Effects of prenatal antibiotic treatment on early infant health: a retrospective study in a rural health facility in Ghana.

Background: Infant mortality remains a major developmental challenge in many low-income countries. Epidemiological evidence suggests that infant acquisition of maternal microbiome is essential for programming of immunity and metabolism. As such, irrational maternal antibiotic use may affect infant health. Objectives: The aim of the study was to determine the effects of prenatal antibiotic use on early postnatal life (90 days) in a low-income community in Ghana. Methodology: The study was a retrospective study of 412 mother-baby pair medical records in a low-income community in rural Ghana. Results: During the ninety-day period, the prevalence and relative risk of neonatal sepsis, respiratory disorders, and dermatitis were significantly higher in infants treated prenatally with antibiotics compared to untreated infants. Prenatal antibiotic treatment was not significantly associated with the risk of developing neonatal jaundice and conjunctivitis. However, prenatally antibiotic exposed infants were three times likely to visit the hospital for a non-scheduled/non-review treatment within the first 90 days compared to unexposed babies. Conclusions: Intrapartum antibiotic treatment is associated with poor early infant health. Rationalizing antibiotic use during pregnancy may contribute to reducing infant mortality.

Pharmacotherapy for Infertility in Ghana: A Prospective Study on Prescription Patterns and Treatment Outcomes among Women undergoing Fertility Treatment.

Background: Pharmacotherapy remains a first-line and major treatment option for couples struggling with infertility, especially in sub-Saharan Africa, where other expensive alternatives are rarely available. Despite the reliance on pharmacotherapy for treating infertility in the subregion, especially for those diagnosed with unexplained infertility, little is known about the actual influence of drug therapies on conception. Objectives: The study aimed to prospectively assess the prescription patterns and outcomes of pharmacotherapy for women undergoing fertility treatment in Ghana. Methods: This prospective cohort study involved 482 infertile women presenting for fertility treatment in 4 fertility clinics in the Cape Coast Metropolis of Ghana between March 2019 and February 2021. A simple random sampling technique was used to recruit subjects for the study. The women were followed up for 12 months to assess the outcome of drug therapy on conception. Data analysis was done using Stata version 14. Logistic regression was used to assess the association between trends with dichotomous outcomes. Results: The study identified that approximately 45.2% of the patients received monotherapy, whereas 24.1% received a combination of 2 drugs. Patients treated with a combination of 3 drugs were more likely to conceive (adjusted odds ratio = 4.10; 95% CI, 1.29-13.02; P = 0.02) than those without treatment. Conclusions: Patients treated with combination therapies had higher chances of conception than those without medications. However, a combination of nutritional and herbal therapies were associated with improved outcomes compared with conventional and nutritional supplements. The study's outcome could provide fertility specialists and stakeholders insight into choosing appropriate treatment options for prospective couples seeking fertility care. Consequently, fertility patients can access specific treatment options to meet their desired needs.

Pharmacotherapy of infertility in Ghana: Why do infertile patients discontinue their fertility treatment?

BACKGROUND: Globally, millions of people of reproductive age experience infertility. With that notwithstanding, most infertile patients undergoing pharmacotherapy withdraw from treatment before achieving the desired outcome. The reasons for their withdrawal, particularly in sub-Saharan Africa, have not been well examined, hence the need for this study. OBJECTIVES: The aim of the study was to examine why infertile patients discontinue pharmacotherapy prior to achieving conception. METHODS: The study employed an exploratory qualitative design. Purposive sampling technique was used to recruit subjects into the study. Twenty infertile patients (fourteen females and six males) who discontinued their treatment, and eight attending health professionals who provided direct care to these patients were interviewed. Telephone and face-to-face interviews were conducted using a semi-structured interview guide. The data collected were transcribed, coded, and generated into themes using thematic content analysis. RESULTS: The major reasons for discontinuation of infertility treatment included lack of support from male partners, seeking alternative treatment, unmet outcome, poor medical services, distance, stigmatization, and relocation. CONCLUSIONS: Patients and healthcare personnel shared both similar and diverse views on reasons for discontinuation of infertility treatment that reflect situations in a typical African setting, most of which are not reported in existing studies. The outcome of this study will provide insight for fertility therapists and policy makers in designing appropriate measures to facilitate maximum compliance and improvement in treatment outcome.

The Pharmacologically Active Alkaloid Cryptolepine Activates a Type 1 Interferon Response That Is Independent of MAVS and STING Pathways.

Type 1 interferons (IFN-1) are pleiotropic cytokines with well-established anticancer and antiviral properties, particularly in mucosal tissues. Hence, natural IFN-1-inducing treatments are highly sought after in the clinic. Here, we report for the first time that cryptolepine, a pharmacoactive alkaloid in the medicinal plant Cryptolepis sanguinolenta, is a potent IFN-1 pathway inducer. Cryptolepine increased the transcript levels of JAK1, TYK2, STAT1, STAT2, IRF9, and OAS3, as well as increased the accumulation of STAT1 and OAS3 proteins, similar to recombinant human IFN-α. Cryptolepine effects were observed in multiple cell types including a model of human macrophages. This response was maintained in MAVS and STING-deficient cell lines, suggesting that cryptolepine effects are not mediated by nucleic acids released upon nuclear or organelle damage. In agreement, cryptolepine did not affect cell viability in concentrations that triggered potent IFN-1 activation. In addition, we observed no differences in the presence of a pharmacological inhibitor of TBK1, a pleiotropic kinase that is a converging point for Toll-like receptors (TLRs) and nucleic acid sensors. Together, our results demonstrate that cryptolepine is a strong inducer of IFN-1 response and suggest that cryptolepine-based medications such as C. sanguinolenta extract could be potentially tested in resource-limited regions of the world for the management of chronic viral infections as well as cancers.

Cryptolepine inhibits hepatocellular carcinoma growth through inhibiting interleukin-6/STAT3 signalling.

BACKGROUND: Diverse signalling pathways are involved in carcinogenesis and one of such pathways implicated in many cancers is the interleukin 6/signal transducer and activator of transcription 3 (IL-6/STAT3) signalling pathway. Therefore, inhibition of this pathway is targeted as an anti-cancer intervention. This study aimed to establish the effect of cryptolepine, which is the main bioactive alkaloid in the medicinal plant Cryptolepis sanguinolenta, on the IL-6/STAT3 signalling pathway. METHODS: First, the effect of cryptolepine on the IL-6/STAT3 pathway in human hepatoma cells (HepG2 cells) was screened using the Cignal Finder Multi-Pathway Reporter Array. Next, to confirm the effect of cryptolepine on the IL-6/STAT3 signalling pathway, the pathway was activated using 200 ng/mL IL-6 in the presence of 0.5-2 µM cryptolepine. The levels of total STAT3, p-STAT3 and IL-23 were assessed by ELISA. RESULTS: Cryptolepine downregulated 12 signalling pathways including the IL-6/STAT3 signalling pathway and upregulated 17 signalling pathways. Cryptolepine, in the presence of IL-6, decreased the levels of p-STAT3 and IL-23 in a dose-dependent fashion. CONCLUSION: Our results demonstrated that cryptolepine inhibits the IL-6/STAT3 signalling pathway, and therefore cryptolepine-based remedies such as Cryptolepis sanguinolenta could potentially be used as an effective immunotherapeutic agent for hepatocellular carcinoma and other cancers.

Antiplasmodial and Antipyretic Activity and Safety Evaluation of the Methanolic Leaf Extract of Murraya exotica (L.).

BACKGROUND: The increasing mortality and morbidity of malaria in Africa coupled with the recent reports of antimalarial drug resistance reinforces the need for novel antimalarial agents from natural plant products with folkloric use for the disease. Murraya exotica (L.) (Rutaceae) is widely used as an ornamental plant used indigenously to treat fever, cough, and infectious wounds and eliminate pain from injury and trauma. This study was conducted to evaluate extracts of the leaves of Murraya exotica (L.) (Rutaceae) for its safety and antipyretic and antimalarial activity in rodent models. METHOD: In this study, the Peters 4-day suppressive and curative test in Plasmodium berghei-infected mice was used to demonstrate the antiplasmodial activity of the methanolic leaf extract of Murraya exotica (L.) (MEE). The study also evaluated the subacute toxicity study and the antipyretic activity of MEE on baker's yeast-induced hyperthermia in rodent models. RESULTS: Murraya exotica (L.) extract demonstrated curative antimalarial activity, with a percentage suppression of 45.84, 64.32 ± 0.33, 56.74 ± 2.16, and 64.61 ± 0.67 at doses of 50, 100, 300, and 600 mg/kg, respectively. In the Peters 4-day suppressive test, MEE at dose 600 mg/kg had the highest chemosuppression (76.02 ± 1.38%) compared with artesunate (2 mg/kg, p.o.) (82.56 ± 0.97%). Subacute oral toxicity studies in Sprague-Dawley rats documented no deaths, with no significant changes in clinical signs, organ weights, and hematological and biochemical parameters. The LD50 of MEE was estimated to be above 1000 mg/kg in Sprague-Dawley rats. All doses of MEE and paracetamol reduced pyrexia in 1 h and 2 h after their administration. The percentage reduction of rectal temperature (T R ) for the positive control (paracetamol, 150 mg/kg, p.o.) was 44.36% while the Murraya exotica extract at doses 50 mg/kg, 100 mg/kg, 300 mg/kg, and 600 mg/kg recorded 67.74%, 40.78%, 66.42%, and 59.42%, respectively. Murraya exotica at dose 100 mg/kg exhibited significant reduction (p < 0.05) in baker's yeast-induced pyrexia. CONCLUSIONS: The findings in this study show the antipyretic, curative, and suppressive antiplasmodial activity as well as the safety of the methanolic leaf extract of Murraya exotica (L.) supporting its traditional use for malaria and fever.

Synthesis and In Vitro Antimicrobial and Anthelminthic Evaluation of Naphtholic and Phenolic Azo Dyes.

The antimicrobial activity of 2-naphtholic and phenolic azo compounds was determined against seven microbial species, Staphylococcus aureus (ATCC 25923), Streptococcus pyrogenes (clinical), and Enterococcus faecalis (ATCC 29212), Salmonella typhi (clinical), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 251922), and Candida albicans (ATCC 10231), using the high-throughput spot culture growth inhibition assay (HT-SPOTi). The minimum inhibitory concentrations (MIC) were determined for the active azo dyes. All the azo compounds (A1-B4) were screened for anthelmintic activity against adult Ghanaian earthworms, Hyperiodrilus spp. As part of the systematic investigation for biological activity, all the azo compounds exhibited good antimicrobial activity against the seven human pathogenic microorganisms. All the compounds exhibited anthelminthic activity against adult Ghanaian earthworms, Hyperiodrilus spp.

Flavonoid-Rich Extract of Dissotis rotundifolia Whole Plant Protects against Ethanol-Induced Gastric Mucosal Damage.

Dissotis rotundifolia is a plant in the family Melastomataceae. The methanolic extract of the whole plant is reported to be rich in C-glycosylflavones such as vitexin and orientin. Though there are several reports on the ethnomedicinal use of this plant extract in stomach ulcers, experimental-based data is unavailable. The drive for carrying out this research was to obtain data on the possible ameliorative effect of the whole plant extract of Dissotis rotundifolia (DRE) in gastric ulcerations induced by ethanol in Sprague Dawley (SD) rats. SD rats were pretreated with 100, 300, and 500 mg/kg of DRE for 14 days after which an ulcerogen-ethanol was administered. Gross examinations of the stomach lining and histological analysis of gastric lesions were carried out coupled with an assessment of the antioxidant activity of gastric mucosa using MDA, GSH, CAT, and SOD as indicators. The data suggested a significant attenuation in gastric mucosal damage in DRE-pretreated ethanol-induced gastric ulcer reflected in the antioxidant status. There was also a reduction or absence of hemorrhage, edema, and leucocytes infiltration in DRE-treated groups compared to the negative control group. DRE conserved glutathione (GSH) levels, reduced malondialdehyde (MDA) levels, and enhanced catalase (CAT) and superoxide dismutase (SOD) enzyme levels. The present study shows that DRE possess protective effects against ethanol-induced ulcer damage in the stomach of rats, which could be attributed to its antioxidant activity.

Acetic Acid-Induced Ulcerative Colitis in Sprague Dawley Rats Is Suppressed by Hydroethanolic Extract of Cordia vignei Leaves through Reduced Serum Levels of TNF-α and IL-6.

BACKGROUND: Ulcerative colitis (UC) is a recurrent inflammatory bowel disease (IBD) that causes long-lasting inflammation on the innermost lining of the colon and rectum. Leaf decoctions of Cordia vignei have been used in traditional medicine either alone or in combination with other plant preparations to treat the disease. AIM: In this study, we investigated the effect of hydroethanolic extract of Cordia vignei have been used in traditional medicine either alone or in combination with other plant preparations to treat the disease. METHOD: Male Sprague Dawley rats received oral treatment of either saline (10 ml/kg), sulfasalazine (500 mg/kg), or CVE (30-300 mg/kg) daily for 7 days. On day 4, colitis was induced by a single intrarectal administration of 500 µl of acetic acid (4% v/v/. RESULTS: CVE significantly (P < 0.05) prevented colonic ulceration and reduced the inflammatory score. Serum levels of TNF-α and IL-6 were significantly reduced. Depletion of superoxide dismutase (SOD) and catalase (CAT) activities by acetic acid was significantly inhibited while lipid peroxidation indexed as malondialdehyde (MDA) level in the colon was reduced. However, loss of body weight was not significantly affected by treatment with CVE. CONCLUSION: This data suggest that CVE has a potential antiulcerative effect.

Pharmacotherapy of infertility in Ghana: retrospective study at the cape coast teaching hospital.

BACKGROUND: Infertility is a major challenge for couples globally. Due to low income levels and the high cost of other assisted reproductive techniques, pharmacotherapy remain the major first line treatment option for infertility in Sub-Saharan Africa. OBJECTIVE: The aim of this study was to assess the prevalence of infertility as well as the effectiveness and success achieved following infertility pharmacotherapy at the Cape Coast Teaching Hospital in Ghana. METHODS: This study was a retrospective observational study of 825 couples attending infertility clinic at the hospital. RESULTS: Prevalence of infertility at the study center was estimated to be 12.3%. Treatment mainly involved the use of clomiphene citrate, antioxidants, herbo-mineral drugs (Ayurveda), multivitamin and antibiotics. Pharmacotherapy resulted in successful conception in one out of every five couples (19.4%; n = 160). Secondary infertility, although more prevalent in the study population (44.8%; n = 370), had lower conception rates during pharmacotherapy than primary infertility (15% vs 26.2%). Age, kind of infertility, employment status but not educational level were significantly associated with pharmacotherapy success. In ovulation induction, clomiphene citrate plus folic acid and vitamin E adjuncts improved ovulation rates during cycle treatments compared to clomiphene citrate alone. Pharmacotherapy of idiopathic infertility (39%, n = 323) was a major challenge with very limited success rates. Interestingly, it was noted that treating couples or female partners only for idiopathic infertility resulted in higher success rates than treating the male partner only. Again, 90-day treatment regimen doubled conception rates when compared with corresponding 30-day treatment regimen. However, zinc sulfate even in short term treatment regimens (30 days) enhanced conception rates in idiopathic infertility. CONCLUSIONS: Prevalence of infertility was estimated to be about 12.3%. One out of every five infertile couples achieved success with pharmacotherapy. Factors such as age, type of infertility, employment status, but not education were significantly associated with treatment success.

Cryptolepine, the Main Alkaloid of the Antimalarial Cryptolepis sanguinolenta (Lindl.) Schlechter, Induces Malformations in Zebrafish Embryos.

BACKGROUND: Previous studies on cryptolepine, the antimalarial and cytotoxic alkaloid of Cryptolepis sanguinolenta, showed that it preferentially accumulates in rapidly proliferating cells and melanin-containing tissues. Subsequently, we demonstrated that cryptolepine was toxic to murine embryos in vivo but no signs of teratogenicity. in vivo developmental studies can be confounded by maternal effects. Here, we hypothesized that cryptolepine-induced embryo toxicity occurs at least partly through direct inhibition of embryogenesis rather than indirectly through the induction of maternal toxicity. AIM: To determine the effects of cryptolepine on developing zebrafish embryos ex vivo. METHODS: Healthy synchronized zebrafish eggs were treated with cryptolepine (10-1 - 5 × 102 µM), benzyl penicillin (6 - 6 × 102 µM), or mercury chloride (3.7 × 10-1 - 3.7 × 101 nM) from 6 to 72 hours postfertilization. Developing embryos were assessed at 24, 48, 72, and 96 hours under microscope for lethality, hatching rate, and malformation. RESULTS: LC50 for cryptolepine in the study was found to be 260 ± 0.174 µM. Cryptolepine induced dose- and time-dependent mortality from the 24 to 96 hours postfertilization. Lower cryptolepine concentration (<100 µM) caused mortality, approximately 15-18%, only after the 48 hours postfertilization. The most sensitive period of embryo lethality corresponded well with the pharyngula (24 to 48 hours) and hatching (48 to 72 hours) stages of embryonic development. Cryptolepine (10-1 - 5 × 102 µM) dose dependently inhibited the hatching rate. At doses above 500 µM, hatching was completely inhibited. Mercury chloride (3.7 × 10-1 - 3.7 × 101 nM), used as positive control, induced a consistent pattern of embryo lethality at all stages of development, whereas benzyl penicillin (6 - 6 × 102 µM), used as negative control, did not induce any significant embryo lethality. Morphological examination of (postfertilization day 5) of eleutheroembryos treated during embryonic development with cryptolepine showed decreased body length (growth inhibition), decreased eye diameter and bulginess, enlarged pericardia, and enlarged yolk sac and muscle malformations. CONCLUSION: Cryptolepine induces malformations, growth retardation, and mortalities in rapidly dividing zebrafish embryos ex vivo.

Isolation of Helicobacter pylori from Gastric Biopsy of Dyspeptic Patients in Ghana and In Vitro Preliminary Assessment of the Effect of Dissotis rotundifolia Extract on Its Growth.

Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the human stomach. Infection with this microaerophilic bacterium causes gastric and duodenal ulcer. This study sought to isolate H. pylori, from gastric biopsy samples of dyspeptic patients in Ghana using a 2,3,5-triphenyltetrazolium chloride (TTC) dye incorporated medium method. This TTC dye method was further used in an antimicrobial susceptibility assay involving Dissotis rotundifolia extract (DRE). H. pylori were successfully isolated from gastric biopsy of dyspeptic patients. Pure cultures of H. pylori in 2,3,5-triphenyltetrazolium chloride (TTC) dye incorporated medium were seen as sparkling colonies. Isolates, identified as H. pylori, were gram-negative and urease, catalase, and oxidase positive and showed characteristic morphology as spiral-shaped bacteria under the microscope. The organisms were found to be susceptible to cephalothin and resistant to nalidixic acid. Above all, the observation that H. pylori grew only at 37°C and not 25°C or 42°C affirms that the bacterium is neither Helicobacter cinaedi nor Helicobacter fenneliae. The anti-H. pylori study depicts a statistically lower zone of inhibition for DRE compared to standard drugs [amoxicillin and clarithromycin] (p<0.05), whereas metronidazole showed no zone of inhibition. This study reports the first successful isolation and culturing of H. pylori in Ghana using TTC dye. It also shows that DRE possess an in vitro anti-H. pylori activity and that DRE has some therapeutic potential against H. pylori infection.

DNA Damage Protecting Activity and Antioxidant Potential of Launaea taraxacifolia Leaves Extract.

BACKGROUND: The leaf extract of Launaea taraxacifolia commonly known as African Lettuce is used locally to treat dyslipidemia and liver diseases, which are associated with oxidative stress. Methanol extract from L. taraxacifolia leaves was tested for its antioxidant activity and its ability to protect DNA from oxidative damage. MATERIALS AND METHODS: In vitro antioxidant potential of the leaf extract was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO), and hydroxyl (OH) radical scavenging assays. Ferric reducing power, total antioxidant capacity (TAC), metal chelating, and anti-lipid peroxidation ability of the extract were also examined using gallic acid, ascorbic acid, citric acid, and ethylenediaminetetraacetic acid as standards. RESULTS: L. taraxacifolia leaves extract showed antioxidant activity with IC50 values of 16.18 µg/ml (DPPH), 123.3 µg/ml (NO), 128.2 µg/ml (OH radical), 97.94 µg/ml (metal chelating), 80.28 µg/ml (TAC), and 23 µg/ml (anti-lipid peroxidation activity). L. taraxacifolia leaves extract exhibited a strong capability for DNA damage protection at 20 mg/ml concentration. CONCLUSION: These findings suggest that the methanolic leaf extract of L. taraxacifolia could be used as a natural antioxidant and also as a preventive therapy against diseases such as arteriosclerosis associated with DNA damage.

In vitro H+/K+-ATPase Inhibition, Antiradical Effects of a Flavonoid-rich Fraction of Dissotis rotundifolia, and In silico PASS Prediction of its Isolated Compounds.

BACKGROUND: Dissotis rotundifolia, commonly referred to as pink lady, has several medicinal uses including peptic ulcer. This study investigated the inhibitory effects of D. rotundifolia extract on H+/K+-ATPase and also assessed its antiradical activity. In silico study of some isolated compounds of this plant was also carried out to affirm the suspected binding properties of extract to H+/K+-ATPase enzyme. MATERIALS AND METHODS: D. rotundifolia whole plant extract was obtained after extraction process and then assessed for its ability to scavenge free radicals in four in vitro test models. Its ability to inhibit the activity of H+/K+-ATPase enzyme was also evaluated. Molecular docking was carried out on phytoconstituents, namely, vitexin, isovitexin, orientin, and isoorientin reported to be present in the whole plant extract. RESULTS: Data obtained indicated that D. rotundifolia extract (DRE) exhibits strong antioxidant activity. DRE also showed inhibitory effects on H+/K+-ATPase enzyme activity. Docking studies affirmed the in vitro binding effect of the extract to H+/K+-ATPase. CONCLUSION: These findings suggest that the plant extract possess antioxidant and antipeptic ulcer activity.

In vitro anti-malarial interaction and gametocytocidal activity of cryptolepine.

BACKGROUND: Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues. METHODS: The resazurin-based assay was employed in evaluating the gametocytocidal properties of C. sanguinolenta and cryptolepine against the late stage (IV/V) gametocytes of Plasmodium falciparum (NF54). A fixed ratio method based on the SYBR Green I fluorescence-based assay was used to build isobolograms from a combination of cryptolepine with four standard anti-malarial drugs in vitro using the chloroquine sensitive strain 3D7. RESULTS: Cryptolepis sanguinolenta (IC50 = 49.65 nM) and its major alkaloid, cryptolepine (IC50 = 1965 nM), showed high inhibitory activity against the late stage gametocytes of P. falciparum (NF54). In the interaction assays in asexual stage, cryptolepine showed an additive effect with both lumefantrine and chloroquine with mean ΣFIC50s of 1.017 ± 0.06 and 1.465 ± 0.17, respectively. Cryptolepine combination with amodiaquine at therapeutically relevant concentration ratios showed a synergistic effect (mean ΣFIC50 = 0.287 ± 0.10) whereas an antagonistic activity (mean ΣFIC50 = 4.182 ± 0.99) was seen with mefloquine. CONCLUSIONS: The findings of this study shed light on the high gametocytocidal properties of C. sanguinolenta and cryptolepine attributing their potent anti-malarial activity mainly to their effect on both the sexual and asexual stages of the parasite. Amodiaquine is a potential drug partner for cryptolepine in the development of novel fixed dose combinations.

Identification of cryptolepine metabolites in rat and human hepatocytes and metabolism and pharmacokinetics of cryptolepine in Sprague Dawley rats.

BACKGROUND: This study aims at characterizing the in vitro metabolism of cryptolepine using human and rat hepatocytes, identifying metabolites in rat plasma and urine after a single cryptolepine dose, and evaluating the single-dose oral and intravenous pharmacokinetics of cryptolepine in male Sprague Dawley (SD) rats. METHODS: The in vitro metabolic profiles of cryptolepine were determined by LC-MS/MS following incubation with rat and human hepatocytes. The in vivo metabolic profile of cryptolepine was determined in plasma and urine samples from Sprague Dawley rats following single-dose oral administration of cryptolepine. Pharmacokinetic parameters of cryptolepine were determined in plasma and urine from Sprague Dawley rats after single-dose intravenous and oral administration. RESULTS: Nine metabolites were identified in human and rat hepatocytes, resulting from metabolic pathways involving oxidation (M2-M9) and glucuronidation (M1, M2, M4, M8, M9). All human metabolites were found in rat hepatocyte incubations except glucuronide M1. Several metabolites (M2, M6, M9) were also identified in the urine and plasma of rats following oral administration of cryptolepine. Unchanged cryptolepine detected in urine was negligible. The Pharmacokinetic profile of cryptolepine showed a very high plasma clearance and volume of distribution (Vss) resulting in a moderate average plasma half-life of 4.5 h. Oral absorption was fast and plasma exposure and oral bioavailability were low. CONCLUSIONS: Cryptolepine metabolism is similar in rat and human in vitro with the exception of direct glucuronidation in human. Clearance in rat and human is likely to include a significant metabolic contribution, with proposed primary human metabolism pathways hydroxylation, dihydrodiol formation and glucuronidation. Cryptolepine showed extensive distribution with a moderate half-life.

Antibiotic use during pregnancy: a retrospective study of prescription patterns and birth outcomes at an antenatal clinic in rural Ghana.

BACKGROUND: Babies are increasingly being exposed to antibiotics intrapartum in the bid to reduce neonatal and maternal deaths. Intrapartum antibiotic exposure, including even those considered safe in pregnancy, have been associated with childhood obesity and compromised immunity. Data on the extent of antibiotic use, safety and its impact on birth outcomes and neonatal health in Sub-Saharan Africa is very limited. This study sought to ascertain the extent of antibiotic use in pregnancy and its effects on birth outcomes in a rural hospital in Ghana. METHODS: The study was a retrospective randomized study of mothers who delivered babies in a rural hospital between 2011 and 2015 in Ghana. A total of 412 mother/baby records out of 2100 pre-selected met the inclusion criteria of the study. Indicators of neonatal health used were birthweight, Apgar score, incidence of birth defects. RESULTS: Sixty five percent of pregnant women were administered antibiotics at some stage during pregnancy. Beta Lactam antibiotics accounted for more than 67% of all antibiotics prescribed. There was a statistically significant association between antibiotic exposure and pregnancy factors such as stage of pregnancy, parity and mode of delivery but not with socio-economic status of the mother. Intrapartum antibiotic exposure did not significantly affect the birthweight, incidence of congenital birth defect and mean Apgar scores. After adjusting for method of delivery, however, perinatal antibiotic use (24 h to delivery) was associated with lower mean Apgar scores. Birth weight was affected significantly by maternal socio-economic factors such as age and marital status. CONCLUSION: Sixty five percent of women attending the antenatal clinic received antibiotics. Intrapartum antibiotics did not affect early markers of neonatal health such as birthweight, congenital birth defect and mean Apgar scores. However, antibiotic use less than 24 h to delivery was associated with a decrease in mean APGAR score.

Toxicological evaluation and protective effect of ethanolic leaf extract of Launaea taraxacifolia on gentamicin induced rat kidney injury

Objective: To evaluate the toxic potential of Launaea taraxacifolia leaf extract (LTE) in rats within 14 d of oral administration and also assess the potential of LTE in protecting against kidney injury induced by gentamicin using rat model. Methods: The protective ability of LTE was done after sub-acute toxicity evaluation has been carried out. Acute Kidney Injury (AKI) was induced by gentamicin at a dose of 160 mg/kg intraperitoneal i.p. Parameters and indicators considered include mortality, clinical signs, body and organ weights, haematological and clinical chemistry parameters. Gross examination and histopathological assessment was also done on selected internal organs. Results: There were no treatment-related deaths or changes in clinical signs, haemato-logical and clinical chemistry indices during sub-acute toxicity studies with the exception of creatinine levels. This was confirmed by micrographs obtained from histopathological analysis. Co-administration of LTE with 160 mg/kg of gentamicin (i.p) markedly decreased the levels of urea and creatinine when compared to negative control group. Histological studies of kidney tissues showed an insignificant change in tubular epithe-lium in LTE plus gentamicin treated group compared to LTE treated only. Conclusions: Data obtained show that ethanolic leaf extract of Launaea taraxacifolia is non-toxic within a 14 d administration at a maximum dose of 1000 mg/kg bwt and also possesses the ability to protect against gentamicin-induced kidney damage in rats at a dose of 300 mg/kg bwt.

Irrational use of antibiotics and the risk of diabetes in Ghana.

UNLABELLED: Epidemiological studies show clearly that Caesarean birth, perinatal or neonatal irrational antibiotic use is strongly associated with increased risk of obesity and diabetes in later life. Irrational use of antibiotics is a great global public health concern especially in developing economies like Ghana due to poor regulation on medicines. Unfortunately, this concern has been reduced to the fear of development of resistant organisms and the destruction of the world's limited range of antibiotics therapy at the expense of other insidious risks including the development of metabolic and atopic diseases. These risks however appear to have greater implications on public health systems of developing economies. Here, we review the ignored role of antibiotics in the global obesity pandemic and project the risk that it poses to the health system of a developing economy like Ghana. FUNDING: Department of Pharmacology, College of Health Sciences, Kwame Nkrumah university of Science and Technology, Kumasi, Ghana.