Ethnopharmacological Survey, Phytochemical Screening and Antimicrobial Activities of Medicinal Plants Used in the Treatment of Diarrhea in Southeastern Gabon.

Diarrhea is a condition that particularly affects children under five the age of years old in developing countries. The aim of this study was to evaluate the efficacy of medicinal extracts plants used in treatment and to characterize their inhibitory capacity in the growth of bacteria isolates in childhood diarrhea in the southeast region of Gabon. An ethnobotanical survey on the plants used in the treatment of diarrhea in southeastern Gabon was carried out and a phytochemical screening of the collected plants was performed. The antimicrobial activity of aqueous extracts was evaluated; 33 plant species were identified, representing 28 genera and 19 families. Bark (39.5%) was the most commonly used plant part, followed by powder formulations (28.9%). The preferred method of preparation and chewing (44.7%), together with drinking (36.8%), were the most prevalent modes of administration. Phytochemical screening showed a plethora of secondary metabolites (terpenoids, alkaloids and phenolic compounds), and a marked level of anti-diarrheal activity was found with Sida acuta and Santiria. ebo against Shigella spp. (16.22 ± 0.7 mm and 14.05 ± 1.4 mm) and Yersinia pestis (16.35 ± 0.5 mm and 15.51 ± 0.5 mm). The high diversity of secondary plant metabolites and their inhibitory ability against enteric pathogens would justify their use at the local level to treat diarrheal infections.

Role of circulating tumour cells (CTCs) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

Background: Liquid biopsy is emerging as a non-invasive tool, providing a personalized snapshot of a primary and metastatic tumour. It aids in detecting early metastasis, recurrence or resistance to the disease. We aimed to assess the role of circulating tumour cells (CTCs) as a predictive biomarker in recurrent/metastatic head and neck cancer (head and neck squamous cell carcinoma (HNSCC)). Methodology: Thirty-five patients receiving palliative chemotherapy underwent blood sampling [2 mL in Ethylenediaminetetraacetic acid (EDTA) vial] at baseline and at 3 months intervals. The CTCs were isolated and evaluated using anti-epithelial cell adhesion molecule antibody-based enrichment using the OncoDiscover platform. Results: CTCs isolated from 80% of patients (n = 28) showed the sensitivity of cell detection at the baseline and 3 months intervals. The median CTC count was 1/1.5 mL of blood and the concordance with clinic-radiological outcomes was 51.4%. The median CTC count (1 (range:0-4) to 0 (range:0-1)) declined at 3 months in responders, while the non-responders had an increase in levels (0 (range :0-2) to 1 (range :0-3)). Although CTCs positively correlated with progression-free survival (PFS) and overall survival (OS), the association of CTCs did not show a significant difference with these parameters (PFS: 6 months versus 4 months; hazard ratio: 0.68; 95% confidence interval (CI): 0.29-1.58, p = 0.323; OS: 10 months versus 8 months; hazard ratio: 0.54; 95% (CI):0.18-1.57 p = 0.216) between CTC positive and CTC negative patients at 3 months. Conclusion: This study highlights the utility of CTC as a disease progression-monitoring tool in recurrent HNSCC patients. Our findings suggest the potential clinical utility of CTC and the need for exploration in upfront settings of the disease as well (NCT: CTRL/2020/02/023378).

Evaluation of the bioresistance profile of enterobacteria isolated from faeces of children with diarrhoea in the town of Koula-Moutou, Gabon: prospective study.

Introduction: the emergence and expansion of multidrug resistance in Enterobacteriaceae responsible for various infections are increasing in the world. This study was designed to determine the phenotypic profiles of the resistance of enterobacteria strains isolated from the faeces of children with diarrhoeal diseases and to classify them according to the type of resistance. Methods: screening was carried out on 98 isolates divided into 2 groups: opportunistic pathogens and strict enteropathogens. Their sensitivity to 13 antibiotics was evaluated by the Mueller Hinton agar medium diffusion method. Results: a strong resistance to different classes of ß-lactams was found in the strains, 74.0% (n=45) and 83.3% (n=31) for opportunists and enteropathogens, respectively. These strains were completely resistant to doxycycline and erythromycin (100%; n=98) for both types of bacteria. Opportunists and enteropathogens were 95.1% (n=58) and 94.6% (n=35) resistant to gentamicin, and 31.1% (n=19) and 35.1% (n=13) resistant to chloramphenicol, respectively. Similarly, the total resistance of strains was observed with ofloxacin and amounted to 98.4% (n=60) and 96.7% with levofloxacin and norfloxacin, respectively. The analysis of ß-lactam resistance phenotypes revealed a dominance of the carbapenemase-producing strains (28.6%; n=28). However, 24.3% (n=9) of enteropathogens were pan-resistant versus 19.7% (n=12) for opportunists. Conclusion: the results of this study indicate a worryingly high level of antibiotic resistance in enterobacteria which might tend towards total resistance.

Circulating tumor cells as a predictor for poor prognostic factors and overall survival in treatment naïve oral squamous cell carcinoma patients.

OBJECTIVE: The aim of this study was to investigate the presence of circulating tumor cells (CTCs) and their correlation with prognostic factors and clinical outcomes in treatment-naive patients with oral squamous cell carcinoma. STUDY DESIGN: CTCs were isolated using OncoDiscover technique from presurgically obtained peripheral blood of 152 patients with treatment naïve oral squamous cell carcinoma. Sensitivity analysis was performed by including 40 healthy controls. CTCs cutoff values for clinicopathologic factors were obtained from receiver operating characteristic curves. Multivariate models determined the significance of CTC as independent variables. Kaplan-Meier analysis differentiated in overall survival between CTC values corresponding to the stage. RESULTS: Sensitivity, specificity, and accuracy of CTC detection were 94.32%, 98%, and 95.17%, respectively. Platform differentiated true positives at >3.5 CTCs (P < .00001). CTCs above 20.5 were suggestive of nodal metastasis (P < .0001) with a linear trend for detecting occult metastasis (P = .061). Early and advanced stages could be differentiated by >13.5 CTCs (P < .0001). Elevated CTCs were significantly associated with extranodal extension (>21.45 CTCs, P = .025), perineural invasion (>19.35 CTCs, P = .049), and depth of invasion (>12.5 CTCs, P = .0038). Median survival was reduced by 19 months when CTCs were >13. CONCLUSIONS: Preoperative CTC levels demonstrated a strong correlation with adverse clinicopathology factors and suggested its role as a sensitive prognostic marker to predict survival outcome and disease progress.

Antibody mediated cotton-archetypal substrate for enumeration of circulating tumor cells and chemotherapy outcome in 3D tumors.

Circulating tumor cells (CTCs) are distinct cancer biomarkers established in clinical settings for early cancer detection, metastasis progression, and minimal residual disease (MRD) monitoring. Despite numerous advances, the comprehensive molecular characterization of CTCs is extremely challenging owing to their rarity and heterogeneity. Here, we present a novel cotton microfluidic substrate (CMS) as an innovative biomedical matrix that efficiently isolates CTCs while facilitating in vitro CTC expansion to enable a further downstream analysis of these rare cells. CMS enabled static and dynamic isolation of cells from the MCF-7 cancer cell line, as well as from head and neck squamous cell carcinoma (HNSCC) patients' blood and the cell capture efficiencies were further compared with a clinically regulated OncoDiscover® Liquid Biopsy Test. Further, CMS acted as a matrix on which the captured cancer cells were grown in 3D tumor models for studying anti-cancer drug efficacy and multi-drug resistance (MDR) mechanisms. The design of the CMS employed two different surface chemistries, flattened and nanostructured surfaces, each conjugated to anti-EpCAM antibodies to evaluate the CTC capture efficiency and 3D tumor growth dynamics. The nanostructured surface was highly efficient for capturing CTCs and promoted 3D tumor spheroid formation with a 5-fold increase in size from day 03 to day 10 of culture. Moreover, when treated with an anti-cancer drug, cisplatin, an almost 1/2 reduction in tumor size was achieved within 24 hours, followed by a cytostatic threshold and eventual acquisition of drug resistance within 3 days. Conclusively, the CMS matrix exhibits potential for further development of "tissue on chip" and "point-of-care" medical devices in cancer diagnostics, and chemo-therapeutic efficacy evaluations in both drug discovery and development.

Safety Profile, In Vitro Anti-Inflammatory Activity, and In Vivo Antiulcerogenic Potential of Root Barks from Annona senegalensis Pers. (Annonaceae).

Annona senegalensis (Annonaceae) is a tropical shrub widely distributed in Burkina Faso. This plant is traditionally used as a medicine against many pathologies including typhoid fever, gastrointestinal disorders, ulcers, and inflammatory and infectious diseases. The present study was conducted to evaluate the anti-inflammatory and antiulcer properties of Annona senegalensis root bark extracts. Therefore, toxicity tests were first performed, followed by other biological tests. For this purpose, we first undertook to evaluate the toxicity tests before considering the other biological tests in a second step. The results showed that the extracted fractions had a significant effect for the different methods used (protein denaturation inhibition activity, hyaluronidase inhibition activity, and xanthine oxidase inhibition activity). However, of the extracted fractions used, the ethyl acetate fraction was the most anti-inflammatory fraction. The antiulcer activity was evaluated using the best bioactive fraction. The antiulcer effect of the ethyl acetate fraction may be due to both the reduction of gastric acid secretion and gastric cytoprotection. The results of this study also showed that the bioactive fraction reduced ethanol-induced ulceration and pyloric ligation in a dose-dependent manner, and at the highest dose (200 mg/kg), the effect was similar to that of the reference drug. In summary, the ethyl acetate fraction was found to have the best anti-inflammatory and antiulcerogenic activities. The ethyl acetate fraction at a dose of 200 mg/kg also showed a rather interesting level of cytoprotection. The anti-inflammatory and antiulcer activities could be due to the different secondary metabolites contained in the fractions extracted from Annona senegalensis, notably flavonoids, triterpenoids, steroids, saponins, and tannins. As the mechanisms of action are still little or not understood, we will consider in the future identifying the phytoconstituents and the mechanisms of action involved in the results.

Chemo-specific designs for the enumeration of circulating tumor cells: advances in liquid biopsy.

Advanced materials and chemo-specific designs at the nano/micrometer-scale have ensured revolutionary progress in next-generation clinically relevant technologies. For example, isolating a rare population of cells, like circulating tumor cells (CTCs) from the blood amongst billions of other blood cells, is one of the most complex scientific challenges in cancer diagnostics. The chemical tunability for achieving this degree of exceptional specificity for extra-cellular biomarker interactions demands the utility of advanced entities and multistep reactions both in solution and in the insoluble state. Thus, this review delineates the chemo-specific substrates, chemical methods, and structure-activity relationships (SARs) of chemical platforms used for isolation and enumeration of CTCs in advancing the relevance of liquid biopsy in cancer diagnostics and disease management. We highlight the synthesis of cell-specific, tumor biomarker-based, chemo-specific substrates utilizing functionalized linkers through chemistry-based conjugation strategies. The capacity of these nano/micro substrates to enhance the cell interaction specificity and efficiency with the targeted tumor cells is detailed. Furthermore, this review accounts for the importance of CTC capture and other downstream processes involving genotypic and phenotypic CTC analysis in real-time for the detection of the early onset of metastases progression and chemotherapy treatment response, and for monitoring progression free-survival (PFS), disease-free survival (DFS), and eventually overall survival (OS) in cancer patients.

Ecological, parasitological and individual determinants of plasma neopterin levels in a natural mandrill population.

Investigating how individuals adjust their investment into distinct components of the immune system under natural conditions necessitates to develop immune phenotyping tools that reflect the activation of specific immune components that can be measured directly in the field. Here, we examined individual variation of plasma neopterin, a biomarker of Th1 immunity in wild mandrills (Mandrillus sphinx), who are naturally exposed to a suite of parasites, including simian retroviruses and malaria agents. We analyzed a total of 201 plasma samples from 99 individuals and examined the effect of sex, age, social rank, reproductive state and disease status on neopterin levels. We found higher neopterin concentrations in males than females, but were unable to disentangle this effect from possible confounding effects of retroviral infections, which affect nearly all adult males, but hardly any females. We further detected a non-linear age effect with heightened neopterin levels in early and late life. In addition, adult males that harbored very high parasitaemia for Plasmodium gonderi also showed high neopterin levels. There was no effect of social rank in either male or female mandrills, and no effect of female reproductive state. Taken together, these results indicate that plasma neopterin may prove useful to investigate individual variation in investment into specific immune components, as well as to monitor the dynamics of immune responses to naturally occurring diseases that elicit a Th1 immune response.

Bio-efficacy of medicinal plants used for the management of diabetes mellitus in Gabon: An ethnopharmacological approach.

BACKGROUND/AIM: People suffering of diabetes increased significantly worldwide. Population, in Sub-Saharan Africa and mainly in Gabon, rely on medicinal plants to manage diabetes, as well in rural as in urban areas. This study aimed to survey a wide range of Gabonese plants for their antidiabetic activity. MATERIALS AND METHODS: This study focused on the identification of medicinal plants used in the local treatment of diabetes mellitus. Ethnobotanical investigations were carried out in rural and urban areas of three provinces of Gabon using a semi-structured interview. RESULTS: About 50 plant species belonging to 31 families and 50 genera were recorded, a majority of which have been documented previously to have medicinal properties. Most have documented antidiabetic properties with characterized therapeutic chemical compounds. Of the plant parts used for treatment, stem barks were employed most frequently (50%), followed by leaves (26%); the remaining 24% comprised roots, fibers, fruit, bulbs, flowers, rhizom, skin, and stem. Regarding the mode of preparation, decoction was the most widely used (58%), followed by maceration (18%) and infusion (14%). Almost all the plant products were administered orally (98%). CONCLUSIONS: Taken in concert, this study highlights the possibility of exploiting traditional knowledge of specific medicinal plants for the inexpensive treatment and management of diabetes.

Molecular identification of trypanosome species in trypanotolerant cattle from the south of Gabon.

The aim of this study was to provide information on trypanosome species infecting trypanotolerant cattle from southern Gabon. The study was conducted on 224 trypanotolerant cattle from three regions located in southern Gabon, using ITS1 primer-based PCR. Seventy-two (32%) N'dama cattle were found polymerase chain reaction (PCR) positive with trypanosomes. The overall prevalence of trypanosomosis was 57% (63/110), 4% (4/100), and 36% (5/14) in the Gala section of the Nyanga ranch, the Miyama ranch, and Ossiele, respectively. Trypanosoma congolense and Trypanosoma vivax were identified. In Gala section and Ossiele, T. congolense and T. vivax were found. In the Miyama ranch, only T. vivax was identified. Mixed infections were also found. The forest (9%) and savannah (63%) subgroups of T. congolense were identified. The presence of the two subgroups was detected in 16 out of 56 cattle (29%). T. congolense and T. vivax would appear to be the main agents responsible for bovine trypanosomosis in southern Gabon. Although trypanotolerant, N'dama cattle may serve as a reservoir, and this should be further studied. On the other hand, these trypanotolerant cattle can be reared in such tsetse infested areas, which gives them an advantage compared to other trypanosensitive breeds, and this shows that they represent a key factor in biodiversity which has to be promoted.

Ethnopharmacological surveys and pharmacological studies of plants used in traditional medicine in the treatment of HIV/AIDS opportunistic diseases in Gabon.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological surveys were conducted in two regions of Gabon. This led to highlighting some of the medicinal plants used by local populations in the management of HIV/AIDS opportunistic diseases. Two regions with the highest occurrence of HIV/AIDS cases were visited and ethnopharmarcological data was gathered. These regions were the Estuaire Province (Libreville and its neighborhood) and the Haut-Ogooué Province (Franceville and its neighborhood). The opportunistic diseases and symptomatic conditions considered during this study were: diarrhea, respiratory tract infections, cough, tuberculosis, abscesses, stomach ache, skin rashes, venereal diseases, typhoid fever, anemia, general tiredness, hepatitis and vomiting. MATERIALS AND METHODS: The reported species were evaluated through three parameters: specificity, reliability and frequency. Plant parts of relevant species were harvested and extracted with an aqueous alcohol solution (ethanol/water: 1/1). The extracts obtained were submitted to phytochemical screening and in vitro microbiological assays on some clinical isolates and ATCC strains, involved in HIV/AIDS opportunistic diseases through the Agar well diffusion and Microbroth dilution methods. RESULTS: Among the 52 species identified during this survey, Coelocaryon klainei Pierre ex Heckel (Myristicaceae), Dacryodes klaineana (Pierre) H.J. Lam (Bursecaceae), Phyllanthus diandrus Pax (Euphorbiaceae), Saccoglotys gabonensis (Baill.) Urb. (Humiriaceae) and Tetrorchidium didymostemon (Baill.) Pax & K. Hoffm. (Euphorbiaceae) were submitted to in vitro microbiological assays. Phyllanthus diandrus bark and leaves show best antibacterial activities against Pseudomonas aeruginosa and Klebsiella pneumoniae with MIC value of 0.25 respectively. Phytochemical screening revealed the presence in all the plant parts extracts of potentially bioactive molecules, including polyphenols, especially flavonoids and tannins. CONCLUSION: It is concluded that some of these plants might be submitted to further scientific studies, including the identification and isolation of bioactive principles, that could be developed to drugs for the treatment of HIV/AIDS opportunistic diseases.

Suppression of the macrophage proteasome by ethanol impairs MHC class I antigen processing and presentation.

Alcohol binge-drinking (acute ethanol consumption) is immunosuppressive and alters both the innate and adaptive arms of the immune system. Antigen presentation by macrophages (and other antigen presenting cells) represents an important function of the innate immune system that, in part, determines the outcome of the host immune response. Ethanol has been shown to suppress antigen presentation in antigen presenting cells though mechanisms of this impairment are not well understood. The constitutive and immunoproteasomes are important components of the cellular proteolytic machinery responsible for the initial steps critical to the generation of MHC Class I peptides for antigen presentation. In this study, we used an in-vitro cell culture model of acute alcohol exposure to study the effect of ethanol on the proteasome function in RAW 264.7 cells. Additionally, primary murine peritoneal macrophages obtained by peritoneal lavage from C57BL/6 mice were used to confirm our cell culture findings. We demonstrate that ethanol impairs proteasome function in peritoneal macrophages through suppression of chymotrypsin-like (Cht-L) proteasome activity as well as composition of the immunoproteasome subunit LMP7. Using primary murine peritoneal macrophages, we have further demonstrated that, ethanol-induced impairment of the proteasome function suppresses processing of antigenic proteins and peptides by the macrophage and in turn suppresses the presentation of these antigens to cells of adaptive immunity. The results of this study provide an important mechanism to explain the immunosuppressive effects of acute ethanol exposure.

Memory CD4+ T cells are required for optimal NK cell effector functions against the opportunistic fungal pathogen Pneumocystis murina.

Little is known about the role of NK cells or their interplay with other immune cells during opportunistic infections. Using our murine model of Pneumocystis pneumonia, we found that loss of NK cells during immunosuppression results in substantial Pneumocystis lung burden. During early infection of C57B/6 CD4(+) T cell-depleted mice, there were significantly fewer NK cells in the lung tissue compared with CD4(+) T cell-intact animals, and the NK cells present demonstrated decreased upregulation of the activation marker NKp46 and production of the effector cytokine, IFN-γ. Furthermore, coincubation studies revealed a significant increase in fungal killing when NK cells were combined with CD4(+) T cells compared with either cell alone, which was coincident with a significant increase in perforin production by NK cells. Finally, however, we found through adoptive transfer that memory CD4(+) T cells are required for significant NK cell upregulation of the activation marker NK group 2D and production of IFN-γ, granzyme B, and perforin during Pneumocystis infection. To the best of our knowledge, this study is the first to demonstrate a role for NK cells in immunity to Pneumocystis pneumonia, as well as to establish a functional relationship between CD4(+) T cells and NK cells in the host response to an opportunistic fungal pathogen.

Free radical scavenging capacity, anticandicidal effect of bioactive compounds from Sida cordifolia L., in combination with nystatin and clotrimazole and their effect on specific immune response in rats.

BACKGROUND: Infectious diseases caused by fungi are still a major threat to public health, despite numerous efforts by researchers. Use of ethnopharmacological knowledge is one attractive way to reduce empiricism and enhance the probability of success in new drug-finding efforts. In this work, the total alkaloid compounds (AC) from Sida cordifolia L. (Malvaceae) have been investigated for their free radical scavenging capacity, antifungal and immunostimulatory properties. METHOD: The antifungal activity was investigated against five candida strains using the microplate dilution method and the Fractional Inhibitory Concentration Index (FICI) of compounds was evaluated. The antioxidant activity of the samples was evaluate using three separate methods, at last, the immunostimulatory effect on immunosuppressed wistar rats was performed. RESULTS: As for the antifungal activity, result varied according to microorganism. The results obtained in this antifungal activity were interesting and indicated a synergistic effect between alkaloid compounds and the antifungal references such as Nystatin and Clotrimazole. Antioxidant capacity noticed that the reduction capacity of DPPH radicals obtained the best result comparatively to the others methods of free radical scavenging. Our results showed a low immunostimulatory effect and this result could be explained by the lack of biologically active antioxidants such as polyphenol compounds lowly contained in the alkaloid compounds. CONCLUSION: The results of this study showed that alkaloid compounds in combination with antifungal references (Nystatin and Clotrimazole) exhibited antimicrobial effects against candida strains tested. The results supported the utilization of these plants in infectious diseases particularly in treatment of candida infections.

Toxicity assessment and analgesic activity investigation of aqueous acetone extracts of Sida acuta Burn f . and Sida cordifolia L. (Malvaceae), medicinal plants of Burkina Faso.

BACKGROUND: Sida acuta Burn f. and Sida cordifolia L. (Malvaceae) are traditionally used in Burkina Faso to treat several ailments, mainly pains, including abdominal infections and associated diseases. Despite the extensive use of these plants in traditional health care, literature provides little information regarding their toxicity and the pharmacology. This work was therefore designed to investigate the toxicological effects of aqueous acetone extracts of Sida acuta Burn f. and Sida cordifolia L. Furthermore, their analgesic capacity was assessed, in order to assess the efficiency of the traditional use of these two medicinal plants from Burkina Faso. METHOD: For acute toxicity test, mice were injected different doses of each extract by intraperitoneal route and the LD50 values were determined. For the subchronic toxicity evaluation, Wistar albinos rats were treated by gavage during 28 days at different doses of aqueous acetone extracts and then haematological and biochemical parameters were determined. The analgesic effect was evaluated in mice by the acetic-acid writhing test and by the formalin test. RESULTS: For the acute toxicity test, the LD50 values of 3.2 g/kg and 3.4 g/kg respectively for S. acuta Burn f. and S. cordifolia L. were obtained. Concerning the haematological and biochemical parameters, data varied widely (increase or decrease) according to dose of extracts and weight of rats and did not show clinical correlations. The extracts have produced significant analgesic effects by the acetic acid writhing test and by the hot plate method (p <0.05) and a dose-dependent inhibition was observed. CONCLUSION: The overall results of this study may justify the traditional uses of S. acuta and S. cordifolia .

Antibacterial activity against ß- lactamase producing Methicillin and Ampicillin-resistants Staphylococcus aureus: Fractional Inhibitory Concentration Index (FICI) determination.

BACKGROUND: The present study reports the antibacterial capacity of alkaloid compounds in combination with Methicillin and Ampicillin-resistants bacteria isolated from clinical samples. The resistance of different bacteria strains to the current antibacterial agents, their toxicity and the cost of the treatment have led to the development of natural products against the bacteria resistant infections when applied in combination with conventional antimicrobial drugs. METHOD: The antibacterial assays in this study were performed by using inhibition zone diameters, MIC, MBC methods, the time-kill assay and the Fractional Inhibitory Concentration Index (FICI) determination. On the whole, fifteen Gram-positive bacterial strains (MRSA/ARSA) were used. Negative control was prepared using discs impregnated with 10 % DMSO in water and commercially available Methicillin and Ampicillin from Alkom Laboratories LTD were used as positive reference standards for all bacterial strains. RESULTS: We noticed that the highest activities were founded with the combination of alkaloid compounds and conventional antibiotics against all bacteria strains. Then, results showed that after 7 h exposition there was no viable microorganism in the initial inoculums. CONCLUSION: The results of this study showed that alkaloid compounds in combination with conventional antibiotics (Methicillin, Ampicillin) exhibited antimicrobial effects against microorganisms tested. These results validate the ethno-botanical use of Cienfuegosia digitata Cav. (Malvaceae) in Burkina Faso. Moreover, this study demonstrates the potential of this herbaceous as a source of antibacterial agent that could be effectively used for future health care purposes.

Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella pneumoniae in mice.

BACKGROUND: Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia. METHODS: C57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with Klebsiella pneumoniae. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured. RESULTS: Inhaled FP increased bacterial burden in lungs and blood 48 h after infection but affected neither in vivo phagocytosis of bacteria by alveolar macrophages (AM) nor alveolar neutrophil recruitment. AM from FP-treated mice showed impaired expression of infection induced TNF-alpha, IP-10 (CXCL-10), and interleukin 6 (IL-6), and AM also showed a trend towards impaired intracellular pathogen control following in vivo infection. In vitro FP treatment resulted in a dose-dependent impairment of cytokine expression by AM. Furthermore, infection-induced nitric oxide (but not hydrogen peroxide) production was impaired by FP in vivo and in vitro. FP decreased survival in this model. CONCLUSIONS: Exposure to inhaled FP impairs pulmonary clearance of K. pneumoniae in mice, an effect associated with greater systemic bacteremia and death. Decreased AM cytokine and nitric oxide expression parallel the failure to control infection. These results support the study of ICS effects on human pulmonary host defenses.

Antimicrobial activity of polyphenol-rich fractions from Sida alba L. (Malvaceae) against co-trimoxazol-resistant bacteria strains.

BACKGROUND: The increased resistance of microorganisms to the currently used antimicrobials has lead to the evaluation of other agents that might have antimicrobial activity. Medicinal plants are sources of phytochemicals which are able to initiate different biological activities including antimicrobials MATERIALS AND METHODS: In vitro antibacterial (MIC, MBC and time-kill studies) of polyphenol-rich fractions from Sida alba L. (Malvaceae) was assessed using ten bacteria strains (Gram-negative and Gram-positive). RESULTS: All test bacteria were susceptible to the polyphenol-rich fractions. Time-kill results showed that after 5 h exposition there was no viable microorganism in the initial inoculum and the effect of polyphenol-rich fractions was faster on Enterococcus faecalis (Gram-positive bacterium) comparatively to the other bacteria strains. CONCLUSION: The data analysis indicates that the tested of polyphenol-rich fractions has significant effects when compared with the standard antibiotic. These results therefore justify the traditional use of sida alba L., alone or in combination with other herbs to treat bacterial infections.

Dichrostachys cinerea (L.) Wight et Arn (Mimosaceae) hydro-alcoholic extract action on the contractility of tracheal smooth muscle isolated from guinea-pig.

BACKGROUND: Dichrostachys cinerea (L.) Wight et Arn. (Mimosaceae) is largely used in ethno-medically across Africa, and mainly employed for the treatment of asthma in Ivory Coast and Gabon. The paper analyses the relaxation induced by the methanolic extract of D. cinerea (Edici) in the guinea-pig trachea preparations (GPTPs). PURPOSE: This study aimed to bring out the scientific basis to the use of this plant leading to the validation of this phytomedicine. METHOD: The aorta obtained from guinea-pigs was immediately placed in a Mac Ewen solution. Experiments were performed in preparations suspended between two L-shaped stainless steel hooks in a 10 ml organ bath containing Mac Ewen solution. The isometric contractile force of the aorta strips of guinea-pig were recorded by using a strain gauge. The different drugs were directly administered into the organ bath and the magnitude of GPTPs was evaluated. RESULTS: Phytochemical analysis of the methanolic extract of Dichrostachys cinerea (Edici) using chemical methods revealed the presence of flavenoids, tannins, sterols, triterpenes and polyphenols. Pharmacological studies performed in GPTPs show that of Dichrostachys cinerea (0.1 mg/ml - 2 mg/ml) evoked a broncho-constriction in GPTPs. Whereas, at concentration up to 2 mg/ml, Edici induced a significant dose-dependent relaxation in the GPTPs. KCl-, ACh- or histamine-evoked contractions of isolated trachea was significantly inhibited by increasing concentrations of Edici (3.5-10 mg/ml). Edici (10 mg/ml) as well as promethazine (0.25 mg/ml) significantly inhibited contractions induced by increasing concentrations of histamine (1×10-7-1×10-4mg/ml). In the presence of atropine at a concentration of 10-6mg/ml, contractile response curve (CRC) evoked by ACh (1×10-5-1×10-2 mg/ml) was significantly abolished in concentration-dependent manner. Edici did not significantly reduced ACh evoked contraction (10-5-10-2mg/ml). CONCLUSION: These observations suggest that Edici could act through two mechanisms: firstly by activation of ß-adrenergic or histaminergic receptors; and secondly muscarinic receptors may not be greatly involved, that justifying the use of the extract in traditional Medicine in Africa.

Induction of insulin secretion by an aqueous extract of Tabernanhte iboga Baill. (Apocynaceae) in rat pancreatic islets of Langerhans.

The effect of an aqueous extract of Tabernanthe iboga (TBEt) was studied in the rat islets insulin secretion based on its use in traditional medicine for the treatment of diabetes. Rats islets were isolated by collagenase digestion. In insulin release experiments, the insulin content was determined by Enzyme-Link Immunosorbent Assay (ELISA). For experiments on 45Ca(2+) Uptake, the radioactive content was determined using a liquid scintillation analyzer. The extract (10⁻³ µg/ml-100 µg/ml) did not exert a significant increase of insulin secretion (p>0.05) in the presence of 2.8 mM of glucose (a none stimulatory concentration). Whereas, in the presence of 11.1 mM of glucose (stimulatory concentration), TBEt augmented glucose-stimulated insulin secretion in a dose-dependent manner. Interestingly, the secretory effect of the extract was glucose-dependent (5.6-16.7 mM). Furthermore, the insulinotropic effect of TBEt (1 µg/ml) was significantly potentiated (p<0.001) in K(+)-depolarised media as well as in the presence of 2.8 mM and 16.8 mM of glucose concentrations. In contrast, in the same conditions, TBEt failed to stimulate the high K(+) medium-induced insulin release. The extract significantly amplified (p<0.001 and p<0.05) the insulin secretion induced by either IBMX or tolbutamide. Diazoxide, cobalt or calcium removal inhibited the insulinotropic effect of the extract. TBEt increased glucose-induced 45Ca(2+) uptake in rat islets. Overall, our findings suggest that Tabernanthe iboga contains water soluble insulinotropic compounds. The insulin secretion of TBEt's active principles might involve the closure of K(+)-ATP and the intensification of calcium influx through voltage-sensitive Ca(2+) channels.