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1.
Kathmandu Univ Med J (KUMJ) ; 20(77): 61-65, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36273293

RESUMO

Background Cerebral neurocysticerosis is a common parasitic disease of human nervous system but evidence on duration of albendazole therapy and their outcomes in this condition is inadequate Objective To evaluate the impact of varying duration of albendazole therapy on the clinical and radiological outcomes at one month in patients with active solitary neurocysticercosis. Method This is an interventional study conducted at Upendra Devkota Memorial National Institute of Neurological and Allied sciences, Bansbari over 1 year (2017 March - 2018 February). One hundred eighteen patients with new onset seizure secondary to active solitary cysticercal granuloma either received albendazole therapy for 1, 3, 9 or 21 days with the usual care or only received the usual care. Clinical and radiological outcomes were observed at one month follow-up. The difference in the proportion of the outcome measures between intervention and control groups were assessed using chi-square test. Result Our study included 118 patients with male predominance of 61.9%. Albendazole therapy for 3, 9 and 21 days reduced headache by 57.2%, 70.0% and 63.1% respectively which was higher than those with 1-day therapy or without the therapy. This difference in the proportion was statistically significant at p=0.001. Though seizure recurrence also declined but the difference was not significant (p=0.406) between groups. However, at one-month follow-up, majority of patients who received albendazole for 9 days (14, 70%) and 21 days (14, 73.7%) had normal lesion, while most calcified lesion (21, 67.7%) was observed in those who did not receive albendazole therapy. The difference between lesion among the groups was significant (p < 0.001). Conclusion Albendazole therapy in patients with active solitary neurocysticercosis for 9 days is as effective as 21 days and better than 3 days in headache control and lesion dissolution but seizure control could be achieved irrespective of the treatment.


Assuntos
Albendazol , Neurocisticercose , Humanos , Masculino , Feminino , Albendazol/uso terapêutico , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/tratamento farmacológico , Neurocisticercose/complicações , Convulsões/tratamento farmacológico , Convulsões/etiologia , Radiografia , Cefaleia
2.
Kathmandu Univ Med J (KUMJ) ; 18(70): 207-209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33594034

RESUMO

General paralysis of insane is a form of neurosyphilis which brings parenchymatous changes in the central nervous system. Its manifestations include a variety of neuropsychiatric symptoms ranging from cognitive impairment to overt psychosis. Clinicians face difficulties in proper diagnosis as variety of symptoms changes from one form to other within a short period of time. Rarity of the disease at this modern era of penicillin is also another factor in timely diagnosis and management of such cases. Here we present a case of general paralysis of insane who presented with variety of neuropsychiatric symptoms and have had great difficulties to reach into the diagnosis.


Assuntos
Transtornos Mentais , Neurossífilis , Face , Humanos , Neurossífilis/complicações , Neurossífilis/diagnóstico , Neurossífilis/tratamento farmacológico
3.
Eye (Lond) ; 32(2): 375-383, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28912515

RESUMO

PurposeTo evaluate the sensitivity and specificity of a portable non-mydriatic fundus camera to diagnose vision-threatening diabetic retinopathy (VTDR).Patients and methodsA prospective, single-site, comparative instrument validation study was undertaken at the Aravind Eye Care System. Overall, 155 subjects with and without diabetes were recruited. Images from 275 eyes were obtained with the (1) non-mydriatic Smartscope, (2) mydriatic Smartscope, and (3) mydriatic table-top camera of the macular, nasal, and superotemporal fields. A retina specialist performed a dilated fundus examination (DFE), (reference standard). Two masked retina specialists graded the images. Sensitivity and specificity to detect VTDR with the undilated Smartscope was calculated compared to DFE.ResultsGraders 1 and 2 had a sensitivity of 93% (95% confidence interval (CI): 87-97%) and 88% (95% CI: 81-93%) and a specificity of 84% (95% CI: 77-89%) and 90% (95% CI: 84-94%), respectively, in diagnosing VTDR with the undilated Smartscope compared to DFE. Compared with the dilated Topcon images, graders 1 and 2 had sensitivity of 88% (95% CI: 81-93%) and 82% (95% CI: 73-88%) and specificity of 99% (95% CI: 96-100%) and 99% (95% CI: 95-100%).ConclusionsRemote graders had high sensitivity and specificity in diagnosing VTDR with undilated Smartscope images, suggesting utility where portability is a necessity.


Assuntos
Retinopatia Diabética/diagnóstico por imagem , Programas de Rastreamento/métodos , Oftalmoscopia/métodos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Fotografação/métodos , Estudos Prospectivos , Sensibilidade e Especificidade
4.
Br J Dermatol ; 178(2): 535-540, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28714061

RESUMO

BACKGROUND: Hair and scalp problems are common. Unfortunately, many uncertainties exist around the most effective management and treatment strategies for these disorders. OBJECTIVES: To identify uncertainties in hair-loss management, prevention, diagnosis and treatment that are important to both people with hair loss and healthcare professionals. METHODS: A Hair Loss Priority Setting Partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in hair loss. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants; following exclusions 884 uncertainties relating to hair loss (excluding alopecia areata) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that was taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for hair loss (excluding alopecia areata) to guide researchers and funding bodies to support studies important to both patients and clinicians.


Assuntos
Alopecia/terapia , Pesquisa , Alopecia/diagnóstico , Alopecia/prevenção & controle , Consenso , Dermatologia/organização & administração , Pessoal de Saúde , Humanos , Relações Interprofissionais , Inquéritos e Questionários
5.
Equine Vet J ; 49(5): 681-687, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28128865

RESUMO

BACKGROUND: The metacarpophalangeal joint (fetlock) is the most commonly affected site of racehorse injury, with multiple observed pathologies consistent with extreme fetlock dorsiflexion. Race surface mechanics affect musculoskeletal structure loading and injury risk because surface forces applied to the hoof affect limb motions. Race surface mechanics are a function of controllable factors. Thus, race surface design has the potential to reduce the incidence of musculoskeletal injury through modulation of limb motions. However, the relationship between race surface mechanics and racehorse limb motions is unknown. OBJECTIVE: To determine the effect of changing race surface and racehorse limb model parameters on distal limb motions. STUDY DESIGN: Sensitivity analysis of in silico fetlock motion to changes in race surface and racehorse limb parameters using a validated, integrated racehorse and race surface computational model. METHODS: Fetlock motions were determined during gallop stance from simulations on virtual surfaces with differing average vertical stiffness, upper layer (e.g. cushion) depth and linear stiffness, horizontal friction, tendon and ligament mechanics, as well as fetlock position at heel strike. RESULTS: Upper layer depth produced the greatest change in fetlock motion, with lesser depths yielding greater fetlock dorsiflexion. Lesser fetlock changes were observed for changes in lower layer (e.g. base or pad) mechanics (nonlinear), as well as palmar ligament and tendon stiffness. Horizontal friction and fetlock position contributed less than 1° change in fetlock motion. MAIN LIMITATIONS: Simulated fetlock motions are specific to one horse's anatomy reflected in the computational model. Anatomical differences among horses may affect the magnitude of limb flexion, but will likely have similar limb motion responses to varied surface mechanics. CONCLUSIONS: Race surface parameters affected by maintenance produced greater changes in fetlock motion than other parameters studied. Simulations can provide evidence to inform race surface design and management to reduce the incidence of injury.


Assuntos
Marcha/fisiologia , Cavalos/fisiologia , Articulação Metacarpofalângica/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Fenômenos Biomecânicos , Simulação por Computador , Extremidades , Casco e Garras/fisiologia , Articulação Metacarpofalângica/lesões , Amplitude de Movimento Articular , Fatores de Risco , Corrida
6.
Br J Dermatol ; 176(5): 1316-1320, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27696375

RESUMO

BACKGROUND: Alopecia areata (AA) is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. OBJECTIVES: To identify uncertainties in AA management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. METHODS: An AA priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in AA. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to AA (and variants) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for AA to guide researchers and funding bodies to support studies important to both patients and clinicians.


Assuntos
Alopecia em Áreas/terapia , Pesquisa , Cuidadores , Prioridades em Saúde , Inquéritos Epidemiológicos , Humanos , Relações Médico-Paciente , Relações Profissional-Família
7.
s.l; The National medical journal of India; 2017. 4 p.
Monografia em Inglês | PIE | ID: biblio-1008324

RESUMO

Equity in health and equitable access to healthcare has been at the core of health policy in India. The key policy challenge has been how to make that possible? Various health insurance schemes such as the Rashtriya Swasthya Bima Yojana and Arogyasri seek to improve poor people's access to specialist medical care in the public and private sectors. On the other hand, access to primary medical care has been left to the supply side interventions.


Assuntos
Humanos , Assistência Integral à Saúde/economia , Assistência Integral à Saúde/métodos , Disparidades em Assistência à Saúde/economia , Políticas, Planejamento e Administração em Saúde/economia , Índia
8.
Gulf J Oncolog ; 1(19): 57-62, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26499832

RESUMO

UNLABELLED: Lung cancer is the one of the most common cause of cancer mortality among men in India where incidence rates are increasing although they are largely preventable diseases. In India, late presentation is generally responsible for high mortality and morbidity rates and early detection is one of the best ways to control it. The purpose of this study is to measure the level of awareness on lung cancer among women represented by a sample of college teachers in India and the impact of awareness programs in changing or adopting safer practices and the prevention and early detection of the disease. MATERIAL AND METHODS: The assessment was conducted during a Pink Chain Campaign on cancer awareness in 2011 in various women colleges in India. Pre-test related to lung cancer was followed by awareness programs. Posttest using the same questionnaire was conducted at the end of interactive session, at 1 year and 6 months. RESULTS: A total of 156 out of 182 teachers participated in the study (overall response rate was 85.7%). Mean age of the study population was 42.4 years (range- 28-59 yrs). There was a significant increase in level of knowledge regarding lung cancer at 6 months and this was sustained at 1 year. Magazines and newspapers were the primary source for information regarding risk factors, signs and symptoms of lung cancer in more than 60% of teachers whereas more than 30% teachers were educated by doctors. At post-awareness after 1 year and 6 months, there was a significant change in alcohol and smoking habits. The main reasons for not undergoing screening tests are: ignorance (50%), lethargic attitude (44.8 %) and lack of time (34.6 %). CONCLUSION: Knowledge about lung cancer was very low among teachers. Overall awareness of risk factors, signs and symptoms, and screening modalities of lung cancer have improved after 1 year along with practices related to smoking and alcohol consumption. There was a significant improvement in people undergoing regular check-up's. Improved means of communication, access to information and effective warnings about cigarette smoking are necessary to increase public awareness. To ensure the adoption of safe practices in the lifestyle of people who smoke and consume alcohol, awareness programmes such as the pink chain campaign should be conducted regularly, frequently and more widely in various areas of India.

9.
Equine Vet J ; 45(1): 25-30, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22587378

RESUMO

REASONS FOR PERFORMING STUDY: Racetrack surface is a risk factor for Thoroughbred racehorse injury and death that can be engineered and managed. To investigate the relationship between surface and injury, the mechanical behaviour of dirt and synthetic track surfaces must be quantified. OBJECTIVES: To compare dynamic properties of a dirt and a synthetic surface in situ using a track-testing device designed to simulate equine hoof impact; and to determine the effects of impact velocity, impact angle and repeated impact on dynamic surface behaviour. METHODS: A track-testing device measured force and displacement during impact into a dirt and a synthetic surface at 3 impact velocities (1.91, 2.30, 2.63 m/s), 2 impact angles (0°, 20° from vertical), and 2 consecutive impacts (initial, repeat). Surfaces were measured at 3 locations/day for 3 days. The effects of surface type, impact velocity, impact angle and impact number on dynamic surface properties were assessed using analysis of variance. RESULTS: Synthetic surface maximum forces, load rates and stiffnesses were 37-67% of dirt surface values. Surfaces were less stiff with lower impact velocities, angled impacts and initial impacts. The magnitude of differences between dirt and synthetic surfaces increased for repeat impacts and higher impact velocities. CONCLUSIONS: The synthetic surface was generally softer than the dirt surface. Greatly increased hardness for repeat impacts corroborates the importance of maintenance. Results at different impact velocities suggest that surface differences will persist at higher impact velocities. POTENTIAL RELEVANCE: For both surfaces it is clearly important to prevent horse exposure to precompacted surfaces, particularly during high-speed training when the surface has already been trampled. These data should be useful in coordinating racetrack surface management with racehorse training to prevent injuries.


Assuntos
Materiais de Construção , Cavalos , Esportes , Animais , Propriedades de Superfície
10.
Indian J Orthop ; 46(1): 86-91, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22345813

RESUMO

BACKGROUND: C1 lateral mass-C2 transpedicular fixation is an accepted surgical procedure of choice in a large number of cases with traumatic atlanto-axial instability. However, bony and vascular anomalies can predispose to unacceptably high risk with this procedure, And hence are the contraindications for this procedure. The purpose of this study is to analyze the clinical and radiological results in such cases for which only unilateral fixation has been performed in cases where bilateral fixation could not be performed due to various reasons. MATERIALS AND METHODS: Eight patients (7 males, 1 female) with a mean age of 41.12 years (range 12-68 years), who presented with traumatic atlanto-axial instability and in whom bilateral fixation could not be performed, were treated with unilateral C1 lateral mass-C2 transpedicular fixation. Of these cases, preoperative vertebral artery occlusion was noted in one case, iatrogenic vertebral artery injury in two cases and bony anomalies or fractures in the remaining of five cases. All patients were evaluated clinically with the American Spinal Injury Association (ASIA) scale and radiologically with computed tomography scans and serial X-ray using criteria to evaluate stability. RESULTS: All cases were evaluated at 6 months followup with mean followup of 2 years and one month (range 6 months to 4 years). All eight patients showed adequate stability and fusion at 6 months; clinically there was no significant restriction of neck movement in any of the patient. There was no neurological deterioration in any of the patient at their last follow-up. CONCLUSION: Unilateral C1 lateral mass-C2 transpedicular fixation could be considered a viable option in cases of traumatic atlanto-axial instability where vascular and osseous anomalies contradict a bilateral fixation.

11.
Vet Microbiol ; 149(1-2): 242-7, 2011 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-21144677

RESUMO

Characterisation of seven neutralising monoclonal antibodies (mAbs) produced against foot-and-mouth disease virus A(24) Cruzeiro revealed three reactivity groups. Gr-I recognised linear epitopes where as Gr-II was conformation-dependent and trypsin-insensitive. The Gr-III was also conformation-dependent, but trypsin-sensitive. Mar (mAb neutralisation resistant)-mutants could only be produced against Gr-I and Gr-III mAbs. Capsid sequence comparison of Gr-I mar-mutants with parent virus revealed changes in the G-H loop of VP1 at positions 141, 143 and 147. Similarly, a Gr-III mar-mutant showed a change from a highly conserved glycine to a tryptophan at position 148 of VP1 along with three additional changes at the N-terminus of VP1, VP2 and VP4. This residue at 148 of VP1 is located at +2 position after "RGD" and is equivalent to the position identified by the mAb recognising site 5 in serotype O viruses. This site is probably formed because of the interaction of the G-H loop with other residues in different structural proteins.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Antivirais/química , Mapeamento de Epitopos , Vírus da Febre Aftosa/genética , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/genética , Proteínas do Capsídeo/genética , Epitopos/química , Epitopos/imunologia , Vírus da Febre Aftosa/imunologia , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Estrutura Quaternária de Proteína
13.
Kathmandu Univ Med J (KUMJ) ; 7(27): 246-51, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20071871

RESUMO

BACKGROUND: Adult mortality (15-49 years) is one of the major public health issues which remains neglected in many developing counties like Nepal. Only limited data are available which is insufficient to identify the cause and level of mortality among adults. OBJECTIVES: The aim of the study is to explore and compare the adult mortality rate of Nepal between 1996, 2001 and 2006 surveys. MATERIALS AND METHODS: This is comparative study conducted by using secondary data extracted from Nepal Family Health Survey (NFHS, 1996), National Census Report 2001 and Nepal Demographic and Health Survey (NDHS, 2006). Statistical analysis was done using Microsoft excel soft ware. The adjusted mortality rates were computed using 2001 census population as standard population. RESULT: This studied showed there was statistical evidence of declining age specific mortality rate between 1996 and 2006 survey for both men and women respectively (p<0.05). Annually adult men mortality rate and adult women mortality rate was found to be declining by 1% and 3. 2% respectively. Women mortality rate declined by 2.26 times as compared to men mortality rate over ten year's period. CONCLUSION: There is a need of in-depth analysis of adult mortality in the developing countries like Nepal.


Assuntos
Inquéritos Epidemiológicos , Análise de Sobrevida , Adolescente , Adulto , Distribuição por Idade , Feminino , Humanos , Masculino , Nepal/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto Jovem
14.
Toxicol Mech Methods ; 17(2): 101-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-20020978

RESUMO

ABSTRACT Mitogen-activated protein kinase (MAPK) is an important mediator of cellular signaling pathways. In an attempt to investigate the role of these kinases in contact allergen/irritant-induced signaling cascades, we have utilized keratinocyte (A431 cell line) as antigen presenting cells (APCs). This group has previously reported the applicability of A431 as an APC. The role of these kinases in the elicitation pathways of allergic contact dermatitis was investigated using interleukin-12p40 (IL-12p40) as a marker. Inhibitors of the isoforms of MAPK reduced the allergen-induced IL-12 release in the A431 cell line. This result suggests a possible role of the isoforms of MAPK in the development of contact allergy.

15.
Biomarkers ; 10(4): 258-94, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16191485

RESUMO

Cancer is a big problem in the developed world as well as in developing countries. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. RCC is more common in men than in women (2:1), and it most often occurs in patients between the ages of 50-70 years. In all cancers the cancerous cells release particular kind of proteins (called tumour markers) and blood tests are used to detect the presence of these markers. These tumour markers nowadays are an area of interest for oncologists who search for a possible solution in the detection and treatment of RCC. Different kinds of biochemical and molecular markers such as ferritin, MN/CA9, apoptotic index, p53, IL-2, gamma-enolase, CD44, CD95, chromosome instability and loss of heterozygosity have been tested in RCC, but so far no marker fulfils one or the other criteria to be considered as an ideal marker for RCC. This review gives basic and updated information about the different kinds of biomarkers studied in RCC and about the role implementation of genomics and proteomics in RCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Adulto , Antígenos de Neoplasias/análise , Apoptose , Sedimentação Sanguínea , Carcinoma de Células Renais/patologia , Proteínas de Ciclo Celular/análise , Inibidor de Quinase Dependente de Ciclina p21 , Ferritinas/análise , Previsões , Genômica , Humanos , Antígeno Ki-67/análise , Neoplasias Renais/patologia , Neopterina/análise , Proteínas Nucleares/análise , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Proteína Supressora de Tumor p53/análise
16.
J Rheumatol ; 28(4): 805-8, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11327255

RESUMO

OBJECTIVE: To study complement and cell mediated cytotoxicity by antiendothelial cell antibodies (AECA) in Takayasu's arteritis (TA). METHODS: Complement dependent cytotoxicity (CDC) and antibody dependent cellular cytotoxicity (ADCC) of AECA positive/negative TA sera were investigated by colorimetric MTT and 51Cr release assays, respectively, using human umbilical vein endothelial cells (HUVEC) as targets. RESULTS: Seven of 12 (58%) sera positive for IgG and/or IgM AECA exhibited CDC in comparison to none of the 13 AECA negative sera (p = 0.0052). The median value of CDC of the AECA positive group was 14% (range 13-21%) and that of the AECA negative group was 1% (p = 0.0012). Interleukin 1beta (10 U/ml) treatment of HUVEC resulted in enhancement in CDC of 6 of the 7 AECA positive cytotoxic sera, the median enhancement being 17% (range 7-29%). Tumor necrosis factor-alpha (100 U/ml) treatment of the targets resulted in a median enhancement by 36% (range 25-55%) in the CDC of 3 of these 7 sera. No sera exhibited ADCC at any of the effector:target ratios tested (10:1 to 100:1). CONCLUSION: AECA in TA mediate CDC against endothelial cells and may have a pathogenic role in the perpetuation of vascular damage in this disease.


Assuntos
Anticorpos/análise , Citotoxicidade Celular Dependente de Anticorpos , Proteínas do Sistema Complemento/análise , Endotélio Vascular/imunologia , Arterite de Takayasu/imunologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Humanos , Interleucina-1/farmacologia , Fator de Necrose Tumoral alfa/farmacologia
17.
Int J Lang Commun Disord ; 36 Suppl: 216-21, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11340785

RESUMO

An investigation is described which forms the basis for the development of an information package for the Asian carers of people with autism spectrum disorders (ASD) and learning disabilities. The results of semi-structured interviews and planning for questionnaires with three different linguistic Asian groups (Urdu, Gujarati and Bengali) are presented. The views, attitudes and awareness of autism, knowledge of support services and perceived priority of needs are analysed for the three different communities. The investigation concludes with recommendations as to whether separate information is needed by each culture or whether a single information pack can be used and presented in each language format. The possible presentation format in which the information can be produced is also discussed.


Assuntos
Transtorno Autístico/terapia , Impressos Avulsos como Assunto , Cuidadores , Ásia/etnologia , Transtorno Autístico/etnologia , Inglaterra , Educação em Saúde/métodos , Humanos
18.
J Med Chem ; 40(7): 1165-8, 1997 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-9089337

RESUMO

Cubylcarbinylamine (1a), (4-cyclopropylcubyl)carbinylamine (1b), and (4-phenylcubyl)carbinylamine (1c) were synthesized and shown to be time-dependent, irreversible inactivators of monoamine oxidase B (MAO B). Substrate protects the enzyme from inactivation, but beta-mercaptoethanol does not, suggesting that these compounds are mechanism-based inactivators. All three compounds were also substrates for MAO B with partition ratios ranging from 152 to 536. The 4-substituted analogues were more potent inactivators than the unsubstituted analogue, indicating a benefit to 4-substitution in this class of inactivators.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Metilaminas/química , Inibidores da Monoaminoxidase/química , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Cinética , Espectroscopia de Ressonância Magnética , Metilaminas/farmacologia , Especificidade por Substrato
19.
Peptides ; 18(5): 695-701, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9213363

RESUMO

The in vivo and functional effects of several 7-arylidene and 7-heteroarylidene morphinan-6-ones were determined at the mu-, delta-, and kappa-opioid receptors using the guinea pig brain membranes, guinea pig ileum (GPI), and mouse vas deferens (MVD). In vivo effects included the antagonism by these compounds given subcutaneously on the antinociceptive actions of intracerebroventricularly injected [D-Pen2, D-Pen5]enkephalin (DPDPE) and [D-Ala2, Glu4]deltorphin II (deltorphin II), the highly selective putative delta 1- and delta 2-opioid receptor agonists. Finally, the partition coefficients of these compounds were estimated (CLOGP) and determined experimentally at pH 7.4 in the 1-octanol/water system. Compared with E-7-benzylidenenaltrexone (BNTX), most compounds except for E-7-(4-chlorobenzylidene)naltrexone, were more potent at delta-opioid receptors than at the mu-opioid receptor, whereas, in comparison to the kappa-opioid receptor, the activities of the E-7-arylidene or E-7-heteroarylidene naltrexone derivatives at the delta-receptor were in the following order, where the 7-substituents were: 4-fluorobenzylidene- > benzylidene > 3-pyridylmethylene- > 4-pyridylmethylene- > 1-methyl-2-imidazolylmethylene > 4-chlorobenzylidene. In the MVD preparation, the potencies at the delta-opioid receptor, in comparison to BNTX, were in the following order, where the 7-substituents were: benzylidene = 1-methyl-2-imidazolylmethylene- > 4-fluorobenzylidene- = 3-pyridylmethylene- = 4-pyridylmethylene-. All compounds antagonized delta 1, and delta 2-opioid receptor agonist-induced analgesia. The antagonist potencies at the delta 1-opioid receptor were in the following order, where the 7-substituents were: benzylidene- > 4-chlorobenzylidene- > 4-fluorobenzylidene- > 3-pyridylmethylene- > 1-methyl-2-imidazolymethylene- approximately 4-pyridylmethylene-, whereas at the delta 2-opioid receptor, the order was benzylidene- > 4-chlorobenzylidene- > 4-fluorobenzylidene- > 3-pyridylmethylene- > 1-methyl-2-imidazolymethylene- > 4-pyridylmethylene. In general, all compounds exhibited greater potency at the delta 2- than delta 1-opioid receptor. The computed partition coefficients were, as expected, greater than the apparent log P values, which were determined experimentally. Generally, the lipophilicity values in decreasing order were: 4-chlorobenzylidene- > 4-fluorobenzylidene- > benzylidene > 3-pyridylmethylene- = 4-pyridylmethylene- > 1-methyl-2-imidazolylmethylene-. In general, the benzylidene and 4-pyridylmethylene derivatives, which have medium lipophilicities, were equally effective at the delta 1- and delta 2-receptors; the 3-pyridylmethylene and 1-methyl-2-imidazolylmethylene derivatives had lower lipophilicities and were more selective for the delta 2- than delta 1-receptor; the 4-chlorobenzylidene and 4-fluorobenzylidene derivatives were more lipophilic and had intermediate activity. The plot of pED50 values for the in vivo tests for the delta 1- and delta 2-receptors showed that the two receptors are not independent with respect to this series of compounds.


Assuntos
Analgésicos/antagonistas & inibidores , Encefalinas/antagonistas & inibidores , Derivados da Morfina/farmacologia , Naltrexona/farmacologia , Antagonistas de Entorpecentes , Oligopeptídeos/antagonistas & inibidores , Receptores Opioides/efeitos dos fármacos , Animais , Química Encefálica/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , D-Penicilina (2,5)-Encefalina , Encefalinas/administração & dosagem , Cobaias , Íleo/efeitos dos fármacos , Injeções Intraventriculares , Injeções Subcutâneas , Masculino , Camundongos , Derivados da Morfina/administração & dosagem , Naltrexona/análogos & derivados , Oligopeptídeos/administração & dosagem , Receptores Opioides/metabolismo , Distribuição Tecidual , Ducto Deferente/efeitos dos fármacos
20.
Indian J Pathol Microbiol ; 33(2): 179-81, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2391152

RESUMO

In the present paper, fungi isolated from bread samples are being reported. Out of 150 samples of bread, only 20 samples appeared to be infected but when cultured all the samples could not give positive results, except, A. fumigatus. Ten fungi including Aspergillus fumigatus, A. niger, A. flavus, A. glaucous, A. carnous, A. terreus, A. ochraceous, Rhizophus stolonifer, Trichoderma harrianua, and Trichothecium roseum were recovered from the bread samples. Among these A. fumigatus and A. niger were dominant which are known to cause toxicity and pulmonary aspergillosis in human beings.


Assuntos
Aspergillus/isolamento & purificação , Pão , Microbiologia de Alimentos , Fungos/isolamento & purificação , Índia
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