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1.
ISA Trans ; 96: 272-286, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31326079

RESUMO

In variable-pitch wind turbines, pitch angle control is implemented to regulate the rotor speed and power production. However, mechanical loads of the wind turbines are affected by the pitch angle adjustment. To improve the performance and at the same time alleviate the mechanical loads, a gain-scheduling fractional-order PID (FOPID), where a trained RBF neural network chooses its parameters is proposed. The database, which the RBF neural network is trained based on, is created via optimization of a FOPID in several wind speeds with chaotic differential evolution (CDE) algorithm. The simulation results are compared to an RBF based PID controller that is designed via the same method, a conventional gain-scheduling baseline PI controller developed by NREL, an optimal RBF based PI controller, and a FOPI controller. The simulations indicate that the RBF based FOPID improves the control performance of the benchmark wind turbine in comparison to the other controllers, while the applied loads to the structure are mitigated. To validate the performance and robustness, all controllers are implemented on FAST wind turbine simulator. The superiority of the proposed FOPID controller is depicted in comparison to the other controllers.

2.
Diabet Med ; 34(8): 1061-1066, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28430372

RESUMO

AIMS: To investigate retinal nerve fibre layer (RNFL) thickness in people with metabolic syndrome (MetS) and healthy controls. METHODS: A cross-sectional study was performed from March 2014 to January 2016. All participants underwent anthropometric and serological biochemical measurements, ophthalmological examination, and spectral-domain optical coherence tomography (SD-OCT). Individuals with elevated intraocular pressure, glaucoma, diabetic retinopathy and other ocular disorders were excluded. T-test, Chi square and general linear models were used to analyse the data. RESULTS: In total, 278 eyes from 139 participants were investigated [median (interquartile range) age: 37 (32-43) years]. RNFL thickness was lower in the nasal superior (107.8 ± 19.5µm) and temporal superior (135.7 ± 18.9µm) sectors in MetS group compared with the control group (114.6 ± 22.4 µm, P = 0.013 and 140.7 ± 18.2 µm, P = 0.027, respectively). After multiple adjustments for age, gender and the side of the examined [right (OD)/left (OS)] eye, MetS was independently associated with a lower RFNL thickness in the nasal superior (ß = 0.20, P = 0.009) and temporal superior (ß = 0.14, P = 0.048) sectors. RNFL thickness was significantly reduced in participants with higher numbers of metabolic abnormalities, independent of age, gender and the side of the examined eye (P = 0.043). CONCLUSION: Our findings demonstrate that MetS is independently associated with reduced RNFL thickness, suggesting that neurodegeneration is implicated in pathogenesis of MetS.


Assuntos
Síndrome Metabólica/fisiopatologia , Fibras Nervosas Amielínicas/patologia , Doenças Neurodegenerativas/etiologia , Nervo Óptico/diagnóstico por imagem , Retina/diagnóstico por imagem , Adulto , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Estudos de Coortes , Estudos Transversais , Feminino , Hospitais de Ensino , Humanos , Irã (Geográfico) , Modelos Lineares , Masculino , Síndrome Metabólica/complicações , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/patologia , Obesidade Abdominal/complicações , Obesidade Mórbida/complicações , Nervo Óptico/patologia , Tamanho do Órgão , Retina/patologia , Índice de Gravidade de Doença , Tomografia de Coerência Óptica , Circunferência da Cintura
3.
Dose Response ; 11(2): 281-92, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23930107

RESUMO

The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1(st) phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2(nd) phase, 30 male rats were divided into 2 groups of 15 animals. The 1(st) group received microwave exposure. The 2(nd) group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response.

4.
J Pharm Bioallied Sci ; 2(4): 333-6, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21180467

RESUMO

OBJECTIVE: The present study was conducted to monitor adverse drug reactions in patients of bronchial asthma in outpatient department and inpatient department of a university teaching hospital in South Delhi. MATERIALS AND METHODS: About 200 patients irrespective of age and sex with established asthma were interviewed during the time period of January 2006 to April 2006 using structured questionnaire. Naranjo's adverse drug reaction probability scale was used to assess the adverse drug reactions. RESULTS: A total of 15 adverse drug reactions were reported in 13 out of 200 asthmatic patients. Among the 13 patients reported with adverse drug reactions, 5 (38.5%) were male and 8 (61.5%) patients were female. Maximum percentage of ADRs (2 in 15 prescriptions, 13.3%) observed with montelukast, followed by beclomethasone (1 in 12 prescriptions, 8.3%), salbutamol (6 in 109 prescriptions, 5.5%), and ipratropium (3 in 63 prescriptions, 4.8%). CONCLUSIONS: Montelukast was found to be associated with greater percentage of adverse drug reactions as compared to other antiasthamatics. The above findings are constrained by a small sample size and need to be corroborated by conducting long-term studies using a larger sample size.

5.
J Coll Physicians Surg Pak ; 19(1): 43-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19149980

RESUMO

OBJECTIVE: This study was conducted to assess the effect of age on the ultimate outcome measures following single stage surgical procedure of soft tissue release, relocation, capsulorrhaphy, femoral shortening with varus/derotation osteotomy and pelvic osteotomy. STUDY DESIGN: A case series. PLACE AND DURATION OF STUDY: The study with two groups of pretest-posttest design was conducted at Department of Orthopaedic Surgery, Jinnah Postgraduate Medical Centre (JPMC), Karachi, from 1993 to January 2008. METHODOLOGY: Patients included were having neglected, congenital dislocation of the hip joint, aged over 3 years. Patients with failed previous surgery, paralytic, teratological, traumatic or septic dislocations and patients with less than 5 years follow-up were excluded from the study. The patients were divided into two groups, 3-7 years (37 hip joints) and over 7 years (13 hip joints). The single stage surgical procedure of open relocation, femoral shortening/derotation/ varus osteotomy and pelvic osteotomy was the dependent variable; whereas, the final clinico-radiological results based upon Tonnis grading, Severin's clinical/radiological grading, Klisic's overall rating and acetabular index were the independent variables of the study. Pre- and postoperative data was assessed for overall improvement and the difference in outcome measures between the two age groups. RESULTS: Significant overall improvement on all parameters was achieved after surgery. When results were compared between two age groups, there was no significant difference in the final outcome as per Tonnis grading and Severin's clinical typing as modified by Gibson (97.3% versus 84.4% normal hip joints or Tonnis grade 1 and 78.37% versus 53.85% Severin's type 1) but the results based upon Severin's radiological grading (62.16% versus 15.38%) and Klisic's overall rating (62.16% versus 15.38%) were significantly better in 3-7 years as compared to those over 7 years. There was no significant difference between the two age groups when compared for improvement in acetabular index. On further analysis, a progressive deterioration of results with increasing age was observed, yet the results in those aged over 7 years were reasonably justified surgical correction of congenital dislocation of the hip joint. Majority of the complications were seen in children operated at the age of 4-5 years. There were 7 cases (14%) of redislocation/subluxation and 6 were in 3-7 years age group. There were 4 cases (8%) of the avascular necrosis of the femoral head. Three patients had residual coxa vara and 2 had significant limb shortening. Limb lengthening was done in these 2 cases. CONCLUSION: The final results displayed progressive deterioration of clinical, radiological and functional outcome measures with aging after single stage reconstructive surgery for the congenital dislocation of hip joint. However, despite this, the results in children over 7 years were also good/excellent in most of the cases justifying surgery.


Assuntos
Fêmur/cirurgia , Luxação Congênita de Quadril/cirurgia , Instabilidade Articular/cirurgia , Osteotomia/métodos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Luxação Congênita de Quadril/diagnóstico por imagem , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Instabilidade Articular/complicações , Masculino , Radiografia , Procedimentos de Cirurgia Plástica , Resultado do Tratamento
6.
J Bone Joint Surg Br ; 91(1): 124-30, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19092017

RESUMO

Bone surface strains were measured in cadaver femora during loading prior to and after resurfacing of the hip and total hip replacement using an uncemented, tapered femoral component. In vitro loading simulated the single-leg stance phase during walking. Strains were measured on the medial and the lateral sides of the proximal aspect and the mid-diaphysis of the femur. Bone surface strains following femoral resurfacing were similar to those in the native femur, except for proximal shear strains, which were significantly less than those in the native femur. Proximomedial strains following total hip replacement were significantly less than those in the native and the resurfaced femur. These results are consistent with previous clinical evidence of bone loss after total hip replacement, and provide support for claims of bone preservation after resurfacing arthroplasty of the hip.


Assuntos
Artroplastia de Quadril/normas , Fêmur/fisiologia , Prótese Articular/normas , Artroplastia de Quadril/métodos , Fenômenos Biomecânicos/fisiologia , Densidade Óssea/fisiologia , Cadáver , Fêmur/cirurgia , Análise de Elementos Finitos , Humanos , Teste de Materiais/métodos , Desenho de Prótese/normas , Estresse Mecânico , Suporte de Carga/fisiologia
7.
Bull Soc Belge Ophtalmol ; (307): 39-43, 2008.
Artigo em Francês | MEDLINE | ID: mdl-18546925

RESUMO

The orbital apex syndrome is defined by the association of visual loss, ophtalmoplegia, blepharoptosis, proptosis along with forehead and upper eyelid anesthesia. This syndrome is secondary to traumatism, malignancy or infection of orbital apex. Herpes zoster is an uncommon cause. We discuss the physiopathologic mechanism, evolution and management of this affection.


Assuntos
Herpes Zoster/diagnóstico , Doenças Orbitárias/virologia , Aciclovir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Feminino , Herpes Zoster/tratamento farmacológico , Herpes Zoster/virologia , Humanos , Doenças Orbitárias/tratamento farmacológico , Síndrome
8.
Colorectal Dis ; 10(3): 289-93, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17764533

RESUMO

OBJECTIVE: Circumferential margin involvement (CRM) is a powerful predictor of local recurrence, distant metastasis and patient survival in rectal cancer. In this study, we aimed to determine the frequency of retroperitoneal margin involvement in right colon cancer and describe its relationship to tumour stage and outcome of surgical treatment. METHOD: Two hundred and twenty-eight consecutive resections for adenocarcinoma of the ascending colon and caecum were identified between 1998 and 2006. Tumour involvement of the posterior retroperitoneal surgical resection margin (RSRM) was recorded and correlated with tumour stage, grade and clinical outcome. RSRM positive patients were compared with CRM positive rectal tumours resected in the same surgical unit. RESULTS: Nineteen of 228 right hemicolectomies (8.4%) showed tumour involvement of the RSRM (defined as < or = 1 mm). Approximately half of the RSRM positive patients underwent palliative resections because of synchronous distant metastases. Out of nine 'potentially curative' resections where the RSRM was involved, five patients subsequently developed metastatic recurrence and two isolated local recurrence. RSRM positivity was associated with advanced tumour stage and more extensive extramural spread than CRM positive rectal cancers. CONCLUSION: Retroperitoneal surgical resection margin involvement by caecal and ascending colon carcinoma is a marker of advanced tumour stage and associated with a high incidence of synchronous and metachronous distant metastasis. More aggressive surgery to obtain a clear margin or postoperative radiotherapy to the tumour bed is likely to benefit only a minority of patients.


Assuntos
Adenocarcinoma/patologia , Neoplasias do Ceco/patologia , Neoplasias do Colo/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Neoplasias do Ceco/mortalidade , Neoplasias do Ceco/cirurgia , Estudos de Coortes , Colectomia/métodos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Recidiva Local de Neoplasia/mortalidade , Inoculação de Neoplasia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Probabilidade , Sistema de Registros , Espaço Retroperitoneal , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
9.
Calcif Tissue Int ; 71(2): 172-8, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12200649

RESUMO

The search for an ideal bone substitute is ongoing. Multiple osteoconductive bone substitutes are available today. Plaster of Paris (POP) (calcium sulfate) has been used for more than 100 years for treatment of skeletal defects. This implant is compared to a new material, hydroxyapatite/calcium carbonate (HA/CC), in a rabbit tibia model. HA/CC is made from partial conversion of coralline calcium carbonate to hydroxyapatite and has an outer hydroxyapatite layer and an inner calcium carbonate core, a combination that leads to faster resorption than that of pure hydroxyapatite. This study compares the histomorphometric and radiographic properties of POP and HA/CC in a rabbit tibial defect. Both implants preferentially restore bone to the cortex relative to the canal. Plaster of Paris was fully resorbed by 6 weeks both radiographically and histometrically and HA/CC was substantially resorbed by 42 weeks. No significant difference was noted in volume fraction of bone between the two implants at 42 weeks postimplantation. Hydroxyapatite/calcium carbonate is a biocompatible bone graft substitute with a rate of resorption significantly slower than plaster of Paris.


Assuntos
Substitutos Ósseos , Carbonato de Cálcio , Sulfato de Cálcio , Durapatita , Osseointegração , Tíbia/crescimento & desenvolvimento , Animais , Feminino , Teste de Materiais , Microscopia Eletrônica de Varredura , Coelhos , Tíbia/lesões , Tíbia/ultraestrutura
10.
Am J Med ; 110(6): 471-80, 2001 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11331059

RESUMO

Extensive animal studies and a growing number of human clinical trials have now definitively demonstrated the central role of the renin-angiotensin-aldosterone system in the expression and modulation of cardiovascular disease. In contrast to the original hypothesis, the benefits of angiotensin antagonism do not emanate from the antihypertensive effect alone. Subsequent extensive investigations of angiotensin blockade suggest that the benefits of this approach may also result from the pharmacologic alteration of endothelial cell function and the ensuing changes in the biology of the vasculature. The more recent availability of direct antagonists of the AT(1) angiotensin receptor has introduced an element of doubt into this realm of clinical decision making. The receptor antagonists and the more widely studied converting-enzyme inhibitors share many endpoint attributes. Nevertheless, the partially overlapping mechanisms of action for the two classes of angiotensin antagonists confer distinct pharmacologic properties, including side effect profiles, mechanisms of action, and theoretic salutary effects upon the expression of cardiovascular disease. The current review will attempt to contrast the biology of angiotensin converting-enzyme inhibition with angiotensin II receptor antagonism. A discussion of the differential effects of these drug classes on endothelial cell function and on the modulation of vascular disease will be utilized to provide a theoretic framework for clinical decision making and therapeutics.


Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Angiotensinogênio/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Sistema Renina-Angiotensina , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Ensaios Clínicos como Assunto , Endotélio Vascular/efeitos dos fármacos , Humanos , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
11.
Arch Intern Med ; 161(5): 667-72, 2001 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-11231698

RESUMO

Clinical and basic science research has repeatedly confirmed the importance of the renin-angiotensin-aldosterone system in the pathophysiology of chronic heart failure. Accordingly, blockade of this system by angiotensin-converting enzyme (ACE) inhibitors has assumed a central role in the treatment of heart failure. Recently, angiotensin II receptor blockers (ARBs) have gained prominence as a possible substitute for ACE inhibitors in therapy for heart failure. However, clinical data compiled on this use of ARBs have shown them to be useful only as alternative therapy in ACE inhibitor-intolerant patients. Continuing large-scale clinical investigations may lead to an expansion of their role in therapy for various cardiovascular diseases.


Assuntos
Angiotensina II/antagonistas & inibidores , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Bradicinina/fisiologia , Doença Crônica , Ensaios Clínicos como Assunto , Previsões , Insuficiência Cardíaca/fisiopatologia , Humanos , Losartan/uso terapêutico
12.
Muscle Nerve ; 23(6): 851-62, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10842260

RESUMO

Tenotomy is a commonly encountered clinical entity, whether traumatic or iatrogenic. This article reviews the response of skeletal muscle to tenotomy. The changes are subdivided into molecular, architectural, and functional categories. Architectural disruption of the muscle includes myofiber disorganization, central core necrosis, Z-line streaming, fibrosis of fibers and Golgi tendon organs, changes in sarcomere number, and alterations in the number of membrane particles. Molecular changes include transient changes in myosin heavy chain composition and expression of neural cell adhesion molecule (NCAM). Functionally, tenotomized muscle produces decreased maximum tetanic and twitch tension. Alterations in normal skeletal muscle structure and function are clinically applicable to the understanding of pathological states that follow tendon rupture and iatrogenic tenotomy.


Assuntos
Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Traumatismos dos Tendões/cirurgia , Tendões/cirurgia , Animais , Humanos , Traumatismos dos Tendões/fisiopatologia , Tendões/fisiologia
13.
Muscle Nerve ; 23(5): 707-14, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10797393

RESUMO

Rabbit extensor digitorum longus (EDL) tendons were cut with the muscle active (active tenotomy, AT) or with the EDL at rest (passive tenotomy, PT). One, 7, and 21 days after tenotomy, contractile testing was performed. A second experiment was performed in which EDL tendons underwent PT and, after a 7-day delay, muscle-tendon units were restored to their original length. Maximum isometric tension dropped precipitously 1 day after either AT or PT to approximately 50% of normal and continued to decline by day 7. In contrast to PT, where peak tension (P(0)) decreased further by 21 days, after AT, P(0) partially recovered. Differences in muscle mass, cross-sectional area, fiber type, and sarcomere number did not explain the differential response. One day after length restoration of muscles, P(0) rapidly increased by approximately 40%. These observations have implications for understanding the outcome of muscle-tendon unit injury and surgical repair.


Assuntos
Contração Isométrica , Músculo Esquelético/fisiologia , Traumatismos dos Tendões/fisiopatologia , Tendões/fisiologia , Animais , Masculino , Músculo Esquelético/fisiopatologia , Músculo Esquelético/ultraestrutura , Coelhos , Sarcômeros/ultraestrutura , Tendões/cirurgia , Fatores de Tempo , Torque
14.
J Pak Med Assoc ; 50(1): 25-9, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10770044

RESUMO

OBJECTIVE: To evaluate the cost of political violence in terms of human life and its influence on social, psychological and financial aspects of community. DESIGN: Retrospective study conducted from 1987 to 1989. SETTING: Department of Accident and Emergency, Jinnah Postgraduate Medical Centre, Karachi. SAMPLE SIZE: Nine hundred and fifty four victims including two hundred and fifty seven dead. RESULTS: The mean age of the victims was 27.29 +/- 9.46 years with a male to female ratio of 33:1. All ethnic groups suffered to some extent. No case of violence on religious differences was reported during this period. Firearms were frequently used. Most of the deaths (92.2%) occurred due to firearm injuries. Landhi, Korangi, Malir and Shah Faisal Colony were the worst affected areas. There was however no significant difference between them. The projected loss of life for the dead was approximately 3.15 million days. The same was difficult to assess for the injured because of multifactorial reasons. Six thousand four hundred and ninety two close family members suffered from Psychological and Physical Trauma. The number of distant members affected psychologically was estimated to be 0.566 million. Schooling of approximately five thousand four hundred thirty seven children of the victims suffered. CONCLUSION: Political violence has significant short and long term effects on the society in terms of physical and psychological trauma, financial losses, poor schooling and health, biased pattern of child development, migration of families and further division of society into identifiable communities which may prolong the conflict.


Assuntos
Política , Violência , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Paquistão , Estudos Retrospectivos , Violência/estatística & dados numéricos
15.
J Pak Med Assoc ; 49(7): 164-7, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10599203

RESUMO

OBJECTIVE: To evaluate the short term results of extensor mechanism sparing approach to the elbow for fixation of intercondylar fractures of the distal end of humerus and compare it with existing Surgical approaches. DESIGN: This is a prospective study conducted from June, 1992 to June, 1997. SETTING: Department of Orthopaedic Surgery, Jinnah Postgraduate Medical Centre and Mehran Clinic (Pvt.), Karachi. PRINCIPLE OF SURGICAL APPROACH: This approach is based upon the principle that by sparing the extensor mechanism, we reduce the amount of surgical trauma and help in early rehabilitation which can contribute in improving the results of this difficult fracture. RESULTS: There were nine type 2 fractures, eight type 3 fractures and four type 4 fractures according to Rise borough and Radin classification. Based upon the same authors criteria, there were over all 57.14% good 23.81% fair and 19.04% poor results. Adequate exposure was achieved in all of type 2 and seven (87.5%) out of eight type 3 fractures. We failed in type 4 fractures. Mean operating time was 107.38 (+/- 24.67) minutes. CONCLUSION: The results in this series are comparable to other studies. They can however be improved with proper selection of cases, experience with the technique along with better fixation and rehabilitations.


Assuntos
Cotovelo/cirurgia , Fixação Interna de Fraturas , Fraturas Ósseas/cirurgia , Úmero , Humanos , Estudos Prospectivos
16.
Mol Cell Endocrinol ; 156(1-2): 35-43, 1999 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-10612421

RESUMO

In rat astroglial cells, four G(omicronalpha) transcripts were found: G(omicron2alpha) mRNA (5.7 kb) and three G(omicron1alpha) mRNAs (4.0, 3.0 and 2.3 kb). However, G(omicron2alpha) but little G(omicronalpha1) proteins were present in membrane-enriched fractions. Culturing astroglial cells with forskolin (10 microM) or isoproterenol (10 microM) a beta-adrenergic agonist increased transiently in a time-dependent manner the levels of G(omicronalpha) proteins. The degradation rate of G(omicronalpha) proteins was slightly decreased by the cAMP treatment. In parallel, forskolin (10 microM) treatment increased transiently the amounts of both G(omicron1alpha) and G(omicron2alpha) mRNAs. The relative transcription rate of G(omicronalpha) gene was increased by 1.7-fold in forskolin-treated cells whereas the half-lives of G(omicron1alpha) and G(omicron2alpha) mRNAs were not significantly changed. These results suggest that cAMP regulates the transcription rate of G(omicronalpha) gene and this is compatible with the existence of a cAMP responsive element in the promoter of the G(omicronalpha) gene.


Assuntos
Astrócitos/metabolismo , Encéfalo/metabolismo , AMP Cíclico/fisiologia , Regulação da Expressão Gênica , Proteínas Heterotriméricas de Ligação ao GTP/genética , Transcrição Gênica , Animais , Animais Recém-Nascidos , Células Cultivadas , Colforsina/farmacologia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP , Regulação da Expressão Gênica/efeitos dos fármacos , Isoproterenol/farmacologia , Cinética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transcrição Gênica/efeitos dos fármacos
17.
J Neurochem ; 71(6): 2271-7, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9832124

RESUMO

Culture of rat astrocytes in the presence of 10 microM forskolin, isoproterenol, a nonselective beta-adrenergic agonist, or 8-bromo-cyclic AMP increased transiently in a time-dependent manner the levels of G(i alpha2) and G(i alpha3) mRNAs as measured by northern blot analysis. G(i alpha1) mRNA was not expressed in these cells. After 6-9 h of culture with forskolin or isoproterenol the amounts of G(i alpha2) and G(i alpha3) mRNAs were maximal (150-300% over control). In cells challenged with 8-bromo-cyclic AMP, the level of G(i alpha2) mRNA level was maximal after 1 h of culture, while the maximal for G(i alpha3) mRNA was reached after 6 h of culture. For prolonged exposure times (24 h) to these agents the levels of G(i alpha2) and G(i alpha3) mRNAs decreased to the values observed in control cells. The forskolin-induced increase in G(i alpha2) protein expression measured by western blot analysis was similar to the increase in G(i alpha2) mRNA amount. In contrast, forskolin induced only a modest increase in the quantity of G(i alpha3) protein (150% over control) despite a large increase of G(i alpha3) mRNA content. Transcription rates and RNA stability were measured simultaneously after isolation of newly synthesized mRNA was performed. The half-lives of G(i alpha) mRNAs were approximately 0.7 and 3 h for G(i alpha2) and G(i alpha3), respectively. Culturing astrocytes in the presence of forskolin resulted in an increase in the half-lives of G(i alpha2) mRNA and G(i alpha3) mRNA by five- and twofold, respectively. The relative transcription rate of the G(i alpha3) gene was slightly increased by approximately 1.3-1.5-fold in forskolin-treated cells but not that of G(i alpha2) gene. These results suggest that cyclic AMP enhanced G(i alpha2) and G(i alpha3) mRNA expression by both transcriptional and posttranscriptional mechanisms, with an increase of G(i alpha) mRNA stability as one of the major checkpoints.


Assuntos
Astrócitos/metabolismo , AMP Cíclico/fisiologia , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , RNA Mensageiro/metabolismo , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Animais , Células Cultivadas , Estabilidade de Medicamentos , Isoproterenol/farmacologia , Ratos , Ratos Sprague-Dawley , Transcrição Gênica/efeitos dos fármacos
18.
Cell Signal ; 9(6): 431-8, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9376224

RESUMO

We have studied the in vitro effect of sodium saccharin (NaSacch) on the rat adipocyte adenylyl cyclase complex. NaSacch (2.5-50 mM) inhibited significantly in a dose-dependent manner basal and isoproterenol-stimulated cAMP accumulation on isolated rat adipocytes. Similarly, NaSacch (2.5-50 mM) inhibited forskolin-stimulated adenylyl cyclase activity measured in the presence of Mg(2+)-ATP on adipocyte, astrocyte and thyrocyte membrane fractions. In contrast, NaSacch did not inhibit but slightly increased the forskolin-stimulated adenylyl cyclase activity measured in the presence of Mn(2+)-ATP and GDP beta S, a stable GDP analogue. The effect of NaSacch was not mediated through either the A1-adenosine receptor (A1R) or the alpha 2-adrenergic receptor (alpha 2AR). The inhibitory effect of NaSacch was additive to that of A1R agonist and was not blocked by the addition of the alpha 2AR antagonist RX 821002. Pretreatment of adipocytes with pertussis toxin slightly attenuated but did not abolish the inhibitory effect of NaSacch on forskolin-stimulated adenylyl cyclase activity on membrane fractions. These data suggest that the inhibitory effect of NaSacch on forskolin stimulated-adenylyl cyclase in adipocytes does not imply only Gi protein but also other direct or indirect inhibitory pathway(s) which remain to be determined.


Assuntos
Adenilil Ciclases/metabolismo , Adipócitos/enzimologia , Carcinógenos/farmacologia , Sacarina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Toxina Adenilato Ciclase , Adipócitos/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/enzimologia , Tartarato de Brimonidina , Fracionamento Celular , Membrana Celular/enzimologia , Córtex Cerebral/citologia , Colforsina/farmacologia , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Proteínas de Ligação ao GTP/metabolismo , Idazoxano/análogos & derivados , Idazoxano/farmacologia , Masculino , Toxina Pertussis , Fenilisopropiladenosina/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Suínos , Paladar , Glândula Tireoide/citologia , Fatores de Virulência de Bordetella/farmacologia
19.
Brain Res ; 771(1): 45-54, 1997 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-9383007

RESUMO

The activity of hypothalamic pro-opiomelanocortin (POMC) neurons is known to display a circadian cycle. We hypothesized that the existence of a c-Fos responsive element (AP-1 site) within the POMC gene sequence might reflect the ability of POMC neurons to express c-fos proto-oncogene during circadian increase of their neuronal activity. To this aim, adult male rats previously kept under a controlled 12 h light/12 h dark schedule were sacrificed every 4 h throughout the 24 h cycle and their brains processed for Fos and/or POMC immunocytochemistry. Here we show that, specifically during the dark period of the cycle, the mediobasal hypothalamic area spontaneously exhibits a strong Fos immunoreactivity, whereas very low Fos labelling was detected during the light period. As postulated, the simultaneous visualisation of both Fos and POMC antigens allowed us to show that this nocturnal induction of Fos occurs almost exclusively at the nuclear level of POMC-producing neurons. These results not only highlight the mechanisms underlying the physiological functioning of the hypothalamic POMC system, but also demonstrate the feasibility of using c-fos expression as a useful tool to assess the pharmacological effect of drugs on the activity of POMC neurons as is the case for many other neuronal systems. Such drugs might be relevant in the treatment of psychosis since an alteration of POMC-related peptide transmission has been reported in the brains of both schizophrenic and depressive patients.


Assuntos
Ritmo Circadiano , Regulação da Expressão Gênica , Hipotálamo/metabolismo , Neurônios/metabolismo , Pró-Opiomelanocortina/biossíntese , Proteínas Proto-Oncogênicas c-fos/biossíntese , Hormônio Adrenocorticotrópico/biossíntese , Animais , Escuridão , Luz , Masculino , Ratos , Ratos Wistar , beta-Endorfina/biossíntese
20.
J Neurochem ; 67(6): 2532-9, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8931487

RESUMO

Long-term (48-h) forskolin treatment of rat astroglial cells led to a slight decrease (30-40%) in the response to isoproterenol, vasoactive-intestinal peptide, guanyl 5'-(beta gamma-imido)diphosphate, guanosine 5'-O-(3-thiotriphosphate) [GTP(S)], and AIF4- in crude membrane fractions. In contrast, the acute stimulatory effect of forskolin was increased by 1.25-1.5-fold. These two opposite effects of forskolin were mediated by a cyclic AMP-dependent mechanism. No changes in Gs alpha, Gi alpha, or G beta protein levels could be determined by immunoblotting using specific antisera. No significant differences were observed in the ability of G proteins extracted from control and forskolin-treated cells to reconstitute a full adenylyl cyclase activity in membranes from S49 cyc- cells, lacking Gs alpha protein. Gs alpha proteins were detected in two pools of membranes, one in the heavy sucrose fractions and the other in light sucrose fractions. Forskolin treatment of the cells shifted Gs alpha protein toward the light-density membranes. We did not find any significant change in the distribution of adenylyl cyclase. In contrast to the decreased stimulation of adenylyl cyclase activity by agonists acting via Gs alpha, observed in the crude membrane fraction, the responses of adenylyl cyclase to forskolin as well as to GTP(S) were increased in the purified plasma membrane fractions. These results may indicate that sensitization of the catalyst appears to be the dominant component in the astroglial cell response to long-term treatment by forskolin.


Assuntos
Adenilil Ciclases/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Astrócitos/enzimologia , Colforsina/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Western Blotting , Membrana Celular/química , Membrana Celular/enzimologia , Proteínas de Ligação ao GTP/análise , Proteínas de Ligação ao GTP/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Frações Subcelulares/enzimologia , Fatores de Tempo
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