SKINFOLD MEASUREMENTS AS DETERMINANTS OF BLOOD PRESSURE LEVELS AMONG ADULT HYPERTENSIVES ATTENDING A SECONDARY HEALTHCARE CENTRE IN NIGERIA.

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.

Quantity not composition of dietary fats represents the dominant contributor to experimental obesity: Relevance to human pathophysiology.

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.

Patients' Perception of Quality of Diabetes Care Received in Ibadan, Nigeria.

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.

Complete spontaneous regression of a metastatic melanoma of the mandible: a case report and follow-up recommendations.

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.

Changes in mediators of inflammation and pro-thrombosis after 12 months of dietary modification in adults with metabolic syndrome.

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.

Neuroprotective effects of kolaviron against psycho-emotional stress induced oxidative brain injury in rats: The whisker removal model.

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.

Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease.

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).

Metabolic alterations in different stages of hypertension in an apparently healthy nigerian population.

Metabolic syndrome (MS) amplifies hypertension (HTN) associated with increased risk of cardiovascular disease (CVD). MS components and other CVD risk measures were investigated in different stages of hypertension. 534 apparently healthy Nigerian traders aged 18-105 years were participants of a cohort study. The International Diabetes Federation (2005) and the National High Blood Pressure Education Program Coordinating Committee criteria were used for MS and HTN classifications, respectively. Anthropometric indices were obtained by standard methods. Levels of fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDLC) were determined by enzymatic methods, while low-density lipoprotein cholesterol (LDLC) was calculated. Data analysed statistically were significant at P < 0.05. 143 (26.8%), 197 (36.9%), and 194 (36.3%) of the traders had normotension, pre-HTN and HTN (stages 1 and 2), respectively. All indices tested except HDLC were significantly different among BP groups (P < 0.05). Waist to hip (WHR) and waist to height (WHT) ratios were significantly different between HTN groups (P < 0.05). HTN was associated with MS and female gender (P < 0.05). Metabolic alterations and significant HTN were observed. Treatment of the individual components of the syndrome and improvement of modifiable metabolic factors may be necessary to reduce MS and high BP.

Time course of improvement of metabolic parameters after a 12 week physical exercise programme in patients with type 2 diabetes: the influence of gender in a Nigerian population.

Gender is a major determinant of the outcomes of many health interventions. This study documents the order of significant improvements in metabolic parameters of patients with type 2 diabetes mellitus (T2DM) having metabolic syndrome within 12 weeks of physical exercise programmes. Twenty-nine patients, mean age 49.6 ± 3.7 years, presenting with high fasting plasma glucose, high triglycerides, hypertension, and high waist circumference undertook a thrice weekly aerobic and endurance exercise programme in addition to their drugs and diet. Variables were assessed at baseline and end of every two weeks for twelve weeks. Compared with baseline, significant improvement (P < 0.05) in the metabolic parameters occurred in this order for the male participants: fasting glucose (2nd week), triglycerides and waist circumference (4th week), and systolic blood pressure (12th week). For the female participants, it was fasting glucose (4th week), triglycerides (6th week), and waist circumference (10th week). Regardless of the gender, fasting glucose was the first to improve significantly, followed by triglycerides. Hypertension did not improve significantly at all in the female participants as they may require more than twelve weeks of therapeutic exercise for any significant improvement in hypertension.

Salivary flow and composition in diabetic and non-diabetic subjects.

The study investigated the effects of type 2 diabetes mellitus on salivary flow and composition in humans compared to healthy sex and age matched controls. Forty adult human subjects divided into 20 diabetic and 20 non-diabetic healthy subjects were included. Saliva samples were collected and analysed for glucose, total protein, calcium, sodium, potassium, chloride and bicarbonate. Salivary flow rate was also determined. The results showed that salivary glucose and potassium levels were significantly higher (p = 0.01 and 0.002 respectively) in diabetic patients compared with non-diabetic participants. It was also found that the diabetic patients had significant reduction in salivary flow rate when compared with non-diabetic individuals. In contrast, there was no significant difference in levels of total protein, Na+, Ca++, Cl- and HCO3- between the two groups. These results suggest that some oral diseases associated with diabetes mellitus may be due to altered levels of salivary glucose, potassium and flow.

Comparative analysis of salivary glucose and electrolytes in diabetic individuals with periodontitis.

BACKGROUND: A high incidence of periodontal disease has been reported among diabetics, however the role of saliva in the occurrence of this oral disease in these patients is yet to be understood. OBJECTIVE: To determine the effects of type-2 diabetes and periodontal disease on salivary flow rate and biochemical composition. DESIGN: A prospective study involving 40 adult human subjects divided equally into four groups of diabetics with periodontitis (group 1), diabetics without periodontitis (group 2), non diabetics with periodontitis (group 3) and non diabetics without periodontitis (group 4). METHODOLOGY: Saliva samples were collected and analyzed for salivary glucose, total protein, calcium, sodium, potassium, chloride and bicarbonate. Salivary flow rates were also determined. RESULTS: Salivary glucose and potassium levels were significantly higher (P = 0.002 and 0.04 respectively) in diabetic patients regardless of periodontal disease (mean = 100.7 ± 9.33 mg/dl; 111.5 ± 32.85 mg/dl and 23.79 ± 5.19 mg/dl; 22.9 ± 6.25 mg/dl respectively) compared with non diabetic participants (mean = 80.5 ± 30.85 mg/ dl; 62.5 ± 31.89 mg/dl and 19.23 ± 5.04 mg/dl; 17.74 ± 4.68 mg/dl respectively). In contrast, there was no significant difference in saliva flow rates and levels of total protein, Na(+), Ca(++), Cl(-) and HCO3 (-)between the groups. CONCLUSION: Salivary glucose and potassium levels were significantly higher among diabetics with or without periodontitis compared with non-diabetics with or without periodontitis. However, biochemical composition of saliva in diabetic individuals has probably little role in their susceptibility to periodontitis.

Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis.

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.

Physical activity levels of type 2 diabetes patients seen at the outpatient diabetes clinics of two tertiary health institutions in Nigeria.

BACKGROUND: It is uncertain whether physical activity is sufficiently utilized as a complementary therapy in diabetes management by the patients visiting Nigerian hospitals. OBJECTIVES: This study assessed the level of physical activity of Type 2 Diabetes (T2D) patients attending tertiary hospital clinics, and investigates the factors that may expose them to sedentariness. METHODS: Physical activity survey was carried out on 248 T2D patients randomly selected from the University College Hospital, Ibadan, and Aminu Kano Teaching Hospital, Kano, Nigeria; and 248 matched non-diabetic participants. Physical activity level was assessed using the International Physical Activity Questionnaire. Socio-demographic information in addition to any previous expert advice on physical activity was recorded. Chi-Squared tests and regression analysis were conducted at p < 0.05. RESULTS: Significant difference existed between the physical activity levels of the T2D patients and the nondiabetic participants (c2 = 57.1, p = 0.0001). Most of the T2D patients were moderately active (62.1%) and less sedentary (27.4%) compared to the non-diabetic participants who were less moderately active (30.6%) and more sedentary (37.5%). Being female doubles the odds of being sedentary (OR = 2.02; 95% CI = 1.52-3.18) likewise increasing age, paid employment and fewer sessions of expert advice on physical activities encourage sedentariness. CONCLUSION: The T2D patients were more physically active at moderate levels than the non-diabetic participants, although, a substantial proportion of the T2D patients were sedentary. Lack of, or infrequent expert advice on physical activity, older age, being female and in paid employment may contribute to sedentariness among the participants.

Relationship between duration of diagnosis and neuromusculoskeletal complications of middle-aged type 2 diabetes patients.

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.

Neuromusculoskeletal disorders in patients with type 2 diabetes mellitus: outcome of a twelve-week therapeutic exercise programme.

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.

Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials.

BACKGROUND: Benefits and risks of concomitant immunomodulators and maintenance infliximab in inflammatory bowel disease (IBD) patients have not been adequately evaluated. AIM: To assess the effect of concomitant immunomodulator and infliximab maintenance therapy using data from four prospective, randomized Phase 3 trials in IBD patients. METHODS: Overall, 1383 patients from ACCENT I and ACCENT II [luminal and fistulizing Crohn's disease trials] and ACT 1 and ACT 2 [ulcerative colitis trials] were analysed. Patients were treated with placebo or infliximab 5 or 10 mg/kg at weeks 0, 2 and 6 followed by every-8-week maintenance therapy. Clinical response, clinical remission, fistula response, complete fistula response, infection and infusion reaction rates; serum infliximab concentrations and immunogenicity were summarized by baseline concomitant immunomodulator subgroup (use or non-use). RESULTS: Overall, almost 40% of evaluated IBD patients received concomitant immunomodulators. Efficacy, infection, and serious infection rates were generally similar in patients who received maintenance therapy with or without concomitant immunomodulators. There were no consistent differences in serum infliximab concentrations with or without immunomodulators in patients who received scheduled maintenance therapy. Concomitant immunomodulators reduced infusion reactions and immunogenicity. CONCLUSION: Concomitant immunomodulators did not improve efficacy or pharmacokinetics in IBD patients who received maintenance infliximab.

Sociodemographic determinants of attrition in hospital based therapeutic exercise programme for type 2 diabetes patients.

BACKGROUND: Abandoning research programmes by participants may impose disadvantages on the participant, the research and the researcher. This study investigated the contributions of sociodemographic characteristics to the attrition of Type 2 Diabetes (T2D) patients who enrolled into a 12-week therapeutic exercise programme. METHODS: In the 12-week, thrice weekly hospital-based therapeutic exercise programme, the contributions of age, gender, duration of diagnosis, marital status, cohabitation, urbanization, educational and employment status to two sources of attrition (inability to locate and decline to commence or complete) were studied. RESULTS: Participants were aged 48 +/- 9.62 years. Out of the 152 participants who agreed to participate, only 93 (61.18%) actually commenced the exercise programme, while 69 (74.19%) of those who commenced the programme completed it. Risk of attrition due to inability to locate participants was higher in females (OR = 3.25, 95% CI = 2.96-3.91), single or divorced and living in the rural area (OR = 1.37, 95% CI = 1.12-1.52). Risk of decline to commence or complete was higher with increasing age, living alone, longer duration of diagnosis and being in paid employment while this was less likely in individuals who were married and more educated. CONCLUSION: We recorded 25.81% attrition for those who actually commenced the programme. Sociodemographic characteristics contributed to attrition in the 12-week, thrice weekly hospital-based exercise programme and we suggest closer monitoring (based on these sociodemographic characteristics) of T2D patients scheduled for therapeutic exercises in order to minimize attrition, maximise attendance and ensure higher retention.

Quinacrine induces cytochrome c-dependent apoptotic signaling in human cervical carcinoma cells.

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.

Abnormalities in thrombogenic and rheologic factors in Nigerian hypertensive patients.

Platelet aggregation, plasma viscosity and plasma fibrinogen concentration were measured in 20 hypertensive Nigerian patients (10 males and 10 females) aged 32-72 years. Another 20 patients gender-matched normotensive subjects, served as controls. Platelet aggregate ratio was significantly lower (P < 0.05) in hypertensive (0.38 +/- 0.24) than in normotensive subjects (0.80 +/- 0.19). The relative plasma viscosity of the hypertensive patients (2.04 +/- 0.14) was higher (P < 0.05) than the value in control subjects (1.64 +/- 0.25). Plasma fibrinogen concentration, determined by the direct clot weight technique, was also significantly higher (p < 0.05) in hypertensive patients (3.90 +/- 0.62mg/dL) than in normotensive patients (2.70 +/- 0.60mg/dL). There was no evidence of gender differences in all the above variables except in the plasma fibrinogen concentration, which was significantly higher (P < 0.01) in male hypertensive patients. It is thus evident that haemorheological and thrombogenic abnormalities may be present in hypertensive Nigerian patients at the time of diagnosis and therapeutic interventions that reduce the risk of thrombogenesis and rheologic abnormalities should be considered in the management of Nigerian patients with hypertension.

A comparative study of students' performance in preclinical physiology assessed by multiple choice and short essay questions.

This study was designed to compare the performance of medical students in physiology when assessed by multiple choice questions (MCQs) and short essay questions (SEQs). The study also examined the influence of factors such as age, sex, O/level grades and JAMB scores on performance in the MCQs and SEQs. A structured questionnaire was administered to 264 medical students' four months before the Part I MBBS examination. Apart from personal data of each student, the questionnaire sought information on the JAMB scores and GCE O' Level grades of each student in English Language, Biology, Chemistry, Physics and Mathematics. The physiology syllabus was divided into five parts and the students were administered separate examinations (tests) on each part. Each test consisted of MCQs and SEQs. The performance in MCQs and SEQs were compared. Also, the effects of JAMB scores and GCE O/level grades on the performance in both the MCQs and SEQs were assessed. The results showed that the students performed better in all MCQ tests than in the SEQs. JAMB scores and O' level English Language grade had no significant effect on students' performance in MCQs and SEQs. However O' level grades in Biology, Chemistry, Physics and Mathematics had significant effects on performance in MCQs and SEQs. Inadequate knowledge of physiology and inability to present information in a logical sequence are believed to be major factors contributing to the poorer performance in the SEQs compared with MCQs. In view of the finding of significant association between performance in MCQs and SEQs and GCE O/level grades in science subjects and mathematics, it was recommended that both JAMB results and the GCE results in the four O/level subjects above may be considered when selecting candidates for admission into the medical schools.