Absorption and cleavage of enalapril,a carboxyl ester prodrug,in the rat intestine: in vitro,in situ intestinal perfusion and portal vein cannulation models

In recent years prodrug strategy has been used extensively to improve the pharmacokinetic properties of compounds exhibiting poor bioavailability. Mechanistic understanding of the absorption and the role of intestine and liver in the activation of oral prodrugs is crucial. Enalapril, a carboxyl ester prodrug, is reported to be metabolized by human carboxylesterase‐1 (CES1) but not by carboxylesterase‐2 (CES2) to its active metabolite enalaprilat. Further, it has been reported that the small intestines of both rat and human contain mainly CES2. The objective of this work was to understand whether enalapril remains unchanged as it is absorbed through the intestine into the portal circulation. This was evaluated using different intestinal preparations, an in situ intestinal perfusion experiment and a portal vein cannulated rat model. No turnover of enalapril was seen with commercial rat intestinal S9 and microsomes, but reasonable turnover was observed with freshly prepared rat intestinal and mucosal homogenate and S9. In the intestinal perfusion study, both enalapril and enalaprilat were observed in the mesenteric plasma with the data suggesting 32% hydrolysis of enalapril in the intestine. In the portal vein cannulated rat, about 51% of enalapril absorbed into intestine was converted to enalaprilat. Overall, it was demonstrated that even though enalapril has been shown to be a specific substrate for CES1, it is converted to enalaprilat to a significant extent in the intestine. Such experimental techniques can be applied by other scientific groups who are working on prodrugs to determine the region and extent of activation. Copyright © 2015 John Wiley & Sons, Ltd.     

Comparison of knowledge on stroke for stroke patients and the general population in Burkina Faso: a cross-sectional study

BackgroundIn many parts of Africa, there is limited information on awareness of symptoms of stroke, risk factors for stroke and willingness for stroke prevention, both in the general population and in people with stroke. Knowledge and preventive efforts for stroke in patients with a history of the illness are rarely investigated. This study aims to investigate awareness of stroke symptoms in stroke patients who were admitted to hospitals within 72 hours of a confirmed stroke event in Burkina Faso. This study also aims to investigate preventive behavior for stroke for the general population.MethodsFace-to-face interviews were conducted with the participants. The sample included 110 first-time stroke patients who had been admitted to one of three tertiary teaching hospitals in Burkina Faso within 72 hours and 750 participants from the general population, who were recruited through clustered sampling. Knowledge of stroke warning signs and current and future efforts on stroke prevention were also assessed.ResultsOnly 30.9% of the stroke patients believed that they were at risk before the stroke episode. Obvious warning signs were unfamiliar to both groups. Only 1.3% of the respondents from the general population group knew sudden weakness face arm or leg as a sign of stroke. For all future efforts in stroke prevention, stroke patients demonstrated significantly lower willingness to undertake behavioral changes than the general population. Sixty-six percent and 85% of the stroke patients and the general population, respectively, were willing to take steps to reduce blood pressure.ConclusionPublic education on stroke warning signs and strategies to increase willingness to engage in preventive behaviors are urgent in African countries. Strategies to improve public awareness for developing countries such as Burkina Faso should be designed differently from that of developed countries to incorporate local beliefs.     

Malformation in index pregnancy in women with epilepsy is not followed by recurrence in subsequent pregnancy

Use of antiepileptic drugs (AEDs) in pregnant women with epilepsy (WWE) is associated with an increased risk of major congenital malformations (MCM). Previous studies have suggested that WWE who had a malformation in their index pregnancy were at an increased risk of recurrence in future pregnancies. We aimed to assess the risk of recurrence of MCM in 1,616 WWE from Kerala Registry of Epilepsy and Pregnancy. The pregnancy outcome of women (n = 246) with two prospective pregnancies in the registry were analyzed. They had partial seizures with or without generalization (57.3%) or generalized seizures (42.7%). Polytherapy was used in 26.4% (index pregnancy) and 23.6% (follow‐up pregnancy). The mean dosage of AED for valproate was 498 mg/day and carbamazepine was 555 mg/day. The malformation rate in the index pregnancy was 8.5% (21/246) and in the follow‐up pregnancy was 8.9% (22/246) with only one recurrence. There was no increased risk of MCM in follow‐up pregnancy for those who had MCM in the index pregnancy (p = 0.70; OR 0.49; 95% CI 0.06–3.80). The use of any specific drug, continuation of the same drug or a change in drug therapy between two pregnancies did not alter the recurrence risk.     

Profile of Antiepileptic Pharmacotherapy in a Tertiary Referral Center in South India: A Pharmacoepidemiologic and Pharmacoeconomic Study

Summary: Purpose: To study the current pharmacotherapy practices of epilepsy and its economics in a developing country by correlating the epidemiology and economics of antiepileptic drug (AED) treatment in general epilepsy care and comprehensive epilepsy care.
Methods: We compared the AED-use profiles, efficacy, and tolerability at entry and at last follow-up for 972 patients seen at a comprehensive epilepsy care program in South India from 1993 to 1995. The relative cost was expressed as the average percentage of the per capita gross national product (GNP/capita) each individual spent for AED treatment.
Results: At entry, 562 (57.8%) subjects were receiving poly-therapy; at last follow-up, 743 (76.4%) patients were receiving monotherapy, an increase of 34.3% in the use of monotherapy. One or more adverse drug reactions were reported by 28.6% of patients at entry and by 19.8% at last follow-up. The proportion of patients who were seizure free increased from 29.0 to 44.8%. Carbamazepine (CBZ) was the most frequently used AED, followed by diphenylhydantoin (DPH), valproate (VPA), and phenobarbitone (PB). The relative cost (% GNP/capita) for standard AEDs were as follows: PB, 4.4%; DPH, 7.1%; CBZ, 16.8%; and VPA, 29.5%. The average annual cost of AED treatment per patient in U.S. dollars was $64.32 at entry and $47.73 at last follow-up. Reduction in polytherapy resulted in the net annual saving of $16,128 ($16.59 per patient, or 5.4% GNP/capita).
Conclusions: The more frequent use of relatively expensive drugs like CBZ and VPA and the use of polytherapy—still quite prevalent in developing countries—has escalated the cost of AED therapy. Although in recent years AEDs have become more available in developing regions, primary and secondary care physicians have not been adequately educated about the current trends in the pharmacotherapy of epilepsy.     

Utility of susceptibility-weighted MRI in differentiating Parkinson’s disease and atypical parkinsonism

Introduction  

Neuropathological studies report varying patterns of brain mineralization in Parkinson’s diseases (PD), progressive supranuclear palsy (PSP), and Parkinson variant of multiple system atrophy (MSA-P). Susceptibility-weighted imaging (SWI) is the ideal magnetic resonance imaging (MRI) technique to detect mineralization of the brain. The purpose of this study was to test if SWI can differentiate PD, PSP, and MSA-P.     

Interictal regional paroxysmal fast activity on scalp EEG is common in patients with underlying gliosis

Objective

Interictal regional paroxysmal fast activity (RPFA) on scalp EEG is common in patients with focal cortical dysplasia (FCD). Little data exists regarding the presence of RPFA in other etiologies.

Instrumental activities of daily living scale for dementia screening in elderly people

OBJECTIVE: To develop and validate an Instrumental Activities of Daily Living Scale for elderly people (IADL-E) to use in conjunction with cognitive screening tests for dementia in an educationally and socioculturally heterogeneous population. METHOD: Eleven IADL items were selected and weighted for major factors causing heterogeneity in the population--gender, education, social (rural/urban) setting and age. Each item was rated for its applicability (yes/no), degree of disability (scored from 0 to 2) and causative impairment (cognitive and/or physical). From this a composite index of cognitive (CDI) or physical (PDI) disability was derived. Validation was performed retrospectively on 240 subjects: 135 without and 105 with dementia by DSM-IV. RESULTS: The IADL-E had a high internal consistency (alpha = 0.95). The area under the receiver operating characteristic (ROC) curve was 0.97 (CI = 0.94-0.99). A cutoff score of 16 on CDI provided a sensitivity of 0.91, specificity 0.99 and positive predictive value 0.76 (at 5% base rate). IADL-E correlated highly with clinical (DSM-IV, kappa = 0.89), functional (CDR, 0.82) and cognitive (Mini-mental Status Examination, MMSE, 0.74) diagnoses. It showed good responsiveness, with the change on CDI over a median of 23 months correlating significantly with that on MMSE (coefficient = -0.382, CI = -0.667 to -0.098; p=0.009). Individual items had good interrater and test-retest reliability. CONCLUSIONS: The IADL-E is a reliable, sensitive and responsive scale of functional abilities useful in dementia screening in a socioculturally heterogeneous population.     

Emotional facial paresis in temporal lobe epilepsy: its prevalence and lateralizing value.

The selection of patients with medically refractory temporal lobe epilepsy (TLE) for surgery depends on the concordance of data from clinical, imaging and electroencephalographic evaluation. Though clinical examination is often normal, emotional facial paresis has been described in patients with TLE. Utilizing a well-characterized group of mesial TLE (MTLE) patients, who have achieved excellent seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL), we investigated the prevalence, predictive value and associations of emotional facial paresis. When compared to 8 out of 50 control subjects (16%), 36 out of 50 MTLE patients (72%) exhibited unilateral emotional facial paresis; the difference was highly significant (P<0.0001). The presence of contralateral emotional facial paresis correctly predicted the side of ATL in 86.1% patients. The occurrence of emotional facial paresis was significantly associated with longer duration of epilepsy prior to ATL and left ATL. Our observations confirm that emotional facial parersis contralateral to the side of mesial temporal sclerosis (MTS) is a valuable localizing sign in correctly predicting the epileptogenic temporal lobe. We hypothesize that the presence of an intact right hemisphere and pathological changes more extensive than MTS may be required for emotional facial paresis to readily manifest.     

Community-based group intervention for tobacco cessation in rural Tamil Nadu, India: a cluster randomized trial

The objective of this study was to determine the efficacy of community-based group intervention for tobacco cessation. We recruited 400 men (20-40 years) currently using any form of tobacco from 20 villages of the Indian State of Tamil Nadu and randomized them equally into intervention and control groups. A physician offered two sessions of health education 5 weeks apart along with self-help material on tobacco cessation to the intervention group. The control group received only self-help material. The contents of the sessions included tobacco-related health problems, benefits of quitting, and coping strategies for withdrawal symptoms. Follow-up data were available for 92%. Self-reported point prevalence abstinence of 12.5% in the intervention group was significantly higher than the 6.0% in the control group at 2 months. Community-based group intervention has the potential to increase the coverage of tobacco cessation services for men in rural Tamil Nadu.