Department of Pharmacy & Complementary/Alternative Medicine

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Now showing 1 - 7 of 7
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    Antivenin activity of herbs commonly used in Kenya against dendroaspis polylepis (black mamba) snake bite
    (Kenyatta University, 2023) Mwangi, Gladys Wangechi; Nicholas Kamindu Gikonyo; Joseph Kangangi Gikunju; Charles Githua Githinji
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    Anti-ulcer activity and safety of mupal ® in a rat model: a herbal product for management of peptic ulcer disease in Kenya
    (Kenyatta University, 2021-08) Kahiga, Titus Muhu; Nicholas K. Gikonyo; Peter. K. Gathumbi; Julius W. Mwangi
    Peptic ulcer disease (PUD) is a deep gastrointestinal erosion that affects the stomach and the duodenum. There are pharmacological (using conventional drugs) and surgical interventions that form part of management. These interventions have drawbacks, including resistance and adverse effects of conventional drugs. In Kenya, Mupal® powder, a herbal product, has been used to treat peptic ulcers and related disorders for many years. However, a full scientific audit on Mupal® has never been done. The objective of this study was to evaluate Mupal® through an animal model to provide background information on its efficacy, safety, and identification and do a comparative analysis with conventional therapy (Omeprazole) and banana powder in the treatment of peptic ulcer disease. Water and methanol extracts of Mupal® and banana powders were prepared by maceration at room temperature. Mupal® and banana water suspension were prepared by suspending Mupal® powder in distilled water. White albino rats were used as animal models for both toxicity and efficacy investigations. Ulcer induction in animals was done using 1 ml of 100 % ethanol, and treatment was done with water as a negative control, Omeprazole as a positive control, and Mupal® as the test. Histopathological changes were observed on the first day and the sixth day. For acute toxicity, 250,500 and 1000 mg/kg doses of Mupal® suspension were administered daily for 14 days, and their weights, food intake were monitored; any signs of toxicity were noted. On the 14th day, the animals were sacrificed to study gross histology. The animals were subjected to three doses of Mupal® suspension (250, 500, and 1000 mg/kg) for the sub-acute toxicity study for 28 days and a ten-day recovery period. Their weights and food intake were monitored, and gross histology was studied. In vivo studies were done to test the effect of a Mupal® extract on clinical isolates of H. pylori. Some pharmaceutical parameters of Mupal® powder were determined. Efficacy results indicated that Mupal® suspension was comparable to Omeprazole in ulcer scores, acid-lowering, and histological findings. The results showed Mupal® was safe on both acute and sub-acute studies at 250 mg/kg doses. However, Mupal® did not have any antimicrobial effect on Helicobacter pylori. Pharmaceutical parameters investigations revealed that Mupal® contains high levels of saponins and moderate levels of flavonoids. TLC results showed that Mupal® had more compounds as compared to bananas. The current study demonstrated that Mupal® is a safe alternative, efficacious herbal medicine in managing ethanol-induced peptic ulcers in rats. The results warrant further studies that could involve long-term double-blind clinical trials.
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    The effects of crystalloid solutions on the human blood coagulation system
    (Kenyatta University, 2016-06) Ogweno, Gordon Oluoch
    Crystalloid solutions are used in clinical practice for resuscitation and correction of electrolyte imbalances. However, up to 25% of individuals may develop dysfunctions of haemostasis following fluid infusions, complicating resuscitation and outcome. Studies on the effects of crystalloids solutions on human blood coagulation have produced conflicting results: either suggesting procoagulant effects or impaired coagulation. The mechanisms for these discrepant results remain unclear. However, the role of solute composition remains largely unexplored. The main objective of the study was to determine the effects of crystalloid solutions on human coagulation system under conditions of varying solute type and concentrations. Specifically, the study investigated the effects of ionic crystalloids solutions containing Na+ (sodium gluconate and sodium chloride), Cl- (sodium chloride and choline chloride), and non ionic solutions such as mannitol and dextrose, in vitro. The blood samples were obtained from consenting healthy adult human blood donors. The laboratory methods were routine coagulation tests, plasma thrombin generation, and Thromboelastography and Light transmission platelet aggregation. Data analysis was done using STATA version 11.0, Texas, USA. Analysis of variance (ANOVA) and Kruskal Wallis equality of population tests were applied to examine for differences between groups. In routine tests, undiluted control had median prothrombin time 16.1 secs (IQR 15.3-17.1; N=17); median INR 1.2 (IQR 0.99-1.32; N=14); mean activated prothrombin time 33.98secs (SE 0.94; 95% CI 31.94-36.02; N=14) and median fibrinogen level 283.9 mg/dl (IQR 249.9-317.8; N=12). These tests showed significant positive linear increase with NaCl concentration except fibrinogen concentration which decreased with NaCl concentration. Comparison with other crystalloid solutions revealed crystalloid ionic strength had the most influence, and presence and concentration of chloride ions was most significant. In thrombin generation, mannitol had no influence on the thrombin generation parameters either in the extrinsic or intrinsic activation. However, NaCl had most significant effect in intrinsic activation, where there was progressive lengthening of lag time with each concentration though curves remaining qualitatively similar. The median thrombelastography values for undiluted control were: R 12.9(IQR 11.0-17.4); K 5.1 (IQR 3.5-7.0); alpha angle 32.4 (IQR 27.7-46.9); Maximum amplitude 55.8 (IQR 54.3-57). Thrombelastography median parameters had curvilinear relationship with NaCl solutions such that R&K trough inflection point around 0.3 M, as well as alpha angle and Maximum amplitude plateau. Comparison with other ionic crystalloid solutions were qualitatively similar except that from 1200 mOsm, the order of divergence was choline chloride>NaCl> sodium gluconate. Mannitol and dextrose dose dependently decreased thromboelastography alpha and maximum amplitude without much change in R&K. Citrate anticoagulated whole blood samples showed patterns of enhanced coagulation in comparison to neat non-citrate anticoagulated samples. Platelet aggregation was inhibited dose dependently by all the crystalloid solutions irrespective of solute type indicating that platelet activity was sensitive to osmolality rather than ionic strength. This study concludes that the effects of crystalloid solutions on human blood coagulation are dependent on solute content and concentration. Further, increase in chloride concentrations beyond the normal physiological range impairs blood coagulation. It is therefore recommended that the concentrations of solute ions in resuscitation fluids should be within normal plasma levels.
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    Evaluation of anti-trypanosomal activity of extracts of selected meliaceae plant species by in vitro and in vivo assays.
    (Kenyatta University, 2015-11) Wanzala-Mahiri, Everlyne Nafuna
    African human trypanosomiasis (HAT) and African animal trypanosomiasis (AAT) are vector-borne parasitic diseases, which are among the most neglected diseases in the world. They cause major health and economic problems in rural sub-Saharan Africa. Chemotherapy, the main means of controlling the disease is limited due to parasite resistance and toxicity of the current anti-trypanosomal drugs. The development of a vaccine has been thwarted by antigenic variation of the parasite. Thus, the use of natural products is one of the strategies being explored to address some of the problems encountered with allopathic chemical drugs. The main objective of the current research was to evaluate the anti-trypanosomal activity of methanol and aqueous extracts of selected Meliaceae species through in vitro and in vivo assays against Trypanosoma brucei rhodesiense, Trypanosoma brucei brucei and Trypanosoma evansi. Methanol and aqueous extracts of five Meliaceae plant species: Trichilia emetica, Toona ciliata, Azadirachta indica, Turraea mombassana and Melia azedarach were tested for in vitro anti-trypanosomal activity, acute toxicity and in vivo efficacy using mice as animal models. Sequential extraction of powdered plant samples in hexane, ethyl acetate, methanol and water afforded the crude extracts. In vitro assays were carried out in 96-well microtitre plates and melarsoprol and suramin were used as the positive controls. The results revealed that the minimum inhibitory concentrations (MICs) of MeOH extracts were significantly lower than those of the aqueous extracts. The MeOH extracts of M. azedarach stem bark, A. indica stem bark and T. emetica root bark (MIC 9.11±3.44, 9.93±2.88 and 9.11±3.44 μg/ml respectively) showed the best anti-trypanosomal activity against T. b. rhodesiense; the MeOH extract of T. emetica root bark (MIC 9.93±2.88 μg/ml) showed the best anti-trypanosomal activity against T. b. brucei. The methanol extracts of M. azedarach root bark, T. emetica root bark and A. indica stem bark (9.11±3.44, 9.11±3.44 and 9.93±2.88 μg/ml respectively) showed the best anti-trypanosomal activity against T. evansi. Based on the strength of in vitro anti-trypanosomal activity, four extracts were selected and subjected to acute toxicity tests in mice. It was established that the MeOH extract of A. indica stem bark and the aqueous extract of T. mombassana leaves were safe in mice at dose levels of 100, 200 and 400 mg/kg body weight. The LD50 values of T. emetica root bark and M. azedarach root bark were 707.95±229.25 and 229.09.54±95.54 mg/kg body weight respectively. Two extracts (A. indica stem bark and the T. mombassana leaves) were subjected to in vivo efficacy tests using T. b. rhodesiense infected mice. Melarsoprol and suramin at doses of 3.6 and 5 mk/kg bwt respectively were used as positive controls. The infected-untreated group served as negative control. The study showed that the MeOH extract of A. indica stem bark at 200 and 400 mg/kg and the aqueous extract of T. mombassana leaf at 400 mg/kg reduced parasitemia levels, prevented body weight loss and reduced decline in packed cell volume (p < 0.05) in mice. Chromatographic fractionation of the methanol extract of A. indica stem bark led to the isolation of nimbin (55) and 1-detigloyl salannin (84). Toona ciliata stem extract yielded bis(2-ehtylhexyl) phthalate (85) and bis(2-methylheptyl) phthalate (86). Nimbin (55) displayed the highest in vitro antiptrypanosomal activity with MIC values of 9.74±0.93, 11.90±0.02 and 11.89±0.01 μg/ml against T. b. rhodesiense, T. b. brucei and T. evansi respectively. Bis(2-ehtylhexyl) phthalate (85) showed mild activity against the three strains (MIC > 146 μg/ml). In conclusion, the study established that A. indica stem bark and T. mombassana leaves have in vitro and in vivo anti-trypanomal activities and can be considered portential sources of new anti-trypanosomal compounds. Based on the findings of the current study, it is recommended that extracts of A. indica and T. mombassana may be used as alternative remedies for African trypanosomiasis.
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    Safety and Antimicrobial Activities of Herbal Materials used in Management of Oral Health by Traditional Medical Practitioners in Nairobi County, Kenya
    (2014-02-26) Waiganjo, Florence Wanja; Gikonyo, Nicholas K.; Wanjau, R. N.
    The use of herbs for treatment and management of oral diseases is practiced in the developing countries including Kenya. The herbs are used in form of powders, pastes, saps, chewing sticks and seeds. They are sold in Nairobi along streets and open markets with claims of healing all oral diseases. However, safety issues in terms of microbial contaminants, levels of mineral elements profiles, toxicity, phytochemical composition and antimicrobial properties of the herbal materials in the market have not been evaluated. The aim of the study was to evaluate safety aspects and antimicrobial properties of herbal materials used in oral health care in Nairobi. Documentation of herbal materials was carried out by interviewing 60 herbalists using a questionnaire and through informal discussions. Investigation of safety and antimicrobial properties was carried out on 23 herbal products purchased from the herbalists. Evaluation of microbial contaminants was carried out as described by World Health Organisation. Samples were inoculated in enrichment culture medium, then subculturing in selective media, followed by microscopy and biochemical test to confirm the identity of the microbes. Elemental analysis was evaluated by use of Total X-ray Fluorescence Technique. Qualitative phytochemical constituents of herbal materials were investigated using standard methods. The antimicrobial properties were studied using disc and agar well diffusion method. Toxicity effects of herbal materials was investigated by administering 1000 mg/kg body weight of seven herbal material extracts and 3 herbal pastes on mice for twenty one days, and then biochemical, haematological parameters, relative organ weight and their histopathological changes were evaluated. Results indicated that 35 plant species were used in preparation of herbal products for management of oral conditions. Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Candida albicans were isolated in some of the products. High levels of aluminium, phosphorous, potassium, calcium, vanadium, chromium, manganese, iron, nickel, copper, zinc, strontium and lead were observed. Major phytochemical groups were recorded in herbal powders. However, pastes and liquids lacked detectable levels of major phytochemical groups. Antimicrobial properties were reported in 78% of the herbal materials. Mortality was reported in mice treated with herbal materials of Warbugia ugandensis, Zantoxyllum chalybeum and Senna didymobotrya. The extracts of Euclea divinorum and herbal mixtures of Warbugia ugandensis, Z. chalybeum and Terminalia brownii showed retarded growth in mice and hypertrophy of liver and brain. There was significant (P>0.05) alteration of the red blood cells and neutrophils, creatine, alanine aminotransferase and thrombocytes of animals treated with some herbal extracts while severe pathological conditions on vital organs of mice was seen. The toxic effects could be due to presence of heavy metal due to poor handling by herbalists. Most of the products in the market did not meet the WHO standards. These findings may be used to sensitise the Traditional Medical Practitioners, policy makers and consumers on the safety issues and lack of antimicrobial activities in some products. This study recommends that full evaluation of safety and antimicrobial properties of herbal materials be carried out before they are released to the market. .
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    Analyses of class and subclass antibody of circulating immune complexes in children with severe plasmodium Falciparum malaria in endemic regions of Western kenya
    (2011-08-04) Mibei, Erick Kipsang
    Plasmodium falciparum infection is characterized by deadly complications such as severe malaria-associated anaemia (SMA) and cerebral malaria (CM)The exact mechanisms underlying pathogenesis of these severe forms of Plasmodium falciparum malaria are not fully understood yet they are associated with a lot of morbidity and mortality. Studies have shown a link between severe P. falciparum malaria and levels of circulating immune complexes (CIC) but the exact role of these CICs in the pathogenesis of severe P. falciparum malaria is still unclear. This study aimed to investigate the quantitative and qualitative differences in antibody classes and subclasses in serum immune complexes (ICs) between children with the severe forms of P. falciparum malaria and those with uncomplicated malaria as well as identifying the predominant P. falciparum antigens that contribute to IC formation in these clinical groups. A total of 75 children with SMA and 32 children with CM were enrolled from hospitals in western Kenya and matched with 74 and 52 control children respectively with uncomplicated symptomatic malaria. IC levels were measured using solid phase ELISA protocols and antibody classes and subclasses were identified using polyspecific sera for the classes or monoclonal antibodies for the subclasses. ICs were purified using polyethylene glycol (PEG) precipitation. The isolated ICs were dissociated by using an acidic buffer (GlycineHCL pH 2.0). These were then electrophoresed on one-dimensional and two-dimensional polyacrylamide gel blotted by Western transfer and probed using human anti-P. falciparum antibodies. The study showed a general increase in levels of ICs as a result of P. falciparum infection in severe malaria cases and their symptomatic controls. Although IgG IC levels were elevated in children with severe malaria upon enrolment, children with CM had the highest levels of ICs for all the antibody classes. Conditional logistic regression showed a borderline association between IgG4-contaning ICs and increased risk of SMA (OR = 3.11, 95% CI 1.01 to 9.56, P = 0.05). Total IgGcontaining ICs (OR = 2.58, 95% CI 1.20 to 5.53, P < 0.02) and IgE-containing ICs (OR 3.27, OR I .38 to 7.78, P < 0.01) were associated with increased risk of CM. Six specific falciparum antigens were found to be associated with severe malarial anaemia while another three antigens were associated with cerebral malaria when compared to their specific controls. While when SA and CM where compared together, a 91Kda antigen was highly associated with SA (P < 0.01), while a slightly lighter antigen of about 87 Kda was significantly associated with CM (P < 0.01). These findings have demonstrated quantitative and qualitative differences in ICs in children with SMA and CM and this underscores the potential mechanisms of the pathophysiology of the disease. Furthemore the findings of this study suggested having higher IgG4-containing ICs is a risk factor for SMA while higher IgG and also IgE-containing ICs are both associated with CM pathology. This suggest that although SMA and CM were characterized by high levels of ICs, the class and subclass make up of these IlCs as well as the role that they play in each may be distinct. This study demonstrated an association between malaria antigens and severity of the disease hence there is need for full characterization of the parasite antigens. These findings may contribute to a better understanding of the role of different antibody classes and subclasses in protective or damaging mechanisms and may provide new insights into development of effective malaria control strategies and vaccine development.