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1.
Pathophysiology ; 26(3-4): 315-322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31420114

RESUMO

Plant fats are low in saturated fats but high in unsaturated fats compared to animal fats, and are supposedly less obesogenic. This study compared the obesogenic effects of plant and animal derived fatty diets in Wistar rats. Rats of each gender were divided into three dietary (standard chow (SC), high fat diet rich in animal fat (HFDaf) and a high fat diet rich in plant fat (HFDpf)) groups of ten each and fed for 17 weeks. Anthropometric, Adiposity and nutritive variables were assessed using standard methods. Comparing HFDpf to HFDaf: Abdominal circumference (AC),initial feed intaken (IFI), final feed intake(FFI), final body weight (FBW), white adipose tissue (WAT) were increased but brown adipose tissue (BAT) decreased in male rats fed with HFDpf; also, there were increased body length, IFI, FFI but decreased AC, FBW, BAT in female rats fed with HFDpf. Comparing male to female rats: Thoracic circumference, IFI, FFI, energy intake were increased while Adiposity index decreased across diet groups in male rats; the AC, FBW increased while WAT, BAT decreased in HFDpf fed group, also, BAT was increased but AC, FBW decreased in HFDaf fed group in male rats. Palatability and high feed efficiency of consumed diets were more associated with obesogenic risk than just the level of saturation. Therefore, Obesogenic effects of fatty diets in both genders is more dependent on the quantity (amount) of fatty diet consumed than the dietary fat composition alone.

2.
Afr J Med Med Sci ; 45(3): 253-260, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29462530

RESUMO

BACKGROUND: The study investigated the neuroprotective potentials of kolaviron (a biflavonoid complex of Garcinia kola) against psycho-emotional stress induced oxidative brain injury in Wistar rats. METHODS: Twenty-four adult Wistar rats (180-220g) randomly divided into four groups (1-1V,n=6) were used for the study . Group 1 served as control (non stressed), group 11 consisted of stressed rats induced by complete removal' of the whiskers around the mouth and the nose without anaesthesia. The rats in group 111 were pre- treated with 200mg/kg kolaviron per oral (p.o), daily for seven days before being subjected to the stress procedure' while group 1V rats also had 200mg/kg oral kolaviron alone without being stressed. The animals were later euthanized by cervical dislocation, cerebellum and frontal cortex removed and then subjected to biochemical and histopathological analysis. RESULTS: Whisker removal significantly(p<0.05) increased lipid peroxidation (U/mg protein) in the cerebellum (3.82±0.22 vs 6.50±0.41) and the cerebral cortex (14.57±2.50 vs 30.11± 4.70) compared with their controls, it also produced significant reductions 'in catalase activities (U/min/mg protein) in cerebellum (169.65±11.02 vs 87.72, p <0.001) and the cerebral cortex (264.5 ± 40.57 vs 122.71 ± 15.70,p< 0.001). Glutathione levels (U/mg protein) were similarly significantly (P<0.001) reduced in both cerebellum (132.40 ± 4.81 vs 37.60 ± 1.50) and the cerebral cortex (370.42 ±20.51 vs 120.51± 25.35) compared with their corresponding controls. There were also histological abnormalities like cellular degeneration and necrosis in both the frontal cortex and the cerebellum of the stressed rats. Pre- treatment with kolaviron not only reversed these biochemical alterations but also significantly attenuated these observed histopathological changes. CONCLUSION: The present study demonstrated the neuroprotective potential of kolaviron against psycho-emotional stress-induced oxidative brain injury through the inhibition of oxidative stress.


Assuntos
Encéfalo/efeitos dos fármacos , Flavonoides/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Psicológico/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Catalase/efeitos dos fármacos , Catalase/metabolismo , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Masculino , Ratos , Ratos Wistar , Estresse Psicológico/patologia , Vibrissas
3.
Ann Ib Postgrad Med ; 20(2): 169-176, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37384341

RESUMO

Background: Background: The prevalence of obesity is increasing globally, making it a growing pandemic affecting adults and children. Obesity is associated with multiple morbidities and mortalities increasing the burden on the health care system. Objective: There is inadequacy of data in Nigeria on the prevalence of obesity among adult patients with hypertension and adequate data on these conditions would help in their comprehensive management. Methods: This was a cross-sectional study of 354 patients with hypertension, and the systematic sampling technique was used to recruit patients. The data were analysed using SPSS software version 23. Logistic regressions and linear regressions were done to determine the predictors of obesity and blood pressure levels. Results: The mean age of the respondents was 52.60(SD±8.26) years and the prevalence of obesity was 53.1%. After adjusting for other variables, the predictors of obesity were female sex. Females were about six times more likely to be obese than males (OR=6.23; 95%CI= 3.16 - 12.32). For every 1 unit increase in triceps skinfold, there was a statistically significant increase in diastolic blood pressure by about 2.77units (95% C.I equals 2.63 to 2.91, p-value= 0.0001). Also, for every 1 unit increase in biceps skinfold, there was a statistically significant increase in systolic blood pressure by about 5.78 units (95% C.I equals 5.46- 6.10, p-value= 0.0001). Conclusion: The prevalence of obesity was high, and the predictors of obesity were female sex. Triceps skinfold measurements were predictors of diastolic blood pressure while biceps skinfold measurements were predictors of systolic blood pressure.

4.
Int J Clin Pharmacol Ther ; 48(5): 297-308, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20420786

RESUMO

OBJECTIVES: Infliximab, an IgG1 monoclonal antibody (mab), has large inter-individual serum concentration variability. The objective was to determine the extent of the association of baseline albumin concentration and infliximab disposition in patient with ulcerative colitis. METHOD: Data from 728 patients with ulcerative colitis from two clinical trials were analyzed to evaluate trends between infliximab pharmacokinetics and serum albumin, or liver or kidney function. Response in the placebo and treated groups were compared by baseline serum albumin concentrations (SAC) groups. RESULTS: Patients with higher SAC maintained higher infliximab concentrations, lower clearance, and longer half-life than patients with lower SAC. When analyzed by SAC quartiles, patients in the highest quartile had several-fold greater trough infliximab concentrations when compared with those in the lowest quartile. These observations were consistent in both studies and at different dose levels. Generally, clinical response in patients did not vary with SAC when the SAC was within the normal range, apparently because serum infliximab concentrations remained at therapeutic levels. However, patients with SAC lower than the normal laboratory reference range had much lower median serum infliximab concentrations and lower response rates compared with patients within normal SAC. Infliximab pharmacokinetics did not correlate with SGOT or creatinine clearance. CONCLUSIONS: It is hypothesized that the common rescue pathway for both albumin and IgG involving the neonatal Fc receptor may be responsible for the relationship between serum albumin and serum infliximab levels. Baseline albumin level may serve as a valuable and convenient measure of mab pharmacokinetic expectations in these patients.


Assuntos
Anticorpos Monoclonais/farmacocinética , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/farmacocinética , Albumina Sérica/metabolismo , Adulto , Anticorpos Monoclonais/uso terapêutico , Método Duplo-Cego , Feminino , Fármacos Gastrointestinais/uso terapêutico , Meia-Vida , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Imunoglobulina G/sangue , Infliximab , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Fc/metabolismo , Resultado do Tratamento , Adulto Jovem
5.
West Afr J Med ; 29(6): 393-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21465447

RESUMO

BACKGROUND: Patients with Type 2 Diabetes (T2D) often present with complications involving the neuromusculoskeletal system which creep in as the condition advances in years. Hence there is a need to further understand how the duration of diagnosis of diabetes (DD) relates to the neuromusculoskeletal complications in order to design timely preventive programmes. OBJECTIVE: To investigate the relationship between the duration of diabetes and neuromusculoskeletal complications in type 2 diabetes. METHODS: This was a cross-sectional survey involving 139 consenting T2D patients and 139 age and sex-matched nondiabetic individuals. The participants were assessed for the DD and selected neuromusculoskeletal complications including muscle weakness, ranges of motion (ROM), pain and foot ulceration. RESULTS: The mean DD was 7.82 ± 2.41 years. There were significant differences (p < 0.01) between the clinical variables of both groups. In the diabetic participants, significant inverse relationships (P<0.05) were obtained between the DDD and each of muscle strength {{lbow flexors (r =-0.57), knee extensors (r=-0.63), handgrip (r=-0.82)}; ROM {wrist extension (r=-0.64) and ankle planterflexion (r=-0.63)}. Significant and direct relationships were obtained between the DDD and each of pain (r=0.62) and ulcerative grading (r= 0.81). CONCLUSIONS: Type 2 Diabetes patients have poorer neuromusculoskeletal variables and longer duration of diabetes is associated with reduced muscle strength, diminished ROM, gradual ulceration of skin of the feet and higher level of foot pain. Immediate therapeutic exercises against these complications soon after diagnosis of diabetes may help to decelerate their progression.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Úlcera do Pé/complicações , Debilidade Muscular/complicações , Adulto , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/complicações , Doenças Musculoesqueléticas/diagnóstico , Doenças Neuromusculares/complicações , Doenças Neuromusculares/diagnóstico , Amplitude de Movimento Articular/fisiologia , Fatores de Risco , Fatores de Tempo
6.
Niger J Clin Pract ; 13(4): 403-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21220854

RESUMO

BACKGROUND AND OBJECTIVES: Usual line of management of diabetes patients is drug and diet with their physical needs usually receiving minimal attention. Among the physical needs, requiring attention is their neuromusculoskeletal disorders. This study was designed to investigate the effect of a twelve-week therapeutic exercise on neuromusculoskeletal disorders of Type 2 Diabetes (T2D) patients. METHODS: Forty-three participants from the Diabetes Specialty Clinic of Aminu Kano Teaching Hospital, Kano completed the study. Selected neuromusculoskeletal disorders including pain, dermatological foot grades, disorders of ranges of motion and strength of selected joints and muscles were assessed before and after a period of twelve weeks of therapeutic exercises. Participants were followed up for another twelve weeks without therapeutic exercises. RESULTS: Baseline assessment revealed poor neuromusculoskeletal status. Significant improvements (P < 0.05) were obtained for pain, Severity of Dermatological Foot Grading, Muscle strength (One Repetition Maximum) and Range of Motions at the end of the exercises except that of right wrist extension (P > 0.05). CONCLUSIONS: T2D patients presented with neuromusculoskeletal disorders at baseline. Therapeutic exercises however assisted in the improvement of these disorders but relapsed when exercises were suspended. Engagement in therapeutic exercises enhanced neuromusculoskeletal health, while withdrawal from the exercise contributed to a decline. T2D patients should be encouraged to participate in therapeutic exercises in order to promote their health and function.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Terapia por Exercício , Doenças Neuromusculares/terapia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Músculo Esquelético/fisiopatologia , Doenças Neuromusculares/etiologia , Nigéria , Medição da Dor , Estudos Prospectivos , Amplitude de Movimento Articular , Resultado do Tratamento
7.
Int J Oral Maxillofac Surg ; 47(12): 1519-1522, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29970290

RESUMO

Regression of metastatic melanoma is very rare and occurs in only 0.23% of cases. Metastasis to the oral cavity is particularly uncommon and accounts for only 1-3% of all oral malignancies. This report presents a case of spontaneous and complete regression of a metastatic melanoma in the mandibular ramus. The patient remains asymptomatic more than 2 years after diagnosis. The patient was followed up regularly. It is recommended that further surveillance imaging be performed in asymptomatic patients following discussion with the surgical and oncological teams. This type of surveillance, together with new systemic treatments, is advocated due to its potential to increase long-term survival even after relapse.


Assuntos
Neoplasias Mandibulares/patologia , Melanoma/patologia , Idoso , Humanos , Biópsia Guiada por Imagem , Masculino , Neoplasias Mandibulares/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Estadiamento de Neoplasias , Remissão Espontânea
8.
Arch Basic Appl Med ; 6(1): 119-125, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29974057

RESUMO

Diabetes Mellitus (DM) is one of the diseases of public health concerns of the 21st century with rising burden in developing countries. The evaluation of care for diabetes from patients' perspective an important indicator of measuring quality of health services and improving treatment approaches but data of the nature are scarce in Nigeria. The study therefore investigated Patients' Evaluation of the Quality of Diabetes care (PEQD) in Ibadan. This descriptive cross-sectional study recruited 384 diabetic patients from three hospitals where specialised services are offered in Ibadan. A semi-structured pre-tested questionnaire was used to collect data. A 42-point PEQD questionnaire scale was used to collect data and a score of >21 was rated as good Perceived Quality of Care (PQC). Data were analysed using descriptive statistics, chi-square test and logistic regression set at 5% level of statistical significance. Mean age of respondents was 62.5 + 10.8 years and mean diabetes duration was 8.4 + 7.6. Majority (58.3%) of the respondents didn't know the type of diabetes they had. Patients aged less than 60 years were less likely to PQC received as good (OR: 0.21; CI: 0.05 - 0.91) compared to those who were above 60 years. More than half (55.0%) of the respondents perceive quality of care as good. Patients' assessment of the quality of diabetes care received was perceived good. There is need to sustain current satisfactory services in diabetic care and institutionalize periodic survey patients' satisfaction to provide feedback for future quality improvement.

9.
Afr Health Sci ; 17(2): 453-462, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29062341

RESUMO

OBJECTIVE: This study evaluated the effects of a 12-month dietary modification on indices of inflammation and pro-thrombosis in adults with metabolic syndrome (MS). MATERIALS AND METHODS: This longitudinal study involved 252 adults with MS recruited from the Bodija market, Ibadan and its environs. Participants were placed on 20%, 30% and 50% calories obtained from protein, total fat and carbohydrate respectively and were followed up monthly for 12 months. Anthropometry and blood pressure were measured using standard methods. Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), fibrinogen, plasminogen activator inhibitor-1 (PAI-1)], interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured using spectrophotometric methods and ELISA as appropriate. Data was analysed using ANCOVA, Student's t-test, Mann-Whitney U and Wilcoxon signed-rank tests. P-values less than 0.05 were considered significant. RESULTS: After 6 months of dietary modification, there was a significant reduction in waist circumference (WC), while the levels of HDL-C, fibrinogen and PAI-1 were significantly increased when compared with the corresponding baseline values. However, WC and fibrinogen reduced significantly, while HDL-C and IL-10 significantly increased after 12 months of dietary modification as compared with the respective baseline values. CONCLUSION: Long-term regular dietary modification may be beneficial in ameliorating inflammation and pro-thrombosis in metabolic syndrome.


Assuntos
Síndrome Metabólica/dietoterapia , Adulto , Glicemia/análise , Colesterol/sangue , HDL-Colesterol/sangue , Dieta , Feminino , Fibrinogênio/análise , Humanos , Inflamação/prevenção & controle , Interleucina-10/sangue , Interleucina-6/sangue , Estudos Longitudinais , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Nigéria , Inibidor 1 de Ativador de Plasminogênio/sangue , Trombose/prevenção & controle , Triglicerídeos/sangue , Circunferência da Cintura
10.
J Clin Oncol ; 16(5): 1803-10, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9586894

RESUMO

PURPOSE: O6-Benzylguanine is a potent inactivator of the DNA-repair protein, O6-alkylguanine-DNA alkyl-transferase (AGT), that enhances sensitivity to nitrosoureas in tumor-cell lines and tumor-bearing animals. The objective of this study was to determine the pharmacokinetics and metabolic fate of O6-Benzylguanine in humans and its effect on AGT activity in peripheral-blood mononuclear cells (PBMCs). PATIENTS AND METHODS: Twenty-five cancer patients were treated with O6-Benzylguanine at a dose level of 10, 20, 40, and 80 mg/m2 intravenously (IV) over 1 hour. Plasma and urine samples were collected and analyzed for O6-Benzylguanine and O6-Benzyl-8-oxoguanine concentrations. AGT activity in PBMCs was determined up to 2 weeks postinfusion. RESULTS: There was no toxicity attributable to O6-Benzylguanine alone at all doses tested. O6-Benzylguanine rapidly disappeared from plasma and was converted to a major metabolite, O6-Benzyl-8-oxoguanine. The half-life of O6-Benzyl-8-oxoguanine increased with dose from 2.8 to 9.2 hours at doses of 10 and 80 mg/m2, respectively. The maximum concentration Cmax and area under the concentration-time curve (AUC) for O6-Benzyl-8-oxoguanine were, respectively, 2.2- and 12- to 29-fold greater than those of O6-Benzylguanine. At all doses, depletion of AGT activity was observed in lymphocytes with a return to baseline by 1 week posttreatment. CONCLUSION: This study demonstrates that administration of O6-Benzylguanine to humans results in a rapid conversion to O6-Benzyl-8-oxoguanine, which follows nonlinear kinetics. Both compounds contribute to an effective depletion of AGT activity in lymphocytes; however, prolonged depletion of AGT activity is likely due primarily to the effect of O6-Benzyl-8-oxoguanine.


Assuntos
Antineoplásicos/farmacocinética , Guanina/análogos & derivados , Alquil e Aril Transferases/sangue , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/farmacocinética , Guanina/farmacologia , Meia-Vida , Humanos , Infusões Intravenosas , Leucócitos Mononucleares/enzimologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
11.
J Clin Oncol ; 16(6): 2032-7, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9626200

RESUMO

PURPOSE: This multicenter phase II trial investigated the efficacy and safety of a combination of paclitaxel and topotecan in patients with pretreated metastatic breast cancer. Plasma levels of paclitaxel and topotecan were obtained during cycle 1 to correlate pharmacokinetic parameters with toxicity. PATIENTS AND METHODS: Paclitaxel was administered intravenously (i.v.) at 230 mg/m2 over 3 hours on day 1 followed by topotecan 1.0 mg/m2 i.v. over 30 minutes on days 1 to 5. Patients received an abbreviated premedication regimen that consisted of ranitidine 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of dexamethasone, all administered i.v. 30 minutes before paclitaxel. Granulocyte colony-stimulating factor (GCSF) was administered at 5 micrograms/kg/d subcutaneously starting on day 6 and continuing until the absolute granulocyte count (AGC) was greater than 10,000/microL. Plasma paclitaxel and topotecan concentrations were assessed during the first cycle using limited-sampling strategies. RESULTS: Seventeen patients were treated. The majority had visceral metastases. Four patients experienced neutropenic fever and one had mild bronchospasm. Only one partial response (PR) was observed. Nadir AGC correlated strongly with both duration of paclitaxel levels greater than 0.05 mumol/L and maximum concentration (Cmax) of paclitaxel. CONCLUSION: This regimen does not produce a response rate superior to that expected with single-agent paclitaxel at doses that do not require growth factor support.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Paclitaxel/administração & dosagem , Topotecan/administração & dosagem , Adenocarcinoma/patologia , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Paclitaxel/farmacocinética , Análise de Regressão , Topotecan/efeitos adversos , Topotecan/farmacocinética , Resultado do Tratamento
12.
Aliment Pharmacol Ther ; 42(2): 188-202, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25996351

RESUMO

BACKGROUND: Vedolizumab, an anti-α(4)ß(7) integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb concentrations have been associated with greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help to optimise dosing. AIMS: To characterise vedolizumab pharmacokinetics in patients with UC and CD, to identify clinically relevant determinants of vedolizumab clearance, and to describe the pharmacokinetic-pharmacodynamic relationship using population modelling. METHODS: Data from a phase 1 healthy volunteer study, a phase 2 UC study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic analysis for repeated measures was conducted using nonlinear mixed effects modelling. Results from the base model, developed using extensive phase 1 and 2 data, were used to develop the full covariate model, which was fit to sparse phase 3 data. RESULTS: Vedolizumab pharmacokinetics was described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half-life of vedolizumab was 25.5 days; linear clearance (CL(L)) was 0.159 L/day for UC and 0.155 L/day for CD; central compartment volume of distribution (V(c)) was 3.19 L; and peripheral compartment volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35% for CLL and 19% for V(c); residual variance was 24%. Only extreme albumin and body weight values were identified as potential clinically important predictors of CL(L). CONCLUSIONS: Population pharmacokinetic parameters were similar in patients with moderately to severely active UC and CD. This analysis supports use of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers: NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI 3).


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/farmacocinética , Fármacos Gastrointestinais/uso terapêutico , Adolescente , Adulto , Idoso , Albuminas/uso terapêutico , Peso Corporal , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Adulto Jovem
13.
J Immunol Methods ; 184(2): 163-7, 1995 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-7658020

RESUMO

Use of whole blood for lymphocyte proliferation experiments have advantages over the usual isolated lymphocyte procedure. We have systematically optimized methodology for whole blood lymphocyte proliferation in male Sprague-Dawley rats. Both phytohemagglutinin (PHA) and concanavalin A (ConA) stimulate lymphocyte blastogenesis in whole blood. The response of rat lymphocytes to ConA at supra-optimum conditions doubled that of PHA in contrast to what is observed in human lymphocytes. Proliferation rates relate non-linearly to concentrations of both mitogens with profiles showing lag, log and decline phases with increasing concentrations. The effect of incubation period followed a similar pattern with an optimum growth rate at 72 h. Whole blood from adrenalectomized rats gave higher proliferation rates than blood from intact normal rats. Advantages of the technique include: use of as little as 8 microliters of blood for each determination; rats need not be killed, the technique is less cumbersome, less time consuming, and cheaper to carry out than the traditional isolated lymphocyte method.


Assuntos
Linfócitos/citologia , Adrenalectomia , Animais , Divisão Celular , Células Cultivadas , Concanavalina A , Técnicas Imunológicas , Linfócitos/imunologia , Masculino , Fito-Hemaglutininas , Ratos , Ratos Sprague-Dawley
14.
Life Sci ; 57(14): PL175-80, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7564875

RESUMO

Halofantrine hydrochloride (HF), one of the latest antimalarial agents currently undergoing clinical trials, and its active metabolite, N-desbutylhalofantrine (DHF), were examined for their effects on human and rat lymphocytes. HF has a biphasic concentration-dependent effect on phytohemagglutinin stimulated proliferation of human lymphocytes. Concentrations lower than 2.25 microM enhance, while higher concentrations inhibit proliferation. The IC50 values were 9.4 microM for HF, 4.5 microM for DHF and 14.7 microM for chloroquine. In human lymphocytes, enhanced proliferation was not detected for DHF unlike for HF. Combined achievable plasma concentrations of HF and DHF may sometimes be in the range where reduced lymphocyte proliferation occurs in vitro when based on simple additive dynamics. It remains to be confirmed if malarial treatment with HF leads to reduced T-cell responsiveness to antigenic challenges since HF and DHF persist for several days.


Assuntos
Antimaláricos/farmacologia , Linfócitos/efeitos dos fármacos , Fenantrenos/farmacologia , Adulto , Análise de Variância , Animais , Antimaláricos/metabolismo , Divisão Celular/efeitos dos fármacos , Cloroquina/farmacologia , Humanos , Técnicas In Vitro , Linfócitos/citologia , Masculino , Fenantrenos/metabolismo , Ratos , Ratos Sprague-Dawley
15.
Int J Cardiol ; 32(3): 401-3, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1791094

RESUMO

A case of severe congestive cardiac failure of unidentified etiology demonstrating an extreme electrical QRS axis is presented. The axis is about -120 degrees. This electrocardiographic manifestation is rare, and, to the best of our knowledge, there have been no previously reported cases in congestive cardiac failure in our environment. This finding, in view of the clinical state of our patient, may be indicative of extreme severity resulting in widespread patchy myocardial fibrosis.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Eletrocardiografia , Diagnóstico Diferencial , Fibrose Endomiocárdica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria
16.
Arch Pharm Res ; 24(2): 126-35, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11339632

RESUMO

Quinacrine (QU), a phospholipase-A2 (PLA-2) inhibitor has been used clinically as a chemotherapeutic adjuvant. To understand the mechanisms leading to its chemotherapeutic effect, we have investigated QU-induced apoptotic signaling pathways in human cervical squamous carcinoma HeLa cells. In this study, we found that QU induced cytochrome c-dependent apoptotic signaling. The release of pro-apoptotic cytochrome c was QU concentration- and time-dependent, and preceded activation of caspase-9 and -3. Flow cytometric FACScan analysis using fluorescence intensities of DiOC6 demonstrated that QU-induced cytochrome c release was independent of mitochondrial permeability transition (MPT), since the concentrations of QU that induced cytochrome c release did not alter mitochondrial membrane potential (delta pai(m)). Moreover, kinetic analysis of caspase activities showed that cytochrome c release led to the activation of caspase-9 and downstream death effector, caspase-3. Caspase-3 inhibitor (Ac-DEVD-CHO) partially blocked QU-induced apoptosis, suggesting the importance of caspase-3 in this apoptotic signaling mechanism. Supplementation with arachidonic acid (AA) sustained caspase-3 activation induced by QU. Using inhibitors against cellular arachidonate metabolism of lipooxygenase (Nordihydroxyguaiaretic Acid, NDGA) and cyclooxygenase (5,8,11,14-Eicosatetraynoic Acid, ETYA) demonstrated that QU-induced apoptotic signaling may be dependent on its role as a PLA-2 inhibitor. Interestingly, NDGA attenuated QU-induced cytochrome c release, caspase activity as well as apoptotic cell death. The blockade of cytochrome c release by NDGA was much more effective than that attained with cyclosporin A (CsA), a MPT inhibitor. ETYA was not effective in blocking cytochrome c release, except under very high concentrations. Caspase inhibitor z-VAD blocked the release of cytochrome c suggesting that this signaling event is caspase dependent, and caspase-8 activation may be upstream of the mitochondrial events. In summary, we report that QU induced cytochrome c-dependent apoptotic signaling cascade, which may be dependent on its role as a PLA-2 inhibitor. This apoptotic mechanism induced by QU may contribute to its known chemotherapeutic effects.


Assuntos
Antimaláricos/farmacologia , Apoptose/efeitos dos fármacos , Grupo dos Citocromos c/fisiologia , Inibidores Enzimáticos/farmacologia , Quinacrina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/patologia , Western Blotting , Caspase 8 , Caspase 9 , Caspases/metabolismo , Interações Medicamentosas , Ativação Enzimática/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Fosfolipases A/antagonistas & inibidores , Fosfolipases A2 , Quinacrina/antagonistas & inibidores , Espectrometria de Fluorescência
17.
West Afr J Med ; 18(3): 183-6, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10593154

RESUMO

To determine the effect of diuretic therapy on osmotic fragility of red blood cells of hypertensive patients, 25 hypertensive and 15 normotensive subjects were followed up for 12 weeks. Osmotic fragility of erythrocytes of the hypertensive subjects were determined before treatment and at 6 weeks and 12 weeks after the start of diuretic therapy. The red cell size was larger in hypertensive subjects than in normal controls. With treatment, however, the red cell size was similar in the two groups of subjects. Osmotic fragility was higher in hypertensive subjects than in normotensive subjects. The osmotic fragility also became similar in the two groups with control of blood pressure in the hypertensive group. Osmotic fragility of red blood cells may be determined as a screening tool for hypertensive patients who will benefit from diuretic therapy.


Assuntos
Diuréticos/efeitos adversos , Índices de Eritrócitos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Fragilidade Osmótica , Estudos de Casos e Controles , Humanos , Hipertensão/etiologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Seleção de Pacientes
18.
Afr J Med Med Sci ; 23(4): 333-9, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7653400

RESUMO

In forensic science, the need to adequately identify cocaine and differentiate it from closely related compounds within a short time is desirable. Application of ultraviolet (UV) spectroscopy in this respect is limited because of the broadness of UV peaks. Derivative transformation of UV spectra, a relatively new technique, is shown in this work to enhance characteristic information from UV spectra to aid identification of cocaine. Cocaine is characterized with a triplet peak at around 230 nm in the second order derivative. Ratio of peak amplitude was also used to characterize cocaine. The ratio of the negative to positive peak amplitude around 230 nm differentiates cocaine from other compounds tested. In addition, the ratio of a pair of peak amplitudes around 275 nm in the second order derivative gave characteristic properties which are statistically significant in the differentiation of cocaine from benzoic acid and benzocaine. Application of derivative spectroscopy for identification purposes is a promising area for more extensive exploitation in forensic science.


Assuntos
Cocaína/química , Espectrofotometria Ultravioleta , Detecção do Abuso de Substâncias/métodos , Benzoatos/química , Benzocaína/química , Ácido Benzoico , Cocaína/análogos & derivados , Medicina Legal , Humanos
19.
Afr J Med Med Sci ; 25(3): 231-4, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10457796

RESUMO

Basal metabolic rate (BMR) was measured by open circuit indirect calorimetry on 3 consecutive days in 25 highly trained men aged 19-32 years. On day 1, the subjects abstained from all forms of exercise beyond normal sedentary activities. On day 2, they increased the level of exercise beyond their usual level of exertion. Measurements of BMR on day 3 showed a significant but small rise. It is suggested that in the prescription of exercise to patients in weight reduction programmes, bouts of vigorous exercise interspersed by one or more days of relative inactivity, will be more effective than a constant level of exercise.


Assuntos
Metabolismo Basal/fisiologia , Terapia por Exercício/métodos , Esforço Físico/fisiologia , Aptidão Física/fisiologia , Adulto , Calorimetria Indireta , Dieta Redutora , Metabolismo Energético , Humanos , Masculino , Obesidade/prevenção & controle , Fatores de Tempo , Redução de Peso
20.
Afr J Med Med Sci ; 29(2): 161-5, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11379450

RESUMO

The effect of adrenoceptor blockers on nicotine induced hyperglycemia were studied in fasted normal and thyroidectomised rats. Blood glucose was estimated using the modified glucose oxidase method. The control experiments consisted of sham operated rats with intact thyroid glands. Pre-treatment of the rats with either the alpha adrenoceptor blocker prazosin or the beta adrenoceptor blocker propranolol before intravenous injection of nicotine (50 micrograms/kg) significantly reduced the hyperglycemia induced by nicotine in normal rats, while a combination of propranolol and prazosin abolished nicotine induced hyperglycemia. In the thyroidectomised group, nicotine also caused hyperglycemia. However, the basal glucose level and peak of glycemic response were lowered compared to that in the control group. The results therefore seem to suggest that both alpha and beta adrenoceptors are involved in nicotine-induced hyperglycemia in the rat.


Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Modelos Animais de Doenças , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Nicotina/efeitos adversos , Prazosina/farmacologia , Propranolol/farmacologia , Hormônios Tireóideos/fisiologia , Tireoidectomia/efeitos adversos , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Hiperglicemia/metabolismo , Hiperglicemia/prevenção & controle , Masculino , Ratos , Ratos Wistar , Fatores de Tempo
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