Publications

Found 23 results

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2016
2015
K. A. Sinei, J.W.Mwangi, R. W. Munenge, Mwaura AM. "The contractile action of Adenia Globosa Engl. on mammalian smooth muscle." Kenya Science, Technology and Innovation Journal . 2015;4 and 5:53-64._the_contractile_action_of_adenia_globosa_engl._on_mammalian_smooth_muscle.pdf
Mukungu N.A., C.K M, Sinei K.A, Mutai, E.B.K., Ongarora D.S.B, E.W. K. "Jatropha Curcas Poisoning in Children in Western Kenya – A Case Report. ." East and Central African Journal of Pharmaceutical Sciences . 2015;18 :32-34.
Khaemba CN, Guantai EM, Oluka MO, Sinei KA. "Medication Errors among Paediatric Inpatients at a Rural Referral Hospital in Kenya." Pharmacoepidemiology and Drug Safety (Wiley,USA). 2015;24:278.
Makori J., M. Ambetsa, K. A. Sinei, G. O. Oanjo, A.N.Guantai, S. McClelland, M. N. Oluka, Okalebo FA. "Patterns and risk factors for alanine aminotransferase elevation among HIV patients on nevirapine regimens." African Journal of Pharmacology and Therapeutics. 2015;4(2).
2014
Kimani S, Moterroso V, Morales P, Wagner J, Sinei K, Bukachi F, Maitai C, Tshala-Katumbay D. "Cross-species and tissue variations in cyanide detoxification rates in rodents and non human primates on protein-restricted diet." Food and Chemical toxicology . 2014;66:203-209. Abstract

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (∼8weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6weeks. Macaca fascicularis monkeys (∼12years old) (N=12) were exclusively fed cassava for 5weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ∼80× faster in the nervous system (14ms to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ∼2× relative to that of rodents. The nervous system susceptibility to cyanide may result from a “multiple hit” by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC

Onyango MA, FA O, Nyamu DG, Osanjo GO, Sinei K. "Determinants of antibiotic dose adjustment in patients with chronic kidney disease at Kenyatta National Hospital, Kenya." The African Journal of Pharmacology and Therapeutics . 2014;3(1):19-28. Abstract

Background: Reduced renal function in chronic kidney disease (CKD) necessitates appropriate dose alterations to avoid drug accumulation.

Objectives: The main objective of the study was to determine the prevalence of inappropriate antibiotic dosing in patients with CKD in the largest referral hospital in eastern Africa. Variables associated with inappropriate dosing were identified.

Methods: The design was a retrospective review of patients’ records. The study population was adult patients, with CKD admitted between January, 2006 and December, 2010. Data was abstracted from patient files. Logistic regression was used to determine variables associated with appropriate antibiotic dosing.

Results: Ceftriaxone and amoxicillin-clavulanic acid were the most frequently prescribed antibiotics. Dose adjustment was required for 379 (59.9%) antibiotic prescriptions. Of these, 105 doses (27.7% [95% CI: 23.2 – 32.2%]) were appropriate and 274 (72.3% [95% CI 67.8 – 76.8%]) were inappropriate. The resultant dosing errors were: 271 (98.9%) and 3 (1.1%) cases of over and under dosing respectively. Key explanatory variables for appropriate dosing were: stage of renal disease (adjusted odds ratio (OR) 0.159 [95% CI: 0.082, 0.309]); administration; (adjusted OR 1.724 [95% CI:1.185, 2.508]); and treatment with amoxicillin-clavulanic acid (adjusted OR 0.101 [95% CI 0.024, 0.420].

Conclusion: Antibiotic doses in patients with CKD were often inappropriate.
Keywords: Antibiotic, dose adjustment, chronic kidney disease

Kimani S, Sinei K, Bukachi F, Tshala-Katumbay D, Maitai C. "Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents." Metabolic Brain Disease. 2014;29(1):105-112. Abstract

Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 μl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F 2, 19 = 4.57 p < 0.05), higher working memory errors (WME) (F 2, 19 = 5.09, p < 0.05) and longer RAM navigation time (F 2, 19 = 3.91, p < 0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F 2, 19 = 7.45, p < 0.01) and increased working memory errors (F 2, 19 = 9.35 p < 0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate

2013
Kimani S, Moterroso V, Lasarev M, Sinei K, Bukachi F, Maitai C, David L, Tshala-Katumbay D. "Carbamoylation correlates of cyanate neuropathy and cyanide poisoning: relevance to the biomarkers of cassava cyanogenesis and motor system toxicity." Springerplus. 2013;2:647. Abstract

We sought to elucidate the protein carbamoylation patterns associated with cyanate neuropathy relative to cyanide poisoning. We hypothesized that under a diet deficient in sulfur amino acids (SAA), the carbamoylation pattern associated with cyanide poisoning is similar to that of cyanate neuropathy. Male rats (6-8 weeks old) were fed a diet with all amino acids (AAA) or 75%-deficiency in SAA and treated with 2.5 mg/kg/body weight (bw) NaCN, or 50 mg/kg/bw NaOCN, or 1 μl/g/bw saline, for up to 6 weeks. Albumin and spinal cord proteins were analyzed using liquid chromatography mass spectrometry (LC-MS/MS). Only NaOCN induced motor deficits with significant levels of carbamoylation. At Day 14, we found a diet-treatment interaction effect on albumin carbamoylation (p = 0.07). At Day 28, no effect was attributed to diet (p = 0.71). Mean number of NaCN-carbamoylated sites on albumin was 47.4% higher relative to vehicle (95% CI:16.7-86.4%). Only NaOCN carbamoylated spinal cord proteins, prominently, under SAA-restricted diet. Proteins targets included myelin basic and proteolipid proteins, neurofilament light and glial fibrillary acidic proteins, and 2', 3' cyclic-nucleotide 3'-phosphodiesterase. Under SAA deficiency, chronic but not acute cyanide toxicity may share biomarkers and pathogenetic similarities with cyanate neuropathy. Prevention of carbamoylation may protect against the neuropathic effects of cyanate.

Nderitu FW, Gikonyo GK, Sinei K. "Detection and Management of Adverse Drug Reactions Related to Antiretroviral Drugs among HIV/AIDS Patients in Kiambu Sub-County, Kenya." East and Central African Journal of Pharmaceutical Sciences. 2013;In press. Abstract

The objective of this study was to establish the prevalence, detection and management of various adverse drug reactions associated with antiretroviral drugs occurring in patients attending Comprehensive Care Centre (CCC) of Kiambu District Hospital. The study was a cross sectional survey where the patients included were those attending the CCC on a monthly basis. The results revealed that 65.2% of the patients had experienced symptoms suggestive of adverse drug reactions (ADRs). Of these, 67.2% did not associate the symptoms to the medicines they were taking but rather to the AIDS syndrome. The most prominent reaction was peripheral neuropathy at 0.395 (0.344-0.447 at 95% confidence interval) while the least common was hepatotoxicity. Whereas 71.5% could tell the frequency of the daily dosage, 92.1% did not know the names of the medicines they were taking but could describe them by shape and colour. There was a significant association between occurrence and reporting of ADRs and age (P<0.001), weight (P=0.001), marital status (P=0.016), occupation (P<0.001), religious participation (P<0.001) and education level (P<0.001). Although the health care providers displayed adequate knowledge in management of these reactions, they complained of inadequacy of the current reporting tool (MOH 257) in capturing ADRs. The patients were ill equipped in recognizing the adverse drug reactions.

Sinei K, Mwangi JW, Munenge RW, Mwaura AM. An in vitro study on the oxytocic action of Adenia globosa Engl.. Second International Scientific Conference of the College of Health Sciences,University of Nairobi & Kenyatta National Hospital; 2013. Abstract

BACKROUND: Adenia globosa Engl. (Passifloracea) is found in many parts of Kenya, Tanzania and Somalia. It is a shrub or climber with stems emerging from above-ground tuber of up to 2.5M wide. Some local names (of Adenia ssp.) are: Kilyambiti, Kasikimara, Ghole, Ngoli, Mugore, Mgore, Munua Nyoka etc.

PROPERTIES AND USES: Many of the Adenia species are extremely toxic and have been used for homicidal or suicidal purposes or for poisoning wild animals and fish. Nevertheless, several of the species are used in traditional herbal medicine: an anthelmintic, remedy for snake bite, antidote for arrow poison, orchitis, malaria and syphilis. It is also claimed that freshly prepared juice of the tuber of given to cows and goats that have difficulty in giving birth to hasten the process.

OBJECTIVES: The objectives of the study was to investigate the effect of the water extract of Adenia globosa on the isolated preparation of the rat uterus and how this could be affected by well known uterine stimulants such as ergometrine, oxytocin and prostaglandin F2α. and also by antagonists of acetylcholine and adrenaline.

SETTING: Department of Pharmacology and Pharmacognosy Laboratory, School of Pharmacy, University of Nairobi, KNH Campus.
STUDY DESIGN: It was a laboratory based study. The crude extract and the other drugs were tested on isolated rat uterus set up in an organ bath under the usual laboratory conditions.

RESULTS: The results obtained demonstrated that the plant extract caused a dose-depended contraction of the rat uterus which was not antagonized by atropine nor phenoxybenzamine. The contractile effect was however potentiated by small doses of ergometrine, oxytocin and prostaglandin F2α.

CONCLUSIONS: It was concluded from these observations that the contractile action was not mediated through cholinergic nor adrenergic system. Secondly, it was postulated that since prostaglandin F2α and oxytocin are also released at the time of labour, the potentiatory action probably occurs in vivo when the plant preparation is given to domestic animals to ease and speed up the process of giving birth as claimed in the traditional use of this plant. This traditional use of the plant preparation is therefore scientifically justifiable

Sinei K, Okalebo FA, Mugo HN, Mwalukumbi JM. "An investigation of anti-microbial activity of Acmella caulirhiza." The African Journal of Pharmacology and Therapeutics. 2013;2(4):130-133. Abstract

Background: Acmella Caulirhiza is a plant that is used traditionally to treat several disorders such as oral thrash, mouth ulcers, toothache and earache, among others. It is a small annual or perennial herb whose location is widespread worldwide.

Objectives: The objective of the study was to determine whether the leaves, stem and the flowers extract of the plant possess antibacterial and antifungal activity and to find out which part of the plant is the most active, if any.

Methodology: Acmella caulirhiza was collected from the wild in Kericho County. The flower heads, the leaves and the stems were dried separately, ground into a powder and extracted with chloroform. The plant extracts were tested for activity against Escherichia Coli, Staphylococcus aureus, Candida albicans and Bacillus pumilus.

Results and Discussion: The plant extracts significantly inhibited the growth of Escherichia Coli, Staphylococcus aureus and Bacillus pumilus. The activity was highest in the stems extracts. The extracts, however, did not have any anti-fungal activity when tested against Candida albicans. It was concluded from these results that the anti-bacterial activity may aid in the efficacy when the plant is used to treat mouth ulcers or oral thrash.

2012
Sinei KA, Redfern PH. "The Time-Dependent Effect of the Antidepressant Drug Paroxetine on the Synthesis of 5-Hydroxytryptamine in the Rat Brain." East Cent. Afri. J. Pharm. Sci.. 2012;15(2):46-54. Abstractabstract

The effect of paroxetine on the day--night variations in the synthesis of 5HT was determined in the rat brain in an effort to gain an insight into the mechanism of action of this drug. This was done by determining its effect on the activity of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of 5HT in serotonergic neurons. The enzyme activity was determined in two brain regions, cortex and the brainstem, at two time points of 12hr light/12hr dark cycle, namely, mid-light and mid-dark. The results obtained showed that the activity of tryptophan hydroxylase was significantly greater in control animals during the dark than light phase both in the cortex and brainstem. They also demonstrate that the rate of synthesis of 5HT was affected by paroxetine in a time-dependent manner. It was therefore concluded that these time-dependent changes observed in paroxetine effect may influence the activity of serotonergic input into the suprachiasmatic nucleus and hence the regulation or expression of certain circadian rhythms. This action may help correct or compensate for abnormalities present in depressive illness.

1997
Achola KJ, Mwangi JW, Sinei KA, Munenge RW, Mwaura AM. "Pharmacological activities of gutenburgia cordifolia." International Journal of Pharmacognosy. 1997;35(1):60-62. Abstract

A methanol extract of Gutenburgia cordifolia showed a greater fall in diastolic than systolic blood pressure in anaesthetised rats. The plant extract produced cardiodepressant activity on isolated rabbit heart and caused contraction on isolated rabbit ileum. The contraction was re¬duced but not abolished with atropine. On isolated guinea pig ileum, the contraction was abolished by atropine, the presence of an acetylcholine-like compound in the plant extract is indicated.

1995
Sinei KA, JW M. "Effect of the tuber of Adenia globosa extract on the isolated rat uterus." Int. J. Pharmacog.. 1995;33 (3).
Mwangi JW, Sinei KA, Lwande W, others. "Essential Oil constituents of Artemisia Afra Willd." J. Essent. Oli Res.. 1995;7:97-99.
1994
1993
1987
Sinei KA. The effect of Antidepressant Drugs on the Circadian Rhythm of 5-Hydroxytrptamine Synthesis in The Central Nervous System. Redfern. S:PH, ed. Bath, England: PhD Thesis, University of Bath; 1987.
1986
1985
Redfern PH, Sinei KA. "24-Hr variation in synaptosomal tryptophan-5- hydroxylase activity in the rat brain.". In: Circadian Rhythms in the Central Nervous System. London: MacMillan Press; 1985.

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