Sani Ibrahim

In vitro trypanocidal effect of methanolic extract of some Nigerian savannah plants

Methanol extracts from twenty three plants harvested from the Savannah vegetation belt of Nigeria were analyzed in vitro for trypanocidal activity against Trypanosoma brucei brucei and Trypanosoma congolense at concentrations of 4 mg/ml, 0.4 mg/ml and 0.04 mg/ml. Extracts of Khaya senegalensis, Piliostigma reticulatum, Securidaca longepedunculata and Terminalia avicennoides were strongly trypanocidal to both organisms while extracts of Anchomanes difformis, Cassytha spp, Lannea kerstingii, Parkia clappertioniana, Striga spp, Adansonia digitata and Prosopis africana were trypanocidal to either T. brucei brucei or T. congolense. These findings provide evidence of the effects of some plants in the traditional management of trypanosomiasis.

Identification and Characterization of an Immunogenic Hybrid Epitope Formed by both HIV gp120 and Human CD4 Proteins

ABSTRACT Certain antibodies from HIV-infected humans bind conserved transition state (CD4 induced [CD4i]) domains on the HIV envelope glycoprotein, gp120, and demonstrate extreme dependence on the formation of a gp120-human CD4 receptor complex. The epitopes recognized by these antibodies remain undefined although recent crystallographic studies of the anti-CD4i monoclonal antibody (MAb) 21c suggest that contacts with CD4 as well as gp120 might occur. Here, we explore the possibility of hybrid epitopes that demand the collaboration of both gp120 and CD4 residues to enable antibody reactivity. Analyses with a panel of human anti-CD4i MAbs and gp120-CD4 antigens with specific mutations in predicted binding domains revealed one putative hybrid epitope, defined by the human anti-CD4i MAb 19e. In virological and immunological tests, MAb 19e did not bind native or constrained gp120 except in the presence of CD4. This contrasted with other anti-CD4i MAbs, including MAb 21c, which bound unliganded, full-length gp120 held in a constrained conformation. Conversely, MAb 19e exhibited no specific reactivity with free human CD4. Computational modeling of MAb 19e interactions with gp120-CD4 complexes suggested a distinct binding profile involving antibody heavy chain interactions with CD4 and light chain interactions with gp120. In accordance, targeted mutations in CD4 based on this model specifically reduced MAb 19e interactions with stable gp120-CD4 complexes that retained reactivity with other anti-CD4i MAbs. These data represent a rare instance of an antibody response that is specific to a pathogen-host cell protein interaction and underscore the diversity of immunogenic CD4i epitope structures that exist during natural infection.

Genetic Characteristics, Coreceptor Usage Potential and Evolution of Nigerian HIV-1 Subtype G and CRF02_AG Isolates

HIV-1 CRF02_AG and subtype G (HIV-1G) account for most HIV infections in Nigeria, but their evolutionary trends have not been well documented. To better elucidate the dynamics of the epidemic in Nigeria we characterised the gag and env genes of North-Central Nigerian HIV-1 isolates from pregnant women. Of 28 samples sequenced in both genes, the predominant clades were CRF02_AG (39%) and HIV-1G (32%). Higher predicted proportion of CXCR4-tropic (X4) HIV-1G isolates was noted compared to CRF02_AG (p = 0.007, Fishers exact test). Phylogenetic and Bayesian analysis conducted on our sequences and all the dated available Nigerian sequences on the Los Alamos data base showed that CRF02_AG and HIV-1G entered into Nigeria through multiple entries, with presence of HIV-1G dating back to early 1980s. This study underlines the genetic complexity of the HIV-1 epidemic in Nigeria, possible subtype-specific differences in co-receptor usage, and the evolutionary trends of the predominant HIV-1 strains in Nigeria, which may have implications for the design of biomedical interventions and better understanding of the epidemic.

Ameliorative Effects of Acacia Honey against Sodium Arsenite-Induced Oxidative Stress in Some Viscera of Male Wistar Albino Rats

Cancer is a leading cause of death worldwide and its development is frequently associated with oxidative stress-induced by carcinogens such as arsenicals. Most foods are basically health-promoting or disease-preventing and a typical example of such type is honey. This study was undertaken to investigate the ameliorative effects of Acacia honey on sodium arsenite-induced oxidative stress in the heart, lung and kidney tissues of male Wistar rats. Male Wistar albino rats divided into four groups of five rats each were administered distilled water, Acacia honey (20%), sodium arsenite (5 mg/kg body weight), Acacia honey, and sodium arsenite daily for one week. They were sacrificed anesthetically using 60 mg/kg sodium pentothal. The tissues were used for the assessment of glutathione peroxidase, catalase, and superoxide dismutase activities, protein content and lipid peroxidation. Sodium arsenite significantly (P < 0.05) suppressed the glutathione peroxidase, catalase, superoxide dismutase activities with simultaneous induction of lipid peroxidation. Administration of Acacia honey significantly increased (P < 0.05) glutathione peroxidase, catalase, and superoxide dismutase activities with concomitant suppression of lipid peroxidation as evident by the decrease in malondialdehyde level. From the results obtained, Acacia honey mitigates sodium arsenite induced-oxidative stress in male Wistar albino rats, which suggest that it may attenuate oxidative stress implicated in chemical carcinogenesis.

A Preliminary Study of the Mechanism of Hypoglycaemic Activity of Nauclea latifolia Leaf Ethanolic Extract

Abstract The aim of this study was to determine the possible underlying mechanism of the hypoglycaemic activity of the ethanolic extract of Nauclea latifolia leaves in rats. The extract, glibenclamide or water was administered orally in a glucose, sucrose and maltose tolerance tests. In addition, the effect of the extract on α-glucosidase enzymes was also studied. The ethanolic extract at 200mg/kg body weight inhibited the increase in glucose level after both oral and intraperitoneal glucose loads as did glibenclamide. The extract also dose dependently inhibited both maltase and sucrase activities in vitro but not in vivo. The hypoglycaemic effect of N. latifolia leaf ethanolic extract thus appears to be most probably exerted through a mechanism similar to that of glibenclamide which is related to increased insulin release from pancreatic β-cells.

Stabilization of Aspergillus parasiticus cytosine deaminase by immobilization on calcium alginate beads improved enzyme operational stability

Cytosine deaminase (CD) from Aspergillus parasiticus, which has half-life of 1.10 h at 37°C, was stabilized by immobilization on calcium alginate beads. The immobilized CD had pH and temperature optimum of 5 and 50°C respectively. The immobilized enzyme also stoichiometrically deaminated Cytosine and 5-fluorocytosine (5-FC) with the apparent KM values of 0.60 mM and 0.65 mM respectively, displaying activation energy of 10.72 KJ/mol. The immobilization of native CD on calcium alginate beads gave the highest yield of apparent enzymatic activity of 51.60% of the original activity and the enzymatic activity was lost exponentially at 37°C over 12 h with a half-life of 5.80 h. Hence, the operational stability of native CD can be improved by immobilization on calcium alginate beads.

Community-based intervention is necessary for the control of HIV in North-Central Nigeria

OBJECTIVES To determine factors associated with the observed high prevalence of HIV in North-Central Nigeria. METHODS In a cross-sectional multisite study conducted in 2007, behavioral, medical, and demographic data were obtained from pregnant women (N = 1011) who were tested for the presence of antibody against HIV-1 and HIV-2. RESULTS The overall prevalence of HIV-1 in the 1011 women included in the study was 10.3% (95% confidence interval (CI) 8.4-12.2). In the multivariate analysis, HIV-1 seropositivity was significantly associated with women from the Makurdi (odds ratio (OR) 31.3, 95% CI 3.8-255.7) and Minna (OR 15.4, 95% CI 1.7-135.1) sites in comparison with Panyam site. The presence of tuberculosis (OR 10.7, 95% CI 2.4-48.3) was also significantly associated with HIV-1 seropositive status. Factors associated with HIV-1 also differed between sites. The presence of antibody against HIV-2 was not observed. CONCLUSIONS The high HIV-1 prevalence observed in this study corroborates previous observations in North-Central Nigeria. Disparity in the prevalence across communities was also seen. This is the only detailed socio-epidemiological and behavioral study that has explored potential factors associated with HIV-1 in North-Central Nigeria, and it revealed that differences in risk factors explain the disparity in prevalence across communities.

Socio-economic status of patients with type 2 diabetes and hypertension attending the Ahmadu Bello University Teaching Hospital, Zaria, North-West Nigeria.

Hypertension (HTN) and Type 2 diabetes (T2D) are lifestyle interrelated diseases of global significance. Interestingly, the prevalence of these diseases in Africa and indeed Nigeria seems to be on the increase. This study, therefore, investigated the socioeconomic status (based on income, education and occupational activity) of 400 subjects (52% female and 48% male) aged 20 years and above who were sampled randomly among the newly diagnosed HTN and/or T2D cases at the Ahmadu Bello University Teaching Hospital, Zaria, North-West Nigeria. A semi-structured questionnaire was used to collect information from the subjects. From the result obtained, most of the respondents who live in towns or city suffer from either HTN or T2D while more town dwellers (28%) suffer from a combination of both diseases. It was also discovered that most respondents who suffer from HTN and from a combination of HTN and T2D belong to the old generation (60-79 years). There is higher prevalence rate of diabetes among the respondents who had no formal education or attended only basic Arabic schools. Most respondents who earn good income (₦50,000-₦100,000 and above ₦100,000) suffer HTN, T2D and a combination of both diseases. Those engaged in heavy occupational activities had the lowest prevalence of the disease compared with those of light or moderate occupational activities. These data will be found useful in planning intervention healthcare preventive programs especially on public enlightenment workshops and seminars to educate the populace on the importance of lifestyle modification, healthy diet and regular exercises.

An analysis of dietary fiber and fecal fiber components including pH in rural Africans with colorectal cancer

Background/Aims Colorectal cancer (CRC) is now a major public health problem with heavy morbidity and mortality in rural Africans despite the lingering dietary fiber-rich foodstuffs consumption. Studies have shown that increased intake of dietary fiber which contribute to low fecal pH and also influences the activity of intestinal microbiota, is associated with a lowered risk for CRC. However, whether or not the apparent high dietary fiber consumption by Africans do not longer protects against CRC risk is unknown. This study evaluated dietary fiber intake, fecal fiber components and pH levels in CRC patients. Methods Thirty-five subjects (CRC=21, control=14), mean age 45 years were recruited for the study. A truncated food frequency questionnaire and modified Goering and Van Soest procedures were used. Results We found that all subjects consumed variety of dietary fiber-rich foodstuffs. There is slight preponderance in consumption of dietary fiber by the control group than the CRC patients. We also found a significant difference in the mean fecal neutral detergent fiber, acid detergent fiber, hemicellulose, cellulose and lignin contents from the CRC patients compared to the controls (P<0.05). The CRC patients had significantly more fecal pH level than the matched apparently healthy controls (P=0.017). Conclusions The identified differences in the fecal fiber components and stool pH levels between the 2 groups may relate to CRC incidence and mortality in rural Africans. There is crucial need for more hypothesis-driven research with adequate funding on the cumulative preventive role of dietary fiber-rich foodstuffs against colorectal cancer in rural Africans “today.”

Abstract B27: Assessment of chemotherapeutic responses to neoadjuvant FOLFOX and Aspirin on BIRC7 in colorectal adenocarcinoma cells induced in Albino rats

Chemotherapeutic resistance is a problem in the management of malignant tumors especially colorectal adenocarcinoma. Overexpression of Baculoviral IAP repeat-containing protein-7 (BIRC7) was previously reported by this study group to limit the cytotoxic efficacy of neoadjuvant folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy regimen on human colorectal cancer cells in-vivo. And a significant inhibitory effect of Aspirin on the BIRC7 protein in p53 mutant SW480 colon cancer cells in-vitro was also found. Our aim now is to access the efficacy of the addition of Aspirin to neoadjuvant FOLFOX-chemotherapy on colorectal cancer cells in-vivo using the N-methyl-N-nitrosourea (NMU) carcinogen-induced model on albino rats per rectum. A total of 180 male Albino rats whose weight falls between 110-150g will be used. They will be grouped into 18 sets of 10 rats each and a three staged study will be performed. Namely, assessment of health parameters before the cancer induction, assessments on confirmation of cancer induction and assessments after chemotherapeutic intervention. The chemotherapeutic intervention will be further subdivided into mono, bi or tri therapy in various combinations with and without the addition of the Aspirin. The addition of Aspirin to the chemotherapy regimen will be further divided into concurrent and sequential addition. NMU will be administered at a dose of 2 mg/kg intra rectally every other day until the development of colorectal cancer which, will be confirmed by barium enema and histological analysis. Aspirin will be administered at a dose of 25 mg/kg or 12.5 mg/kg. Folinic acid will be administered at a dose of 7 mg/kg or 3.5 mg/kg intraperitoneally (i.p). Oxaliplatin will be dministered at a dose of 3 mg/kg or 1.5 mg/kg i.p. And 5-FU will be administered at a dose of 50 mg/kg or 25 mg/kg i.p. The animals9 hemogram and other pertinent investigations will be done ultimately including culling for histological assessment of tumors. The tumors will be processed for HE May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B27.