Community engagement and antimalarial drugs medication as the first line of defense in the fight against antimalarial drug resistance in some endemic localities in Cameroon.

Objectives: Malaria burden is primarily owing to resistance of parasites and vectors to frontline drugs and insecticides, respectively. Increasing awareness of factors contributing to parasite resistance to antimalarials within communities is crucial. This study assessed how community knowledge, attitudes, and practices (KAPs) influence factors contributing to antimalarial resistance across four malaria ecological zones in Cameroon. Methods: To accomplish this, structured questionnaires were administered to 980 volunteers from four geographical locations in English or French (the official languages of Cameroon). The data were organized and tested for normality. Spearman rank correlation was used to examine the connection between KAP and malaria. Results: The mean KAP scores were 5.69 ± 1.47, 5.91 ± 1.25, and 5.66 ± 1.84, respectively, on a nine-point scale. Antimalarials commonly used were artemisinin-based combination therapies (37.96%), chloroquine (4.29%), quinine (22.24%), paracetamol (12.96%), and native drugs (19.80%). Up to 49.49% of the participants practiced self-medication, whereas 76.43% bought medications from licensed pharmacies, 10.61% bought from roadside vendors, and 23.57% relied on traditional/herbal medicines. We observed significant and medium positive linear correlations at P <0.01 between knowledge-attitude (r = 0.528), knowledge-practice (r = 0.400), and attitude-practice (r = 0.496). Conclusions: Despite the general fair level of awareness of proper management and use of antimalarial drugs in the communities, the high level of self-medication and gross neglect of certain risk factors that may promote the emergence and spread of drug-resistant parasites is concerning.

Association between malaria and undernutrition among pregnant women at presentation for antenatal care in health facilities in the Mount Cameroon region.

In resource limited settings, malaria and undernutrition are major public health problems in pregnancy. Therefore, this study assessed the association between malaria infection and undernutrition among pregnant women in the Mount Cameroon area. This cross-sectional study enrolled 1,014 pregnant women consecutively over a year. A structured questionnaire was used to collect socio-demographic information and clinical data. Maternal nutrition was assessed using dietary diversity (DD). Peripheral blood samples collected were used for the diagnosis of malaria parasitaemia by microscopy whereas haemoglobin (Hb) levels were determined using an Hb meter. Logistic regression was used to determine factors associated with malaria and dietary diversity. The prevalence of malaria infection and undernutrition was 17.8% and 89.6% respectively. In addition, of those infected with malaria, geometric mean parasite density was 301/µL of blood (range: 40-9280) while mean DD score was 3.57±0.82 (range: 1-7). The odds of being infected with malaria parasitaemia was highest among women enrolled in the rainy season (OR = 1.58, P = 0.043), who were farmers (OR = 2.3, P = 0.030), had a household size of < 4 individuals (OR = 1.48, P = 0.026) and who were febrile (OR = 1.87, P < 0.001). Also, attending clinic visits in Mutengene Medical Centre (OR = 2.0, P = 0.012) or Buea Integrated Health Centre (OR = 2.9, P = < 0.001), being < 25 years (OR = 2.4, P = 0.002) and a farmer (OR = 10.6, P = 0.024) as well as < 4 clinic visits (OR = 1.62, P = 0.039) were identified as predictors of undernutrition. Furthermore, the association between malaria and DD was statistically significant (P = 0.015). In this study, undernutrition was highly frequent than malaria infection. Thus, there is an urgent need to improve maternal awareness through nutritional counselling and health campaigns on the benefits of consuming at least five food groups. Besides, improved maternal dietary nutrient intake is likely to have impact on the burden of malaria parasite infection.

Traumatic Brain Injury in Cameroon: A Prospective Observational Study in a Level I Trauma Centre.

Background and Objective: About 14 million people will likely suffer a traumatic brain injury (TBI) per year by 2050 in sub-Saharan Africa. Studying TBI characteristics and their relation to outcomes can identify initiatives to improve TBI prevention and care. The objective of this study was to define the features and outcomes of TBI patients seen over a 1-year period in a level-I trauma centre in Cameroon. Materials and Methods: Data on demographics, causes, clinical aspects, and discharge status were collected over a period of 12 months. The Glasgow Outcome Scale-Extended (GOSE) and the Quality-of-Life Questionnaire after Brain Injury (QoLIBRI) were used to evaluate outcomes six months after TBI. Comparisons between two categorical variables were done using Pearson's chi-square test. Results: A total of 160 TBI patients participated in the study. The age group 15-45 years was most represented (78%). Males were more affected (90%). A low educational level was seen in 122 (76%) cases. Road traffic incidents (RTI) (85%), assaults (7.5%), and falls (2.5%) were the main causes of TBI, with professional bike riders being frequently involved (27%). Only 15 patients were transported to the hospital by ambulance, and 14 of these were from a referring hospital. CT-imaging was performed in 78% of cases, and intracranial traumatic abnormalities were identified in 64% of cases. Financial constraints (93%) was the main reason for not performing a CT scan. Forty-six (33%) patients were discharged against medical advice (DAMA) due to financial constraints. Mortality was 14% (22/160) and high in patients with severe TBI (46%). DAMA had poor outcomes with QoLIBRI. Only four patients received post-injury physical therapy services. Conclusions: TBI in Cameroon mainly results from RTIs and commonly affects young adult males. Lack of pre-hospital care, financial constraints limiting both CT scanning and medical care, and a lack of acute physiotherapy services likely influenced care and outcomes adversely.

Ameliorative effects of Albizia adianthifolia aqueous extract against pentylenetetrazole-induced epilepsy and associated memory loss in mice: Role of GABAergic, antioxidant defense and anti-inflammatory systems.

Albizia adianthifolia (Schumach.) (Fabaceae) is a medicinal herb used for the treatment of epilepsy and memory impairment. This study aims to investigate the anticonvulsant effects of Albizia adianthifolia aqueous extract against pentylenetetrazole (PTZ)-induced spontaneous convulsions in mice; and determine whether the extract could mitigate memory impairment, oxidative/nitrergic stress, GABA depletion and neuroinflammation. Ultra-high performance liquid chromatography/mass spectrometry analysis was done to identify active compounds from the extract. Mice were injected with PTZ once every 48 h until kindling was developed. Animals received distilled water for the normal group and negative control groups, doses of extract (40, 80, or 160 mg/kg) for the test groups and sodium valproate (300 mg/kg) for the positive control group. Memory was measured using Y maze, novel object recognition (NOR) and open field paradigms, while the oxidative/nitrosative stresses (MDA, GSH, CAT, SOD and NO), GABAergic transmission (GABA, GABA-T and GAD) and neuro-inflammation (TNF-α, IFN-γ, IL- 1ß, and IL-6) were determined. Brain photomicrograph was also studied. Apigenin, murrayanine and safranal were identified in the extract. The extract (80-160 mg/kg) significantly protected mice against seizures and mortality induced by PTZ. The extract significantly increased the spontaneous alternation and the discrimination index in the Y maze and NOR tests, respectively. PTZ kindling induced oxidative/nitrosative stress, GABA depletion, neuroinflammation and neuronal cells death was strongly reversed by the extract. The results suggest that the anticonvulsant activity of Albizia adianthifolia extract is accompanied by its anti-amnesic property, and may be supported by the amelioration of oxidative stress, GABAergic transmission and neuroinflammation.

Anaemia, iron deficiency and inflammation prevalence in children in the Mount Cameroon area and the contribution of inflammatory cytokines on haemoglobin and ferritin concentrations: a cross sectional study.

BACKGROUND: Iron deficiency (ID) and anaemia of inflammation (AI) coexist where infections and nutritional deficiencies are common. The aim of this study was to determine burden of ID, anaemia, inflammation and AI in children in malaria endemic Limbe, Mount Cameroon as well as decipher the contribution of some inflammatory cytokines on the concentration of haemoglobin and ferritin. METHODS: A total of 520 children aged ≤ 15 years old from the Limbe Health District (LHD) were randomly selected and examined in a cross-sectional study for iron deficiency, anaemia, inflammation and inflammation anaemia. Collected blood samples were used for full blood count and inflammatory marker analyses with the aid of a haemoanalyzer and ELISA machine, respectively. Spearman's rank correlation analysis was used to determine the correlation between cytokines and haemoglobin while multiple linear regression analysis was used to evaluate the effects of inflammatory cytokines on haemoglobin and ferritin concentrations. RESULTS: The overall prevalence of anaemia, ID, IDA, inflammation and AI were respectively, 67.5%, 34.6%, 12.9%, 63.1% and 30.2%. Children aged 12‒15 years (P = 0.001), enrolled from the community (P < 0.001), whose parents are civil servants (P < 0.001), living in a home with 6‒10 occupants (P = 0.016), afebrile (P < 0.001) and malaria negative (P = 0.007) had the highest prevalence of ID while, children ≤ 5 years old (P = 0.001), with a family size of 1‒5 occupants (P = 0.033) had the highest prevalence of AI. Haemoglobin concentration positively correlated with concentrations of IFN-γ (P < 0.001), TNF-α (0.045) and ferritin (P < 0.001) while a negative correlation was observed with IL-10 (P = 0.003). In the multiple linear regression analysis only IL-6 significantly (P = 0.030) influenced haemoglobin concentration. CONCLUSIONS: While IL-6 is of significance in the pathology of anaemia, iron deficiency and anaemia of inflammation are of moderate public health concerns in the Mount Cameroon area. Hence, appropriate intervention against anaemia, ID and AI should be directed at children ≤ 5 years and counterparts > 10 years old that bear the highest burden.

Succinimido-Ferrocidiphenol Complexed with Cyclodextrins Inhibits Glioblastoma Tumor Growth In Vitro and In Vivo without Noticeable Adverse Toxicity.

SuccFerr (N-[4-ferrocenyl,5-5-bis (4-hydroxyphenyl)-pent-4-enyl]-succinimide) has remarkable antiproliferative effects in vitro, attributed to the formation of a stabilized quinone methide. The present article reports in vivo results for a possible preclinical study. SuccFerr is lipophilic and insoluble in water, so the development of a formulation to obviate this inconvenience was necessary. This was achieved by complexation with randomly methylated cyclodextrins (RAMEßCDs). This supramolecular water-soluble system allowed the in vivo experiments below to proceed. Application of SuccFerr on the glioblastoma cancer cell line U87 indicates that it affects the cellular cycle by inducing a blockade at G0/G1 phase, linked to apoptosis, and another one at the S phase, associated with senescence. Using healthy Fischer rats, we show that both intravenous and subcutaneous SuccFerr: RAMEßCD administration at 5 mg/kg lacks toxic effects on several organs. To reach lethality, doses higher than 200 mg/kg need to be administered. These results prompted us to perform an ectopic in vivo study at 1 mg/kg i.v. ferrocidiphenol SuccFerr using F98 cells xenografted in rats. Halting of cancer progression was observed after six days of injection, associated with an immunological defense response linked to the active principle. These results demonstrate that the properties of the selected ferrocidiphenol SuccFerr transfer successfully to in vivo conditions, leading to interesting therapeutic perspectives based on this chemistry.

Anticonvulsant effects of Cymbopogon giganteus extracts with possible effects on fully kindled seizures and anxiety in experimental rodent model of mesio-temporal epilepsy induced by pilocarpine.

ETHNOPHARMACOLOGICAL RELEVANCE: Epilepsy is a neurological disorder of the brain characterized by periodic and unpredictable occurrence of a transient behavior alteration due to the rhythmic, synchronous and disordered firing of brain neuron. Worldwide, approximately 50 million people currently live with epilepsy and close to 80% of people with epilepsy live in poor countries. However, it was noticed in many countries worldwide that people with epilepsy and their families suffer from stigma and discrimination and that situation exposes them to high psychological conditions such as depression and anxiety as well as more physical problems including bruising and fractures from injuries related to seizures. However, several plants-based products used for epilepsy and anxiety treatments in different system of folk medicine have exhibited a significant anti-epileptic and antianxiety activities using animal models with fewer side effects. AIM OF THE STUDY: The study aimed at evaluating the antiepileptic, status post-epilepticus and anxiolytic effects of Cymbopogon giganteus decoction in rat model induced by pilocarpine. MATERIALS AND METHODS: A total of 90 rats were partitioned into 7 groups and treated as follow: animals of groups I (normal control) and II (considered the negative control) received distilled water (10 mL/kg); while groups III, IV, V, and VI were treated with the C. giganteus extract at 34, 85, 170 and 340 mg/kg p.o, respectively; and the group VII (considered positive control) received sodium valproate at 300 mg/kg, i.p. After 40 min post-treatment, a single dose of n-methyl-scopolamine (1 mg/kg, i.p) was administered to animals of groups (II, III, IV, V, VI, VII) followed by pilocarpine (360 mg/kg, i.p). Animal of group I (normal group) received distilled water. Rats were further observed for 6 h to evaluate the severity and the duration of the acute seizures of epilepsy according to Racine scale. Anxious behavior status post-epilepticus was also assessed in the same rats used above in the Elevated Plus Maze and number of entries into the open or closed arms and the time spent on either open or closed arms of the platform were recorded. Animals were also evaluated on Open Field Test and the number of rearing, crossing, grooming, defecation and center time were registered. RESULTS: C. giganteus decoction significantly (P < 0.05) reduced the animal mortality, the number and duration of convulsions and effectively increased the latency of convulsions. The plant extract significantly (P < 0.05) improved GSH level and SOD activity, reduced MDA and CAT activity, increased GABA level and decreased GABA-t activity in hippocampus. The anxiety induced by pilocarpine was also significantly (P < 0.05) inhibited by the extract of the plant. CONCLUSIONS: Thus, C. giganteus has demonstrated its antiepileptic and anxiolytic activities in rat model and may be used as preventive measure for patients suffering from epilepsy seizures and anxiety.

Demographics, Causes, and Outcome of Traumatic Brain Injury among Trauma Cases in Cameroon: A Multi-Center Five Year's Retrospective Study.

Traumatic brain injury (TBI) is a huge public health challenge worldwide. Epidemiological monitoring is important to inform healthcare policy. We aimed at determining the prevalence, outcome, and causes of TBI in Cameroon by conducting a 5-year retrospective study in three referral trauma centers. Data on demographics, causes, injury mechanisms, clinical aspects, and discharge status were recorded. Comparisons between two categorical variables were done using Pearson's chi-square test or Fisher's exact test. A total of 6248 cases of TBI were identified of 18,151 trauma cases, yielding a prevalence of 34%. The number of TBI cases increased across the years (915 in 2016, 1406 in 2020). Demographic data and causes of TBI were available for 6248 subjects and detailed data on clinical characteristics on 2178 subjects. Median age was 30.0 (24.0, 41.0) years. Males were more affected (80%). Road traffic incidents (RTIs; 75%) was the main cause of TBI, with professional bike riders being more affected (17%). Computed tomography (CT) imaging was performed in 67.7% of cases. Of the 597 (27.4%) cases who did not undergo neuroimaging, 311 (52.1%) did not have neuroimaging performed because of financial constraints, among which 7% were severe TBI cases. A total of 341 (19.6%) patients were discharged against medical advice, of which 83% had financial limitations. Mortality was 10.3% (225 of 2178) in the overall population, but disproportionately high in patients with severe TBI (55%) compared to those in high-income settings (27%). TBI occurrence is high in Cameroon, and RTIs are the main causes. Disparities in care provision were identified as attributable to financial constraints regarding CT scanning and continuation of care. The data presented can inform preventive interventions to improve care provision and transport policies. Implementation of a universal health insurance may be expected to improve hospital care and reduce the adverse effects of TBI among Cameroonians.

Protective Effects of Anthocleista djalonensis Extracts against Pentylenetetrazole-Induced Epileptic Seizures and Neuronal Cell Loss: Role of Antioxidant Defense System.

Oxidative stress and neurodegeneration are involved in the initiation of epileptogenesis and progression of epileptic seizures. This study was aimed at investigating the anticonvulsant, antioxidant, and neuroprotective properties of active fractions isolated from Anthocleista djalonensis root barks in pentylenetetrazole mouse models of epileptic seizures. Bioactive-guided fractionation of Anthocleista djalonensis (AFAD) extracts using acute pentylenetetrazole (90 mg/kg) induced generalised tonic-clonic seizures, which afforded a potent anticonvulsant fraction (FPool 5). Further fractionation of AFAD was performed by high-performance liquid chromatography, which yielded fifteen subfractions, which were chemically characterised. In addition, AFAD was tested against convulsions or spontaneous kindled seizures induced, respectively, by acute (50 mg/kg) or subchronic (30 mg/kg) injection of pentylenetetrazole. Finally, oxidative stress markers, brain GABA content, and neuronal cell loss were evaluated in AFAD-treated pentylenetetrazole-kindled mice. Administration of AFAD significantly protected mice against acute pentylenetetrazole (90 mg/kg)-induced convulsions. In acute pentylenetetrazole (50 mg/kg)-induced hippocampal and cortical paroxysmal discharges, AFAD significantly decreased the number of crisis, the cumulative duration of crisis, and the mean duration of crisis. Additionally, AFAD significantly decreased the number of myoclonic jerks and improved the seizure score in subchronic pentylenetetrazole-induced kindled seizures. The pentylenetetrazole-induced alteration of oxidant-antioxidant balance, GABA concentration, and neuronal cells in the brain were attenuated by AFAD treatment. This study showed that AFAD protected mice against pentylenetetrazole-induced epileptic seizures possibly through the enhancement of antioxidant defence and GABAergic signalling. These events might be correlated with the amelioration of neuronal cell loss; hence, AFAD could be a potential candidate for the treatment of epilepsy.

An aqueous extract of Canarium schweinfurthii attenuates seizures and potentiates sleep in mice: Evidence for involvement of GABA Pathway.

About 30% of epileptic patients continue to have seizures. The present study investigates the anticonvulsant and sedative effects of an aqueous extract of C. schweinfurthii in mice. Anticonvulsant effects of C. schweinfurthii aqueous extract (0.01-300 mg/kg, p.o.) were tested against 4-aminopyridine (4-AP, 15 mg/kg, i.p.) -, pilocarpine (PILO, 380 mg/kg, i.p.) - and pentylenetetrazole (PTZ, 75 mg/kg, i.p.) -induced seizures, while sedative effects were tested on diazepam (35 mg/kg, i.p.)-induced sleep. Afterward, the most effective dose of the extract (11.9 mg/kg) was antagonized with N-methyl-ß-carboline-3-carboxamide or flumazenil. In another set of experiments, mice were sacrificed for the estimation of GABA content and GABA-T activity in the cerebral cortex. The dose of the extract that protected 50% of mice (ED50) against 4-AP, PILO, and PTZ was respectively 4.43 mg/kg (versus 12.01 for phenobarbital), 9.59 mg/kg (vs 8.67 for diazepam), and 2.12 mg/kg (vs 0.20 for clonazepam). Further, the ED50 of the extract that increased the duration of sleep was 0.24 mg/kg (vs 0.84 for phenobarbital). N-methyl-ß-carboline-3-carboxamide or flumazenil antagonized (p < 0.001) the anticonvulsant effect of C. schweinfurthii in PTZ-induced seizures and diazepam-induced sleep when compared to the negative control group. The extract at all doses increased (p < 0.001) the GABA content and decreased (p < 0.001) GABA-T activity. These findings suggest that C. schweinfurthii possesses anticonvulsant and sedative effects. These effects seem to be mediated via the modulation of the GABA neurotransmission. These data explain the use of this plant to treat epilepsy in Cameroon traditional medicine.

In vivo antimalarial activity of a probiotic bacterium Lactobacillus sakei isolated from traditionally fermented milk in BALB/c mice infected with Plasmodium berghei ANKA.

ETHNOPHARMACOLOGICAL RELEVANCE: Milk production, processing and consumption are integral part of traditional practices in Fulani tribe of Cameroon. It has been observed that Fulani are resistant to malaria. Dairy products traditionally processed by Fulani are intensively used in the ritual treatment of malarial, inflammations and behavioural disorders. Many studies have demonstrated that fermented milk is a rich source of probiotic bacteria. However, the antimalarial activity of probiotics isolated from this natural source has not been experimentally tested. AIM OF THE STUDY: Hence, this study was therefore aimed at evaluating the antimalarial activity of a probiotic bacterium Lactobacillus sakei isolated from traditionally fermented milk in mice infected with chloroquine sensitive Plasmodium berghei ANKA. MATERIALS AND METHODS: The probiotic bacterium was isolated from the Cameroonian Mborro Fulani's traditionally fermented milk and identified using the 16S r RNA gene sequencing. The schizontocidal activity of Lactobacillus sakei on established malaria infection was evaluated. Eighty-four healthy young adult Balb/c mice infected with Plasmodium berghei parasite were randomly divided into two sets of seven group of six mice each, and were given three different doses of Lactobacillus sakei, chloroquine and sulfadoxine/pyrimethamine for seven and fourteen days respectively. The level of parasitaemia, body temperature, survival time and haematological parameters were evaluated. RESULTS: The parasite growth inhibition was observed to increase with increasing dose of probiotic bacterium with maximum suppression being 100 % at dose 3 on day 20. Also, the probiotic bacterium significantly prevented body weight loss and was associated with body temperature reduction and prevented (p<0.05) a decrease in haematological parameters compared to that untreated malaria infected mice. CONCLUSION: The results obtained suggest that Lactobacillus sakei is a probiotic bacterium with antimalarial activity in mice infected with chloroquine sensitive Plasmodium berghei.

Microcytic and Malarial Anaemia Prevalence in Urban Children ≤15 Years in the Mount Cameroon Area: A Cross-Sectional Study on Risk Factors.

BACKGROUND: Anaemia, a common nutritional deficiency, is a public health problem in the Mount Cameroon area. This study determined the prevalence and possible risk factors of microcytic and malarial anaemia in children less than ≤15 years residing in the Buea and Limbe municipalities in the Mount Cameroon area. METHODS: A total of 566 children were clinically examined in a cross-sectional study from December 2018 to August 2019 for anaemia and malaria parasites. Blood samples collected were used in evaluating full blood count with the aid of an automated haemoanalyser, and malaria parasite was confirmed by microscopy. Anaemia was defined based on WHO standards while microcytic anaemia and malarial anaemia were defined as microcytosis + anaemia and malaria + anaemia, respectively. Factors that showed significance in the bivariate analysis were entered into a multinomial logistic regression to determine risk factors for microcytic and malarial anaemia. RESULTS: The overall prevalence for anaemia, microcytosis, microcytic anaemia, and malarial anaemia was, respectively, 68.7%, 48.9%, 36.9%, and 19.6% with microcytic anaemia representing 53.7% of all anaemic cases. Risk factors for microcytic anaemia included child age of 1-5 years (P=0.007), forest ethnicity (P=0.019), parents being farmers (P=0.038) or jobless (P=0.009), and having moderate malaria parasitaemia (P=0.048) while those for malarial anaemia were child age of 6-10 years (P=0.008), parents' age of 26-35 years (P=0.049), parents being jobless (P=0.023), and consuming plantains 3-4 times (P=0.024) a week. CONCLUSION: Microcytic anaemia is getting to be a severe public health concern while malarial anaemia is a mild public health issue in children residing in urban areas of Mount Cameroon. Parents' occupation was directly linked to all anaemia forms; hence, any intervention to curb anaemia should consider aspects that will raise the socioeconomic status of the population.

Scopolamine-Induced Memory Impairment in Mice: Neuroprotective Effects of Carissa edulis (Forssk.) Valh (Apocynaceae) Aqueous Extract.

Alzheimer's disease is first characterised by memory loss related to the central cholinergic system alteration. Available drugs provide symptomatic treatment with known side effects. The present study is aimed to evaluate the properties of Carissa edulis aqueous extract on a Scopolamine mouse model as an attempt to search for new compounds against Alzheimer's disease-related memory impairment. Memory impairment was induced by administration of 1 mg/kg (i.p.) of Scopolamine for 7 days, and mice were treated with Carissa edulis aqueous extract. Behavioural studies were performed using T-maze and novel object recognition task for assessing learning and memory and open field test for locomotion. Brain acetylcholinesterase enzyme (AChE) activity was measured to evaluate the central cholinergic system. The level of MDA, glutathione, and catalase activity were measured to evaluate the oxidative stress level. Administration of Scopolamine shows a decrease in learning and memory enhancement during behavioural studies. A significant decrease in the time spent in the preferred arm of T-maze, in the time spent in the exploration of the novel object, and in the discrimination index of the familiar object was also observed. The significant impairment of the central cholinergic system was characterised in mice by an increase of AChE activity to 2.55 ± 0.10 mol/min/g with an increase in oxidative stress. Treatment with the different doses of Carissa edulis (62.8, 157, 314, and 628 mg/kg orally administrated) significantly increased the memory of mice in T-maze and novel object recognition tests and also ameliorated locomotion of mice in the open field. Carissa edulis aqueous extract treatment also decreases the AChE activity and brain oxidative stress. It is concluded that administration of Carissa edulis aqueous extract enhances memory of mice by reducing AChE activity and demonstrating antioxidant properties. This could be developed into a novel therapy against memory impairment related to Alzheimer's disease.

Aptamer Efficacies for In Vitro and In Vivo Modulation of αC-Conotoxin PrXA Pharmacology.

The medical staff is often powerless to treat patients affected by drug abuse or misuse and poisoning. In the case of envenomation, the treatment of choice remains horse sera administration that poses a wealth of other medical conditions and threats. Previously, we have demonstrated that DNA-based aptamers represent powerful neutralizing tools for lethal animal toxins of venomous origin. Herein, we further pursued our investigations in order to understand whether all toxin-interacting aptamers possessed equivalent potencies to neutralize αC-conotoxin PrXA in vitro and in vivo. We confirmed the high lethality in mice produced by αC-conotoxin PrXA regardless of the mode of injection and further characterized myoclonus produced by the toxin. We used high-throughput patch-clamp technology to assess the effect of αC-conotoxin PrXA on ACh-mediated responses in TE671 cells, responses that are carried by muscle-type nicotinic receptors. We show that 2 out of 4 aptamers reduce the affinity of the toxin for its receptor, most likely by interfering with the pharmacophore. In vivo, more complex responses on myoclonus and mice lethality are observed depending on the type of aptamer and mode of administration (concomitant or differed). Concomitant administration always works better than differed administration indicating the stability of the complex in vivo. The most remarkable conclusion is that an aptamer that has no or a limited efficacy in vitro may nevertheless be functional in vivo probably owing to an impact on the biodistribution or pharmacokinetics of the toxin in vivo. Overall, the results highlight that a blind selection of aptamers against toxins leads to efficient neutralizing compounds in vivo regardless of the mode of action. This opens the door to the use of aptamer mixtures as substitutes to horse sera for the neutralization of life-threatening animal venoms, an important WHO concern in tropical areas.

Traditional uses, phytochemistry and pharmacological properties of African Nauclea species: A review.

ETHNOPHARMACOALOGICAL RELEVANCE: The genus Nauclea in Africa comprises seven species. Among them, N. latifolia, N. diderrichii and N. pobeguinii are widely used by the local population in traditional remedies. Preparation from various parts of plants (e.g. roots, bark, leaves) are indicated by traditional healers for a wide range of diseases including malaria, pain, digestive ailments or metabolic diseases. MATERIALS AND METHODS: A literature search was conducted on African species of the genus Nauclea using scientific databases such as Google Scholar, Pubmed or SciFinder. Every document of ethnopharmacological, phytochemical or pharmacological relevance and written in English or French were analyzed. RESULTS AND DISCUSSION: The Nauclea genus is used as ethnomedicine all along sub-Saharan Africa. Several local populations consider Nauclea species as a major source of remedies for malaria. In this regard, two improved traditional medicines are currently under development using extracts from N. latifolia and N. pobeguinii. Concerning the chemical composition of the Nauclea genus, indoloquinolizidines alkaloids could be considered as the major class of compounds as they are reported in every analyzed Nauclea species, with numerous structures identified. Based on traditional indications a considerable amount of pharmacological studies were conducted to ensure activity and attempt to link them to the presence of particular compounds in plant extracts. CONCLUSION: Many experimental studies using plant extracts of the African species of the genus Nauclea validate traditional indications (e.g. malaria and pain). However, bioactive compounds are rarely identified and therefore, there is a clear need for further evaluations as well as for toxicity experiments. The sustainability of these plants, especially of N. diderrichii, a threatened species, should be kept in mind to adapt local uses and preparation modes of traditional remedies.

Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides.

Medical means to save the life of human patients affected by drug abuse, envenomation or critical poisoning are currently limited. While the compounds at risks are most often well identified, particularly for bioterrorism, chemical intervention to counteract the toxic effects of the ingested/injected compound(s) is restricted to the use of antibodies. Herein, we illustrate that DNA aptamers, targeted to block the pharmacophore of a poisonous compound, represent a fast-acting and reliable method of neutralization in vivo that possesses efficient and long-lasting life-saving properties. For this proof of concept, we used one putative bioweapon, αC-conotoxin PrXA, a marine snail ultrafast-killing paralytic toxin, to identify peptide-binding DNA aptamers. We illustrate that they can efficiently neutralize the toxin-induced (i) displacement of [125I]-α-bungarotoxin binding onto nicotinic receptors, (ii) inhibition of diaphragm muscle contraction, and (iii) lethality in mice. Our results demonstrate the preclinical value of DNA aptamers as fast-acting, safe and cheap antidotes to lethal toxins at risk of misuse in bioterrorism and offer hope for an alternative method than donor sera to treat cases of envenomation.

Evidence for the involvement of the GABA-ergic pathway in the anticonvulsant activity of the roots bark aqueous extract of Anthocleista djalonensis A. Chev. (Loganiaceae).

BACKGROUND: The root bark of Anthocleista djalonensis A. Chev. (Loganiaceae) is widely used in traditional medicine in Northern Cameroon to treat epilepsy and related conditions, such as migraine, insomnia, dementia, anxiety, and mood disorders. METHODS: To investigate the anticonvulsant effects and the possible mechanisms of this plant, an aqueous extract of Anthocleista djalonensis (AEAD) was evaluated by using animal models of bicuculline-, picrotoxin-, pilocarpine-, and pentylenetetrazole-induced convulsions. Their effects on brain γ-aminobutyric acid (GABA) concentration and GABA-T activity were also determined. RESULTS: This extract significantly protected mice against bicuculline-induced motor seizures. It provided 80% protection against picrotoxin-induced tonic-clonic seizures, and strongly antagonized convulsions induced by pilocarpine. AEAD also protected 100% of mice against pentylenetetrazole-induced seizures. Flumazenil, a central benzodiazepine receptor antagonist and FG7142, a partial inverse agonist in the benzodiazepine site of the GABAA receptor complex, were found to have an inhibitory effect on the anticonvulsant action of AEAD in pentylenetetrazole test. Finally, the brain GABA concentration was significantly increased and GABA-T activity was inhibited by AEAD. CONCLUSIONS: The effects of Anthocleista djalonensis suggested the presence of anticonvulsant properties that might involve an action on benzodiazepine and/or GABA sites in the GABAA receptor complex or by modulating GABA concentration in the central nervous system (CNS).

Neuroprotective and Antiamnesic Effects of Mitragyna inermis Willd (Rubiaceae) on Scopolamine-Induced Memory Impairment in Mice.

Aim. To assess memory improvement and neuroprotective and antioxidant effects of Mitragyna inermis (M. inermis) leaf decoction on the central nervous system. Methodology. Leaf decoction of M. inermis was tested on learning and memory in normal and scopolamine-induced cognitive impairment in mice using memory behavioral tests such as the Morris water maze, object recognition task, and elevated plus maze. Oxidative stress enzymes-catalase, superoxide dismutase, and the thiobarbituric acid reactive substance, a product of lipid peroxidation-were quantified. In each test, mice 18 to 25 g were divided into groups of 5. Results. The extract reversed the effects of scopolamine in mice. The extract significantly increased discrimination index in the object recognition task test and inflexion ratio in the elevated plus maze test. The times spent in target quadrant in MWM increased while the transfer latency decreased in mice treated by M. inermis at the dose of 196.5 mg/kg. The activity levels of superoxide dismutase and catalase were significantly increased, whereas the thiobarbituric acid reactive substance was significantly decreased after 8 consecutive days of treatment with M. inermis at the dose of 393 mg/kg. Conclusion. These results suggest that M. inermis leaf extract possess potential antiamnesic effects.

Malaria, Moderate to Severe Anaemia, and Malarial Anaemia in Children at Presentation to Hospital in the Mount Cameroon Area: A Cross-Sectional Study.

Background. Malaria remains a major killer of children in Sub-Saharan Africa, while anaemia is a public health problem with significant morbidity and mortality. Examining the factors associated with moderate to severe anaemia (MdSA) and malarial anaemia as well as the haematological characteristics is essential. Methodology. Children (1-14 years) at presentation at the Regional Hospital Annex-Buea were examined clinically and blood samples were collected for malaria parasite detection and full blood count evaluation. Results. Plasmodium falciparum, anaemia, and malarial anaemia occurred in 33.8%, 62.0%, and 23.6% of the 216 children, respectively. Anaemia prevalence was significantly higher in malaria parasite positive children and those with fever than their respective counterparts. MdSA and moderate to severe malarial anaemia (MdSMA) were detected in 38.0% and 15.3% of the participants, respectively. The prevalence of MdSA was significantly higher in children whose household head had no formal education, resided in the lowland, or was febrile, while MdSMA was significantly higher in febrile children only. Children with MdSMA had significantly lower mean white blood cell, lymphocyte, and platelet counts while the mean granulocyte count was significantly higher. Conclusion. Being febrile was the only predictor of both MdSA and MdSMA. More haematological insult occurred in children with MdSMA compared to MdSA.