergic neurons in the LDTg and PPTg and non-dopamine neurons in the SNc and VTA. Further experiments looked at the mechanisms of Fos expression after nicotine administration. Fos expression in the LDTg/PPTg and SNc/VTA was suppressed after d-amphetamine, despite an increase in locomotor activity, suggesting that the increased Fos expression after chronic nicotine was not simply due to the locomotor activating effects of sensitized nicotine. Blocking autoreceptors in the dopaminergic midbrain by haloperidol pre-treatment did not increase Fos expression in dopamine neurons indicating that the inhibitory mechanism was not dependent on local autoreceptors. Novel methods of visualising and lesioning GABA neurons in the mesopontine tegmentum and midbrain were also examined. The data suggest that the mechanisms by which dopamine is involved in the pharmacological actions of passively administered nicotine are more complex than was first thought and that the role of non-dopamine neurons in the VTA (possibly GABA or glutamate containing) are also important.

Comparing the efficacy of different treatments in psychiatry is difficult for many reasons, even when they are investigated in `head-to-head' studies. A consensus meeting was, therefore, held to produce best practice guidelines for such studies. This article presents the conclusions of this consensus and illustrates it using published data in the field of antidepressant treatment of generalized anxiety disorder.

This Dissertation analyzes the conditions, problems and potential of rural women&rsquo / s empowerment through a sample of rural women&rsquo / s organizations (two women&rsquo / s cooperative, seven rural development cooperative and one village women associaton) with interpreting DAWN iniative and GAD approach with a socialist feminist perspective. In this study, it is stated that the agricultural sector policies and rural development policy were constructed in relation with the conditions of underdevelopment and thus, in relation with the agreements with IMF, WTO and IPARD Programme of EU which enforced the decreasing of agricultural sector subsidies. It is notable that these policies are formulated with an aim of increasing the influence and significance of capitalist relations in agricultural sector and rural areas without taking precautions for the survival of small sized farming households in rural areas. Despite these general influences of underdevelopment to Turkish Agricultural Sector and patriarchal gender assumptions, these women&rsquo / s organizations could be successful to some extent empowering their members with the recognized dimensions of empowerment such as / psychological, economical, social, organizational and political. All these dimensions are interrelated with each other. In this study, it was observed that while economic empowerment and psychological empowerment is the base of all other dimensions of empowerment, social empowerment and organizational empowerment are the most dynamic processes of empowerment and political empowerment is hardest dimension or outcome to achieve.

The brain is a major target site in acute cyanide intoxication, as indicated by several symptoms and signs. Cyanide inhibits the enzyme cytochrome oxidase. This inhibition causes impaired oxygen utilization in all cells affected, severe metabolic acidosis and inhibited production of energy. In this thesis, some neurotoxic effects of cyanide, in particular, the effects on dopaminergic pathways were studied. In a previous study, decreased levels of striatal dopamine and HVA were found after severe cyanide intoxication (5-20 mg/kg i.p.). However, increased striatal dopamine were found in rats showing convulsions after infusion of low doses of cyanide (0.9 mg/kg i.v.), at the optimal dose rate (the dose rate that gives the treshold dose). Increased striatal dopamine synthesis was observed in rats after cyanide treatment and in vitro. Furthermore, in rat, as well as in pig striatal tissue, cyanide dose- dependently increased the oxidative deamination of 5-HT (MAO-A) and DA (MAO-A and -B) but not that of PEA (MAO-B). Thus cyanide affects both the synthesis and metabolism of dopamine. In rats, sodium cyanide (2.0 mg/kg, i.p.) decreased the striatal dopamine Dj- and D2-receptor binding 1 hour after injection. Increased extracellular levels of striatal dopamine and homovanillic acid were also shown after cyanide (2.0 mg/kg; i.p.). DOPAC and 5-HIAA were slightly decreased. This indicates an increased release or an extracellular leakage of dopamine due to neuronal damage caused by cyanide. Thus the effects of cyanide on dopamine Dj- and D2~receptors could in part be due to cyanide-induced release of dopamine. Because of reported changes in intracellular calcium in cyanide-treated animals, the effects of cyanide on inositol phospholipid breakdown was studied. Cyanide seemed not to affect the inositol phospholipid breakdown in vitro. The effects of cyanide on the synthesis and metabolism of brain GAB A were also examined. A decreased activity of both GAD and GAB A-T were found in the rat brain tissue. The reduced activity of GAB A-T, but not that of GAD returned to the control value after adding PLP in the incubation media. The cyanide-produced reduction of GABA levels will increase the susceptibility to convulsions, and could partly be due to GAD inhibition. In conclusion, cyanide affects the central nervous system in a complex manner. Some effects are probably direct. The main part, however, appears to be secondary, e.g. hypoxia, seizures, changes in calcium levels or transmitter release produced by cyanide. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 7 uppsatser</p> / digitalisering@umu

Due to a growing demand and need for faster results, effectivization as a concept has been pushed to the forefront of medical research. Here, a method transfer between 2 fully automized ELISA instruments is highlighted. The instruments were the Tecan Freedom EVOlyzer and the Dynex DSX.  The Tecan instrument is a more modern instrument with a more extensive LIMS integration, better automatization and increased capacity for samples and assays. The method being transferred was an Anti-GAD ELISA for the diagnosis of Type 1 Diabetes Mellitus. The study design was a result comparison of 20 samples with varying Anti-GAD concentration and 15 replicates of a single sample for a precision study. To successfully transfer the method, acceptance criteria concerning percentual difference in result, intermediate precision, and repeatability had to fall below 20 %. The assay was set up as a sandwich ELISA in accordance with the kit used at the laboratory (Euroimmun), where each sample was set as duplicates. Preliminary programming and testing was performed to ensure proper function. An average bias of +33 % was reported, as was an intra-run variation and an inter-run variation of ca 11 %. Additionally, a recurring issue with samples and calibrators in specific locations on the plate was reported. The issue was deemed systemic and possible solutions include changing programming parameters, or instrument part replacement. Ultimately the method transfer was left incomplete, and several technical details must be overcome before taking Anti-GAD analysis into routine use on the instrument.

Der Beitrag untersucht auf der Grundlage neuer primärärztlicher Befunde die Versorgungsqualität bei der hinsichtlich Chronizität und Arbeitsausfall schwerwiegendsten Angsterkrankung, der Generalisierten Angststörung. Neben einer knappen Einführung in das Störungsbild werden die an über 20 000 Patienten in 558 Hausarztpraxen gewonnenen Kernbefunde der GAD-P-Studie (Generalisierte Angst und Depression in der Primärärztlichen Versorgung) zusammengefasst und Ansatzpunkte zur Verbesserung der Versorgungsqualität dieses selten adäquat behandelten Störungsbildes diskutiert. Insbesondere wird auf die zentrale Bedeutung einer sichereren diagnostischen Erkennung als Voraussetzung für therapeutische Verbesserungen hingewiesen. In Ergänzung zur Verbesserung bestehender Weiterbildungsangebote wird auf Arzt- und Patientenebene der breitere Einsatz bestehender Screeningverfahren, die Nutzung krankheitsspezifischer Patientenratgeber, sowie eine breitere Öffentlichkeitsarbeit zur Information über dieses bislang vernachlässigte, häufig chronisch verlaufende Krankheitsbild empfohlen. / Based on new empirical findings in a large-scale primary care study, the quality of care for the most chronic and debilitating anxiety problem, generalised anxiety disorder, is examined. Following a brief introduction of this disorder, the core findings of the GAD-P study (generalised anxiety and depression in primary care) with more than 20,000 patients of 558 family doctor practices are summarised and measures to improve the quality of care of patients with generalised anxiety disorder, a disorder which is rarely adequately treated, are discussed. This paper particularly emphasises the standard use of time-efficient diagnostic screening instruments, because improved recognition and diagnosis is the prerequisite for appropriate treatment. Further the role of the media to increase awareness of this disorder as well as patient education materials to improve compliance and to enhance treatment outcome effects are highlighted.

A correta classificação do tipo de DM leva mais precocemente ao tratamento adequado e atualmente é dividida em 4 categorias: DM tipo 1, DM tipo 2, Outros tipos e Diabete Gestacional. O DM tipo 1 é geralmente auto-imune, surge em geral antes dos 20 anos de idade e é dependente de insulina para impedir a cetoacidose. O DM tipo 2 é responsável por mais de 90% dos casos, acontece em geral após os 45 anos, com história familiar e associado à síndrome metabólica. Na categoria “outros tipos”, o Maturity Onset Diabetes of the Young (MODY) é um subtipo que inicia abaixo dos 25 anos, não-dependente de insulina e apresenta herança dominante. No entanto, apesar da classificação definir essas categorias através de características peculiares, pode existir uma sobreposição de quadros, principalmente no DM que inicia no adulto jovem. Assim, novos sistemas de classificação têm sido propostos, empregando a presença da auto-imunidade (anticorpos) e índices de função de célula β (peptídeo-C) para definir a patogênese e nomenclatura mais específicas. O objetivo desta revisão é descrever e analisar o desempenho destas ferramentas diagnósticas na classificação do DM. Os anticorpos evidenciam a auto-imunidade do DM 1. O IAA (insulin auto-antibody) está presente quando o início do DM se dá, principalmente, antes dos 5 anos de idade e o anti- GAD (glutamic acid decarboxylase) tem seu melhor desempenho nos indivíduos com início da doença acima dos 20 anos, sendo o teste que permanece positivo por mais tempo. A medida do peptídeo-C avalia a reserva pancreática de insulina e deve ser realizada com glicemia entre 70-200 mg/dl. A medida após estímulo é a mais estudada e <1,5 ng/ml define o paciente como DM 1. O estímulo com refeição mista é o recomendado pela ADA, mas o teste com 1 mg de glucagon é mais simples e igualmente acurado. Dados em relação à utilização da classificação baseada na medida de diferentes anticorpos dirigidos ao pâncreas classificação A (anticorpos) e β (peptídeo-C) pode ser adotada como um método acurado, relativamente simples e preciso de classificação de DM. / The correct classification of DM type leads to earlier appropriate treatment and is currently divided into 4 categories: type 1 DM, type 2 DM, Other types and Gestational DM. Type 1 DM is generally autoimmune, it usually appears before the age of 20 years, and depends on insulin to prevent ketoacidosis. Type 2 DM accounts for over 90% of the cases, it usually occurs after the age of 45, with a family history and metabolic syndrome. In the category “other types”, Maturity Onset Diabetes of the Young (MODY) is a subtype that begins before the age of 25, is non-insulin dependent and presents a dominant heritage. However, although the classification defines these categories through peculiar characteristics, there may be superimposed pictures, especially in the case of DM which begins in the young adult. Thus, new classification systems have been proposed, using the presence of autoimmunity (antibodies) and β cell (C-peptide) indexes to define the pathogenesis and more specific nomenclatures. The purpose of this review is to describe and analyze the performance of these diagnostic tools in the classification of DM. The presence of antibodies show the autoimmunity of type 1 DM. IAA (insulin auto-antibody) is present mainly before the age of 5 years, and anti-GAD (glutamic acid decarboxylase) performs best in individuals who begin the disease above the age of 20, and its test remains positive longest. The C-peptide measure evaluates the pancreatic reserve of insulin and should be performed with a glycemia between 70-200 mg/dl. Post-stimulus measuring is more widely studied and <1.5 ng/ml defines the patient as DM1. Stimulation with a mixed meal is recommended by ADA, but the test with 1 mg of glucagon is simpler and just as effective. Data on classification A (antibodies), β (Cpeptide) suggest that it may be adopted as an effective, relatively simple and precise method for DM classification.

A correta classificação do tipo de DM leva mais precocemente ao tratamento adequado e atualmente é dividida em 4 categorias: DM tipo 1, DM tipo 2, Outros tipos e Diabete Gestacional. O DM tipo 1 é geralmente auto-imune, surge em geral antes dos 20 anos de idade e é dependente de insulina para impedir a cetoacidose. O DM tipo 2 é responsável por mais de 90% dos casos, acontece em geral após os 45 anos, com história familiar e associado à síndrome metabólica. Na categoria “outros tipos”, o Maturity Onset Diabetes of the Young (MODY) é um subtipo que inicia abaixo dos 25 anos, não-dependente de insulina e apresenta herança dominante. No entanto, apesar da classificação definir essas categorias através de características peculiares, pode existir uma sobreposição de quadros, principalmente no DM que inicia no adulto jovem. Assim, novos sistemas de classificação têm sido propostos, empregando a presença da auto-imunidade (anticorpos) e índices de função de célula β (peptídeo-C) para definir a patogênese e nomenclatura mais específicas. O objetivo desta revisão é descrever e analisar o desempenho destas ferramentas diagnósticas na classificação do DM. Os anticorpos evidenciam a auto-imunidade do DM 1. O IAA (insulin auto-antibody) está presente quando o início do DM se dá, principalmente, antes dos 5 anos de idade e o anti- GAD (glutamic acid decarboxylase) tem seu melhor desempenho nos indivíduos com início da doença acima dos 20 anos, sendo o teste que permanece positivo por mais tempo. A medida do peptídeo-C avalia a reserva pancreática de insulina e deve ser realizada com glicemia entre 70-200 mg/dl. A medida após estímulo é a mais estudada e <1,5 ng/ml define o paciente como DM 1. O estímulo com refeição mista é o recomendado pela ADA, mas o teste com 1 mg de glucagon é mais simples e igualmente acurado. Dados em relação à utilização da classificação baseada na medida de diferentes anticorpos dirigidos ao pâncreas classificação A (anticorpos) e β (peptídeo-C) pode ser adotada como um método acurado, relativamente simples e preciso de classificação de DM. / The correct classification of DM type leads to earlier appropriate treatment and is currently divided into 4 categories: type 1 DM, type 2 DM, Other types and Gestational DM. Type 1 DM is generally autoimmune, it usually appears before the age of 20 years, and depends on insulin to prevent ketoacidosis. Type 2 DM accounts for over 90% of the cases, it usually occurs after the age of 45, with a family history and metabolic syndrome. In the category “other types”, Maturity Onset Diabetes of the Young (MODY) is a subtype that begins before the age of 25, is non-insulin dependent and presents a dominant heritage. However, although the classification defines these categories through peculiar characteristics, there may be superimposed pictures, especially in the case of DM which begins in the young adult. Thus, new classification systems have been proposed, using the presence of autoimmunity (antibodies) and β cell (C-peptide) indexes to define the pathogenesis and more specific nomenclatures. The purpose of this review is to describe and analyze the performance of these diagnostic tools in the classification of DM. The presence of antibodies show the autoimmunity of type 1 DM. IAA (insulin auto-antibody) is present mainly before the age of 5 years, and anti-GAD (glutamic acid decarboxylase) performs best in individuals who begin the disease above the age of 20, and its test remains positive longest. The C-peptide measure evaluates the pancreatic reserve of insulin and should be performed with a glycemia between 70-200 mg/dl. Post-stimulus measuring is more widely studied and <1.5 ng/ml defines the patient as DM1. Stimulation with a mixed meal is recommended by ADA, but the test with 1 mg of glucagon is simpler and just as effective. Data on classification A (antibodies), β (Cpeptide) suggest that it may be adopted as an effective, relatively simple and precise method for DM classification.

A correta classificação do tipo de DM leva mais precocemente ao tratamento adequado e atualmente é dividida em 4 categorias: DM tipo 1, DM tipo 2, Outros tipos e Diabete Gestacional. O DM tipo 1 é geralmente auto-imune, surge em geral antes dos 20 anos de idade e é dependente de insulina para impedir a cetoacidose. O DM tipo 2 é responsável por mais de 90% dos casos, acontece em geral após os 45 anos, com história familiar e associado à síndrome metabólica. Na categoria “outros tipos”, o Maturity Onset Diabetes of the Young (MODY) é um subtipo que inicia abaixo dos 25 anos, não-dependente de insulina e apresenta herança dominante. No entanto, apesar da classificação definir essas categorias através de características peculiares, pode existir uma sobreposição de quadros, principalmente no DM que inicia no adulto jovem. Assim, novos sistemas de classificação têm sido propostos, empregando a presença da auto-imunidade (anticorpos) e índices de função de célula β (peptídeo-C) para definir a patogênese e nomenclatura mais específicas. O objetivo desta revisão é descrever e analisar o desempenho destas ferramentas diagnósticas na classificação do DM. Os anticorpos evidenciam a auto-imunidade do DM 1. O IAA (insulin auto-antibody) está presente quando o início do DM se dá, principalmente, antes dos 5 anos de idade e o anti- GAD (glutamic acid decarboxylase) tem seu melhor desempenho nos indivíduos com início da doença acima dos 20 anos, sendo o teste que permanece positivo por mais tempo. A medida do peptídeo-C avalia a reserva pancreática de insulina e deve ser realizada com glicemia entre 70-200 mg/dl. A medida após estímulo é a mais estudada e <1,5 ng/ml define o paciente como DM 1. O estímulo com refeição mista é o recomendado pela ADA, mas o teste com 1 mg de glucagon é mais simples e igualmente acurado. Dados em relação à utilização da classificação baseada na medida de diferentes anticorpos dirigidos ao pâncreas classificação A (anticorpos) e β (peptídeo-C) pode ser adotada como um método acurado, relativamente simples e preciso de classificação de DM. / The correct classification of DM type leads to earlier appropriate treatment and is currently divided into 4 categories: type 1 DM, type 2 DM, Other types and Gestational DM. Type 1 DM is generally autoimmune, it usually appears before the age of 20 years, and depends on insulin to prevent ketoacidosis. Type 2 DM accounts for over 90% of the cases, it usually occurs after the age of 45, with a family history and metabolic syndrome. In the category “other types”, Maturity Onset Diabetes of the Young (MODY) is a subtype that begins before the age of 25, is non-insulin dependent and presents a dominant heritage. However, although the classification defines these categories through peculiar characteristics, there may be superimposed pictures, especially in the case of DM which begins in the young adult. Thus, new classification systems have been proposed, using the presence of autoimmunity (antibodies) and β cell (C-peptide) indexes to define the pathogenesis and more specific nomenclatures. The purpose of this review is to describe and analyze the performance of these diagnostic tools in the classification of DM. The presence of antibodies show the autoimmunity of type 1 DM. IAA (insulin auto-antibody) is present mainly before the age of 5 years, and anti-GAD (glutamic acid decarboxylase) performs best in individuals who begin the disease above the age of 20, and its test remains positive longest. The C-peptide measure evaluates the pancreatic reserve of insulin and should be performed with a glycemia between 70-200 mg/dl. Post-stimulus measuring is more widely studied and <1.5 ng/ml defines the patient as DM1. Stimulation with a mixed meal is recommended by ADA, but the test with 1 mg of glucagon is simpler and just as effective. Data on classification A (antibodies), β (Cpeptide) suggest that it may be adopted as an effective, relatively simple and precise method for DM classification.

Abstract In the 1970s women started to be taken specifically into consideration when talking about development. Over time several approaches appeared where the focus varied from integrating women into existing structures in society (Women In Development (WID)) to changing the socially constructed gender roles (Gender And Development (GAD)). The latter was accepted by the international community in 1995. In 1993 a Swedish organisation who called themselves Kvinna till Kvinna (KtK) was founded with the goal to help and support women in conflicted countries to become equal to the male population. An organisation that was founded almost simultaneously as the gender approach was accepted into the international community - which approach would they go for? Which approach seemed to be the best in order to achieve equality? According to an ideology analysis of KtK's activity reports from 1994 to 2012, which was performed in this thesis, KtK seemed to have started out closer to the WID approach for a short time span, while rather quickly moving towards the GAD approach with which they have held on to date.