Impact of Type 1 Diabetes on Renal Parameters in Children Aged One to 17 at the Mother and Child University Hospital in N'Djamena, Chad.

Background Diabetes is a metabolic disease caused by a defect in the secretion of insulin or its misuse. It is a major public health problem worldwide. While type 2 diabetes generally affects people of advanced age, type 1 diabetes generally occurs in people of younger ages and its prevalence is increasingly high among children in Chad. When it is poorly managed, it can be accompanied by several functional complications including renal failure. In order to have an overview of the incidence of this complication in children suffering from type 1 diabetes and to contribute to its better follow-up, a study was conducted at the Mother and Child University Hospital in N'Djamena whose objective was to assess the impact of type 1 diabetes on renal parameters in children aged one to 17 years. Methodology A cross-sectional study was conducted from April to June 2023 at the Mother and Child University Hospital Center in N'Djamena on 61 children with type 1 diabetes aged one to 17 years. A questionnaire sheet was submitted to the parents of the participants and the data from this sheet were analyzed while biochemical parameters were evaluated using standard commercial kit methods, the IONIX SFRI automated ion analyzer, HemoCue HbA1c501® hemoglobinometer, and spectrophotometer (BioSystems). Results Participants were ranked according to glycemic control and duration of diabetes discovery. 73.61% of the children showed alterations in renal parameters, some of which increased and others decreased; 86.9% had poor glycemic control, which is associated with alterations in renal parameters in study participants. Multiple logistic regression showed hypercreatinemia, hyperuremia, hyperglycemia, hyperhemoglobinemia, hyperchloremia, hyponatremia, hypokalemia, hyperglycemia, hyperketonuria, hyperproteinuria, and decreased glomerular filtration rate (GFR). Conclusion It appears from this study that type 1 diabetes through glycemic control and the duration of discovery has an increasing impact on certain renal parameters and a decrease in others, leading to impaired renal function.

Antibiotic-Potentiating Effect of Some Bioactive Natural Products against Planktonic Cells, Biofilms, and Virulence Factors of Pseudomonas aeruginosa.

Background: Pseudomonas aeruginosa is an opportunistic human pathogen that causes infections that are mediated by both virulence factor production and biofilm formation. In addition, many antibiotics are increasingly losing their efficacy due to the development of resistance. The screening of potentially bioactive natural compounds that have both antivirulence and antibiofilm activities to enhance antibiotic efficacy and reverse antibiotic resistance is a good strategy to overcome these issues. In this study, the antibacterial, antibiofilm, and antivirulence factor activities of some bioactive natural products in combination with conventional antibiotics were evaluated against clinical isolates of P. aeruginosa. Methods: The broth microdilution method was used to determine the antibacterial and antibiofilm activities. The checkerboard method was used to evaluate the combination interactions. Spectrophotometric and agar plate techniques were used to assess the effect of the combination on the pyocyanin production and the motility in P. aeruginosa ATCC 27853 strain. Results: Out of the eighteen combinations tested, ten exhibited synergistic effects against planktonic cells, seven against biofilm inhibition, and five against the eradication of mature biofilm of P. aeruginosa biofilm. The best synergistic effect was the association of amikacin and sinapic acid against planktonic cells (FICI = 0.08) with a 70-fold reduction in the MIC value of amikacin. The same combination showed significant synergistic inhibition of biofilm formation (FICI = 0.1) and biofilm eradication (FICI = 0.15) reducing the MBIC and MBEC of amikacin by 32-fold. Some selected synergistic combinations showed statistically significant differences (p < 0.01 or p < 0.001) in the inhibition of virulence factors compared to the antimicrobials alone. Conclusion: In summary, this study revealed sinapic acid as an antibiotic adjuvant and antivirulence compound to overcome P. aeruginosa infections. This finding indicates that the combinations of amikacin plus sinapic acid, ceftazidime plus thymol, and norfloxacin plus curcumin could be considered promising candidates for the development of combination therapies targeting virulence factors against P. aeruginosa infections.

Use of WhatsApp®, for distance teaching during COVID-19 pandemic: Experience and perception from a sub-Saharan African setting.

BACKGROUND: In the midst of the COVID-19 pandemic, to palliate to the lockdown and cover academic programs, the faculty of medicine and pharmaceutical sciences (FMPS) of the university of Dschang (UDs) in Cameroon has implemented e-learning using WhatsApp®. AIM: Describe the opinion of students and lecturers after its implementation of e-learning at the FMPS of UDs. METHODS: We designed a uniform teaching scheme using WhatsApp® during the university lockdown. Students and members of the teaching staff of the FMPS of UDs were enrolled after receiving clear information on the study implementation. At the end of the online-teaching period of two and a half months, we surveyed our students and teaching staff. Sociodemographic characteristics and opinions about e-learning were collected using a standard questionnaire. RESULTS: We enrolled 229 students and 40 lecturers of the FMPS. Students reported a decremented quality of internet connection (p < 0.001, p-homogeneity < 0.001) despite an increased expenditure related to internet use. Electronic devices were broadly used before the implementation of mobile learning. The use of course materials was significantly more challenging among students because of the size/format of lecture notes and internet connection/cost (all p < 0.05). Perception of discipline compared to classroom-based lessons was not significantly different among students compared to lecturers (all p > 0.05). While lecturers were mainly more comfortable conveying the contents of their lectures, students tended to be less prone to actively participate. The motivation and satisfaction of the latter group toward e-learning were modest compared to classroom-based lectures while their feedback about the organization was positive. CONCLUSIONS: E-learning using WhatsApp® could be an effective alternative to conventional classroom-based lessons in the context of COVID-19 pandemic. The use of a blended-learning program including classroom-based sessions could help improve its limitations.

Chemical constituents and anti-inflammatory activity of the total alkaloid extract from Melodinus cochinchinensis (Lour.) Merr. and its inhibition of the NF-κB and MAPK signaling pathways.

BACKGROUND: Melodinus cochinchinensis (Lour.) Merr. is a medicinal plant, which is used as a folk medicine for treating meningitis and fractures. However, the anti-inflammatory activity of total alkaloid extract from M. cochinchinensis (MCTA) and its molecular mechanism are still not studied. PURPOSE: The aim of this study is to investigate the main chemical constituents of MCTA and explore its anti-inflammatory potential in both in vitro and in vivo assessments. METHODS: UHPLC-ESI-HRMS/MS was applied to analyze the chemical profiling. The anti-inflammatory efficacy of MCTA was evaluated on lipopolysaccharide (LPS) induced RAW 264.7 cells and two common inflammation models in mice. The production of pro-inflammatory mediator and cytokine was tested using the ELISA method. The pathological change was analyzed by histological assessment. The expression of NF-κB, MAPKs and PPAR-γ proteins was evaluated using western blot analysis. RESULTS: A total of 21 monoterpenoid indole alkaloids (MIAs) were characterized by UHPLC-ESI-HRMS/MS. Aspidospermine- and quinolone-type alkaloids were found to be the major compounds. MCTA significantly decreased the production of NO, IL-1ß, IL-6 and TNF-α in LPS-induced RAW 264.7 macrophages. MCTA significantly inhibited the phosphorylation of ERK1/2, JNK and p38 MAPK, suppressed the NF-κB transcriptional activation and improved the PPAR-γ expression. Moreover, the in vivo experiment exhibited that MCTA pretreatment markedly alleviated the xylene-induced ear edema and carrageenan-induced paw edema in mice and decreased the IL-1ß, IL-6 and TNF-α expressions. CONCLUSION: MCTA is rich in MIAs and exhibited a significant inhibitory effect on the production proinflammatory cytokines. The mechanism might be related to the inhibition of activation of NF-κB and MAPK pathways.

Isolation, characterization and in vitro anti-salmonellal activity of compounds from stem bark extract of Canarium schweinfurthii.

BACKGROUND: Bacteria belonging to the Salmonella genus are major concern for health, as they are widely reported in many cases of food poisoning. The use of antibiotics remains a main stream control strategy for avian salmonellosis as well as typhoid and paratyphoid fevers in humans. Due to the growing awareness about drug resistance and toxicities, the use of antibiotics is being discouraged in many countries whilst advocating potent benign alternatives such as phyto-based medicine. The objective of this work was to isolate, characterise the bioactive compounds of Canarium schweinfurthii; and evaluate their anti-salmonellal activity. METHODS: The hydro-ethanolic extract of Canarium schweinfurthii was fractionated and tested for their anti-salmonellal activity. The most active fractions (i.e. chloroform and ethyl acetate partition fractions) were then explored for their phytochemical constituents. Fractionation on normal phase silica gel column chromatography and size exclusion chromatography on Sephadex LH-20 led to the isolation of four compounds (maniladiol, scopoletin, ethyl gallate and gallic acid) reported for the first time in Canarium schweinfurthii. RESULTS: Result indicated that scopoletin and gallic acid had greater activity than the crude extracts and partition fractions. Among the isolated compounds, scopoletin showed the highest inhibitory activity with a MIC of 16 µg/ml against Salmonella Typhimurium and Salmonella Enteritidis. CONCLUSIONS: The overall results of this study indicates that the hydro-ethanolic extract as well as some of isolated compounds have interesting anti-salmonellal activities that could be further explored for the development of potent therapy for salmonellosis. Furthermore, the study adds credence to the folkloric applications of the plant.

Acute and Sub-Acute Toxicological Evaluations of Bioactive Alkaloidal Extract from Melodinus henryi and Their Main Chemical Constituents.

Melodinus henryi is a good source of terpenoid indole alkaloids, and traditionally used as a folk medicine in the treatment of meningitis and fracture. In order to further exploit their potential uses, its anti-inflammatory and immunosuppressive activities, safety evaluations and chemical profiles have been illustrated. Compared to the crude methanol extract from M. henryi and its non-alkaloidal fraction, the total alkaloidal fraction (MHTA) had the strongest anti-inflammatory and immunosuppressive activities. In the acute oral toxicity assay, the half lethal dose (LD50) of MHTA was more than 2000 mg/kg. The sub-acute toxicity assay for consecutive 28 days exhibited MHTA at a lower concentrations of less than 500 mg/kg might be regarded as safe, and might damage spleen, liver, kidney, and heart when the dose is higher than 1000 mg/kg. In addition, a phytochemical investigation on MHTA led to the isolation of 15 monoterpenoid indole alkaloids. Thus, in regard with the potent side effects of MHTA, it should be used with caution in the development of phytomedicine.

Acute and Chronic Toxicity of Indole Alkaloids from Leaves of Alstonia scholaris (L.) R. Br. in Mice and Rats.

Alstonia scholaris (L.) R. Br. (Apocynaceae) is an evergreen tree that has been used to treat lung diseases. In this study, the toxicity profile of indole alkaloids from leaves of A. scholaris was investigated. In acute toxicity tests, mice were administered total alkaloids (TA) and five indole alkaloids. In a chronic toxicity test, rats were continuously administered TA (50, 100, and 300 mg/kg bw) for 13 weeks, followed by a 4-week recovery. A single administration of TA affected the behavior of mice, and at 12.8 g/kg bw, prone position, shortness of breath, wheezing, and convulsion were observed. The half-lethal dose (LD50) in mice was 5.48 g/kg bw, almost 2740 times the clinical dose in humans. Among the five indole alkaloids, the maximum tolerance dose in mice ranged from 0.75 to 4 g/kg bw. The TA-treated rats did not die and showed no adverse effects or dose-dependent changes in weight or food and water consumption, despite fluctuations in hematological and biochemical parameters compared with historical data. Furthermore, both gross and histopathological observations revealed no abnormalities in any organ. With daily oral administration to rats, the non-observed-adverse-effect-level of TA was 100 mg/kg bw. The results indicate that TA is safe for clinical use.

Racemic immunosuppressive seco-aporphine derivatives from Thalictrum wangii.

Thallactones A (1) and B (2), enantiomeric aporphine alkaloids with rare cleaved rings A and B, as well as thaliglucine N-oxide (3) and their biosynthetically related precursor, northalphenine (4), were isolated from the whole plant of Thalictrum wangii. Their structures with absolute configurations were elucidated by spectral techniques and electronic circular dichroism (ECD). Moreover, compounds 1, 3, and northalphenine inhibited concanavalin A (Con A)-stimulated proliferation of mice splenocyte significantly in a dose-dependent manner.

Benzoxazinone-thiosemicarbazones as antidiabetic leads via aldose reductase inhibition: Synthesis, biological screening and molecular docking study.

Aldose reductase is an important enzyme in the polyol pathway, where glucose is converted to fructose, and sorbitol is released. Aldose reductase activity increases in diabetes as the glucose levels increase, resulting in increased sorbitol production. Sorbitol, being less cell permeable tends to accumulate in tissues such as eye lenses, peripheral nerves and glomerulus that are not insulin sensitive. This excessive build-up of sorbitol is responsible for diabetes associated complications such as retinopathy and neuropathy. In continuation of our interest to design and discover potent inhibitors of aldo-keto reductases (AKRs; aldehyde reductase ALR1 or AKR1A, and aldose reductase ALR2 or AKR1B), herein we designed and investigated a series of new benzoxazinone-thiosemicarbazones (3a-r) as ALR2 and ALR1 inhibitors. Most compounds exhibited excellent inhibitory activities with IC50 values in lower micro-molar range. Compounds 3b and 3l were found to be most active ALR2 inhibitors with IC50 values of 0.52 ±â€¯0.04 and 0.19 ±â€¯0.03 µM, respectively, both compounds were more effective inhibitors as compared to the standard ALR2 inhibitor (sorbinil, with IC50 value of 3.14 ±â€¯0.02 µM).

Antibacterial activities and toxicological study of the aqueous extract from leaves of Alchornea cordifolia (Euphorbiaceae).

BACKGROUND: A. cordifolia is a plant widely used in Africa to solve many health problems. In Cameroon, it is used in the treatment of urogenital infections. As a continuation of our search for pharmacologically active agents from natural sources, the antimicrobial activity of A. cordifolia leaf extracts against E. coli and the toxicity of this extract were investigated. METHODS: The antibacterial activity of the aqueous extract from leaves of Alchornea cordifolia was carried out in vitro on Escherichia coli, as well as in vivo on E. coli-infected rat model. Phytochemical screening was performed using standard methods. The acute toxicity was investigated in mice, while at the end of treatment of infected rats, some biochemical, hematological and histological markers of toxicity were evaluated. RESULTS: The extract exhibited a bacteriostatic activity with MIC value of 1500 µg/ml. Phytochemical screening revealed the presence of phenols, tannins, triterpens, flavonoids, alkaloids, anthraquinones, anthocyanins, saponins and coumarins in the extract. The acute toxicity study showed LD50 values of 8.6 g/kg and 3.8 g/kg in male and female mice respectively. In vivo, the oral administration of the extract showed a dose-dependent decrease of the bacterial load as the extract at 232, 112 and 58 g/kg were able to eradicate the infection after 9, 11 and 13 days of treatment. The infected rats showed a significant (p < 0.05) increase in the level of serum creatinine, ALAT, white blood cells, and a significant (p < 0.05) decrease in the level of food and water intake, the relative weight of lungs, heart and spleen. In the treated rats, a significant (p < 0.05) increase in food and water intake and ALAT was observed at the doses of 116 and 232 mg/kg. A decrease in the red blood cells count and serum protein levels was also observed. These observations corroborate liver damages as revealed by the histopathological examination of the cross sections of this organ. CONCLUSION: The results of this assay thus showed that the extract of A. cordifolia is bacteriostatic, therapeutic at 58 g/kg bw and may be considered as slightly and almost non-toxic on females and males mice respectively.

Antibacterial and antioxidant properties of crude extract, fractions and compounds from the stem bark of Polyscias fulva Hiern (Araliaceae).

BACKGROUND: In our previous work, the dichloromethane-methanol (1:1 v/v) extract, fractions and isolated compounds from Polyscias fulva stem bark showed interesting antifungal activity. As a continuity of that work, this study aimed to bring out complementary informations about the antimicrobial properties of P. fulva stem bark that may be useful in the standardization of phytomedicine from this plant. METHODS: The antibacterial activities of the crude extract, fractions (n-hexane, ethyl acetate, n-butanol and residual) and isolated compounds from Polyscias fulva stem bark were assayed by broth microdilution techniques. Their antioxidant activity were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), pyrogallol (superoxide anion) and ß-carotene - linoleic acid assays. RESULTS: The crude extract presented antibacterial activities against S. typhi (ATCC 6539), E. aerogenes (ATCC 13045), P. aeruginosa (PA01) and E. coli (ATCC 10536) with MIC values of 2000 to 8000 µg/ml. The fractionation led the ethyle acetate and n-butanol fractions relatively more active (MIC = 500 to 1000 µg/ml) as compared to the crude extract. ß-sitosterol and 3-O-α-L- arabinopyranosyl-hederagenin were the most active compounds on the tested bacteria with MIC values ranging from 6.25 to 100 µg/ml. The most sensitive was P. aeruginosa (PA01) on which all the tested compounds were active with MICs ranging from 6.25 to 400 µg/ml. Among all the tested substances, the crude extract (RSa50 = 84.86 µg/ml) and the methyl atrarate (RSa50 = 14.77 µg/ml), showed the highest scavenging activities against DPPH free radicals and those arising from the oxidation of the linoleic acid respectively. CONCLUSION: From this study, the results obtained reveal that the stem bark of P. fulva possesses antibacterial and antioxidant activities. It may then be useful in the development of an antimicrobial phytomedicine with a large spectrum of actvity endowed with antioxidant properties which can be standardised based on the isolated compounds.

Anti-Staphylococcus aureus activity of methanol extracts of 12 plants used in Cameroonian folk medicine.

BACKGROUND: The emergence of bacterial infections including those associated with Staphylococcus aureus causes a benefit of interest to medicinal plants as an effective means of control. The present study was designed to investigate the activities of 12 selected Cameroonian medicinal plants against S. aureus isolates. METHODS: The plant extracts were prepared by maceration in methanol at laboratory temperature. Qualitative phytochemical analysis was performed by chemical reaction methods. The broth microdilution method was used to evaluate the activities of plant extracts against 11 S. aureus clinical isolates. RESULTS: Dacryodes edulis was found to have significant antibacterial activity on all the S. aureus isolates (MIC = 64-256 µg/ml). Occimum gratissimum revealed significant inhibitory activity on 9 of the 11 isolates while Commelina erecta and Spilanthes filicaulis revealed similar results on 6 of the 11 clinical isolates. CONCLUSION: The present findings showed that D. eduli, O. gratissimum, C. erecta and S. filicaulis possess interesting inhibitory properties against S. aureus species. These plants could therefore be good candidates to overcome infectious diseases associated with these microorganisms.

Antifungal properties of a new terpernoid saponin and other compounds from the stem bark of Polyscias fulva Hiern (Araliaceae).

BACKGROUND: In our previous studies, it was evident that the dichloromethane-methanol (1:1 v/v) stem barks extract of Polyscias fulva and fractions (ethyl acetate, n-butanol and residue) demonstrated interesting antidermatophytic activities. So, as a continuity of that, this work aimed at identifying active principles with antifungal properties from P. fulva that could be used as markers for possible standardization of this plant as phytomedicine. METHODS: The ethyl acetate, n-butanol and residual fractions of the dichloromethane-methanol (1:1 v/v) stem bark extract of Polyscias fulva were further fractionated by column chromatography and the structures of isolated compounds elucidated based on their spectroscopic data in comparison with existing literature information. Antifungal activity was assayed by broth microdilution techniques on yeasts and dermatophytes spores. RESULTS: The fractionation of the crude dichloromethane-methanol (1:1 v/v) stem bark extract of Polyscias fulva led to the isolation of 10 known compounds (1 to 10) and one new saponin (11: 3-O-[α-L-rhamnopyranosyl (1-2)-α-L-arabinopyranosyl]-28-O-[α-L-4-O-acetyl-rhamnopyranosyl (1-4)-ß-D-glucopyranosyl-(1-6)-ß-D-glucopyranosyl]-hederagenin). Among these compounds, 3-O-α-L- arabinopyranosyl-hederagenin and 3-O-[α-L-rhamnopyranosyl (1-2)-α-L-arabinopyranosyl]-hederagenin were the most active on the tested fungi with MIC values ranging from 0.78 to 100 µg/ml against both yeasts and dermatophytes. CONCLUSION: The results of this work constitute a step forward in the possible development of an antidermatophytic phytomedicine from Polyscias fulva stem bark, the isolated compounds being possible markers for the standardisation.

In vitro and in vivo antidermatophytic activity of the dichloromethane-methanol (1:1 v/v) extract from the stem bark of Polyscias fulva Hiern (Araliaceae).

BACKGROUND: During the last decades, the number of people suffering from dermatophytoses has seriously increased, mainly due to the development of resistant strains of microorganisms to a range of formally efficient antibiotics. Polyscias fulva, a medium size tree which grows in the West Region of Cameroon is traditionally used for local application against dermatoses and orally against venereal infections. The dichloromethane-methanol (1:1 v/v) extract from the stem bark of Polyscias fulva was evaluated for its in vitro and in vivo antifungal activities. METHODS: The plant extract was prepared by maceration of its stem bark powder in CH(2)Cl(2)-MeOH (1:1 v/v). The extract obtained was successively partitioned in hexane, ethyl acetate and n-butanol. Phytochemical screening was performed using standard methods. In vitro antidermatophytic activity was assayed by the well diffusion and broth microdilution methods. The degree of dermal irritation of the crude extract was determined in guinea pigs using the occluded dermal irritation test method. The in vivo antidermatophytic activity of the extract-oil formulation (1.25, 2.5 and 5% w/w concentrations) was evaluated using Trichophyton mentagrophytes-induced dermatophytosis in a guinea pigs model. RESULTS: Phytochemical screening indicated that, the crude extract, ethyl acetate, n-butanol and residue fractions contain in general saponins, tannins, alkaloids, anthraquinones and phenols while the hexane fraction contains only alkaloids. The ethyl-acetate, n-butanol and residue fractions displayed higher antifungal activities (MIC = 0.125-0.5 mg.mL(-1)) against eight dermatophytes as compared to the crude extract (MIC = 0.5-1 mg.mL(-1)). This latter appeared to have slight perceptible erythema effects on guinea pigs as the primary irritation index (PII) was calculated to be 0.54. In vivo, the antidermatophytic activities of the extract-oil formulations were dose-dependent. Griseofulvin-oil 5% at 0.01 g/kg and formulated extract-oil (5%) at 0.1 g/kg eradicated the microbial infection after thirteen and fourteen days of daily treatment respectively. CONCLUSIONS: The results of preclinical in vitro and in vivo evaluations indicate that the extract-oil formulation at 5% may constitute an alternative means to alleviate fungal infections caused by dermatophytes.