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1.
Proc Inst Mech Eng H ; 235(5): 583-596, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33645309

RESUMO

BACKGROUND: The complex anatomical structure, limited field of vision, and easily damaged nerves, blood vessels, and other anatomical structures are the main challenges of a cranio-maxillofacial (CMF) plastic surgical robot. Bearing these characteristics and challenges in mind, this paper presents the design of a master-slave surgical robot system with a force feedback function to improve the accuracy and safety of CMF surgery. METHODS: A master-slave CMF surgical robot system based on force feedback is built with the master tactile robot and compact slave robot developed in the laboratory. Model-based master robot gravity compensation and force feedback mechanism is used for the surgical robot. Control strategies based on position increment control and ratio control are adopted. Aiming at the typical mandibular osteotomy in CMF surgery, a scheme suitable for robot-assisted mandibular osteotomy is proposed. The accuracy and force feedback function of the robot system under direct control and master-slave motion modes are verified by experiments. RESULTS: The drilling experiment of the mandible model in direct control mode shows that the average entrance point error is 1.37 ± 0.30 mm, the average exit point error is 1.30 ± 0.25 mm, and the average posture error is 2.27° ± 0.69°. The trajectory tracking and in vitro experiment in the master-slave motion mode show that the average position following error is 0.68 mm, and the maximum force following error is 0.586 N, achieving a good tracking and force feedback function. CONCLUSION: The experimental results show that the designed master-slave CMF robot can assist the surgeon in completing accurate mandibular osteotomy surgery. Through force feedback mechanism, it can improve the interaction between the surgeon and the robot, and complete tactile trajectory movements.


Assuntos
Desenho de Equipamento , Face/cirurgia , Retroalimentação , Osteotomia Mandibular , Fenômenos Mecânicos , Procedimentos Cirúrgicos Robóticos , Cirurgia Assistida por Computador , Tato , Humanos
2.
IEEE Trans Haptics ; 14(3): 646-659, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33315572

RESUMO

Conventional force rendering methods in haptic applications often suffer stability issues when simulating interactions with stiff objects such as a virtual wall. This paper argues that the emphasis in such scenarios is to minimize the penetration into the virtual wall instead of modeling the wall as a spring-damper system. Therefore, we propose an approach using a position controller to achieve better haptic rendering of the virtual wall. The proposed approach exploits model-based development tools to obtain the linear control system model without the need for an analytical model of the dynamics of the haptic device. A simulation-based performance comparison of two different controllers has been made for a 6-DOF parallel structure haptic device.


Assuntos
Interface Usuário-Computador , Simulação por Computador , Humanos
3.
Forensic Sci Int ; 301: 331-340, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202146

RESUMO

The structural identification and the monitoring of the relative concentrations of a wide range of major (3) and minor secondary (16) metabolites used as marker substances for profiling of cannabis resin using GC-FID at the Swedish National Forensic Centre (NFC) has facilitated the mapping of their chemical and physical behaviors over a period of 48months whilst stored under different conditions (exposure to light, exposure to air, temperature). In all cases the behavior of this group of sesquiterpenes, sesquiterpenoids, cannabinoids and waxes could be directly related to their chemical lability/functionality. In particular, the identification of homologue triads for both Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) together with a group of seemingly chemically inert substances (for example, cannabicyclol(CBL) and the waxes (n-alkanes)) has created new tools for the establishment of common origins between samples of cannabis resins aged under different conditions. Since sampling of the resin blocks in NFC's method for profiling of cannabis resin is made below the surface, the effects of light incursion were found to be negligible. The effects of exposure to air (and indirectly temperature) were found to be more significant, not unexpectedly as many of the observed transformations were based on oxidation or rearrangement processes.


Assuntos
Canabinoides/química , Cannabis/química , Resinas Vegetais/química , Manejo de Espécimes/métodos , Cromatografia Gasosa , Escuridão , Luz , Temperatura
4.
J Natl Cancer Inst ; 105(12): 869-77, 2013 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-23723420

RESUMO

BACKGROUND: Trichloroethylene (TCE) is a widely used chlorinated solvent with demonstrated carcinogenicity in animal assays. Some epidemiologic studies have reported increased risk of cancer of the kidney, cervix, liver and biliary passages, non-Hodgkin lymphoma, and esophageal adenocarcinoma. METHODS: We established a pooled cohort, including 5553 workers with individual documented exposure to TCE in Finland, Sweden, and Denmark. Study participants were monitored for the urinary TCE metabolite trichloroacetic acid from 1947 to 1989 and followed for cancer. Standardized incidence ratios (SIRs) were calculated based on cancer incidence rates in the three national populations. Cox proportionate hazard analyses were used for internal comparisons. Tests of statistical significance are two-sided. RESULTS: Overall, 997 cases of cancer (n = 683 in men; n = 314 in women) were identified during 154 778 person-years of follow-up. We observed statistically significant elevated standardized incidence ratios for primary liver cancer (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervical cancer (2.31; 95% CI = 1.32 to 3.75). The standardized incidence ratio for kidney cancer was 1.01 (95% CI = 0.70 to 1.42) based on 32 cases; we did not observe a statistically significant increased risk of non-Hodgkin's lymphoma (SIR = 1.26; 95% CI = 0.89 to 1.73) or esophageal adenocarcinoma (SIR = 1.84; 95% CI = 0.65 to 4.65). Tobacco- and alcohol-associated cancers were not statistically significantly increased. CONCLUSIONS: Our results suggest TCE exposure is possibly associated with an increased risk for liver cancer. The relationship between TCE exposure and risks of cancers of low incidence and those with confounding by lifestyle and other factors not known in our cohort require further study.


Assuntos
Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/epidemiologia , Solventes/envenenamento , Tricloroetileno/envenenamento , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/epidemiologia , Adulto , Idoso , Estudos de Coortes , Dinamarca/epidemiologia , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Esofágicas/epidemiologia , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/epidemiologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/epidemiologia , Linfoma não Hodgkin , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Suécia/epidemiologia , Ácido Tricloroacético/urina , Tricloroetileno/metabolismo , Neoplasias do Colo do Útero/induzido quimicamente , Neoplasias do Colo do Útero/epidemiologia
5.
Ambio ; 42(2): 129-45, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23475651

RESUMO

Policies at multiple levels pronounce the need to encompass both social and ecological systems in governance and management of natural capital in terms of resources and ecosystems. One approach to knowledge production and learning about landscapes as social-ecological systems is to compare multiple case studies consisting of large spaces and places. We first review the landscape concepts' biophysical, anthropogenic, and intangible dimensions. Second, we exemplify how the different landscape concepts can be used to derive measurable variables for different sustainability indicators. Third, we review gradients in the three dimensions of the term landscape on the European continent, and propose to use them for the stratification of multiple case studies of social-ecological systems. We stress the benefits of the landscape concepts to measure sustainability, and how this can improve collaborative learning about development toward sustainability in social-ecological systems. Finally, analyses of multiple landscapes improve the understanding of context for governance and management.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Geografia , Comportamento Cooperativo , Europa (Continente) , Humanos , Aprendizagem
6.
Ambio ; 42(2): 146-59, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23475652

RESUMO

Barriers and bridges to implement policies about sustainable development and sustainability commonly depend on the past development of social-ecological systems. Production of metals required integration of use of ore, streams for energy, and wood for bioenergy and construction, as well as of multiple societal actors. Focusing on the Swedish Bergslagen region as a case study we (1) describe the phases of natural resource use triggered by metallurgy, (2) the location and spatial extent of 22 definitions of Bergslagen divided into four zones as a proxy of cumulative pressure on landscapes, and (3) analyze the consequences for natural capital and society. We found clear gradients in industrial activity, stream alteration, and amount of natural forest from the core to the periphery of Bergslagen. Additionally, the legacy of top-down governance is linked to today's poorly diversified business sector and thus municipal vulnerability. Comparing the Bergslagen case study with other similar regions in Russia and Germany, we discuss the usefulness of multiple case studies.


Assuntos
Conservação dos Recursos Naturais , Metalurgia/história , Cidades , Agricultura Florestal , Geografia , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , Suécia , Abastecimento de Água
7.
Ambio ; 42(2): 160-73, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23475653

RESUMO

This paper analyzes how sustained yield (SY) forestry is defined and implemented in Sweden and Russia, two countries with different forest-industrial regimes. We first compare definitions of SY forestry in national legislation and policies. Then we study forest management planning in two large forest management units with respect to: delivered forest products and values, how the harvest level of timber is defined, where the harvest takes place, and what treatments are used to sustain desired forest products and values. In Sweden SY forestry is maximum yield based on high-input forest management, and in Russia it is forestry based on natural regeneration with minimum investments in silviculture. We conclude that how SY forestry contributes to SFM depends on the context. Finally, we discuss the consequences of SY forestry as performed in Sweden and Russia related to its ability to support diverse forest functions, as envisioned in sustainable forest management policy.


Assuntos
Conservação dos Recursos Naturais , Agricultura Florestal/estatística & dados numéricos , Fidelidade a Diretrizes , Federação Russa , Suécia
8.
Ambio ; 42(2): 201-14, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23475656

RESUMO

Protected area (PA) is an indicator linked to policies on ecological sustainability. We analyzed area, size, and categories of PAs in the European boreal forest biome in Norway, Sweden, Finland, and Russia from 1900 to 2010. The PA increased from 1.5 × 10(3) ha in 1909 to 2.3 × 10(7) ha in 2010. While the total PA in the boreal biome was 10.8 %, the figures ranged from 17.2 % in the northern, 7.9 % of the middle, and 8.7 % of the southern boreal sub-regions. The median size of PAs varied from 10 to 124 ha among countries. The categories of less strictly PAs increased over time. The proportion of area occupied by PAs is an important response indicator for conservation efforts. However, the use of PA as an indicator of ecological sustainability needs to consider ecosystem representation, functional connectivity and management categories.


Assuntos
Conservação dos Recursos Naturais/tendências , Agricultura Florestal , Ecossistema , Europa (Continente) , Árvores
9.
Ambio ; 42(2): 215-28, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23475657

RESUMO

Policies on economic use of natural resources require considerations to social and cultural values. In order to make those concrete in a planning context, this paper aims to interpret social and cultural criteria, identify indicators, match these with verifier variables and visualize them on maps. Indicators were selected from a review of scholarly work and natural resource policies, and then matched with verifier variables available for Sweden's 290 municipalities. Maps of the spatial distribution of four social and four cultural verifier variables were then produced. Consideration of social and cultural values in the studied natural resource use sectors was limited. The spatial distribution of the verifier variables exhibited a general divide between northwest and south Sweden, and regional rural and urban areas. We conclude that it is possible to identify indicators and match them with verifier variables to support inclusion of social and cultural values in planning.


Assuntos
Conservação dos Recursos Naturais , Planejamento Social , Cidades , Cultura , Geografia , Políticas , Formulação de Políticas , Valores Sociais , Suécia
10.
Ambio ; 42(2): 254-65, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23475660

RESUMO

Translating policies about sustainable development as a social process and sustainability outcomes into the real world of social-ecological systems involves several challenges. Hence, research policies advocate improved innovative problem-solving capacity. One approach is transdisciplinary research that integrates research disciplines, as well as researchers and practitioners. Drawing upon 14 experiences of problem-solving, we used group modeling to map perceived barriers and bridges for researchers' and practitioners' joint knowledge production and learning towards transdisciplinary research. The analysis indicated that the transdisciplinary research process is influenced by (1) the amount of traditional disciplinary formal and informal control, (2) adaptation of project applications to fill the transdisciplinary research agenda, (3) stakeholder participation, and (4) functional team building/development based on self-reflection and experienced leadership. Focusing on implementation of green infrastructure policy as a common denominator for the delivery of ecosystem services and human well-being, we discuss how to diagnose social-ecological systems, and use knowledge production and collaborative learning as treatments.


Assuntos
Conservação dos Recursos Naturais , Comunicação Interdisciplinar , Resolução de Problemas , Comportamento Cooperativo , Humanos , Aprendizagem
11.
Stud Health Technol Inform ; 180: 1174-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22874391

RESUMO

A national patient portal for secure communication between the patients/citizens and primary care (Mina vårdkontakter) is available in Sweden. This system was used in a pilot project in the Stockholm County where patients were invited to prepare the visit to their physician for the discussion on the need for prolonged sickness leave by filling out a web based questionnaire on their current health status and working conditions. The opinions of the patients and their primary care physicians about the system were analyzed with positive feedback.


Assuntos
Certificação , Avaliação da Deficiência , Sistemas de Comunicação no Hospital , Participação do Paciente/métodos , Relações Médico-Paciente , Poder Psicológico , Licença Médica , Comunicação , Internet , Médicos de Atenção Primária , Suécia
12.
Acta Obstet Gynecol Scand ; 89(9): 1140-8, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20804339

RESUMO

OBJECTIVE: To study the impact of pregnancy on estimated peak oxygen uptake (VO(2 peak, est.)), physical activity and perceived health. DESIGN: Prospective cohort study. SETTING: Maternal health centers. POPULATION: A cohort of pregnant women. Methods. Cycle ergometer test and questionnaires in early pregnancy and 5 months postpartum. MAIN OUTCOME MEASURES: VO(2 peak, est.), physical activity and perceived health. RESULTS: Regular physical activity was reported by a successively lower proportion of women as pregnancy advanced but the proportion was regained postpartum. Despite this the difference between average absolute VO(2 peak, est.) in early pregnancy and postpartum of 2.44 and 2.42 l/minute, respectively, was not significant. The adjusted absolute VO(2 peak, est.) in early pregnancy successively increased with age to a maximum at 35 years, after which it decreased and among women of the same age the time between 8 and 12 weeks lowered the VO(2 peak, est.) by 0.130 l/minute. With the Short Form 36 (SF-36) questionnaire in early pregnancy the women scored their mean mental health to 72.0 and mean physical health to 79.7. At the postpartum appointment these scores were higher (p < 0.0001). Absolute and relative VO(2 peak, est.) in early pregnancy were positively correlated to the variation of SF-36's mean physical health in early pregnancy (p < 0.0001) and postpartum (p < 0.0001). CONCLUSIONS: Pregnancy had a moderate influence on physical fitness and perceived health half a year postpartum despite less regular physical activity during pregnancy. VO(2 peak, est.) in early pregnancy was positively correlated to perceived physical health.


Assuntos
Comportamentos Relacionados com a Saúde , Nível de Saúde , Atividade Motora/fisiologia , Consumo de Oxigênio/fisiologia , Gravidez/fisiologia , Adulto , Feminino , Humanos , Saúde Mental , Aptidão Física/fisiologia , Período Pós-Parto , Trimestres da Gravidez , Estudos Prospectivos , Inquéritos e Questionários
13.
Scand J Gastroenterol ; 44(4): 401-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19089754

RESUMO

OBJECTIVE: Wistar Kyoto (WKY) rats are more susceptible to stress-evoked ulcerations than Sprague-Dawley (SPD) rats. We have already demonstrated that gastrin cells are more active and ghrelin cells less active in WKY rats than in SPD rats. The purpose of this study was to compare endocrine cell activity and gastric acid output in WKY and SPD rats. MATERIAL AND METHODS: Gastric acid output was determined in conscious rats with gastric fistula. Plasma gastrin and ghrelin levels were measured after an overnight fast. Acid secretagogues (gastrin, histamine and carbachol) were given by continuous subcutaneous infusion. RESULTS: The volume of gastric juice, and the acidity and acid output were all significantly lower (p <0.05) in fasted WKY rats than in fasted SPD rats. Gastrin evoked a 4-fold (p <0.01) and 3-fold (p <0.05) increase in gastric acid output in SPD rats and WKY rats, respectively. Histamine raised the acid output 1.6-fold in SPD rats (p=0.06) and 3-fold in WKY rats (p <0.05), while carbachol failed to affect the acid output (weak increase, p >0.05). Fasting plasma ghrelin levels were 2-fold higher in SPD rats than in WKY rats (p <0.01) while fasting gastrin levels were 10-fold higher in WKY rats than in SPD rats (p <0.05). Neither the parietal-cell density nor the oxyntic mucosal thickness differed between the two strains. CONCLUSIONS: The results of the present study suggest that a high gastrin cell activity in WKY rats is secondary to a low gastric acidity. Whether the high gastrin cell activity is linked to susceptibility to stress ulcer in WKY rats warrants further investigation.


Assuntos
Ansiedade/metabolismo , Ácido Gástrico/metabolismo , Células Secretoras de Gastrina/fisiologia , Gastrinas/fisiologia , Animais , Ansiedade/patologia , Metabolismo Basal/fisiologia , Carbacol , Feminino , Fístula Gástrica , Grelina , Histamina , Ratos , Ratos Endogâmicos WKY , Ratos Sprague-Dawley , Estimulação Química
14.
Toxicol Pathol ; 36(5): 727-37, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18648100

RESUMO

Dogs treated with AR-H047108, an imidazopyridine potassium competitive acid blocker (P-CAB), developed clinical signs of hepatic dysfunction as well as morphologically manifest hepatotoxicity in repeat-dose toxicity studies. An investigative one-month study was performed, with interim euthanasia after one and two weeks. A detailed histopathological and immunohistochemical characterization of the liver lesions was conducted, including markers for fibrosis, Kupffer cell activation, apoptosis, and endothelial injury. In addition, hepatic retinoid and procollagen 1alpha2 mRNA levels in livers of dogs treated with AR-H047108 were analyzed. The results showed an early inflammatory process in central veins and centrilobular areas, present after one week of treatment. This inflammatory reaction was paralleled by activation of stellate/Ito cells to myofibroblasts and was associated with sinusoidal and centrivenular fibrosis. The early activation of stellate cells coincided with a significant decrease in retinyl ester levels, and a significant increase in procollagen 1alpha2 mRNA levels, in the liver. At later time points (three and six months), there was marked sinusoidal fibrosis in centrilobular areas, as well as occlusion of central veins resulting from a combination of fibrosis and increased thickness of smooth muscle bundles in the vessel wall. The pattern of lesions suggests a veno-occlusive-disease (VOD)-like scenario, possibly linked to the imidazopyridine chemical structure of the compound facilitated by specific morphological features of the dog liver.


Assuntos
Hepatopatia Veno-Oclusiva/patologia , Hepatócitos/patologia , Imidazóis/toxicidade , Fígado/patologia , Inibidores da Bomba de Prótons/toxicidade , Piridinas/toxicidade , Animais , Cães , Relação Dose-Resposta a Droga , Feminino , Fibrose/induzido quimicamente , Fibrose/patologia , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/metabolismo , Hepatócitos/metabolismo , Imidazóis/química , Imuno-Histoquímica , Células de Kupffer/metabolismo , Células de Kupffer/patologia , Fígado/metabolismo , Masculino , Estrutura Molecular , Inibidores da Bomba de Prótons/química , Piridinas/química , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica
15.
Acta Vet Scand ; 50: 25, 2008 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-18593470

RESUMO

BACKGROUND: The aim of this study was to get information on post mortem diagnoses of sows found dead or euthanised and to understand the diagnoses aetiology (causative background). Moreover, the study was to evaluate the association between the clinical symptoms observed on farm and post mortem findings. METHODS: A large Swedish herd was studied from January to September 2006. During the 32-week period 3.9% of the removed sows and gilts (old enough to be mated) were found dead, 12.0% were euthanised and the rest were sent to slaughter. Of 32 sows/gilts found dead 17 (53%) were post mortem examined, and of 98 sows euthanised 79 (81%) were examined. The 96 examined carcasses were after 70 sows and 26 gilts. The findings at examination were together with data from the herd monitoring program PigWin Sugg the base for the descriptive statistics presented. RESULTS: The average parity number at removal was 2.8 for those found dead and 2.1 for those euthanised. The highest number euthanised and found dead was in parity 0 (gilts). The main proportion of post mortem examinations was made on sows being in the period = 28 d of gestation at death (37.5%), followed by weaning to next service period (24.0%). Arthritis, with an incidence of 36.4% was the most common main finding of pathological-anatomical diagnosis (PAD). Of sows/gilts found dead were circulatory/cardiac failure (23.5%) and trauma related injuries (23.5%) most common PAD. The most commonly observed clinical symptom and reason for euthanasia of the sows/gilts was lameness. Notably, in 43% of the cases with PAD arthritis, the clinical symptoms suggested it being a fracture. Further one or more abscesses (38.5%) and teeth injuries (31.0%) were common findings when also incidental findings were included. CONCLUSION: This post mortem study based on carcasses from sows/gilts found dead or euthanised showed that arthritis was a significant problem in the studied herd and that post mortem examination was important to get proper diagnosis.


Assuntos
Eutanásia Animal/estatística & dados numéricos , Doenças dos Suínos/patologia , Animais , Artrite/mortalidade , Artrite/patologia , Artrite/veterinária , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/veterinária , Feminino , Paridade , Gravidez , Complicações na Gravidez/mortalidade , Complicações na Gravidez/patologia , Complicações na Gravidez/veterinária , Reprodução , Suécia/epidemiologia , Suínos , Doenças dos Suínos/mortalidade , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/patologia , Ferimentos e Lesões/veterinária
16.
Anim Reprod Sci ; 108(1-2): 37-48, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17714891

RESUMO

The objective of this study was to evaluate the long-term effect of a gonadotropin-releasing hormone (GnRH) vaccine, Improvac (Pfizer Ltd.), on the levels of GnRH antibodies, testosterone, estrone sulphate (E1S) and androstenone, as well as skatole and indole in male pigs. Additionally, the long-term effect of immunocastration on social and sexual behaviour was studied. Male pigs were assigned to two treatment groups: a treatment group given two doses of Improvac (n=12) and a control group of entire male pigs (n=12). The pigs were kept either 16 or 22 weeks after vaccination. Blood samples were collected five or six times; prior to both first and second vaccination, then three or four times during the 16 or 22 week period after second vaccination. Immunocastration significantly reduced levels of testosterone and E1S in plasma, and levels of androstenone in fat (P<0.001 for all). Skatole and indole levels in plasma and fat were also lower in immunocastrated pigs than in entire male pigs. These effects lasted up to 22 weeks after the second vaccination. Testis weight and bulbourethral gland length were lower in immunocastrated pigs at slaughter and these pigs showed less social, manipulating and aggressive behaviour than entire male pigs. The immunocastrated pigs remained sexually inactive throughout the study. Our study represents a further step in the evaluation of the effectiveness of Improvac as an alternative to surgical castration of entire male pigs. It shows that Improvac may have an extended effect compared with that currently implied by the directions for use.


Assuntos
Hormônio Liberador de Gonadotropina/imunologia , Orquiectomia/veterinária , Comportamento Sexual Animal/fisiologia , Suínos/fisiologia , Vacinas/imunologia , Tecido Adiposo/química , Androsterona/análise , Androsterona/sangue , Animais , Anticorpos/sangue , Glândulas Bulbouretrais/crescimento & desenvolvimento , Estrona/análogos & derivados , Estrona/análise , Estrona/sangue , Indóis/análise , Indóis/sangue , Masculino , Orquiectomia/métodos , Tamanho do Órgão , Escatol/análise , Escatol/sangue , Testículo/crescimento & desenvolvimento , Testosterona/análise , Testosterona/sangue
17.
Biochem Pharmacol ; 73(2): 198-205, 2007 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17081503

RESUMO

AZD0865 is a member of a drug class that inhibits gastric H(+),K(+)-ATPase by K(+)-competitive binding. The objective of these experiments was to characterize the mechanism of action, selectivity and inhibitory potency of AZD0865 in vitro. In porcine ion-leaky vesicles at pH 7.4, AZD0865 concentration-dependently inhibited K(+)-stimulated H(+),K(+)-ATPase activity (IC(50) 1.0+/-0.2 microM) but was more potent at pH 6.4 (IC(50) 0.13+/-0.01 microM). The IC(50) values for a permanent cation analogue, AR-H070091, were 11+/-1.2 microM at pH 7.4 and 16+/-1.8 microM at pH 6.4. These results suggest that the protonated form of AZD0865 inhibits H(+),K(+)-ATPase. In ion-tight vesicles, AZD0865 inhibited H(+),K(+)-ATPase more potently (IC(50) 6.9+/-0.4 nM) than in ion-leaky vesicles, suggesting a luminal site of action. AZD0865 inhibited acid formation in histamine- or dibutyryl-cAMP-stimulated rabbit gastric glands (IC(50) 0.28+/-0.01 and 0.26+/-0.003 microM, respectively). In ion-leaky vesicles at pH 7.4, AZD0865 (3 microM) immediately inhibited H(+),K(+)-ATPase activity by 88+/-1%. Immediately after a 10-fold dilution H(+),K(+)-ATPase inhibition was 41%, indicating reversible binding of AZD0865 to gastric H(+),K(+)-ATPase. In contrast to omeprazole, AZD0865 inhibited H(+),K(+)-ATPase activity in a K(+)-competitive manner (K(i) 46+/-3 nM). AZD0865 inhibited the process of cation occlusion concentration-dependently (IC(50) 1.7+/-0.06 microM). At 100 microM, AZD0865 reduced porcine renal Na(+),K(+)-ATPase activity by 9+/-2%, demonstrating a high selectivity for H(+),K(+)-ATPase. Thus, AZD0865 potently, K(+)-competitively, and selectively inhibits gastric H(+),K(+)-ATPase activity and acid formation in vitro, with a fast onset of effect.


Assuntos
Inibidores Enzimáticos/farmacologia , Imidazóis/farmacologia , Inibidores da Bomba de Prótons , Piridinas/farmacologia , Estômago/efeitos dos fármacos , Animais , Cátions , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Cinética , Estômago/enzimologia , Suínos
18.
Forensic Sci Int ; 169(1): 86-99, 2007 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-17182203

RESUMO

Amphetamine samples were analysed by gas chromatography-mass spectrometry (GC-MS), and the peak areas of 33 target compounds were transformed by applying various pretreatment techniques. The objective was to optimise the ability of a number of distance metrics to establish links between samples of amphetamine originating from the same batch (henceforth referred to as linked distances). Furthermore, partial least squares discriminant analysis (PLS-DA) was used to evaluate the effects of various pretreatment methods on separation of amphetamine batches synthesised by the Leuckart reaction, reductive amination of benzyl methyl ketone, and the nitrostyrene route. The most efficient way to pretreat GC-MS data varied for the different distance metrics, although best results were obtained when data were normalised to the sum of peak areas, and either the fourth root or a logarithm was applied to the normalised data. When pretreating normalised data by fourth root transformation, Pearson correlation was the distance metric that was most successful at finding linked samples. Normalisation and the use of fourth root also represented the best method of pretreating data when employing PLS-DA to separate samples synthesised by different routes. To achieve a faster and more user-friendly procedure for evaluating chromatograms, experiments were performed in which the number of target compounds used to compare samples was reduced. The effect of each compound that was removed was studied by applying PLS-DA and by using Pearson correlation to calculate linked distances as well as unlinked distances (between samples from different batches of amphetamine). Considering both links between samples from the same batch and separation of samples synthesised by different routes, the best results were obtained with the data set comprising 26 compounds. Finally, it was found that the profiling method developed in this work was superior to an existing technique with respect to separating linked and unlinked distances.

19.
Forensic Sci Int ; 169(1): 64-76, 2007 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-17134863

RESUMO

The suitability of liquid-liquid extraction (LLE) and solid-phase extraction (SPE) for the preparation of impurity extracts intended for gas chromatographic profiling analyses of amphetamine were evaluated. Both techniques were optimised with respect to the extraction of selected target compounds by use of full factorial designs in which the variables affecting the performance were evaluated. Test samples consisted of amphetamine synthesised by the Leuckart reaction, by reductive amination of benzyl methyl ketone and by the nitrostyrene route. The performance of LLE and SPE were comparable in terms of repeatability and recovery of the target compounds. LLE was considered the better choice for the present harmonised amphetamine profiling method due to the lack of information on the long-term stability of SPE columns.

20.
Forensic Sci Int ; 169(1): 77-85, 2007 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-17178203

RESUMO

This paper is the fifth in a series of six in relation to the development of a harmonised method for the profiling of amphetamine [L. Aalberg, K. Andersson, C. Bertler, H. Borén, M.D. Cole, J. Dahlén, Y. Finnon, H. Huizer, K. Jalava, E. Kaa, E. Lock, A. Lopes, A. Poortman-van der Meer, E. Sippola, Development of a harmonised method for the profiling of amphetamines I. Synthesis of standards and compilation of analytical data, Forensic Sci. Int. 149 (2005) 219-229; L. Aalberg, K. Andersson, C. Bertler, M.D. Cole, Y. Finnon, H. Huizer, K. Jalava, E. Kaa, E. Lock, A. Lopes, A. Poortman-van der Meer, E. Sippola, J. Dahlén, Development of a harmonised method for the profiling of amphetamines II. Stability of impurities in organic solvents, Forensic Sci. Int. 149 (2005) 231-241]. The third paper [K. Andersson, K. Jalava, E. Lock, L. Aalberg, Y. Finnon, H. Huizer, E. Kaa, A. Lopes, A. Poortman-van der Meer, M.D. Cole, J. Dahlén, E. Sippola, Development of a harmonised method for the profiling of amphetamines III. Development of the gas chromatographic method, Forensic Sci. Int., in press] dealt with the optimisation of the gas chromatographic and detection methods whereas the fourth paper [K. Andersson, K. Jalava, E. Lock, Y. Finnon, S. Stevenson, L. Aalberg, H. Huizer, E. Kaa, A. Lopes, A. Poortman-van der Meer, M.D. Cole, J. Dahlén, E. Sippola, Development of a harmonised method for the profiling of amphetamines IV. Optimisation of sample preparation, Forensic Sci. Int., in press] concerned the optimisation of the extraction method prior to GC analysis. This paper is a study of the optimised method in order to determine its stability. Investigations of within and between day variations were carried out in four laboratories. Moreover, variations between laboratories were also determined. Both flame ionisation detector (FID) and MS detection were used. One laboratory studied nitrogen-phosphorous detector (NPD) detection as well. For this task, 12 batches of amphetamine were prepared. Six of them were synthesised via the Leuckart route, three via the nitrostyrene route and three via the reductive amination route [A.M.A. Verweij, Impurities in illicit drug preparations: amphetamine and methamphetamine, Forensic Sci. Rev. 1 (1989) 2-11]. Taking into account all studied target compounds and the average results from four laboratories, the within day variation was around 6% for FID and 5% for MS, the between days variation was around 10% for FID and 8% for MS. For NPD detection, within day variation was 5% and between days variation 9% (only one laboratory). Finally, the inter-laboratory variation was about 12% for FID (four laboratories) and 10% for MS (three laboratories).

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