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Over 80% of cultural societies in low-income countries use plant preparations in traditional medicine with unknown potency and safety profiles. Uvariodendron anisatum root extracts are used by some Kenyan herbalists. However, the claims of the plant to remove retained placenta during birth have remained uninvestigated. Therefore, the current study evaluated its uterotonic activities. Acute toxicity in Wistar rats and the phytochemical composition of the plant were also studied. The plant was collected from Embu County in Kenya. The water and ethanol extracts were prepared by maceration. Uterine strips were isolated from primed mature female Wistar rats and used to study the uterotonic activities of the extracts. De Jalon's solution and oxytocin were used as negative and positive controls, respectively. Acute oral toxicity studies were done following the OECD 423 guideline and phytochemical screening were based on standard phytochemical procedures. The study met all the approval requirements before commencement. Data obtained from the uterotonic activity were analysed by using GraphPad Prism Version 8.0.1 software and expressed as a percentage increase or decrease of mean as mean ± SEM relative to the controls. The findings of acute oral toxicity were expressed using LD 50 . Additionally, the phytochemical components of the U. anisatum were tabulated. The uterotonic effect of Uvariodendron anisatum root water extract was higher than that of ethanol extract. A single dose of the Uvariodendron anisatum root water extract at 2000 mg/kg did not cause mortality in the tested Wistar rats. Besides, there were no changes in hematological and biochemical parameters. The extracts did not reveal changes in the gross morphology of the liver, kidney, heart, and lung of the tested Wistar rats. However, the histopathological studies of Uvariodendron anisatum root water extracts exhibited toxicity in the liver, kidney, and lung tissues of Wistar rats at a concentration of 2000 mg/kg. Alkaloids, glycosides, saponins, phytosterols, terpenes, proteins, phenols, and oils were recorded in Uvariodendron anisatum. The findings from this study provided scientific evidence which is useful in validating the use of Uvariodendron anisatum extracts in the stimulation of the uterus during birth., Competing Interests: The authors declare that they have no conflicts of interest in this study., (Copyright © 2022 Kanji Benson Muthee et al.)

Plant-based medicines have effectively managed several ailments in humans and animals since prehistoric times. However, the pharmacologic efficacy and safety of many plants currently used in traditional medicine have not been explored empirically, which raises serious public health concerns, derailing further research and their integration into the conventional healthcare system. Despite the longstanding ethnomedicinal usage of Yushania alpina shoot extract to treat inflammation, microbial infections, and diarrhoea, among other diseases, there is insufficient scientific data to appraise its toxicity profile and safety. Accordingly, we investigated the subacute toxicity of the aqueous shoot extract of Y. alpina in Sprague Dawley rats (both sexes) for 28 days based on the Organisation for Economic Cooperation and Development guideline 407. In this study, all the experimental rats treated orally with 40 mg/Kg BW, 200 mg/Kg BW, and 1000 mg/Kg BW of the aqueous shoot extract of Y. alpina remained normal, like the control group rats, and did not show any clinical signs of subacute toxicity, and no morbidity or mortality was recorded. Besides, the weekly body weight gains and the haematological and biochemical parameters of experimental rats orally administered with the studied plant extract at the tested doses and in the control group were comparable ( P > 0.05). No pathologic alterations in internal organs were observed following necroscopy. Further, the differences in weights of the liver, kidney, and spleen of experimental rats which were subacutely treated with the studied plant extract and the control rats were insignificant ( P > 0.05). Moreover, no histopathological changes were observed in tissue sections of the liver, kidney, and spleen obtained from all the experimental rats. Our findings demonstrate that the aqueous shoot extract of Y. alpina may be safe as it does not elicit subacute toxicity in Sprague Dawley rats. Further toxicological and pharmacological studies using other model animals and in clinical setups are encouraged to fully appraise the efficacy and safety of the studied plant extract., Competing Interests: The authors declare no conflicts of interest whatsoever regarding this study., (Copyright © 2022 Joseph Ngugi Wanjiru et al.)

Background: The Mbeere South community of Embu County consume leaves of Catha edulis for its stimulant and euphoretic actions. Other indigenous uses of the plant are undocumented. Information on the pharmacology and safety of this plant is also scanty. This study aimed to document the ethnopharmacology, antimicrobial properties, and toxicity of C. edulis leaves collected from the Mbeere South community in Kenya. Methods: Ethnopharmacological data was collected from 35 informants using semi-structured questionnaires. Leaf extracts of C. edulis were prepared using acetone, water, and methanol. The antimicrobial properties of these extracts were evaluated against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans . The toxicity of the aqueous extract was determined using hematological, biochemical, and histopathological parameters in male and female Sprague Dawley rats at 250 mg/kg, 500 mg/kg, and 1000 mg/kg doses over 28 days. p<0.05 was considered significant. Results: All informants were male, most were married, >50 years old, with >10 years of experience. The sources, local names, preparation, storage conditions, indications, frequency of use, dosage, and side effects of C. edulis were documented. All extracts were ineffective against E. coli , P. aeruginosa, and C. albicans. They had limited efficacy against B. cereus and S. aureus. Significant differences were observed in the hematological and biochemical parameters of rats at the tested doses. Low, intermediate, and high doses of the aqueous extract of C. edulis produced local congestion of the cardiac and hepatic vessels. Localized interstitial connective tissue proliferation, multifocal kidney interstitial hemorrhage, and localized tubular epithelium necrosis were also observed in female rats. Conclusions: The ethnobotanical uses of C. edulis among the Mbeere South community were documented for the first time. Limited antimicrobial efficacy and toxicity at high doses limit the use of leaves of C. edulis ., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Githua KK et al.)

Snakebite envenomation (SBE) is a life-threatening global public health problem affecting over 2.7 million persons annually, with a bigger burden lying in the developing world. Despite the successful management of SBE by antivenom therapy in conventional medicine, it is of low efficacy due to the diverse venom composition across snake types, which limits its usefulness. As a result, inhabitants of the sub-Sahara region, where SBE incidence is high, utilise medicinal plants as an alternative remedy for SBE. However, most plants have not been ethnobotanically documented and validated empirically and hence this study is needed. An ethnobotanical survey to document medicinal plants used to manage SBE in Migwani ward, Mwingi West Subcounty, Kitui County, was conducted between January and February, 2021. Ethnobotanical data were collected from 45 purposefully sampled respondents from Migwani ward using semistructured questionnaires, field walks, and oral interviews. In this study, 14 medicinal plants which are used to manage SBE were documented. Four plants with the highest Relative Frequency of Citation (RFC) ( Entada leptostachya Harms-stem bark (0.58), Senna singueana -roots (0.53), Securidaca longipendunculata -roots (0.36), and Strychnos henningsii -stem bark (0.46)) were selected and extracted using water, methanol, and dichloromethane according to the standard procedures. Qualitative phytochemical analysis of the plant extracts and their cytotoxic effects on brine shrimp nauplii (brine shrimp lethality assay) was conducted according to the standard techniques. Qualitative phytochemical screening revealed the presence of anti-SBE-associated phytochemicals, such as alkaloids, saponins, tannins, phenols, and flavonoids, in the aqueous and methanolic extracts of the studied plant extracts. However, the tested phytochemicals were not detected in dichloromethane extracts of all the studied extracts. The anti-SBE effects of the documented plants could be attributable to these associated bioactive phytocompounds, which are synthesized by the studied plants and transfered to humans when consumed. Furthermore, the aqueous and methanolic extracts of Entada leptostachya and Senna singueana had high LC 50 of >1000  µ g/ml and were considered noncytotoxic. However, Securidaca longipendunculata had an LC 50 of <1000  µ g/ml and was considered slightly cytotoxic. Further empirical investigations to characterise the bioactive phytochemicals and their safety should be done., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Stella Kwamboka Mokua et al.)

The purpose of this study was to evaluate and compare plasma phenytoin concentration versus time profiles following intravenous (i.v.) and intramuscular (i.m.) administration of fosphenytoin sodium with those obtained following administration of standard phenytoin sodium injection in the rabbit. Twenty-four adult New Zealand White rabbits (2.1 +/- 0.4 kg) were anaesthetized with sodium pentobarbitone (30 mg/kg) followed by i.v. or i.m. administration of a single 10 mg/kg phenytoin sodium or fosphenytoin sodium equivalents. Blood samples (1.5 ml) were obtained from a femoral artery cannula predose and at 1, 3, 5, 7, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 min after drug administration. Plasma was separated by centrifugation (1000 g; 5 min) and fosphenytoin, total and free plasma phenytoin concentrations were measured using high performance liquid chromatography (HPLC). Following i.v. administration of fosphenytoin sodium plasma phenytoin concentrations were similar to those obtained following i.v. administration of an equivalent dose of phenytoin sodium. Mean peak plasma phenytoin concentrations (Cmax) was 158% higher (P = 0.0277) following i.m. administration of fosphenytoin sodium compared to i.m. administration of phenytoin sodium. The mean area under the plasma total and free phenytoin concentration-time curve from time zero to 120 min (AUC(0-120)) following i.m. administration was also significantly higher (P = 0.0277) in fosphenytoin treated rabbits compared to the phenytoin group. However, there was no significant difference in AUC(0-180) between fosphenytoin and phenytoin-treated rabbits following i.v. administration. There was also no significant difference in the mean times to achieve peak plasma phenytoin concentrations (Tmax) between fosphenytoin and phenytoin-treated rabbits following i.m. administration. Mean plasma albumin concentrations were comparable in both groups of animals. Fosphenytoin was rapidly converted to phenytoin both after i.v. and i.m. administration, with plasma fosphenytoin concentrations declining rapidly to undetectable levels within 10 min following administration via either route. These results confirm the rapid and complete hydrolysis of fosphenytoin to phenytoin in vivo, and the potential of the i.m. route for administration of fosphenytoin delivering phenytoin in clinical settings where i.v. administration may not be feasible.

The efficacies of pyrethrum marc and of albendazole against experimental sheep gastrointestinal nematode infection were compared. Sheep was infected orally with 10,000 larvae (Haemonchus spp. (60.1%), Oesophagostomum spp. (13.9%), Trichostrongylus spp. (13.2%), Cooperia spp. (8.3%), Nematodirus spp. (3.5%), Strongyloides spp. (0.8%) and Ostertagia spp. (0.2%). Faecal egg count reduction in albendazole-treated sheep was 100% by day 4 following treatment, compared to 37.03%, 31.3%, 38.9% and 51.8% on days 4, 6, 8 and 10 in pyrethrum mare-treated sheep. These reductions were statistically significant on days 8 and 10 post-treatment (p < 0.05). The potential for using pyrethrins for helminth treatment is discussed.

The effect of experimentally induced Pasteurella haemolytica pneumonia on the pharmacokinetics of doxycycline (Doxycen Retard) administered intramuscularly was studied in seven East African dwarf goats. The study was conducted in two consecutive phases, separated by a washout period of four weeks. The experimental infection, induced by intratracheal administration of 5 ml of 10(7) to 10(9) cfu/ml of Pasteurella haemolytica, produced a temperature rise, depression and laboured breathing within 6-12 days after inoculation. The concentrations of doxycycline in the serum were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus cereus var mycoides (ATCC 11778) as the test organism, with a level of detectability of approximately 0.05 micrograms/ml. The concentration-time curve of doxycycline in the serum after intramuscular injection of 20 mg/kg bodyweight of the long-acting formulation before and after experimental infection was adequately described by a one-compartment open model. The maximum serum concentrations (Cmax) of doxycycline were lower in pneumonic goats than in healthy goats (3.87 +/- 0.52 and 5.56 +/- 0.213 micrograms/ml, respectively), suggesting an increased distribution volume in the peripheral compartment. The mean +/- SEM absorption rate (ka) before infection (1.13 +/- 0.02 h-1) was smaller than the after infection (8.23 +/- 3.81 h-1), but the difference was not significant. The apparent elimination half-life (t 1/2 beta) (24.51 +/- 0.02 h) after infection was significantly increased (p < 0.05), while the corresponding rate constant (beta) was decreased (p < 0.01). The absorption half-life (t 1/2(alpha)) (0.137 +/- 0.03 h) was significantly decreased (p < 0.01) after infection. The distribution volume (Vd(beta)) was significantly increased after infection (p < 0.05). It is concluded that, although experimental infection had an effect on the disposition kinetics of doxycycline, this was not sufficiently pronounced to require alteration of the dosage during disease.

Twenty laying birds were divided into four groups (n = 5) and given drinking water containing 0, 400, 600, and 800 mg/l of oxytetracycline respectively for 7 days. Eggs were collected continuously for 17 days after drug administration and stored at +4 degrees C. The oxytetracycline residues in yolk and albumen were analysed using a microbiological method with Bacillus cereus var. mycoides ATCC 11778 as the test organism. The mean maximum concentration of oxytetracycline was observed 2 days earlier in the albumen than in the yolk. The mean values in yolk and albumen were 0.526 and 0.280 mg/kg respectively. The depletion period was shorter for albumen than for yolk and oxytetracycline was detected in the yolk and albumen up to days 13 and 10 respectively. Withdrawal periods depended on the concentration of the antibiotic administered. Oxytetracycline residues reached a peak faster in albumen than in yolk, although the residues persisted for longer periods in the yolk.

Paracetamol, a widely used non-narcotic analgesic, has the same analgesic, and antipyretic efficacy as acetylsalicylic acid (ASA). In contrast to ASA, paracetamol has traditionally been claimed to have little or no anti-inflammatory effect. There is, however, increasing support for the view that paracetamol has anti-inflammatory activity and reduces pain and swelling in inflammatory conditions other than rheumatoid arthritis. Overall, paracetamol seems to be equally effective as ASA. Since ASA has a greater potential for adverse effects, paracetamol is increasingly preferred to ASA, particularly in children.

Five matched pairs of horses were used to investigate the effects of phenylbutazone on a range of physiological, biochemical and haematological variables. The drug was given by mouth daily for 15 consecutive days at the manufacturer's recommended dose rates to one group of horses (Group A); the second group (Group B) received equivalent doses of a placebo. For some of the measured parameters, significant changes were recorded in both groups, indicating background instability. Significant decreases in serum total protein, albumin, plasma pH, viscosity and magnesium, and an increase in albumin: globulin ratio occurred in Group A, but not in Group B. These changes were, therefore, attributed to phenylbutazone or its metabolites. Toxicologically, the change in pH is probably unimportant but the decrease in protein concentration may have resulted from a protein losing enteropathy and/or from decreased synthesis in the liver. In one animal which received phenylbutazone, clinical signs of toxicity (lethargy, inappetence, oedema) were observed and evidence of hepatotoxicity and haematological changes were also noted in this horse. It is concluded that recommended dose rates of phenylbutazone should never be exceeded and that the period for which the highest dose (4.4 mg/kg body weight twice daily for four days) is administered should be reduced. In clinical cases, where phenylbutazone toxicity is suspected, measurement of serum or plasma protein concentration might provide an indication of the need to reduce dose levels or stop therapy.

The pharmacokinetics, metabolism, excretion and tissue residues of phenylbutazone (PBZ) in the horse were studied following both intravenous and oral administration of the drug at a dose rate of 4.4 mg/kg. A 72-hour blood sampling schedule failed to demonstrate a third exponential phase; the plasma disposition following intravenous injection being described by a two compartment open model, with the following elimination phase parameters: beta = 0.13h-1, t1/2 beta = 5.46h, Vdarea = 0.141 1/kg and C1B = 17.9 ml/kg/h. The hydroxylated metabolites oxyphenbutazone (OPBZ) and gamma-hydroxyphenylbutazone (OHPBZ) were present in detectable concentrations in plasma for 72 and 24 h, respectively. After 36 h OPBZ concentrations exceeded plasma PBZ concentrations. In urine the principal metabolites were OPBZ and OHPBZ but smaller concentrations of another compound, probably gamma-hydroxyoxyphenbutazone (OHOPBZ), were also detected. The percentages of the administered dose recovered from urine were 30.7, 39.0 and 40.3 after 24, 48 and 72 h from the time of injection. Recovery of PBZ and its metabolites from urine was significantly reduced in the first 24 h after oral dosing when the horses had free access to hay, probably as a result of markedly delayed absorption, but this did not occur in animals deprived of food for a few hours before and after dosing. Determination of approximate values of urine/plasma (U/P) concentration ratios for PBZ and its metabolites relative to endogenous creatinine U/P concentration ratio suggested that PBZ was filtered in small amounts only because of the high degree of plasma protein binding and then excreted by diffusion trapping in the alkaline urine. Much higher U/P ratios were obtained for the hydroxylated derivatives, and one at least (OHPBZ) was secreted into urine.

Five pairs of matched horses were used to study the biochemical and haematological effects of a revised dosage schedule of phenylbutazone. One group of five horses received a phenylbutazone paste formulation daily for 12 days and a second group of five animals received a placebo preparation for a similar time. Some statistically significant differences were recorded from pretreatment levels in both groups of horses. These changes represented instability in baseline levels and could not be ascribed to phenylbutazone administration.

A clinical dose rate (4.4 mg/kg bodyweight) of phenylbutazone was administered intravenously and orally to six Welsh mountain ponies to provide data on the pharmacokinetics and bioavailability of the drug. In three, three-year-old ponies, clearance of the drug from plasma after intravenous administration was almost twice as rapid as in three ponies aged eight to 10 years. After oral administration, plasma phenylbutazone levels were greater in the older ponies, the area under the plasma concentration time curve being almost twice as high. This did not result from more efficient absorption but from slower plasma clearance. The fractional absorption of phenylbutazone was similar in young and older ponies, 0.78 and 0.75, respectively. The 24 hour urinary excretion of phenylbutazone and its hydroxylated metabolites, oxyphenbutazone and gamma-hydroxyphenylbutazone, accounted for approximately 25 per cent of the administered intravenous dose in both young and older ponies. The possible fate(s) of the remaining 75 per cent were considered.

The disposition of phenylbutazone (4.4 mg/kg), administered intravenously to six Welsh Mountain ponies, was described by a two-compartment open model. Pharmacokinetic parameters were not significantly different after morning dosing in comparison with afternoon dosing. When phenylbutazone (4.4 mg/kg) was administered orally to the same ponies, marked variations in time to peak concentrations were produced with different feeding schedules. When access to hay was permitted before and after dosing, the mean time to peak concentration was 13.2 +/- 1.2 h and double peaks in the plasma concentration-time curve were common. Double peaks were also encountered when phenylbutazone was given to ponies deprived of food prior to, and allowed access to hay after, dosing. In this circumstance, mean times to peak concentration were much shorter (3.8 +/- 1.3 h after morning dosing and 5.3 +/- 1.5 h followed afternoon dosing). Absorption was more regular and double peaks were less apparent when food was withheld both before and after dosing. In order to explain these findings, it is tentatively postulated that, whereas some of the administered dose of phenylbutazone may be absorbed quickly, some may become adsorbed on to the feed and subsequently released by fermentative digestion in the large intestine and/or caecum. The consequences of delayed absorption in fed animals for toxicity and clinical efficacy, and for the use of phenylbutazone in equestrian sports, are considered. Delayed absorption in ponies given access to hay was not accompanied by a significant reduction in total absorption. Bioavailability was estimated to be approximately 69% in fed and 78% in unfed ponies. Estimates of bioavailability gave similar values for morning (72%) and afternoon (71%) dosing.

The absorption, metabolism and urinary excretion of phenylbutazone were investigated in six adult cattle in a cross-over study involving administration intravenously, intramuscularly and orally at a dose rate of 4.4 mg kg-1. Following intravenous injection plasma disposition was described by a three compartment open model with mean elimination half-life (t1/2 beta) and clearance (ClB) values of 35.9 hours and 2.77 ml kg-1 h-1, respectively. Somewhat longer t1/2 beta values were obtained after oral and intramuscular dosing and these may have resulted from sequestration within and slow absorption from the gastrointestinal tract and continual uptake from intramuscular sites following precipitation as a depot. Absorption was more complete after intramuscular than after oral dosing; area under curve values were almost twice as high for the intramuscular route. Double peaks in the plasma concentration time curves after oral dosing were recorded in some cows. These may have resulted from drug adsorption on to and subsequent desorption from hay or as a consequence of enterohepatic shunting. There was no evidence for opening of the oesophageal groove and direct passage of the drug into the abomasum. Two hydroxylated metabolites of phenylbutazone, oxyphenbutazone and gamma-hydroxyphenylbutazone were detected in trace amounts in plasma for 72 hours and in much higher concentrations in urine for 168 hours. Approximate urine:plasma (U/P) concentration ratios for the metabolites approached and occasionally exceeded the U/P ratio for endogenous creatinine, indicating poor reabsorption and, possibly, tubular secretion. Cumulative urinary excretion data indicated that the hydroxylated derivatives of phenylbutazone are probably formed more slowly in cattle than in horses.