Comparative incidence of adverse drug reaction during the first and subsequent year of antiretroviral therapy in a Nigerian HIV infected Cohort.

BACKGROUND: Despite close to two decades of antiretroviral therapy (ART) in Nigeria, data on late on-onset ART-associated adverse drug reactions (ADRs) are sparse. OBJECTIVES: To describe early and late-onset ADRs and compare their incidence in an outpatient HIV positive Cohort on ART. METHOD: We described the incidence of clinical ADRs identified and documented in an outpatient clinic cohort of HIV-positive patients treated between June 2004 and December 2015 at a tertiary health facility in Nigeria. Incidence rates of ADRs during the first and subsequent years of ART were compared. RESULTS: of the 13,983 patients' data analyzed, 9317 were females (66%), and those in the age bracket of 25 to 45 years made up 78% of the studied population. During 52,411 person-years (py) of ART, 1485 incident ADRs were recorded; Incidence rate (IR) 28.3 (95% confidence interval [CI] 26.9:29.8) ADRs per 1000 person-years (py) of ART. The IR of ADRs was about two times higher in the first year of ART compared to subsequent years of treatment; crude incidence rate ratio (IRR) 1.77 (95% CI 1.59:1.97). Anemia, hypersensitivity reactions, and nervous system disorders had 7, 23, and 5 times higher incidence, respectively, in the first year of therapy, compared to subsequent years. CONCLUSION: The first year of ART is the period of highest risk of ADRs. Individual and programmatic treatment success in resource-limited settings requires strategies for early identification and management of ADR during the period of greatest risk of ADRs.

Traditional medicine policy and regulation in Nigeria: an index of herbal medicine safety.

BACKGROUND: The requirements and methods for research and evaluation of the safety and efficacy of herbal medicines are more complex than those for conventional pharmaceuticals. In addition to the aforementioned and contrary to the general belief that herbal medicines are safe and despite the profound therapeutic advantages possessed by medicinal plants, some of their constituents have been shown to be potentially toxic, carcinogenic, mutagenic, and teratogenic. Thus, traditional medicine policy and regulation have been made an integral part of the WHO proposed critical determinants of herbal medicine safety. OBJECTIVE: Therefore, this study is designed to assess the policy and regulation guiding herbal medicine in Nigeria as this information may form a safety index of herbal medicine use in Nigeria. METHODOLOGY: Structured questionnaire adopted from WHO was used to obtain the opinions of relevant stakeholders in the field of herbal medicine on the policy and regulation of herbal medicine in Nigeria. RESULTS: The results show that 68.8% of respondents agreed that there is a national policy on TM with 31.2% disagreeing on this issue. 75% of respondents agreed that implementation of the manufacturing requirements of herbal medicines is ensured by control mechanisms while 25% disagreed. Only 25% said herbal medicines are sold by licensed practitioners, with 75% believing that herbal medicines are sold by non-licensed practitioners. 87.5% said support from the WHO is needed and should be in the form of workshops on national capacity building on safety monitoring of herbal medicines. CONCLUSION: There is need for the Federal Ministry of Health to harmonize the varying opinions on traditional medicine and policy as documented in this study through collaboration and workshops on traditional medicine. These proposed approaches may guarantee the safety and regulation of herbal medicine use in Nigeria.

Effects of Mucuna pruriens protease inhibitors on Echis carinatus venom.

The medicinal plant Mucuna pruriens, with reputed anti-snake venom properties has been reported to contain a kunitz-type trypsin inhibitor. This study was undertaken to further evaluate the protease inhibitory potential of gpMuc, a multiform glycoprotein, and other protein fractions from M. pruriens seeds against trypsin, chymotrypsin, Echis carinatus snake venom, ecarin and thrombin. The results showed that gpMuc inhibited both trypsin and chymotrypsin activities and was thermally stable, maintaining its trypsin inhibitory activity at temperatures of up to 50°C. Its structural conformation was also maintained at pH ranges of 4-7. Immunoreactivity study confirms that it contains protease-recognizing epitope on one of its isoforms. The whole protein extract of M. pruriens seeds inhibited prothrombin activation by ecarin and whole E. carinatus venom, and also thrombin-like activity using chromogenic assay.

Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom.

Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value.

The protective effect of Mucuna pruriens seeds against snake venom poisoning.

ETHNOPHARMACOLOGICAL RELEVANCE: The seed, leaf and root of Mucuna pruriens have been used in traditional medicine for treatments of various diseases. In Nigeria, the seed is used as oral prophylactics for snakebite. AIM OF THE STUDY: To study the protective effects of Mucuna pruriens seed extract against the lethalities of various snake venoms. MATERIALS AND METHODS: Rats were pre-treated with Mucuna pruriens seed extract and challenged with various snake venoms. The effectiveness of anti-Mucuna pruriens (anti-MPE) antibody to neutralize the lethalities of snake venoms was investigated by in vitro neutralization. RESULTS: In rats, MPE pre-treatment conferred effective protection against lethality of Naja sputatrix venom and moderate protection against Calloselasma rhodostoma venom. Indirect ELISA and immunoblotting studies showed that there were extensive cross-reactions between anti-MPE IgG and venoms from many different genera of poisonous snakes, suggesting the involvement of immunological neutralization in the protective effect of MPE pre-treatment against snake venom poisoning. In vitro neutralization experiments showed that the anti-MPE antibodies effectively neutralized the lethalities of Asiatic cobra (Naja) venoms, but were not very effective against other venoms tested. CONCLUSIONS: The anti-MPE antibodies could be used in the antiserum therapy of Asiatic cobra (Naja) bites.

Proteomic analysis of the pathophysiological process involved in the antisnake venom effect of Mucuna pruriens extract.

Previously, we reported the antisnake venom properties of a Mucuna pruriens seed extract (MPE) and tested its in vivo efficacy against Echis carinatus venom (EV) in short- (1 injection) and long-term (three weekly injections) treatments. The aim of the present study was to investigate plasma proteome changes associated with MPE treatments and identify proteins responsible for survival of envenomated mice (CHALLENGED mice). Six treatment groups were studied. Three control groups: one saline, one short-term and one long-term MPE treatment. One group received EV alone. Two test groups received EV with either a short-term or long-term MPE treatment (CHALLENGED mice). The plasma from each group was analysed by 2-DE/MALDI-TOF MS. The most significant changes with treatment were: albumin, haptoglobin, fibrinogen, serum amyloid A and serum amyloid P. Most of these changes were explained by EV effects on coagulation, inflammation and haemolysis. However, MPE treatments prevented the EV-induced elevation in HPT. Consequently, HPT levels were similar to controls in the plasma of CHALLENGED mice. The plasma of CHALLENGED mice showed substantial proteomic modifications. This suggests the mechanism of MPE protection involves the activation of counterbalancing processes to compensate for the imbalances caused by EV.

Protection of Mucuna pruriens seeds against Echis carinatus venom is exerted through a multiform glycoprotein whose oligosaccharide chains are functional in this role.

In a previous paper we demonstrated that extracts of Mucuna pruriens seeds (MPE) protect mice against Echis carinatus venom (EV) by an immunological mechanism. In this paper we demonstrate that the MPE immunogen generating the antibody that cross-reacts with the venom proteins is a multiform glycoprotein (gpMuc) whose immunogenic properties mainly reside in its glycan-chains. The glycoprotein was purified from the protein extract of M. pruriens seeds using Concanavalin A affinity chromatography. Using 2-D gel electrophoresis it separated into seven isoforms having MWs in the range from 20.3 to 28.7 kDa and pIs from 4.8 to 6.5. N-terminal sequencing of these spots revealed close similarity since all of them contained the consensus sequence DDREPV-DT found in soybean Kunitz-type trypsin inhibitor. We suggest that gpMuc contains both N- and O-glycans. Mild alkaline treatment but not PNGase F led to loss of reactivity, indicating that O-glycans are probably involved in the antigenicity of gpMuc.

Proteins from Mucuna pruriens and enzymes from Echis carinatus venom: characterization and cross-reactions.

Mucuna pruriens seeds have been widely used against snakebite in traditional medicine. The antivenin property of a water extract of seeds was assessed in vivo in mice. The serum of mice treated with extract was tested for its immunological properties. Two proteins of Echis carinatus venom with apparent molecular masses of 25 and 16 kDa were detected by Western blot analysis carried out using IgG of mice immunized with extract or its partially purified protein fractions. By enzymatic in-gel digestion and electrospray ionization-mass spectrometry/mass spectrometry analysis of immunoreactive venom proteins, phospholipase A(2,) the most toxic enzyme of snake venom, was identified. These results demonstrate that the observed antivenin activity has an immune mechanism. Antibodies of mice treated with non-lethal doses of venom reacted against some proteins of M. pruriens extract. Proteins of E. carinatus venom and M. pruriens extract have at least one epitope in common as confirmed by immunodiffusion assay.