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1.
Braz. j. biol ; 84: e253613, 2024. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345548

RESUMO

Abstract Soybean meal is an inexpensive plant origin protein which has been used in practical diets as a replacement of animal protein such as fish meal or chicken meal, due to the uneconomical price of animal protein diets. Consequently, a research study was conducted on some commercial species of Indian major carps i.e. Catla (Cattla cattla), Rohu (Labeo rohita) and Mrigala (Cirhinus mrigala) (Hamilton, 1822) to estimate optimum dietary protein requirement of soy bean meal in diet in an intensive polyculture. Three different diets (SBM I, SBM II and SBM III) were formulated by 80%, 50% and 20% replacement of fish meal with soybean meal from a 45% fish meal diet (control).Highest monthly mean weight gain was obtained by SBM II (with 35% CP and about 50% substitution of fish meal), while SBM III (45% Crude Protein and about 20% substitution of fish meal) was stood second. All tested diets respond enormously by producing high yield as compare to control diet, though SBM II generated highest yield among all. On the bases of the following research, it was revealed that the SBM can surrogate even50% fish meal without any augmentation of other amino acids in the diet of Indian major carps.


Resumo O farelo de soja é uma proteína de origem vegetal de baixo custo que tem sido usada em dietas práticas como um substituto da proteína animal, como farinha de peixe ou farinha de frango, devido ao preço não econômico das dietas com proteína animal. Consequentemente, um estudo/pesquisa foi realizado com algumas espécies comerciais de carpas principais indianas, ou seja, Catla (Cattla cattla), Rohu (Labeo rohita) e Mrigala (Cirhinus mrigala) (Hamilton, 1822), para estimar a necessidade ideal de proteína dietética de farelo de soja na dieta em uma policultura intensiva. Três dietas diferentes (SBM I, SBM II e SBM III) foram formuladas por 80%, 50% e 20% de substituição de farinha de peixe por farelo de soja de uma dieta de 45% de farinha de peixe (controle). O maior ganho de peso médio mensal foi obtido por SBM II (com 35% PB e cerca de 50% de substituição de farinha de peixe), enquanto SBM III (45% de proteína bruta e cerca de 20% de substituição de farinha de peixe) ficou em segundo lugar. Todas as dietas testadas respondem enormemente produzindo alto rendimento em comparação com a dieta controle, embora SBM II tenha gerado o maior rendimento entre todas. Com base na pesquisa a seguir, foi revelado que o SBM pode substituir até 50% da farinha de peixe sem qualquer aumento de outros aminoácidos na dieta das carpas principais indianas.


Assuntos
Animais , Carpas , Cyprinidae , Soja , Alimentos Marinhos , Dieta/veterinária , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal
2.
Braz. j. biol ; 84: e253948, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355909

RESUMO

Abstract The assessment of the comparative effect of biosal (phytopesticide), deltamethrin, and lambda-cyhalothrin (pyrethroids) were made against two fodder pests, Hermolaus modestus and Hermolaus ocimumi by filter paper impregnation method. The activity of total protein contents, GPT (glutamic-pyruvic transaminase) and GOT (glutamic oxaloacetate transaminase) were affected in Hermolaus modestus and Hermolaus ocimumi against biosal, deltamethrin, and lambda cyhalothrin. The activity of total protein contents in H. modestus was 31.053%, 4.607%, and 24.575%, against biosal, deltamethrin, and lambda-cyhalothrin, respectively. The activity of total protein contents was observed as 24.202%, 15.25%, and 56.036% against deltamethrin, lambda-cyhalothrin, and biosal, respectively in H. ocimumi. The activity of GOT was observed as 98.675% for biosal 33.95% for deltamethrin and 83.619% for lambda-cyhalothrin in H. modestus. The GOT activity was estimated in H. ocimumi as 78.831%, 47.645%, and 71.287% against biosal, deltamethrin, and lambda-cyhalothrin, respectively. The efficacy of GPT enzyme against biosal, deltamethrin, and lambda-cyhalothrin was calculated as 89.26%, 73.07%, and 47.58%, respectively in H. modestus. The H. ocimumi showed GPT activity as 77.58% for biosal, 68.84% for deltamethrin, and 52.67% for lambda-cyhalothrin, respectively.


Resumo A avaliação do efeito comparativo do biosal (fitopesticida), deltametrina e lambda-cialotrina (piretróides) foi feita contra duas pragas forrageiras, Hermolaus modestus e Hermolaus ocimumi, pelo método de impregnação com papel de filtro. A atividade do conteúdo de proteína total, GPT (transaminase glutâmico-pirúvica) e GOT (oxaloacetato transaminase glutâmico) foram afetados em Hermolaus modestus e Hermolaus ocimumi contra biosal, deltametrina e lambda cialotrina. A atividade do conteúdo de proteína total em H. modestus foi 31.053%, 4.607% e 24.575%, contra biosal, deltametrina e lambda-cialotrina, respectivamente. A atividade do conteúdo de proteína total foi observada como 24.202%, 15.25% e 56,036% contra deltametrina, lambda-cialotrina e biosal, respectivamente em H. ocimumi. A atividade do GOT foi observada em 98.675% para o biosal, 33,95% para a deltametrina e 83.619% para a lambda-cialotrina em H. modestus. A atividade do GOT foi estimada em H. ocimumi como 78.831%, 47.645% e 71.287% contra biosal, deltametrina e lambda-cialotrina, respectivamente. A eficácia da enzima GPT contra biosal, deltametrina e lambda-cialotrina foi calculada como 89.26%, 73.07% e 47.58%, respectivamente em H. modestus. A H. ocimumi apresentou atividade GPT de 77.58% para biosal, 68.84% para deltametrina e 52.67% para lambda-cialotrina, respectivamente.


Assuntos
Animais , Piretrinas , Inseticidas , Heterópteros , Alanina Transaminase , Ração Animal , Nitrilas
3.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469250

RESUMO

Abstract Soybean meal is an inexpensive plant origin protein which has been used in practical diets as a replacement of animal protein such as fish meal or chicken meal, due to the uneconomical price of animal protein diets. Consequently, a research study was conducted on some commercial species of Indian major carps i.e. Catla (Cattla cattla), Rohu (Labeo rohita) and Mrigala (Cirhinus mrigala) (Hamilton, 1822) to estimate optimum dietary protein requirement of soy bean meal in diet in an intensive polyculture. Three different diets (SBM I, SBM II and SBM III) were formulated by 80%, 50% and 20% replacement of fish meal with soybean meal from a 45% fish meal diet (control).Highest monthly mean weight gain was obtained by SBM II (with 35% CP and about 50% substitution of fish meal), while SBM III (45% Crude Protein and about 20% substitution of fish meal) was stood second. All tested diets respond enormously by producing high yield as compare to control diet, though SBM II generated highest yield among all. On the bases of the following research, it was revealed that the SBM can surrogate even50% fish meal without any augmentation of other amino acids in the diet of Indian major carps.


Resumo O farelo de soja é uma proteína de origem vegetal de baixo custo que tem sido usada em dietas práticas como um substituto da proteína animal, como farinha de peixe ou farinha de frango, devido ao preço não econômico das dietas com proteína animal. Consequentemente, um estudo/pesquisa foi realizado com algumas espécies comerciais de carpas principais indianas, ou seja, Catla (Cattla cattla), Rohu (Labeo rohita) e Mrigala (Cirhinus mrigala) (Hamilton, 1822), para estimar a necessidade ideal de proteína dietética de farelo de soja na dieta em uma policultura intensiva. Três dietas diferentes (SBM I, SBM II e SBM III) foram formuladas por 80%, 50% e 20% de substituição de farinha de peixe por farelo de soja de uma dieta de 45% de farinha de peixe (controle). O maior ganho de peso médio mensal foi obtido por SBM II (com 35% PB e cerca de 50% de substituição de farinha de peixe), enquanto SBM III (45% de proteína bruta e cerca de 20% de substituição de farinha de peixe) ficou em segundo lugar. Todas as dietas testadas respondem enormemente produzindo alto rendimento em comparação com a dieta controle, embora SBM II tenha gerado o maior rendimento entre todas. Com base na pesquisa a seguir, foi revelado que o SBM pode substituir até 50% da farinha de peixe sem qualquer aumento de outros aminoácidos na dieta das carpas principais indianas.

4.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469298

RESUMO

Abstract The assessment of the comparative effect of biosal (phytopesticide), deltamethrin, and lambda-cyhalothrin (pyrethroids) were made against two fodder pests, Hermolaus modestus and Hermolaus ocimumi by filter paper impregnation method. The activity of total protein contents, GPT (glutamic-pyruvic transaminase) and GOT (glutamic oxaloacetate transaminase) were affected in Hermolaus modestus and Hermolaus ocimumi against biosal, deltamethrin, and lambda cyhalothrin. The activity of total protein contents in H. modestus was 31.053%, 4.607%, and 24.575%, against biosal, deltamethrin, and lambda-cyhalothrin, respectively. The activity of total protein contents was observed as 24.202%, 15.25%, and 56.036% against deltamethrin, lambda-cyhalothrin, and biosal, respectively in H. ocimumi. The activity of GOT was observed as 98.675% for biosal 33.95% for deltamethrin and 83.619% for lambda-cyhalothrin in H. modestus. The GOT activity was estimated in H. ocimumi as 78.831%, 47.645%, and 71.287% against biosal, deltamethrin, and lambda-cyhalothrin, respectively. The efficacy of GPT enzyme against biosal, deltamethrin, and lambda-cyhalothrin was calculated as 89.26%, 73.07%, and 47.58%, respectively in H. modestus. The H. ocimumi showed GPT activity as 77.58% for biosal, 68.84% for deltamethrin, and 52.67% for lambda-cyhalothrin, respectively.


Resumo A avaliação do efeito comparativo do biosal (fitopesticida), deltametrina e lambda-cialotrina (piretróides) foi feita contra duas pragas forrageiras, Hermolaus modestus e Hermolaus ocimumi, pelo método de impregnação com papel de filtro. A atividade do conteúdo de proteína total, GPT (transaminase glutâmico-pirúvica) e GOT (oxaloacetato transaminase glutâmico) foram afetados em Hermolaus modestus e Hermolaus ocimumi contra biosal, deltametrina e lambda cialotrina. A atividade do conteúdo de proteína total em H. modestus foi 31.053%, 4.607% e 24.575%, contra biosal, deltametrina e lambda-cialotrina, respectivamente. A atividade do conteúdo de proteína total foi observada como 24.202%, 15.25% e 56,036% contra deltametrina, lambda-cialotrina e biosal, respectivamente em H. ocimumi. A atividade do GOT foi observada em 98.675% para o biosal, 33,95% para a deltametrina e 83.619% para a lambda-cialotrina em H. modestus. A atividade do GOT foi estimada em H. ocimumi como 78.831%, 47.645% e 71.287% contra biosal, deltametrina e lambda-cialotrina, respectivamente. A eficácia da enzima GPT contra biosal, deltametrina e lambda-cialotrina foi calculada como 89.26%, 73.07% e 47.58%, respectivamente em H. modestus. A H. ocimumi apresentou atividade GPT de 77.58% para biosal, 68.84% para deltametrina e 52.67% para lambda-cialotrina, respectivamente.

5.
Braz J Biol ; 84: e249124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35946727

RESUMO

Current cross-sectional study was carried out between September 2019 to January 2020 at the Department of Pathology, Mardan Medical Complex (MMC), Mardan, and District Headquarter Hospital North Waziristan, Khyber Pakhtunkhwa (KP), Pakistan. The objectives of the current study were to determine the prevalence of leishmaniasis and its associated risk factors in selected districts of KP province, Pakistan. Altogether, three hundred and seventy-four (n=374) leishmaniosis patients were included in the current study. Skin specimen from the ulcer border were collected. The slides were stained by Giemsa stain and examined for the presence of amastigote. The prevalence of leishmania infected patients in different region of KP were as follows: North Waziristan region 53.7 (n=201) District Mardan 34.7% (n=130); District Nowshera 6.7% (n=25), District Swabi 1.1% (n=4) and other Districts i.e. Dir, Malakand, Buner and Bajawarr were 3.7% (n=14). The frequency of leishmaniasis were more in male and majority of the infected patients were in the age group of <10 years. Among n=374 patients 95.7% (n= 358) had cutaneous leishmaniasis while 3% (n= 11) had mucocutaneous type of infection and 1.3% (n= 5) patients had both cutaneous and mucocutaneous infection. Upon treatment by Sodium stibogluconate (SSG) 97% (n=362) showed clinical signs of complete or partial recovery of their skin lesions. Conclusively, highest incidence of leishmania infection occurred during short study period and majority of the cases showed positive response to treatment.


Assuntos
Leishmaniose Cutânea , Criança , Estudos Transversais , Feminino , Humanos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/etiologia , Masculino , Paquistão/epidemiologia , Prevalência , Fatores de Risco
6.
Folia Morphol (Warsz) ; 81(2): 481-486, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34018177

RESUMO

BACKGROUND: Panoramic radiographs are the most common radiographic tool used by the dental clinicians to evaluate teeth, mandible and other related structures of the jaws. Mandibular condyle is an important anatomical landmark for facial growth, expressed in an upward and backward direction. The presentation of mandibular condyle differs widely among different group of ages and individuals. MATERIALS AND METHODS: The retrospective cross-sectional study was conducted from November 2018 to March 2019 at Dow International Dental College Karachi that includes radiographic evaluation of 500 mandibular condyles. All retrievable orthopantomograms were obtained and data were extracted regarding age, gender and condylar morphology. RESULTS: The morphological appearances of mandibular condyle have great variation among different age groups and subjects. Normally, we recognise five basic shapes i.e. oval, bird beak, crooked finger, diamond and mixed. Out of 250 pair of condylar heads that were evaluated, 50% were oval, 40% bird beak, 4.8% crooked finger and diamond 4.8%. CONCLUSIONS: All four morphological types of mandibular condyles were observed and the oval shape condyles were most prevalent among both genders and all age groups. In future studies, the inclusion of other parameters and large sample size may provide unique information.


Assuntos
Mandíbula , Côndilo Mandibular , Estudos Transversais , Feminino , Humanos , Masculino , Côndilo Mandibular/diagnóstico por imagem , Radiografia Panorâmica , Estudos Retrospectivos
7.
Braz J Biol ; 84: e253948, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34932640

RESUMO

The assessment of the comparative effect of biosal (phytopesticide), deltamethrin, and lambda-cyhalothrin (pyrethroids) were made against two fodder pests, Hermolaus modestus and Hermolaus ocimumi by filter paper impregnation method. The activity of total protein contents, GPT (glutamic-pyruvic transaminase) and GOT (glutamic oxaloacetate transaminase) were affected in Hermolaus modestus and Hermolaus ocimumi against biosal, deltamethrin, and lambda cyhalothrin. The activity of total protein contents in H. modestus was 31.053%, 4.607%, and 24.575%, against biosal, deltamethrin, and lambda-cyhalothrin, respectively. The activity of total protein contents was observed as 24.202%, 15.25%, and 56.036% against deltamethrin, lambda-cyhalothrin, and biosal, respectively in H. ocimumi. The activity of GOT was observed as 98.675% for biosal 33.95% for deltamethrin and 83.619% for lambda-cyhalothrin in H. modestus. The GOT activity was estimated in H. ocimumi as 78.831%, 47.645%, and 71.287% against biosal, deltamethrin, and lambda-cyhalothrin, respectively. The efficacy of GPT enzyme against biosal, deltamethrin, and lambda-cyhalothrin was calculated as 89.26%, 73.07%, and 47.58%, respectively in H. modestus. The H. ocimumi showed GPT activity as 77.58% for biosal, 68.84% for deltamethrin, and 52.67% for lambda-cyhalothrin, respectively.


Assuntos
Inseticidas , Piretrinas , Alanina Transaminase , Ração Animal , Animais , Heterópteros , Nitrilas
8.
Braz J Biol ; 84: e253613, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34730702

RESUMO

Soybean meal is an inexpensive plant origin protein which has been used in practical diets as a replacement of animal protein such as fish meal or chicken meal, due to the uneconomical price of animal protein diets. Consequently, a research study was conducted on some commercial species of Indian major carps i.e. Catla (Cattla cattla), Rohu (Labeo rohita) and Mrigala (Cirhinus mrigala) (Hamilton, 1822) to estimate optimum dietary protein requirement of soy bean meal in diet in an intensive polyculture. Three different diets (SBM I, SBM II and SBM III) were formulated by 80%, 50% and 20% replacement of fish meal with soybean meal from a 45% fish meal diet (control).Highest monthly mean weight gain was obtained by SBM II (with 35% CP and about 50% substitution of fish meal), while SBM III (45% Crude Protein and about 20% substitution of fish meal) was stood second. All tested diets respond enormously by producing high yield as compare to control diet, though SBM II generated highest yield among all. On the bases of the following research, it was revealed that the SBM can surrogate even50% fish meal without any augmentation of other amino acids in the diet of Indian major carps.


Assuntos
Carpas , Cyprinidae , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Alimentos Marinhos , Soja
9.
Knee ; 26(2): 416-421, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30777666

RESUMO

BACKGROUND: The management of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) is the subject of ongoing debate. In part 1 of this two-part series, we present an overview of current practice regarding the management of the IPFP in elective TKA among surgeons in the UK. METHODS: A web-based survey was offered to 269 delegates of the BASK 2017 annual conference. RESULTS: The survey showed a large variation in practice. Of the 173 responders, 86.7% were consultants; 62.4% partially resected the IPFP; 23.1% totally resected the IPFP, and 9.8% preserved it. Forty percent felt that resection made a difference. Only 23% stated that they were aware of guidelines/evidence. CONCLUSION: There is wide variation in practice with regard to the IPFP in TKA. The available literature with regard to resection or preservation of the IPFP is not conclusive. IMPLICATIONS: There are no definitive guidelines available for the management of the IPFP in TKA resulting in a wide variation in practice amongst surgeons.


Assuntos
Tecido Adiposo/cirurgia , Artroplastia do Joelho/métodos , Competência Clínica , Procedimentos Cirúrgicos Eletivos/métodos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Patela/cirurgia , Congressos como Assunto , Humanos , Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/fisiopatologia , Patela/diagnóstico por imagem , Cirurgiões/normas , Inquéritos e Questionários , Reino Unido
10.
Knee ; 26(2): 422-426, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30738721

RESUMO

BACKGROUND: The management of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) is the subject of ongoing debate. In part 2 of this two part series the authors aimed to investigate if resection of the IPFP affects clinical outcomes. METHODS: A systematic search of CENTRAL Cochrane library, Medline, Embase and Web-of-science databases for the past 10 years was performed. Studies of patients undergoing primary TKA comparing outcomes between IPFP resection and preservation were included. The meta-analysis was performed with Review Manager 5.3. RESULTS: Seven studies, involving 2815 patients (3312 knees) were included in the systematic review, of which two were RCTs. Outcome measures included patellar tendon length (PTL), post-operative pain, Knee Society Scores (KSS) and Functional Scores. Meta-analysis identified a trend toward shortening of the patellar tendon with IPFP resection. Resection correlated with a lower incidence of post-operative pain at one to two months, however at three to six months pain scores were higher in this group. No statistical difference was found in KSS and Functional Scores. CONCLUSION: There is wide variation in practice with regard to the IPFP in TKA. The available literature with regard to resection or preservation of the IPFP is not conclusive. IMPLICATIONS: There is no clear consensus in the literature on the resection or preservation of the IPFP indicating a clear need for high quality studies in the future to provide meaningful answers.


Assuntos
Tecido Adiposo/cirurgia , Artroplastia do Joelho/métodos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Dor Pós-Operatória/prevenção & controle , Ligamento Patelar/cirurgia , Humanos , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Amplitude de Movimento Articular/fisiologia
11.
Ann R Coll Surg Engl ; 98(6): 376-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27055409

RESUMO

Introduction Internal fixation of undisplaced intracapsular femoral neck fractures with cannulated hip screws is a widely accepted surgical technique, despite reported failure rates of 12%-19%. This study determined whether preoperative serum albumin levels are linked to fixation failure. Methods We retrospectively reviewed 251 consecutive undisplaced intracapsular femoral neck fracture patients treated with cannulated hip screws in a district general hospital. Preoperative albumin levels were measured, and the fixation technique, classification and posterior tilt on radiography assessed. Fixation failure was defined as a screw cut, avascular necrosis (AVN) or non-union. Results Of the patients, 185 were female and 66 male. The mean age was 77 years (range 60-101 years). Thirty seven (15%) patients had fixation failure: 10 (4%) due to AVN; 12 (5%) due to non-union; and 15 (6%) due to fixation collapse. Low serum albumin levels were significantly associated with failure (p=0.01), whereas gender (p=0.56), operated side (p=0.62), age (p=0.34) and screw configuration (p=0.42) were not. A posterior tilt angle greater than 20° on lateral radiography significantly predicted failure (p=0.002). Conclusions Preoperative serum albumin is an independent predictor of cannulated hip screw fixation failure in undisplaced femoral neck fractures. Nutritional status should therefore be considered when deciding between surgical fixation and arthroplasty to avoid the possibility of revision surgery, along with an increased risk of morbidity and mortality.


Assuntos
Parafusos Ósseos , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Albumina Sérica , Idoso , Idoso de 80 Anos ou mais , Feminino , Necrose da Cabeça do Fêmur/etiologia , Fraturas não Consolidadas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Período Pré-Operatório , Estudos Retrospectivos
12.
Br J Pharmacol ; 172(13): 3242-53, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25231155

RESUMO

Platelet-expressed GPCRs are critical regulators of platelet function. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis associated with coronary atherosclerosis and ischaemic stroke. However, anti-thrombotic drug therapy is associated with high inter-patient variability in therapeutic response and adverse bleeding side effects. In order to optimize the use of existing anti-platelet drugs and to develop new therapies, more detailed knowledge is required relating to the molecular mechanisms that regulate GPCR and therefore platelet function. One approach has been to identify rare, function-disrupting mutations within key platelet proteins in patients with bleeding disorders. In this review, we describe how an integrated functional genomics strategy has contributed important structure-function information about platelet GPCRs with specific emphasis upon purinergic and thromboxane A2 receptors. We also discuss the potential implications these findings have for pharmacotherapy and for understanding the molecular basis of mild bleeding disorders.


Assuntos
Receptores Acoplados a Proteínas G/genética , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Variação Genética , Humanos , Inibidores da Agregação Plaquetária/farmacologia , Receptores Acoplados a Proteínas G/metabolismo
13.
J Thromb Haemost ; 12(5): 716-25, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24612435

RESUMO

BACKGROUND: The study of patients with bleeding problems is a powerful approach in determining the function and regulation of important proteins in human platelets. We have identified a patient with a chronic bleeding disorder expressing a homozygous P2RY(12) mutation, predicting an arginine to cysteine (R122C) substitution in the G-protein-coupled P2Y(12) receptor. This mutation is found within the DRY motif, which is a highly conserved region in G-protein-coupled receptors (GPCRs) that is speculated to play a critical role in regulating receptor conformational states. OBJECTIVES: To determine the functional consequences of the R122C substitution for P2Y(12) function. PATIENT/METHODS: We performed a detailed phenotypic analysis of an index case and affected family members. An analysis of the variant R122C P2Y(12) stably expressed in cells was also performed. RESULTS: ADP-stimulated platelet aggregation was reduced as a result of a significant impairment of P2Y(12) activity in the patient and family members. Cell surface R122C P2Y(12) expression was reduced both in cell lines and in platelets; in cell lines, this was as a consequence of agonist-independent internalization followed by subsequent receptor trafficking to lysosomes. Strikingly, members of this family also showed reduced thrombin-induced platelet activation, owing to an intronic polymorphism in the F2R gene, which encodes protease-activated receptor 1 (PAR-1), that has been shown to be associated with reduced PAR-1 receptor activity. CONCLUSIONS: Our study is the first to demonstrate a patient with deficits in two stimulatory GPCR pathways that regulate platelet activity, further indicating that bleeding disorders constitute a complex trait.


Assuntos
Plaquetas/citologia , Hemorragia/enzimologia , Mutação , Polimorfismo Genético , Receptor PAR-1/genética , Receptores Purinérgicos P2Y12/genética , Motivos de Aminoácidos , Linhagem Celular Tumoral , Doença Crônica , Feminino , Homozigoto , Humanos , Masculino , Fenótipo , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Mutação Puntual , Conformação Proteica , Receptor PAR-1/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Análise de Sequência de DNA
14.
J Thromb Haemost ; 11(3): 547-54, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23279270

RESUMO

BACKGROUND: Genetic variations that affect the structure of the thromboxane A2 receptor (TP receptor) provide insights into the function of this key platelet and vascular receptor, but are very rare in unselected populations. OBJECTIVES: To determine the functional consequences of the TP receptor Trp29Cys (W29C) substitution. PATIENTS/METHODS: We performed a detailed phenotypic analysis of an index case (P1) with reduced platelet aggregation and secretion responses to TP receptor pathway activators, and a heterozygous TP receptor W29C substitution. An analysis of the variant W29C TP receptor expressed in heterologous cells was performed. RESULTS: Total TP receptor expression in platelets from P1 was similar to that of controls, but there was reduced maximum binding and reduced affinity of binding to the TP receptor antagonist [(3) H]SQ29548. HEK293 cells transfected with W29C TP receptor cDNA showed similar total TP receptor expression to wild-type (WT) controls. However, the TP receptor agonist U46619 was less potent at inducing rises in cytosolic free Ca(2+) in HEK293 cells expressing the W29C TP receptor than in WT controls, indicating reduced receptor function. Immunofluorescence microscopy and cell surface ELISA showed intracellular retention and reduced cell surface expression of the W29C TP receptor in HEK293 cells. Consistent with the platelet phenotype, both maximum binding and the affinity of binding of [(3) H]SQ29548 to the W29C TP receptor were reduced compared to WT controls. CONCLUSION: These findings extend the phenotypic description of the very rare disorder TP receptor deficiency, and show that the W29C substitution reduces TP receptor function by reducing surface receptor expression and by disrupting ligand binding.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Plaquetas/metabolismo , Variação Genética , Agregação Plaquetária , Receptores de Tromboxano A2 e Prostaglandina H2/sangue , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Transtornos da Coagulação Sanguínea/genética , Plaquetas/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes , Cálcio/sangue , Ensaio de Imunoadsorção Enzimática , Ácidos Graxos Insaturados , Predisposição Genética para Doença , Células HEK293 , Humanos , Hidrazinas/metabolismo , Ligantes , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Fenótipo , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/genética , Ensaio Radioligante , Receptores de Tromboxano A2 e Prostaglandina H2/agonistas , Receptores de Tromboxano A2 e Prostaglandina H2/deficiência , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Transfecção
15.
Diabet Med ; 28(11): 1337-42, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21726277

RESUMO

AIMS: Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited neurodegenerative disorder, first evident in childhood as an association of juvenile-onset diabetes mellitus and optic atrophy, followed by diabetes insipidus and deafness. The aim of the study was to examine the clinical profile of patients with DIDMOAD syndrome presenting to a tertiary care hospital in north India. METHODS: Clinical presentation of juvenile-onset diabetes mellitus fulfilling the diagnosis of Wolfram syndrome was studied using a prepared standardized form. RESULTS: Subjects with juvenile-onset non-autoimmune diabetes mellitus attending the diabetic clinic at a tertiary care centre in north India were followed for 10 years and a diagnosis of fully developed Wolfram syndrome was confirmed in seven individuals. The series consisted of five male and two female patients with a mean age of 17.5 ±7.34 years. Two subjects had consanguinity and none had any other family member affected. Optic atrophy was present in all, sensorineural hearing loss in 4/7, central diabetes insipidus in 4/7 and nephrogenic diabetes insipidus in 2/7 subjects. The new associations found were: spastic myoclonus, short stature with pancreatic malabsorption, nephrogenic diabetes insipidus, cyanotic heart disease and choledocholithiasis with cholangitis. Genetic analysis revealed mutation in exon 8 of the WFS1 gene in all the cases studied. CONCLUSIONS: The present clinical series of Wolfram syndrome reveals a varied clinical presentation of the syndrome and some new associations.


Assuntos
Perda Auditiva Neurossensorial/diagnóstico , Proteínas de Membrana/genética , Mutação , Atrofia Óptica/diagnóstico , Síndrome de Wolfram/diagnóstico , Adolescente , Adulto , Sequência de Bases , Criança , Colangite/diagnóstico , Coledocolitíase/diagnóstico , Consanguinidade , Análise Mutacional de DNA , Feminino , Transtornos do Crescimento/diagnóstico , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/genética , Humanos , Índia/epidemiologia , Imageamento por Ressonância Magnética , Síndromes de Malabsorção/diagnóstico , Masculino , Mioclonia/diagnóstico , Atrofia Óptica/epidemiologia , Atrofia Óptica/genética , Linhagem , Síndrome de Wolfram/epidemiologia , Síndrome de Wolfram/genética , Adulto Jovem
16.
Pediatr Neurosurg ; 47(1): 22-30, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21613777

RESUMO

We present our experience after analyzing retrospectively the clinicopathological characteristics, surgical approaches, immediate and long-term postoperative complications and survival outcome of pediatric spinal epidural tumors treated over a period of 10 years from 2000 to 2009 in a tertiary-care hospital. Our study included benign and malignant tumors. The majority of our patients were boys (14:8). The duration of symptoms was longer in benign lesions. Non-Hodgkin's lymphoma was the commonest malignant tumor and aneurysmal bone cyst was the commonest benign tumor. The mean duration of follow-up was 19 months (range 3-48 months). Most of the patients improved in their neurological grade after surgery; however, the degree of excision had no bearing on the length of survival for malignant lesions.


Assuntos
Neoplasias Epidurais/diagnóstico , Neoplasias Epidurais/etnologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Neoplasias Epidurais/terapia , Feminino , Seguimentos , Humanos , Índia/etnologia , Estimativa de Kaplan-Meier , Masculino , Paquistão/etnologia , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/etnologia , Neoplasias da Coluna Vertebral/terapia
17.
Br J Pharmacol ; 159(3): 518-33, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20128803

RESUMO

BACKGROUND AND PURPOSE: We have investigated the effect of deletions of a postsynaptic density, disc large and zo-1 protein (PDZ) motif at the end of the COOH-terminus of the rat A(2B) adenosine receptor on intracellular trafficking following long-term exposure to the agonist 5'-(N-ethylcarboxamido)-adenosine. EXPERIMENTAL APPROACH: The trafficking of the wild type A(2B) adenosine receptor and deletion mutants expressed in Chinese hamster ovary cells was studied using an enzyme-linked immunosorbent assay in combination with immunofluorescence microscopy. KEY RESULTS: The wild type A(2B) adenosine receptor and deletion mutants were all extensively internalized following prolonged treatment with NECA. The intracellular compartment through which the Gln(325)-stop receptor mutant, which lacks the Type II PDZ motif found in the wild type receptor initially trafficked was not the same as the wild type receptor. Expression of dominant negative mutants of arrestin-2, dynamin or Eps-15 inhibited internalization of wild type and Leu(330)-stop receptors, whereas only dominant negative mutant dynamin inhibited agonist-induced internalization of Gln(325)-stop, Ser(326)-stop and Phe(328)-stop receptors. Following internalization, the wild type A(2B) adenosine receptor recycled rapidly to the cell surface, whereas the Gln(325)-stop receptor did not recycle. CONCLUSIONS AND IMPLICATIONS: Deletion of the COOH-terminus of the A(2B) adenosine receptor beyond Leu(330) switches internalization from an arrestin- and clathrin-dependent pathway to one that is dynamin dependent but arrestin and clathrin independent. The presence of a Type II PDZ motif appears to be essential for arrestin- and clathrin-dependent internalization, as well as recycling of the A(2B) adenosine receptor following prolonged agonist addition.


Assuntos
Arrestina/metabolismo , Clatrina/metabolismo , Dinaminas/metabolismo , Receptores Purinérgicos P1/metabolismo , Motivos de Aminoácidos , Animais , Células CHO , Membrana Celular/metabolismo , Cricetinae , Cricetulus , Ensaio de Imunoadsorção Enzimática , Feminino , Glutamina/metabolismo , Leucina/metabolismo , Microscopia de Fluorescência , Fenilalanina/metabolismo , Estrutura Terciária de Proteína , Transporte Proteico , Ratos , Receptor A2B de Adenosina/metabolismo , Deleção de Sequência
18.
Phys Rev Lett ; 102(1): 011801, 2009 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-19257180

RESUMO

Using 2.45x10;{7} psi(2S) decays collected with the CLEO-c detector at the Cornell Electron Storage Ring we present the most precise measurements of magnetic dipole transitions in the charmonium system. We measure B(psi(2S)-->gammaeta_{c})=(4.32+/-0.16+/-0.60)x10;{-3}, B(J/psi-->gammaeta_{c})/B(psi(2S)-->gammaeta_{c})=4.59+/-0.23+/-0.64, and B(J/psi-->gammaeta_{c})=(1.98+/-0.09+/-0.30)%. We observe a distortion in the eta_{c} line shape due to the photon-energy dependence of the magnetic dipole transition rate. We find that measurements of the eta_{c} mass are sensitive to the line shape, suggesting an explanation for the discrepancy between measurements of the eta_{c} mass in radiative transitions and other production mechanisms.

19.
Phys Rev Lett ; 101(19): 192001, 2008 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-19113261

RESUMO

We report the first observation of Upsilon(2S)-->etaUpsilon(1S), with a branching fraction B=(2.1(-0.6)+0.7(stat)+/-0.3(syst)) x 10(-4) and a statistical significance 5.3sigma. Data were acquired with the CLEO III detector at the CESR e+e(-) symmetric collider. This is the first process observed involving a b-quark spin flip. For related transitions, 90% confidence limits in units of 10(-4) are B(Upsilon(2S)-->pi0Upsilon(1S)) < 1.8, B(Upsilon(3S)-->etaUpsilon(1S)) < 1.8, B(Upsilon(3S)-->pi0Upsilon(1S)) < 0.7, and B(Upsilon(3S)-->pi0Upsilon(2S)) < 5.1.

20.
Phys Rev Lett ; 101(20): 201601, 2008 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-19113327

RESUMO

In this Letter, we describe a search for lepton flavor violation (LFV) in the bottomonium system. We search for leptonic decays Upsilon(nS)-->mutau (n=1, 2, and 3) using the data collected with the CLEO III detector. We identify the tau lepton using its leptonic decay nu_{tau}nu[over ]_{e}e and utilize multidimensional likelihood fitting with probability density function shapes measured from independent data samples. We report our estimates of 95% C.L. upper limits on LFV branching fractions of Upsilon mesons. We interpret our results in terms of the exclusion plot for the energy scale of a hypothetical new interaction versus its effective LFV coupling in the framework of effective field theory.

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