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A critical review of the therapeutic potential of dibenzyl trisulphide isolated from Petiveria alliacea L (guinea hen weed, anamu)

The data compiled in the present review on dibenzyl trisulphide (DTS) isolated from Petiveria alliacea L (the guinea hen weed or anamu) revealed that the compound and its derivatives could be of tremendous pharmaceutical interest. The mode of action elucidated for DTS revealed that it is a mitogen activated protein extracellular regulated kinases 1 and 2 (MAPKinases erk1 and erk 2) signal transduction molecule. Dibenzyl trisulphide caused hyper-phosphorylation of growth factor induced MAPKinases (erk 1 and erk 2) phosphorylation, a process critical for the improvement of long term memory, and is implicated in neuronal growth. Dibenzyl trisulphide and its derivatives exhibited potent anti-proliferation/cytotoxic activity on a wide range of cancer cell lines. The cytotoxic activity of DTS was increased by 70-1000 fold when bound to albumin in vitro. Dibenzyl trisulphide seems to have a cytokine switching mechanism in which it down regulates cytokines from the Type I helper cells (Th -1 cell) pathway which contained several pro-inflammatory cytokines and up-regulates those on the Type 2 helper cells (Th-2) pathway. The trisulphide up-regulates some reticuloendothelial system parameters eg granulocyte counts and increased thymic and Peyers patches masses via cell proliferation processes which are known to be regulated via the MAPKinase signal transduction pathway. When the zygotes ofAsternia pectinifera (Starfish) were exposed to DTS at concentration of 10 mM, a dose lethal to all cancer cells tested, it was observed that the sensitive process of protein biosynthesis was not affected Similarly, the proliferation of the HOFA human fibroblast, a noncancerous cell line, was not severely affected by DTS at 8.9 microM over seven days, a concentration also lethal to most cancer cell lines tested The implications of the findings will be highlighted in the present review.

HTLV‐1 associated polymyositis in Jamaica

The clinical, laboratory and epidemiological characteristics of 38 adult Jamaican patients with polymyositis were evaluated. Twenty‐four patients (63%) were human T‐lymphotropic virus 1 (HTLV‐1) seropositive and 14 patients (37%) were HTLV‐1 seronegative. Polymyositis runs a more protracted course in seropositive patients who had more frequent hospital admissions and a significantly longer duration of symptoms prior to presentation. Joint swelling, chest pain and dyspnoea were more frequent complaints among the seronegative patients. There was no significant difference between the two serological groups in muscle enzyme levels, antinuclear antibody positivity or frequency of Jo‐1 antibodies. HTLV‐1 infection may define a subgroup of polymyositis patients with a more insidious presentation and poorer response to corticosteroid therapy.

IgA antiphospholipid antibodies in HTLV-1-associated tropical spastic paraparesis.

A retrovirus, human T cell lymphotropic virus type 1 (HTLV-1), is an essential but not a sufficient aetiologic factor for tropical spastic paraparesis (TSP). Because some TSP patients have biological false positive tests for treponemal infections (BFP-STS), we used ELISA to study BFP-STS and anticardiolipin antibodies in 42 Jamaican TSP patients. The data indicate that in TSP anticardiolipin antibodies occur in about 26% of patients, are associated with biological false positive treponemal serology, are relatively restricted to the IgA isotype and may be induced by HTLV-1 or other non- treponemal infections.

ANTIBODIES TO CARDIOLIPIN AND BETA 2-GLYCOPROTEIN-1 IN HTLV-1-ASSOCIATED MYELOPATHY TROPICAL SPASTIC PARAPARESIS

Anticardiolipin and anti-β2GP1 antibodies were measured in 50 patients with HTLV-1-associated Myelopathy-Tropical Spastic Paraparesis (HAM-TSP) and the results were compared with those obtained for 34 HTLV-1-positive and 35 HTLV-1-negative controls, as well as 128 SLE patients. aCL but not anti-β2GP1 was associated with HTLV-1 infection. aCL was more prevalent than anti-β2GP1 (32% vs 8%) and was not associated with anti-β2GP1 in HAM-TSP. IgA was the dominant isotype of aCL and anti-β2GP1. The data suggest that tin HAM-TSP, IgA aCL are frequent and are associated with HTLV-1 infection.

Angiotensin converting enzyme inhibiting and anti‐dipsogenic activities of Euphorbia hirta extracts

The methanol extract obtained from the leaves and stems of Euphorbia hirta inhibited the activity of angiotensin converting enzyme (ACE) by 90% and 50% at 500 μg and 160 μg respectively using enzyme linked immunosorbent assay (ELISA). The effect of the extract on thirst was examined using Wistar rats. Intraperitoneal administration of 10 mg/100 mg body wt of the extract significantly (p <0.05) decreased the amount of water consumed by rats. This effect lasted for 2 h.

The mean levels of adherence and factors contributing to non-adherence in patients on highly active antiretroviral therapy

OBJECTIVE To determine the mean level of adherence and factors contributing to non-adherence in patients on Highly Active Antiretroviral Therapy (HAART). METHODS An observational study was done on 101 HIV/AIDS patients attending the Centre for HIV/ AIDS Research, Education and Services (CHARES) - University Hospital of the West Indies, between May 2006 and August 2006. A questionnaire was administered asking questions re: prescribed and actual dosing frequency and number of antiretroviral tablets for the previous week, reasons for nonadherence, duration of Highly Active Antiretroviral Therapy, age, employment status and level of education. Mean levels of adherence were calculated using self and social worker/nurse reported dosing frequency and number of tablets. Good adherence was defined as 95% or greater. Multiple regression analysis was used to determine factors impacting on adherence. RESULTS Ninety-six patients were included for final analysis. Mean levels of adherence were as follows: 87.66%--self-report for tablets; 88.70%--self-report for dosing frequency; 87.02%--social worker/ nurse report for tablets; 88.10%--social worker/nurse report for dosing frequency. There were significant positive correlations between self and social worker/nurse reports using dosing frequency (Spearman Rho correlation coefficient 0.943, p = 0.01) or number of tablets (Spearman Rho correlation coefficient 0.955, p = 0.01). Adherence to self-reported number of tablets and dosing frequency were 58.4% and 56.4% respectively. Duration of HAART was found to have a significant negative correlation with the level of self-reported adherence to tablets (p = 0.002). CONCLUSION Adherence to HAART is sub-optimum in patients at the CHARES. This must be urgently addressed to prevent the development of resistant HIV strains and treatment failure.

Human immunodeficiency virus type-1 (HIV-1) subtypes in Jamaica

The subtypes of 141 isolates of human immunodeficiency virus type-1 (HIV-1) from Jamaica were determined by a combination of env and gag heteroduplex mobility analysis (HMA) genotyping. The majority of HIV-1 isolates were subtype B (131/141, 93.0%); one (0.8%) isolate each of subtypes C, D and E was found and 7 (4.9%) were indeterminate. These results and the failure of the sets of primers used to amplify some of the HIV-1 isolates provide strong evidence of genetic diversity of the HIV/AIDS epidemic in Jamaica. Surveillance of the circulating HIV-1 genetic subtypes is a pre-requisite for developing regional vaccine strategies and understanding the transmission patterns of the virus. This is the first study of its kind in Jamaica and the findings complement data from other Caribbean countries. This work supports the view of colleagues from the French and Spanish-speaking Caribbean that an epidemiological network supported by regional laboratories will help track this epidemic accurately with positive outcomes for the public.

Human T-cell lymphotropic virus-1-associated renal disease in Jamaican children.

Abstract This report documents the clinicopathological features in two Jamaican children who presented with infective dermatitis, glomerulonephritis, renal failure and human T-cell lymphotropic virus (HTLV-1) seropositivity. Severe hypertension with hypertensive encephalopathy was the most impressive clinical feature. Histological findings from renal biopsy specimens in both cases revealed significant glomerulosclerosis with fibrosis, chronic inflammatory cell infiltrates in the interstitium, and arteriolar hypertensive changes. Membranoproliferative glomerulonephritis (MPGN) was demonstrable in case 1 and marked focal glomerulosclerosis in case 2. Case 1 developed end stage renal failure and died within 3 years of diagnosis. Case 2 remains hypertensive and in chronic renal failure. Although a causal relationship between HTLV-1 infection and renal disease cannot be proven by these two cases, it appears that renal involvement in children with HTLV-1 infection is severe, with the potential for chronic renal failure and malignant hypertension. HTLV-1 nephropathy should be suspected in children with infective dermatitis and renal disease.

Seroprevalence of HTLV-1 in chronic disease patients in Jamaica

A high seropositivity rate of human T cell lymphotropic virus type 1 (HTLV-1) infection was found in Jamaican patients with chronic diseases. However, except for tropical spastic paraparesis, polymyositis, adult T cell leukaemia/lymphoma and polyneuropathies of undetermined cause, HTLV-1 seropositivity rates in chronic disease patients were not significantly different from that found in healthy Jamaicans. These results indicate that there is no increased risk of HTLV-1 infection or HTLV-1 associated disease in patients with chronic diseases compared to the general Jamaican population. The association of unclassified polyneuropathies with HTLV-1 reported herein is a novel one which requires further studies to elucidate its nature.

Cardiac Disease in Dialysis Patients in a Jamaican Hospital Echocardiographic Findings that Predict Mortality

The aim of the study was to assess, by echocardiography, the cardiac abnormalities in a group of patients with chronic renal failure and to determine the cardiovascular predictors of mortality. The study comprised forty-five patients from the Renal Unit, University Hospital of the West Indies, Kingston, Jamaica, and was undertaken between October 1, 1998 and July 31, 2000. All echocardiography was done by a single operator. The parameters assessed were systolic dysfunction, diastolic dysfunction, ejection fraction, regional wall motion abnormalities and valvular disease. Left ventricular cavity size, septal and posterior wall thickness were measured and left ventricular mass calculated. Demographic data were obtained directly from each patient by interview. The patients were mainly of African/mixed-African origin. Their mean age was 43.2 +/- 16.0 years. The average body mass index was 23.7 +/- 6.9. Twenty-eight (60.9%) patients were male and seventeen (39.1%) female. Hypertension, chronic glomerulonephritis and diabetes mellitus were the leading causes of chronic renal failure. Blood pressure was controlled at a mean value of 145/90 mm Hg pre-dialysis and 140/90 mm Hg postdialysis. The mean duration of renal failure was 2.8 years. Echocardiographic M-mode and two dimensional apical, four chamber view measurements indicated that mean left ventricular internal diameter (LVID) diastole was 55.7 +/- 7.9 mm (normal 38-56 mm) and LVID systole was 38.9 +/- 9.8 mm (normal 24-45 mm); the mean thickness of the chamber walls was 10.3 +/- 2.8 mm and 10.6 +/- 2.4 mm for the interventricular septum (normal 6-11 mm) and left ventricular posterior wall (normal 6-11 mm) respectively. Diastolic dysfunction was seen in 15 (34%) patients and systolic dysfunction in 12 (23%) patients who had ejection fractions less than 50%. The mean left ventricular ejection fraction was 56.3% +/- 16% (normal 65-85%), mean stroke volume was 82.9 +/- 27.2 mls (normal 51-96 ml). After 21 months enrolment in the study, Kaplan Meier analysis revealed a two-year mortality of 28.3%. Cox regression analysis indicated that a history of smoking current or past, low haemoglobin level, high aorta flow velocities, severity of mitral regurgitation and a negative association with serum creatinine were independent predictors of mortality. The correction of anaemia and control of other factors that impact negatively on cardiac function in dialysis patients is vital to enhance survival.