Cutaneous leishmaniasis is an infectious-parasitic disease that is vector-transmitted by female Phlebotomus species through a blood meal. The drugs recommended by the Ministry of Health show moderate efficacy and numerous adverse reactions, making it necessary to develop new drugs. However, it is essential to establish new and vibrant diagnostic techniques detecting and quantifying the parasites in experimental animals in the pre-clinical phase. Therefore, the aim of this project was to evaluate clinical and parasitological aspects in Mesocricetus auratus infected with Leishmania amazonensis, thus making it possible to compare the diagnostic methods used in in-vivo trials for new therapeutic agents for cutaneous leishmaniasis. L. amazonensis promastigotes were inoculated into 12 adult hamsters. The trial was divided into two groups, one treated with Glucantime® and the other untreated. During treatment, the animals were monitored clinically and the lesion area was measured. After the 40th day, the animals were euthanized to obtain fragments of the lesions for parasitological, histopathological, and molecular analysis. The GLUC group had nodular lesions, while the CONT- group had ulcerated lesions with a 445.9% increase in volume. The parasitological and histopathological analyses corroborated the results obtained from real-time PCR, showing a lower parasite load, mild dermatitis and a significant reduction in the concentration of parasite DNA compared to CONT-group. The study confirms that clinical assessment and application of parasitological, histopathological, and molecular diagnostic techniques are essential in determining the clinical and parasite profile more accurately in experimental animals used for pre-clinical which can be used to test and recommend new therapeutic drugs for cutaneous leishmaniasis. Key words: Cutaneous leishmaniasis, mesocricetus auratus, Glucantime®, Leishmania amazonensis, diagnostic tests.
Drug promotion influences physicians in such a way that they have a tendency for irrational prescribing, preference for newer, more expensive drugs and an inability to identify incorrect claims about drug products. Therefore, this study assessed interactions of drug promoters and physicians and its effect on prescribing in Ethiopia. A cross sectional study was conducted among physicians working both in private and public health facilities, and drug promoters in Dessie town, Ethiopia. Data was collected using a structured self-administered questionnaire. Statistical analysis was carried out using SPSS 20 software. This study found that drug promoters visited most of physicians and half of them accepted a gift from drug promoters. Drug sample, office stationery and invitation for training were the most common types of gifts offered to physicians. Regarding to perception of physicians, nearly two third of physicians perceived that the information received from drug promoters is not adequate. Most of the physicians said that promoters did not influence the prescribing behaviour of physicians about newly promoted drugs. About half of the physicians believed that drug promoters should not promote their products in the way they are doing currently. Drug companies were claimed to be sources of information for physicians to learn about drugs; however, they perceived that information received from drug promoters is biased in favour of their products. Key words: Social and environmental factors, drug promotion, Ethiopia.
Alzheimer's disease is one of the most common neurodegenerative diseases characterized by beta-amyloid plaques and neurofibrillary tangles. Alzheimer's is associated with various cellular changes including oxidative stress, neuronal inflammation, and mitochondrial disorders, ultimately leading to neuronal death. Flavonols found in the chamomile plant (Matricaria recutita) exert beneficial effects on brain disorders like Alzheimer's disease owing to their antioxidant properties. In this study, the flavonoids from the methanolic extract of chamomile (M. recutita) were isolated and purified using column chromatography and TLC methods. Flavonols from the flavonoid compounds were then extracted, separated, and identified using spectroscopic methods such as 1H-NMR, 13C-NMR, Mass, and IR. 56 adult male rats were divided into 7 groups, including control (vehicle 1, solvent of flavonol, and solvent of streptozotocin drug), Alzheimer's, and flavonoid doses of 120, 250, and 400 mg/kg. Diabetes was induced by a single intraperitoneal injection of streptozotocin at a dose of 60 mg/kg, and flavonols were administered for 15 days. Memory and learning were assessed using the shuttle box device. Data analysis was conducted using SPSS 22 software, ANOVA, and Tukey tests, with significance set at p ≤ 0.05. The results indicated that doses of 250 and 400 mg/kg of flavonol extracts from chamomile caused significant changes, compared to the control group, ultimately improving avoidance memory in rats. Additionally, oxidative stress parameters were significantly reduced in the Alzheimer's groups treated with chamomile flavonol. Plant flavonols demonstrated the ability to restore spatial memory function and normalize oxidative stress parameters in streptozotocin-treated groups. Key words: Alzheimer, Flavonoid, Flavonol, learning, rat.
Tolerance of treatments is an important factor in compliance and quality of care for various pathologies. The objective of our study was to evaluate the prevalence of adverse events observed in patients at the Abidjan Cardiology Institute (ACI). This descriptive, observational, cross-sectional study involved 200 patients of all ages who were undergoing drug treatment for cardiovascular diseases or other pathologies. These patients were either outpatients coming for consultations or were hospitalized in the medicine department of the Abidjan Cardiology Institute from February 1 to April 1, 2017, and all agreed to participate in the study after providing informed consent. The average age of the patients was 51.7 years (±18 years), with a predominance of women, resulting in a sex ratio of 0.81. The prevalence of adverse events was 24.5%. The majority of these events were dermatological and neurological, predominantly pruritus (39%) and dizziness (10.2%). Additionally, 79.6% of patients reported experiencing such an event once before. In 85.7% of these cases, the similar episode had occurred several years previously. In 69.4% of cases, the adverse events had resulted in incapacity or disability. Nevertheless, all patients had a favorable outcome with no sequelae. The drugs most frequently suspected of causing adverse events were antimalarial drugs (chloroquine; 37%), antihypertensives (26.5%), and analgesics (14.2%). The frequency of adverse events among patients at the ACI was considerable. Establishing a robust pharmacovigilance system at the ACI and integrating adverse event reporting into patients' therapeutic education would help to better assess this safety profile. Key words: Cardiology, prevalence, pharmacovigilance, tolerance.
Highly active antiretroviral therapy (HAART) effectively controls HIV replication in HIV-positive individuals, but chronic immune activation persists, leading to increased virus replication, T cell depletion, and exhaustion, necessitating lifelong HAART to prevent disease progression. This study explores the potential of supplementing HAART with Artemisia annua and Moringa oleifera leaf powders as adjuvants to restore immune function and control viral replication in people living with HIV/AIDS (PLWH). A nested cohort study was conducted with 31 PLWH on HAART randomized to the control group (n = 15) and the intervention group (n = 16) that supplemented HAART with A. annua and M. oleifera leaf powder. Peripheral blood mononuclear cells (PBMCs) were obtained from the study participants to measure the expression of activation markers (IFN-γ, IL-2, IL-10, and HLA-DR), inhibitory and degranulation receptors (PD-1 and CD107a, respectively) expressed by CD4+ and CD8+ T cells using flow cytometry at baseline and 12 months. Viral load was also measured using quantitative polymerase chain reaction (qPCR). Compared to the controls on HAART only, patients in the intervention group had increased frequencies of CD4+ T cells (p = 0.003), decreased viral load (p = 0.046), and decreased production of IL-10 (p = 0.010). A non-significant trend showing a decrease in the degranulation marker (CD107a), exhaustion marker (PD-1), and activation markers (HLA-DR, IL-2, and IFN-γ) produced by CD4+ and CD8+ T cells were also observed. The study revealed that HAART supplementation with M. oleifera and A. annua causes faster viral load suppression and elevation of CD4+ T cells with suppressed IL-10 expression. Co-supplementation also increases the expression of CD4+ T cells associated with the suppression of PD-1 and elevation of IL-2 expression, suggesting virological and immunological recovery among patients on HAART. Key words: Artemisia annua, Moringa oleifera, people living with HIV/AIDS (PLWH), T cells, viral load, highly active antiretroviral therapy (HAART), exhaustion.
Limited sampling strategies (LSS) for estimating the area under the concentration-time curve (AUC) of mycophenolic acid (MPA) in renal transplant children receiving concomitant tacrolimus have been developed, but they have not yet undergone full validation. The objectives of the present study were to evaluate the predictive performance of previously published LSS of MPA in an independent pediatric population and to validate a reliable and clinically applicable LSS for routine clinical practice. Published MPA LSS in renal transplant children were screened from the literature, and MPA predicted AUCs were calculated using these LSS. These predicted AUCs were then compared with the reference AUCs, which were calculated by the trapezoidal rule. External validation was prospectively performed in an independent validation group consisting of 44 renal transplant children. This group had a mean age of 12 years (range 3.45 - 20.57) and a mean weight of 35.8 kg (range 15.5 - 77.5). In this external validation dataset, the LSS2 equation: MPA-AUC0-12 = 12.6 + 7.78.C0 + 0.9.C1 + 1.3.C2 demonstrated good predictive performance. The correlation between the predicted and reference AUC using the LSS2 equation was r2= 0.88, with a percent error (PE) of 6.64, a root mean square error (RMSE) of 9.63, and a Bland-Altman bias of -1.36. The mean MPA-AUC0-12h values obtained from the LSS1 equation (MPA-AUC0-12 = 10.0 + 3.95×C0 + 3.24×C0.5 + 1.01×C2) and LSS2 were 65.23±33.84 µg.h/ml, 50.24±19.41 µg.h/ml, and 51.75±19.41 µg.h/ml, respectively. The correlation (r2) between full MPA-AUC0-12h and LSS2 (r2 = 0.88) was higher than that with LSS1 (r2 = 0.69). The linear regression value was superior with LSS2 (R2 = 0.77) compared to LSS1 (R2 = 0.472). Additionally, the RMSE was lower for the David Netto method (DNm; RMSE = 9.63) than for LSS1 (RMSE = 28.82). The Bland-Altman plot showed a bias of -1.36 for LSS2 and -14.99 for LSS1. These results indicate that a reliable and clinically applicable LSS was validated to predict the mycophenolic acid (mycophenolate mofetil [MFF]) AUC in renal transplant children receiving concomitant tacrolimus. This LSS can be routinely used to adapt individual doses of MMF. Key words: Limited sampling strategy, mycophenolate mofetil, renal transplantation, children, tacrolimus.
The aim was to determine the benefit of betablockers and/or digoxin on mortality in heart failure in black Africans using a comparative study. This was a prospective, non-interventional, comparative, four-arm follow-up cohort study using the Abidjan Heart Institute database. Patients were divided into four arms: betablocker alone, betablocker plus digoxin, digoxin alone, and a control group with conventional treatment without betablocker or digoxin followed for 2 years. The four groups compared were initially comparable for sociodemographic data for a total follow-up of 730.5 days, including 37 deaths at the end of this study (5.70%). In multivariate analysis, after adjustment, treatment with betablocker alone (RR 0.77, p=0.62) or combined with digoxin compared with control (RR 1.13, p=0.84) was not significantly associated with death, nor was treatment with betablocker vs non-betablocker (RR 0.58, p=0.14). On the other hand, treatment with digoxin alone compared with control (RR 3.13, p=0.0388) was significantly associated with death. Male sex, high natraemia and use of anticoagulants were the necessary factors for mortality in the digoxin group. Compared with betablockers, digoxin does not appear to have a beneficial effect on mortality in black African patients with heart failure. However, these patients on digoxin appear to be more severe. These results could be confirmed by a large, long-term study of black subjects. Key words: Clinical trial, betablocker, digoxin, heart failure, Africa, mortality.
The study aimed to investigate the β-cell protective effects of ethanol extracts of Cassia siamea (Fabaceae) leaves (LECS).Initially, acute toxicity of LECS (2000 mg/kg/day/bw; po) was assessed in rats.In vitro, antioxidant activity was evaluated on HUVEC cultures.Subsequently, acute hypoglycemic and antihyperglycemic properties were examined for three doses of LECS (100, 200, and 400 mg/kg/bw; po) in Wistar rats, along with an assessment of its impact on intestinal glucose absorption.In the third phase, oral treatment with LECS (200 mg/kg/day/bw; po) was conducted for 4 weeks in alloxan-induced diabetic rats, with glibenclamide (10 mg/kg/day/bw; po) as the standard drug control.Various parameters, including fasting blood glucose, body weight, food intake, lipid profile, and biomarkers of liver and kidney functions, were determined.Additionally, histological analysis of pancreatic islets was performed.The data analysis revealed that C. siamea did not induce adverse effects or mortality in rats at a single dose of 2000 mg/kg.Furthermore, LECS significantly prevented oral glucose-induced hyperglycemia, reduced intestinal glucose absorption, and improved lipid profile in diabetic rats.Although the extracts did not significantly modify body weight, they effectively reversed hyperglycemia, enhanced pancreatic islet size and granulation, and exhibited antioxidant properties by reducing the production of reactive oxygen species (ROS) in HUVEC.Overall, these findings suggest that the ethanol extract of C. siamea leaves may have potential in managing diabetes through its antioxidant properties, improvement of β-cell function, and reduction of intestinal glucose absorption.
Cutaneous leishmaniasis (CL) is a non-contagious infectious-parasitic disease caused by protozoa of the genus Leishmania sp. It is considered a neglected tropical disease and involves public health issues because it affects socially vulnerable populations. The therapy recommended by the Brazilian Ministry of Health as the standard treatment for CL presents numerous challenges. Therefore, it is necessary to look for alternative treatments that are more effective and safer without any side effects on the patients. The phenolic compound methyl gallate (MTG) is an alternative candidate for study due to its antileishmanial biological activity. Methyl gallate has shown considerable biological activity against Leishmania amazonensis. Thus, investigating the potential of this compound in combination with Glucantime® and Pentacarinat® against Leishmania species and evaluating its cytotoxic profile is critical in the treatment and management of CL. The experimental design involved in vitro assays with promastigotes of L. amazonensis and L. guyanensis to evaluate the antileishmanial inhibitory activity of methyl gallate in monotherapy and in combination with conventional treatments, as well as to assess its cytotoxic profile using peritoneal macrophages extracted from BALB/c mice. As a result of the antileishmanial activity test, methyl gallate showed parasite inhibitory activity against L. amazonensis and L. guyanensis promastigotes, both in monotherapy and in combination with the conventional CL drugs. Methyl gallate or its combinations did not show any signs of cytotoxicity. These results provide a basis for future studies on this polyphenolic compound as a potential alternative drug for development and adoption in the therapeutic protocol for CL treatment. Key words: Cutaneous leishmaniasis, neglected tropical diseases, methyl gallate, combination therapy, in vitro assays.
