Assessment of Enrofloxacin Usage and Residue Levels of Enrofloxacin-Ciprofloxacin in Breast and Liver Tissues of Commercial Broilers Sold in Kampala-Uganda.

Background: Human exposure to veterinary drugs like fluoroquinolones occurs due to the presence of their residues in foods from animal sources in varying concentrations. The existence of antibiotic residues in foodstuffs can pose great public health problems to consumers. This study aimed to assess enrofloxacin use patterns and assess residue levels of enrofloxacin/ciprofloxacin in breast muscle and liver tissues of broiler chickens sold for consumption in Kampala capital city. Methods: This was a cross-sectional study that involved both field survey and laboratory-based methods. The field study involved the use of qualitative and semi-quantitative data collection tools to interview 34 broiler farmers and 10 veterinary drugs vendors. For the determination of enrofloxacin/ciprofloxacin levels, 68 chicken breast and liver tissue samples were collected from main markets in Kampala over one month and analyzed using HPLC-UV. Results: Enrofloxacin was the most used antibiotic (100%) for the management of poultry diseases, majorly respiratory diseases (100%), salmonella infections (40%), and disease prevention (60%). Over 76% of the farmers knew the meat withdrawal time (WDT) for enrofloxacin, but none of them adhered to this. Over 70% of the farmers reported that the veterinary drugs vendors were not providing meat WDT information. Enrofloxacin/ciprofloxacin residues were identified in 35.3% (12/34) of the muscle and 38.2% (13/34) of the liver tissues analyzed. Of those muscle and liver tissue samples that tested positive, 25% (3/12) and 38.5% (5/13) respectively had drug concentrations higher than the recommended Maximum Residue Limits. The overall mean enrofloxacin/ciprofloxacin concentration in the chicken muscle and liver tissues was 83.6 (±34.5) µg/kg and 171.5 (±75.9) µg/kg. Conclusion: This observed presence of enrofloxacin/ciprofloxacin levels above safety requirements is attributable to inadequate medicines use information provided by veterinary drugs vendors to farmers and also to the non-compliance of some farmers to meat WDT due to the economic implications.

Application of the herbal chemical marker ranking system (Herb MaRS) to the standardization of herbal raw materials: a case study.

INTRODUCTION: Phytochemical standardization of herbal materials involves establishing consistent levels of one or more active ingredients or markers. It ensures the authenticity and quality of herbal materials, extracts, and their products. This research aimed to apply the herbal chemical marker ranking system (Herb MaRS) originally proposed for quality assurance of complex herbal products to establish markers for controlling the quality of herbal raw materials. METHODS: The assessment of compounds for suitability as markers was based on the Herb MaRS, with minor modifications as follows: for more objective scoring, evidence of biological activity of the potential marker compound(s) was determined at three levels based on the number of symptoms of the disease condition a compound can treat or alleviate: (i) one symptom (1 point), two symptoms (2 points), and 3 or more symptoms (3 points). The reported concentrations of the compounds were also scored as follows: concentration not determined (0 points), concentration ≥ 5 ppm (1 point), concentration ≥ 50 ppm (2 points) and availability of analytical standards (1 point). Finally, the compounds were scored for the availability of an analytical method (1 point). The compounds were scored from 0 to 8, where 8 indicated the most suitable chemical marker. RESULTS: The selected markers were as follows: aromadendrine, α-terpineol, globulol, and 1,8-cineol (in Eucalyptus globulus Labill. ); aloin, aloe emodin, acemannan (in Aloe barbadensis (L.) Burm.f. ), lupeol, lupenone, betulinic acid, betulin, and catechin (in Albizia coriaria Oliv.); mangiferin, catechin, quercetin, and gallic acid (in Mangifera indica L.); polygodial (in Warburgia ugandensis Sprague); azadirachtin, nimbin, nimbidin (in Azadirachta indica A. Juss. ); and 6,8,10-gingerols, and 6-shogaol (in Zingiber officinalis Roscoe). CONCLUSIONS: Herb MaRS can be efficiently applied to select marker compounds for quality control of herbal materials. However, for herbs whose phytochemicals have not been sufficiently researched, it is difficult to establish evidence of activity, and there are no analytical standards and/or methods; this is the case for plants exclusively used in Africa. The markers identified should be incorporated into chromatographic fingerprints, their quantitative methods developed, and evaluated for applicability at the various stages of the production chain of herbal medicines; then, they can be included in future local plant monographs. There is also a need to build local capacity to isolate marker compounds, particularly those that are not sold by current vendors.

Chemometric Classification of Mangifera indica L. Leaf Cultivars, Based on Selected Phytochemical Parameters; Implications for Standardization of the Pharmaceutical Raw Materials.

Introduction: Mangifera indica leaves are among the most common materials employed in manufacturing herbal medicinal products. Despite the phytochemical variation of M. indica cultivars, there are no monographs to guide the cultivation, processing, and authentication of the materials. Methods: This study characterized 15 Ugandan M. indica leaf varieties, with reference to extraction index (EI), total phenolic content (TPC), antioxidant activity (AOA), and mangiferin concentration (MC). In addition, HPLC fingerprints were established to evaluate the overall phytoequivalence of the materials. Then, using hierarchical clustering (HC) and principal component analysis (PCA), the materials were assigned quality grades. Results: The mean EI was 9.39 ± 1.64% and varied among the varieties (P=0.001); the TPC varied significantly (P < 0.0001), from 183.29 ± 2.36 mg/g (Takataka) to 79.47 ± 0.58 mg/g (Apple mango). AOA ranged from 16.81 ± 2.85 µg/mL (Doodo red) to 87.85 µg/mL (Asante). MC varied significantly (P < 0.0001), from 105.75 ± 0.60 mg/g (Kate) to 39.53 ± 0.30 mg/g (Asante). HC gave four major grades: A to D (A, varieties with the highest TPC, MC, and AOA). These parameters reduced to below average from group B to group D. The chromatographic fingerprints were visually similar, but the number of peaks varied, from 19 (Kawanda green) to 29 (Kawanda wide), with 23.5 ± 2.9 average peaks. Whole fingerprints were less similar (r < 0.8) than common peak fingerprints (r > 0.9, P < 0.001). PCA grouped the fingerprints into five clusters; loading plots for PC 1 and 2 revealed two important compounds, one at Rt = 15.828 minutes (mangiferin) and the other at 6.021 minutes. Using the standardized common fingerprints, unknown field samples clustered closely with Koona, Kate, and Kawanda green varieties. Conclusions: The EI, TPC, MC, and AOA values can be utilized to monitor consistency in the quality of materials and the production process. The grades generated can be used to select materials for cultivation and manufacturing. Where minimum concentrations are set, materials of different concentrations are used to dilute or concentrate each other. The HPLC fingerprints can be utilized to authenticate the materials. More samples from different agroecological regions of the country should be tested to cater to climatic variations in order to develop GMP-compliant botanical identification methods.

Green tea silver nanoparticles improve physiological motor and cognitive function in BALB/c mice during inflammation.

Information on the basic changes associated with green tea small molecules in acute inflammation is deficient. The purpose of the study was to characterize and establish the effects of green tea silver nanoparticles (AgNPs) following inflammation in BALB/c male mice. In this study, green tea silver nitrate nanoparticles were characterized and the extract were made up to constitute high (100%), medium (10%), and low (1%) concentrations for administration. Acute inflammation was induced in groups I-V of the experimental rodents by injecting 0.5 ml/kg of fresh egg albumin on the subplantar surface of the right hind paw and animals were monitored for 36 h. Group I-III were administered 100%, 10%, 1% green tea nanoparticles extract while group IV was given diclofenac. Group V was the positive control while group VI was the negative control that received the vehicle. Paw edema was measured at a 2 h interval for 3 days, while the pain was assessed by measuring the locomotion activity using the voluntary wheel running and the anxiety-like behavior. Hypersensitivity was measured through the temperature sensation experiment and a non-linear regression analysis was done. Here, synthesized green tea AgNPs registered an absorbance band at 460 nm, phytochemicals due to presence of organic functional groups of O[bond, double bond]C[bond, double bond]O of oxycarbons, of C[bond, double bond]C of a conjugate alkene, C[bond, double bond]O of a stretching bond of a secondary alcohol. The silver green tea nanoparticles were spherical, covered by a slimy layer, capped and stable. Green tea AgNPs significantly decreased temperature hypersensitivity in BALB/c male mice and this demonstrated their protective effects. Low concentrations of green tea nanoparticles inhibited edema thus mimicking effects of diclofenac, however, the percentage of inhibition was highest in medium and high silver-tea nanoparticles concentrations demonstration the importance of concentration in therapeutics. Anxiety was lowest in BALB/c male mice treated with high concentrations of silver green tea nanoparticles, and this led to increased locomotory activity in mice. Green tea AgNPs have strong anti-inflammatory effects at high concentrations. Concentrations of green tea AgNPs modulated basic sensory and motor behaviors in BALB/c male mice demonstrating their importance in complementary and integrative medical practice.

Safety and Efficacy of Medicinal Plants Used to Manufacture Herbal Products with Regulatory Approval in Uganda: A Cross-Sectional Study.

Introduction: The Uganda National Drug Authority requires phytochemical screening, freedom from microbial contamination, and evidence of safety and efficacy of the constituent plants to register herbal products. Since Uganda has no pharmacopeia, safety, efficacy, and plant processing information are not readily available. We documented the plant materials used to manufacture products in Uganda and established evidence of their safety and efficacy and availability of monographs. Methods: The NDA register of herbal products was reviewed, and a product list was extracted. The herbal products were purchased from local pharmacies, and their labels were studied to identify plant ingredients and drug use. Literature was reviewed to document evidence of the safety and efficacy of the plant materials concerning manufacturer's claims. Also, the WHO and available African Pharmacopeia were searched to establish the availability of the plant monographs. Results: Of the 84 NDA-registered local products, only 18 were obtained from the market; 82% were indicated for respiratory tract disorders. Thirty-three plant materials were listed with Eucalyptus globulus Labill, being the commonest. Several in vitro and in vivo studies demonstrate efficacy, thus supporting the use of the selected plant species for empirical treatment as stated on the product label. While most plants were safe, some species such as Albizia coriaria Oliv. had dose-dependent toxicities that cannot be predicted in combinations. The WHO, African Pharmacopoeia, and West African Herbal Pharmacopoeia had only 16 plant monographs of the 33 plants of interest. Nevertheless, Aloe vera (L.) Burm.f., Azadirachta indica A.Juss., Zingiber officinale Roscoe, and Allium sativum L. monographs were published by all three pharmacopoeias. Conclusions: Preclinical evidence of safety and efficacy exists in the literature for most of the plants used to manufacture registered herbal products in Uganda. More specific bioassays and clinical trials are required for the products to provide conclusive evidence of safety and toxicity. Monographs are urgently needed for the Ugandan plants.

Evaluation of the Clinical Use of Ceftriaxone among In-Patients in Selected Health Facilities in Uganda.

Ceftriaxone has a high propensity for misuse because of its high rate of utilization. In this study, we aimed at assessing the appropriateness of the clinical utilization of ceftriaxone in nine health facilities in Uganda. Using the World Health Organization (WHO) Drug Use Evaluation indicators, we reviewed a systematic sample of 885 patients' treatment records selected over a three (3)-month period. Our results showed that prescriptions were written mostly by medical officers at 53.3% (470/882). Ceftriaxone was prescribed mainly for surgical prophylaxis at 25.3% (154/609), respiratory tract infections at 17% (104/609), and sepsis at 11% (67/609), as well as for non-recommended indications such as malaria at 7% (43/609) and anemia at 8% (49/609). Ceftriaxone was mostly prescribed once daily (92.3%; 817/885), as a 2 g dose (50.1%; 443/885), and for 5 days (41%; 363/885). The average score of inappropriate use of ceftriaxone in the eight indicators was 32.1%. Only 58.3% (516/885) of the ceftriaxone doses prescribed were administered to completion. Complete blood count and culture and sensitivity testing rates were 38.8% (343/885) and 1.13% (10/885), respectively. Over 85.4% (756/885) of the patients improved and were discharged. Factors associated with appropriate ceftriaxone use were gender, pregnancy status, days of hospitalization, health facility level of care, health facility type, and type of prescriber.

Correction to: Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats.

An amendment to this paper has been published and can be accessed via the original article.

Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats.

OBJECTIVE: Antimalarials are globally used against plasmodium infections, however, information on the safety of new antimalarial combination therapies on the gastric mucosa is scarce. The aim of this study was to investigate the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on ulcer induction. Malondialdehyde (MDA), reduced glutathione (GSH) and major histological changes in male Wistar rats following ulcer induction using Indomethacin were investigated. Gastric ulcers were in four groups; Group I was administered Artesunate, group II received Artesunate-Amodiaquine, group III received Artemether-Lumefantrine, and group IV was a positive control (normal saline). Group V was the negative control consisting of healthy rats. RESULTS: Antimalarial combination therapies were associated with a high gastric ulcer index than a single antimalarial agent, Artesunate. In addition, levels of MDA were significantly higher in the combination of therapies while levels of GSH were lower in comparison to Artesunate and the negative control. Microscopically, antimalarial combination therapies were associated with severe inflammation and tissue damage than Artesunate in the gastric mucosa showing that antimalarial combination therapies exert their toxic effects through oxidative stress mechanisms, and this leads to cellular damage. Findings in this study demonstrate a need to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries.

Why regulatory indifference towards pharmaceutical pollution of the environment could be a missed opportunity in public health protection. a holistic view.

The last generation has witnessed bludgeoning of the world's population, a spike in disease burden, and unprecedented levels of pharmaceutical consumption and production. Unfortunately, pharmaceuticals have left their industrial and household confines and leaked into the environment. Pharmaceuticals are now major environmental pollutants, and are ubiquitous in waters and soils. Unlike other environmental contaminants, pharmaceutical pollutants are not yet regulated globally, simply because acute risk assessments show insignificant human health hazard. But the pitfalls of pharmaceutical pollutants extend beyond acute effects to delayed effects from bioaccumulation, amplified effects from drug-drug interactions, exacerbation of drug resistance, and reduction in aquatic and terrestrial food production. Therefore, ignoring pharmaceutical pollutants deprives society of holistic public health protection.