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1.
Int J Mol Sci ; 24(13)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37445797

RESUMO

Chemotherapy-induced kidney damage is an emerging problem that restricts cancer treatment effectiveness. The proteasome inhibitor carfilzomib (CFZ) is primarily used to treat multiple myeloma and has been associated with severe renal injury in humans. CFZ-induced nephrotoxicity remains an unmet medical need, and there is an urgent need to find and develop a nephroprotective and antioxidant therapy for this condition. Thymoquinone (TQ) is a bioactive compound that has been isolated from Nigella sativa seeds. It has a wide range of pharmacological properties. Therefore, this experimental design aimed to study the effectiveness of TQ against CFZ-induced renal toxicity in rats. The first group of rats was a normal control (CNT); the second group received CFZ (4 mg/kg b.w.); the third and fourth groups received TQ (10 and 20 mg/kg b.w.) 2 h before receiving CFZ; the fifth group received only TQ (20 mg/kg b.w.). This experiment was conducted for 16 days, and at the end of the experiment, blood samples and kidney tissue were collected for biochemical assays. The results indicated that administration of CFZ significantly enhanced serum marker levels such as BUN, creatinine, and uric acid in the CFZ group. Similarly, it was also noticed that CFZ administration induced oxidative stress by reducing antioxidants (GSH) and antioxidant enzymes (CAT and SOD) and increasing lipid peroxidation. CFZ treatment also enhanced the expression of IL-1ß, IL-6, and TNF-α production. Moreover, CFZ increased caspase-3 concentrations and reduced Nrf2 expression in the CFZ-administered group. However, treatment with 10 and 20 mg/kg TQ significantly decreased serum markers and increased antioxidant enzymes. TQ treatment considerably reduced IL-1ß, IL-6, TNF-α, and caspase-3 concentrations. Overall, this biochemical estimation was also supported by histopathological outcomes. This study revealed that TQ administration significantly mitigated the negative effects of CFZ treatment on Nrf2 expression. Thus, it indicates that TQ may have utility as a potential drug to prevent CFZ-induced nephrotoxicity in the future.


Assuntos
Antioxidantes , Insuficiência Renal , Humanos , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Caspase 3/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Wistar , Mediadores da Inflamação/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Rim/metabolismo , Estresse Oxidativo , Benzoquinonas/farmacologia , Benzoquinonas/uso terapêutico , Insuficiência Renal/metabolismo
2.
Eur Cell Mater ; 44: 21-42, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35938286

RESUMO

The anterior cruciate ligament (ACL) is the most frequently injured ligament in the knee. The current method to treat the injured ligament is reconstruction using autografts and allografts. Reconstruction requires the regeneration of ligament, bone and their interface to ensure proper recovery. Recently, researchers have focused on using tissue-engineered scaffolds made of synthetic materials and biomaterials -such as collagen, decellularised tissues, silk and synthetic polymers produced following different manufacturing methods - for ACL reconstruction,. Different materials can be easily processed using various fabrication methods for mimicking the mechanical properties of the ACL. The advances in technologies play an important role in the production of constructions that can mimic native ACL.. The present review addresses integrative scaffold design, different challenges in the potential materials and manufacturing methods as well as future strategies for ACL repair. Furthermore, the review provides a road map to 3D printing combined with organ-on-chip technology to demonstrate the potential for cost-effective and user-friendly fabrication methods for ACL engineering. Finally, it underlines the potential of 3D bioprinting and organ-on-chip technologies for micro-engineering of ligaments and their associated environment.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Humanos , Engenharia Tecidual/métodos , Alicerces Teciduais
3.
Acta Chir Orthop Traumatol Cech ; 89(5): 344-348, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36322034

RESUMO

PURPOSE OF THE STUDY To characterize constitutional frontal alignment of the ankle in genua vara, valga, and norma. MATERIAL AND METHODS Long-leg standing radiographs of 589 patients presenting between 2011 and 2020 for knee-complaints because of any reason were chosen from our database. Cases with fractures or history of bony-realignment-surgeries were excluded. The Hip-Knee-Ankle angle (HKA), the mechanical Lateral Distal Tibia Angle (mLDTA), and the Tibia-Plafond-Horizontal-Orientation angle (TPHA) were measured in 354 patients. For this study, neutral frontal alignment of the leg was defined as HKA between -3.0° and +4.0°. HKA-values <-3.0° were defined as genua valga and values >4.0° were defined as genua vara. According to these cutoffs, data was categorized into the following three patient groups: genua vara (n=157), genua norma (n=106), genua valga (n=91). For each group, the ankle alignment in the frontal plane was compared to the HKA. Finally, the three groups were compared to each other. RESULTS In the varus-group, the HKA-value was 6.9°±2.4°, the TPHA-value was 4.7°±3.5°, and the mLDTA-value was 87.4°±4.8°. In the neutral-group, the HKA-value was 1.8°±2.0°, the TPHA-value was 2.5°±2.9°, and the mLDTA-value was 87.2°±4.6°. In the valgus-group, the HKA-value was -6.0°±2.7°, the TPHA-value was -0.2°±4.7°, and the mLDTA-value was 85.0°±4.7°. DISCUSSION The frontal alignment of the ankle joint line depends on the overall frontal alignment of the leg. The TPHA correlates with varus or valgus alignment of the knee, but the mLDTA does not. In patients with valgus-aligned long-leg axis, the TPHA demonstrated less valgus alignment than in patients with varus-aligned long-leg axis. This knowledge is especially useful when planning osteotomies for correction of lower extremity malalignment. CONCLUSIONS During the planning process of osteotomies around the knee, the TPHA should be appreciated because it correlates with the constitutional knee alignment. Key words: valgus, varus, frontal alignment, coronal alignment, osteotomy.


Assuntos
Geno Valgo , Osteoartrite do Joelho , Humanos , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Extremidade Inferior , Osteoartrite do Joelho/cirurgia , Estudos Retrospectivos
4.
Biomedicines ; 11(12)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38137459

RESUMO

Cyclophosphamide, an alkylating agent integral to specific cancer chemotherapy protocols, is often curtailed in application owing to its significant hepatotoxic side effects. Therefore, this study was conducted to assess the hepatoprotective potential of sesamin, a plant-originated antioxidant, using rat models. The rats were divided into five groups: a control group received only the vehicle for six days; a cyclophosphamide group received an intraperitoneal (i.p.) single injection of cyclophosphamide (150 mg/kg) on day four; a sesamin group received a daily high oral dose (20 mg/kg) of sesamin for six days; and two groups were pretreated with oral sesamin (10 and 20 mg/kg daily from day one to day six) followed by an i.p. injection of cyclophosphamide on day four. The final and last sesamin dose was administered 24 h before euthanasia. At the end of the experiment, blood and liver tissue were collected for biochemical and histopathological assessments. The results indicated significantly increased liver markers (AST, ALT, ALP, and BIL), cytokines (TNFα and IL-1ß), caspase-3, and malondialdehyde (MDA) in the cyclophosphamide group as compared to the normal control. Additionally, there was a significant decline in antioxidants (GSH) and antioxidant enzymes (CAT and SOD), but the sesamin treatment reduced liver marker enzymes, cytokines, and caspase-3 and improved antioxidants and antioxidant enzymes. Thus, sesamin effectively countered these alterations and helped to normalize the histopathological alterations. In conclusion, sesamin demonstrated the potential for attenuating cyclophosphamide-induced hepatotoxicity by modulating cytokine networks, apoptotic pathways, and oxidative stress, suggesting its potential role as an adjunct in chemotherapy to reduce hepatotoxicity.

5.
Trop Biomed ; 37(4): 963-972, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33612749

RESUMO

Canine Enteric Coronavirus (CCoV) is one of the major enteric pathogen affecting dogs. This study aims to investigate the molecular prevalence, phylogenetic analysis, associated risk factors, and haemato-biochemical alterations in Canine Coronavirus in dogs in district Lahore, Pakistan. 450 fecal samples were collected from symptomatic dogs originating from various pet-clinics and kennels during 2018-2019. Samples were initially analyzed by sandwich lateral flow immunochromatographic assay and then further processed by RT-PCR (reverse transcriptase polymerase chain reaction) targeting the M gene followed by sequencing. RT-PCR based positive (n=20) and negative (n=20) dogs were samples for their blood for the haemato-biochemical analysis. A questionnaire was used to collect data from pet owners, in order to analyze the data for risk factors analysis by chi square test on SPSS. The prevalence of CCoV was 35.1%, and 23.8 % through Sandwich lateral flow immunochromatographic and RT-PCR respectively. Various risk factors like breed, age, sex, vomiting, diarrhea, sample source, body size, cohabitation with other animals, living environment, food, deworming history, contact with other animals or birds feces, and season were significantly associated with CCoV. The CCoV identified in Pakistan were 98% similar with the isolates from China (KT 192675, 1), South Korea (HM 130573, 1), Brazil (GU 300134, 1), Colombia (MH 717721, 1), United Kingdom (JX 082356, 1) and Tunisia (KX156806). Haematobiochemical alterations in CCoV affected dogs revealed anaemia, leucopenia, lymphopenia, neutrophilia, and decreased packed cell volume, and a significant increase in alkaline phosphate and alanine transaminase. It is concluded that infection with canine coronavirus appears widespread among dog populations in district Lahore, Pakistan. This study is the first report regarding the molecular detection and sequence analysis of CCoV in Pakistan.


Assuntos
Infecções por Coronavirus/veterinária , Coronavirus Canino , Doenças do Cão/virologia , Animais , Infecções por Coronavirus/sangue , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Coronavirus Canino/genética , Doenças do Cão/sangue , Doenças do Cão/epidemiologia , Doenças do Cão/metabolismo , Cães , Feminino , Imunoensaio , Masculino , Paquistão/epidemiologia , Filogenia , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Fatores de Risco
6.
Educ Health (Abingdon) ; 21(2): 69, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19039740

RESUMO

CONTEXT: A key element of medical education is patients' willingness to and cooperation in involving a medical student in their care. OBJECTIVE: To assess patients' attitudes and their associated factors toward involving medical students in their care. METHODS: This study was conducted over a period of two months in two hospitals in Riyadh, Saudi Arabia. Six hundred patients were approached to participate in outpatient and inpatient settings of four medical specialty services. A pre-tested questionnaire was used to collect the data. RESULTS: There were 492 respondents (82%), of whom 50% were males, 74% were married, and 51% were outpatients. Sixty percent identified medical students on the team of doctors that had treated them. Eighty-one percent of respondents felt that students' general appearance and manner were important to their willingness to have them participate in their care, and 64% would not object to the presence of medical students during physical examinations. Most (63%) preferred to be informed about students' involvement beforehand. Fifty-five percent believed that they had the right to refuse medical students, with women, married and less educated individuals and those seen in particular departments more likely to believe so. The preferred role for students also varied with gender, marital status and department. CONCLUSION: This study finds that most Saudi patients view medical students' involvement in their care positively. They prefer to be told in advance about students' presence, asked for their permission, and have students' involvement restricted to certain times.


Assuntos
Satisfação do Paciente , Relações Profissional-Paciente , Estudantes de Medicina , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Arábia Saudita , Fatores Sexuais , Inquéritos e Questionários , Recusa do Paciente ao Tratamento , Adulto Jovem
7.
J Indian Soc Pedod Prev Dent ; 26(3): 128-31, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18923226

RESUMO

The concept of 'fibro-osseous lesions' of bone has evolved over the last several decades and now includes two major entities: fibrous dysplasia and ossifying fibroma, as well as the other less common lesions such as florid osseous dysplasia, periapical dysplasia, focal sclerosing osteomyelitis, proliferative periostitis of garrie, and ostitis deformans. The cemento-ossifying fibroma is a central neoplasm of bone as well as periodontium which has caused considerable controversy because of confusion regarding terminology and the criteria for its diagnosis. The cemento-ossifying fibroma is odontogenic in origin, whereas ossifying fibroma is of bony origin. This article reports a rare case of an 11-year-old male who came to us with the history of swelling in the maxillary anterior region causing difficulty in closing of mouth as well as in mastication.


Assuntos
Neoplasias Maxilares/diagnóstico , Tumores Odontogênicos/diagnóstico , Criança , Diagnóstico Diferencial , Fibroma Ossificante/diagnóstico , Displasia Fibrosa Óssea/diagnóstico , Humanos , Masculino , Neoplasias Maxilares/patologia , Tumores Odontogênicos/patologia
8.
J Clin Invest ; 84(3): 824-8, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2547839

RESUMO

We have studied factor IXa binding and factor X activation with normal platelets and with platelets obtained from a patient with a bleeding disorder and an isolated deficiency of platelet procoagulant activity termed Scott syndrome. In the absence of factor VIIIa and factor X, normal, thrombin-treated platelets exposed 560 +/- 35 sites for factor IXa with a Kd of 2.75 +/- 0.27 mM, compared with 461 +/- 60 sites per patient platelet with Kd of 3.2 +/- 0.33 nM. The addition of factor VIIIa and factor X resulted in a decrease in the Kd for normal platelets to 0.68 nM but had no effect on the Kd for patient platelets. The concentrations of factor IXa required for half-maximal rates of factor X activation for normal (0.52 nM) and patient platelets (2.5 nM) were similar to those determined from equilibrium binding studies. Kinetic parameters for factor X activation by factor IXa showed that the Km and Kcat were identical for normal and patient platelets in the absence of factor VIIIa. In the presence of factor VIIIa, and kcat for patient platelets (163 min-1) was only 33% of that for normal platelets (491 min-1): This result can be explained by the difference in affinity for factor IXa between normal and patient platelets in the presence of factor VIIIa, suggesting impaired factor VIIIa binding to Scott syndrome platelets.


Assuntos
Transtornos Plaquetários/sangue , Plaquetas/metabolismo , Fator VIII , Receptores de Superfície Celular/deficiência , Serina Endopeptidases/metabolismo , Serina Endopeptidases/fisiologia , Testes de Coagulação Sanguínea , Fator IXa , Fator Xa , Feminino , Humanos , Cinética , Pessoa de Meia-Idade , Receptores de Superfície Celular/biossíntese , Receptores de Superfície Celular/fisiologia , Síndrome
9.
Orthop Traumatol Surg Res ; 103(5): 801-807, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28546049

RESUMO

A growing burden of gunshot injuries demands evidence-based ballistic trauma management. No comprehensive systematic overview of the current knowledge is available to date. This study aims to identify and analyze the most influential publications in the field of orthopedic ballistic trauma research. All databases available in the Thomson Reuters Web of Knowledge were searched to conduct this bibliometrical study. The most cited orthopedic ballistic trauma articles published between 1950 and 2015 were identified by use of a multi-step approach. Publications with ten citations and more were analyzed for citations, journal, authorship, geographic origin, area of research, anatomical site, study type, study category, and level of evidence. Citations of the 128 included studies ranged from 113 to 10. These were published in fifty different journals between 1953 and 2011. Most publications (n=106; 83%) originated from the USA, were retrospective (n=85; 66.4%), level IV studies (n=90; 70.3%), reported on spinal gunshot injuries (n=49; 38.33%) and were published between 1980 and 2000 (n=111; 86.7%). This bibliometric study provides the first comprehensive overview of influential publications in the field of orthopedic ballistic trauma research. More prospective studies and high-quality systematic reviews are needed. Centres with a high burden of gunshot injuries from the developing world need to share their experience in form of international publications, to provide a more comprehensive picture of the global gun-related orthopedic injury burden. TYPE OF STUDY: bibliometric analysis: level III.


Assuntos
Bibliometria , Ortopedia , Publicações Periódicas como Assunto/estatística & dados numéricos , Esqueleto/lesões , Ferimentos por Arma de Fogo/complicações , Humanos
10.
Bone Joint J ; 98-B(6): 793-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27235522

RESUMO

AIMS: The purpose of this study was to report the experience of dynamic intraligamentary stabilisation (DIS) using the Ligamys device for the treatment of acute ruptures of the anterior cruciate ligament (ACL). PATIENTS AND METHODS: Between March 2011 and April 2012, 50 patients (34 men and 16 women) with an acute rupture of the ACL underwent primary repair using this device. The mean age of the patients was 30 years (18 to 50). Patients were evaluated for laxity, stability, range of movement (ROM), Tegner, Lysholm, International Knee Documentation Committee (IKDC) and visual analogue scale (VAS) scores over a follow-up period of two years. RESULTS: At final follow-up, anteroposterior translation differed from the normal knee by a mean of 0.96 mm (-2 mm to 6 mm). Median (interquartile range) IKDC, Tegner, Lysholm and VAS scores were 98 (95 to 100), 6 (5 to 7), 100 (98 to 100) and 10 (9 to 10), respectively. Pre-injury Tegner activity levels were reached one year post-operatively. A total of nine patients (18%) required a secondary intervention; five developed instability, of whom four underwent secondary hamstring reconstructive surgery, and five required arthroscopic treatment for intra-articular impingement due to scar tissue which caused a fixed flexion deformity. In addition, 30 patients (60%) required removal of the tibial screw. CONCLUSION: While there was a high rate of secondary interventions, 45 patients (90%) retained their repaired ACL two years post-operatively, with good clinical scores and stability of the knee. TAKE HOME MESSAGE: Dynamic intraligamentary stabilisation presents a promising treatment option for acute ACL ruptures, eliminating the need for ACL reconstruction. Cite this article: Bone Joint J 2016;98-B:793-8.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/instrumentação , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Instabilidade Articular/cirurgia , Articulação do Joelho/cirurgia , Escore de Lysholm para Joelho , Masculino , Pessoa de Meia-Idade , Dispositivos de Fixação Ortopédica , Complicações Pós-Operatórias , Reoperação , Ruptura/cirurgia , Escala Visual Analógica , Adulto Jovem
11.
Trop Biomed ; 33(4): 599-607, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33579055

RESUMO

Pakistan is endemic for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections with 10 and 11 million infections, respectively. The epidemiological studies of these virus showed that the information is only from few cities of the country and is relevant to high risk groups. It is of great importance to have an idea about the prevalence of infectious agents in general population to help in identification of hot spot for infections. Identification of hot spots will help in disease management for future. As the there is no report form district Sargodha (Punjab Province) so this study was designed to analyze the prevalence of HBV and HCV in general population. Blood samples of 2373 randomly selected individuals from six different tehsils were collected and were analyzed for HBV and HCV sero-positivity. An overall prevalence of both HBV and HCV in district Sargodha was 28.10% (667/2373). HCV prevalence was (20.01%) and HBV seropositivity was (8.09%). Males were more infected than females, and a significant difference was found in positive cases between male (58.77%) and female (41.22%). The most common routes of transmission of hepatitis virus in present study were shaving assisted by barbers in male patients 143 (21.43%), non sterile or used needles and syringes 127 (19.04%), dental surgical procedures 88 (13.19%), and sharing razors in males 49 (7.34%). In female patients a significant factor is labor and child birth process. Most cases of hepatitis were seen in mesons, farmers and house wives. The prevalence of HBV and HCV in general population of district Sargodha is very high. The study will help for better management of disease to contain the disease spread. The study highlighted that District Sargodha is endemic for these viral infections and it is highly warranted to carry out more studies to get better idea about the infection spread. Community education campaigns are also highly warranted to general population as well as high risk population to control future disease spread.

12.
Trends Cardiovasc Med ; 4(6): 271-8, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-21244878

RESUMO

Platelet membranes provide procoagulant surfaces for the assembly and expression of a variety of coagulation protease complexes. These assembled complexes promote the proteolytic activation of various coagulation proteins resulting in normal hemostasis. Recent studies from our laboratory and others indicate that platelets possess specific, high-affinity, saturable receptors for factor (F) XI, FXIa, FIX, FIXa, FX, FXa, FV, FVa, prothrombin, and thrombin. The molecular mechanisms involved in the assembly of the intrinsic tenase and prothrombinase enzyme-cofactor complexes on platelet membranes are the subject of intense investigation. Whether the procoagulant surface of platelets is defined exclusively by procoagulant phospholipids, or whether specific protein receptors exist for the coagulant cofactors and proteases, is currently unresolved. In this article, we review some of these platelet receptor-mediated coagulation protein interactions and discuss platelet receptor-mediated F-X activation as a point of attack for the development of antithrombotic agents.

13.
Br J Radiol ; 88(1052): 20140542, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26081446

RESUMO

OBJECTIVE: Arthroscopy is "the gold standard" for the diagnosis of knee cartilage lesions. However, it is invasive and expensive, and displays all the potential complications of an open surgical procedure. Ultra-high-field MRI now offers good opportunities for the indirect assessment of the integrity and structural changes of joint cartilage of the knee. The goal of the present study is to determine the site of early cartilaginous lesions in adults with non-traumatic knee pain. METHODS: 3-T MRI examinations of 200 asymptomatic knees with standard and three-dimensional double-echo steady-state (3D-DESS) cartilage-specific sequences were prospectively studied for early degenerative lesions of the tibiofemoral joint. Lesions were classified and mapped using the modified Outerbridge and modified International Cartilage Repair Society classifications. RESULTS: A total of 1437 lesions were detected: 56.1% grade I, 33.5% grade II, 7.2% grade III and 3.3% grade IV. Cartographically, grade I lesions were most common in the anteromedial tibial areas; grade II lesions in the anteromedial L5 femoral areas; and grade III in the centromedial M2 femoral areas. CONCLUSION: 3-T MRI with standard and 3D-DESS cartilage-specific sequences demonstrated that areas predisposed to early osteoarthritis are the central, lateral and ventromedial tibial plateau, as well as the central and medial femoral condyle. ADVANCES IN KNOWLEDGE: In contrast with previous studies reporting early cartilaginous lesions in the medial tibial compartment and/or in the medial femoral condyle, this study demonstrates that, regardless of grade, lesions preferentially occur at the L5 and M4 tibial and L5 and L2 femoral areas of the knee joint.


Assuntos
Doenças das Cartilagens/patologia , Artropatias/patologia , Articulação do Joelho/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fêmur , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tíbia , Adulto Jovem
14.
J Thromb Haemost ; 1(11): 2348-55, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14629468

RESUMO

Activated platelet membranes expose binding sites for the enzyme factor (F)IXa, the substrate (FX) and the cofactor (FVIIIa) that colocalize to assemble the FX-activating complex and promote optimal rates of FX activation. To determine the stoichiometry and affinity of binding to activated platelets, coordinate, equilibrium binding studies with enzyme (125I-FIXa) and cofactor (131I-FVIII or 131I-FVIIIa) were carried out in the presence of saturating concentrations of substrate (FX). Results of these studies indicate that in the presence of FX (1.5 micro m), the enzyme (active-site-inhibited Glu-Gly-Arg-FIXa, EGR-FIXa) and procofactor (FVIII) bind to an equal number (approximately 700 sites/platelet) of receptors whereas the active cofactor (FVIIIa) binds an additional approximately 500 high-affinity FVIIIa binding sites per platelet (Kd approximately 0.8 nm). With excess zymogen (FIX) to block shared FIX/FIXa-binding sites, the stoichiometry of 125I-FIXa and 131I-FVIIIa binding was 1:4. These FIXa/FVIIIa binding studies together with previously reported evidence of the coordinate binding of FVIIIa and FX to equivalent numbers of binding sites on activated platelets provide strong evidence to support the conclusion that FVIIIa comprises the receptor that presents FX to FIXa for efficient catalysis on the activated platelet membrane.


Assuntos
Fator IXa/metabolismo , Fator VIIIa/metabolismo , Fator X/metabolismo , Ativação Plaquetária , Autorradiografia , Sítios de Ligação , Plaquetas/metabolismo , Plaquetas/ultraestrutura , Membrana Celular/química , Membrana Celular/metabolismo , Cisteína Endopeptidases , Humanos , Radioisótopos do Iodo , Cinética , Proteínas de Neoplasias , Ligação Proteica
15.
J Thromb Haemost ; 1(1): 48-59, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12871539

RESUMO

Platelet membranes provide procoagulant surfaces for the assembly and expression of the factor X-activating complex and promote the proteolytic activation and assembly of the prothrombinase complex resulting in normal hemostasis. Recent studies from our laboratory and others indicate that platelets possess specific, high-affinity, saturable, receptors for factors XI, XIa, IX, IXa, X, VIII, VIIIa, V, Va and Xa, prothrombin, and thrombin. Studies described in this review support the hypothesis that the factor X-activating complex on the platelet surface consists of three receptors (for the enzyme, factor IXa; the substrate, factor X; and the cofactor, factor VIIIa), the colocalization of which results in a 24 million-fold acceleration of the rate of factor X activation. Whether the procoagulant surface of platelets is defined exclusively by procoagulant phospholipids, or whether specific protein receptors exist for the coagulant factors and proteases, is currently unresolved. The interaction between coagulation proteins and platelets is critical to the maintenance of normal hemostasis and is pathogenetically important in human disease.


Assuntos
Plaquetas/metabolismo , Fator X/metabolismo , Ativação Plaquetária/fisiologia , Fatores de Coagulação Sanguínea/fisiologia , Endopeptidases/metabolismo , Hemostasia/fisiologia , Humanos , Fosfolipídeos/fisiologia
16.
Thromb Res ; 55(1): 121-33, 1989 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-2781515

RESUMO

This study describes a rapid purification of factor IX, factor X and prothrombin by immunoaffinity and ion exchange chromatography. Human factor IX was purified from plasma in 34% yield using barium sulfate adsorption and immunoaffinity purification. The specific clotting activity of purified factor IX was 269 units/mg, with an apparent molecular weight of 57,000 in the presence of sodium dodecyl sulfate on polyacrylamide gels. The immunodepleted, factor-IX deficient plasma was chromatographed on a dextran sulfate agarose column which resolved prothrombin and factor X in highly purified states and with approximately 50% yield. The specific activities of prothrombin and factor X obtained by this procedure were 24 units/mg and 147 units/mg respectively. Both proteins isolated by this method showed a single component on SDS gel electrophoresis and the molecular weights of intact prothrombin and factor X were 72,000 and 67,000 respectively.


Assuntos
Fator IX/isolamento & purificação , Fator X/isolamento & purificação , Protrombina/isolamento & purificação , Sulfato de Amônio , Antiácidos , Anticorpos Monoclonais , Testes de Coagulação Sanguínea , Proteínas Sanguíneas/análise , Cromatografia de Afinidade , Cromatografia por Troca Iônica , Citratos , Ácido Cítrico , Humanos
17.
Soc Sci Med ; 17(12): 829-35, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6348959

RESUMO

The province of Saskatchewan is the oldest and most unique example of providing universal medicare programs in North America. These programs offer full coverage for every resident, and hence strongly influence the treatment of kidney patients requiring dialysis and transplant. The University Hospital at Saskatoon, however, is the only center in the province with a transplant program. An attempt has been made here to determine if there are geographical variations in the transplant program in terms of such factors as distance, location, occupation, age and sex of the patients and the nature of the donors.


Assuntos
Transplante de Rim , Programas Médicos Regionais , Condições Sociais , Adolescente , Adulto , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Masculino , Saskatchewan
18.
Spine (Phila Pa 1976) ; 19(1): 49-52, 1994 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-8153803

RESUMO

The purpose of this study was to assess repeated exercise on the B-200 Isostation as part of rehabilitation work tolerance for nonsurgical patients with lumbar spine disorders. For a consecutive 7-month period, treatment subjects were randomly assigned according to birth date for participation in two groups: a standard work tolerance program only or standard work tolerance program plus inclusion of exercise on the B-200 Isostation. Each patient had similar referral diagnosis requiring conservative treatment. Treatment groups were compared with a control population of volunteers who had neither back pain nor known underlying spinal pathology. All study patients had objective measurement of range of motion, isometric strength, and velocity of motion, on the B-200 Isostation before treatment and at follow-up 3 weeks after treatment. The data showed no significant difference of percent improvement when comparing patients in either of the randomized assigned treatment groups. There was a higher percentage of improvement for each treatment group as compared with the control individuals, however. Based on our study using the B-200 Isostation, there is little objective justification for including exercise on the B-200 dynametric Isostation as part of the rehabilitation routine for improvement of functional physical capacity.


Assuntos
Terapia por Exercício , Doenças da Coluna Vertebral/reabilitação , Tolerância ao Trabalho Programado , Análise de Variância , Método Duplo-Cego , Feminino , Humanos , Região Lombossacral , Masculino , Movimento , Músculos/fisiopatologia , Estudos Prospectivos , Valores de Referência , Doenças da Coluna Vertebral/fisiopatologia
19.
Pak J Pharm Sci ; 14(1): 47-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16414853

RESUMO

The rearrangements of substituted anilides of propionic acid to amino ketones in a solvent medium were studied, employing bismuth chloride as a catalyst. Rearranged compounds were then characterized by qualitative tests and spectral data.

20.
Artigo | IMSEAR | ID: sea-189350

RESUMO

Carcinoma of the colon and rectum is a relatively uncommon malignancy in Kashmir (north India) when compared with the western world. Colorectal cancer is generally a disease affecting individuals 55 years of age and older and is much less common in persons under 35 years of age. Methods: One hundred and fifty six colonoscopies were performed by a single gastroenterologist in GMC Srinagar. We find the anatomical distribution and age at diagnosis of colorectal cancer patients diagnosed by colonoscopy for evaluation of their symptoms in a teaching hospital in Kashmir India, Records of patients who had complete colonoscopic examination till the cecum, presence of tumor in the colon or rectum, and biopsy showing adenocarcinoma, were scrutinized. Results: Age-stratified incidence of CRC showed that majority of the cases were in the age group 55–65 years (30.76%), followed by 45-55 years (20.5%). There were 19 (12.2%) cases of CRC below the age of 35 years. Conclusion: Colorectal cancer (CRC) in Kashmiri (Indian) occurs at a younger age and is often distal to the splenic flexure.

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