Molecular characterization of high-risk human papillomavirus (HR-HPV) in women in Lomé, Togo.

BACKGROUND: The causative agent of cervical cancer referred to as Human papillomavirus (HPV) remains a real public health problem. Many countries in West Africa, such as Togo have no data on the high-risk HPV (HR-HPV) infection and genotypes distribution. In order to fill the knowledge gap in the field in Togo, the main objective of this study was to determine the prevalence of pre-cancerous lesions of the cervix and HR-HPV genotypes among Togolese women. METHODS: Samples were collected from 240 women by introducing a swab in the cervix. Then, the screening of precancerous cervical lesions using the visual inspection with acetic acid and lugol (VIA / VIL) was conducted. The HR-HPV genotypes were characterised by real-time multiplex PCR. RESULTS: Out of 240 women recruited, 128 (53.3%) were infected by HR-HPV. The most common genotypes were HPV 56 (22.7%), followed by HPV 51 (20.3%), HPV 31 (19.5%), HPV 52 (18.8%) and HPV 35 (17.2%). The least common genotypes were HPV 33 (2.3%) and HPV 16 (2.3%). Among the women, 1.3% (3/240) were positive to VIA/VIL. CONCLUSION: This study allowed HR-HPV genotypes to be characterised for the first time in Lomé, Togo. This will help in mapping the HR-HPV genotypes in West Africa.

The Role of Candida Albicans in Routine Clinically Suspected Otomycosis.

BACKGROUND: Candida albicans and non-albicans Candida species are considered as commensal yeasts of many cavities including the external auditory canal (EAC) in healthy individuals. These fungal microorganisms can also act as opportunist pathogens and cause otomycosis. In this study, the patients of clinically suspected otomycosis were specifically investigated mycologically to elucidate the role of Candida albicans and non-albicans Candida species. MATERIAL AND METHODS: A prospective observational study was conducted from July 2016 and June 2017 at the Laboratory of Parasitology and Mycology of the Sourô SANOU University Hospital in Bobo-Dioulasso, Burkina Faso. Identification of Candida isolates was using conventional phenotypic methods. Antifungal susceptibility tests were carried out by disk diffusion method in accordance with CLSI standard document M44-A for yeasts. RESULTS: Out of 160 patients with clinically diagnosed otomycosis, 77(48.1%) were investigated positive for Candida species. Candida albicans (61%) was the most isolated species and non-albicans Candida species accounted for 39% of the isolates, with mainly Candida spp (22.1%), Candida krusei (10.4%), Candida dubliniensis (5.2%) and Candida glabrata (1.3%). Nystatin showed the highest efficacy (95.9%), followed by ketoconazole (90.4%), clotrimazole (83.6%), miconazole (72.6%) and amphotericin B (63.0%). CONCLUSION: Otomycosis due to Candida species should be especially considered, since they have a wide number of potential virulence factors that cause fungal infections. Also, antifungal susceptibility testing should be performed in order to select the appropriate antifungal therapy.

CONTEXTE: Candida albicans et les espèces de Candida non albicans sont considérées comme des levures commensales de nombreuses cavités, y compris le conduit auditif externe (CAE) chez les individus sains. Ces micro-organismes fongiques peuvent également agir comme des agents pathogènes opportunistes et provoquer une otomycose. Dans cette étude, les patients cliniquement suspectés d'otomycose ont été spécifiquement étudiés mycologiquement pour élucider le rôle des espèces de Candida albicans et non albicans Candida. MATÉRIEL ET METHODS: Une étude observationnelle prospective a été menée de juillet 2016 à juin 2017 au Laboratoire de Parasitologie et Mycologie du CHU Sourô SANOU à BoboDioulasso, Burkina Faso. L'identification des isolats de Candida utilisait des méthodes phénotypiques conventionnelles. Des tests de sensibilité aux antifongiques ont été réalisés par la méthode de diffusion sur disque selon le document standard CLSI M44-A pour les levures. RÉSULTATS: Sur 160 patients atteints d'otomycose cliniquement diagnostiquée, 77 (48,1 %) ont été testés positifs pour les espèces de Candida. Candida albicans (61 %) était l'espèce la plus isolée et les espèces non albicans Candida représentaient 39 % des isolats, avec principalement Candida spp (22,1 %), Candida krusei (10,4 %), Candida dubliniensis (5,2 %) et Candida glabrata (1,3%). La nystatine a montré l'efficacité la plus élevée (95,9 %), suivie du kétoconazole (90,4 %), du clotrimazole (83,6 %), du miconazole (72,6 %) et de l'amphotéricine B (63,0 %). CONCLUSION: L'otomycose due aux espèces de Candida doit être particulièrement considérée, car elles ont un grand nombre de facteurs de virulence potentiels qui provoquent des infections fongiques. En outre, des tests de sensibilité aux antifongiques doivent être effectués afin de sélectionner le traitement antifongique approprié. Mots-clés: Candida albicans; Otomycoses; routine; sensibilité antifongique; Burkina Faso.

Health-related quality of life and long-term sequelae in survivors of epidermal necrolysis: an observational study of 57 patients.

BACKGROUND: Few studies have investigated the global burden of sequelae and health-related quality of life (HRQoL) for survivors of epidermal necrolysis (EN). OBJECTIVES: To investigate the long-term HRQoL for survivors of EN using validated instruments. METHODS: We conducted a single-centre study that enrolled patients who were admitted for EN between 2010 and 2017. HRQoL was assessed via phone interview using the Short Form (SF)-36 questionnaire, Hospital Anxiety and Depression (HAD) scale, Impact of Event Scale-Revised, and general quality-of-life outcomes, including EN-specific sequelae. The primary outcome measure was the physical component summary (PCS) score of the SF-36. RESULTS: In total, 57 survivors of EN [19 (33%) with intensive care unit (ICU) admission] were interviewed via telephone at a median of 3·6 years (1·9-6·1) after hospital discharge. The median PCS score was 0·44 SDs below that of the age- and sex-matched reference population and was significantly lower for survivors of EN who were admitted to the ICU vs. those who were not [43·7 (28·7-49·3) vs. 51·2 (39·4-56·5), P = 0·042]. The proportion of patients with EN who had HAD-anxiety score ≥ 8 or HAD-depression score ≥ 5 was 54% and 21%, respectively. Physical and mental outcomes did not differ between patients with EN who were admitted to the ICU and survivors of septic shock. Reported EN-specific sequelae were cutaneous (77%), ocular (70%), psychological (60%), dental/oral (49%), genital (30%) and respiratory (18%), with median intensity on a visual analogue scale. CONCLUSIONS: Our study confirms the major burden and long-term impact of EN on quality of life for survivors and emphasizes the need for prolonged close follow-up after the acute phase. What's already known about this topic? Long-term sequelae have been reported in 90% of survivors of epidermal necrolysis (EN). Few studies have investigated the global burden of sequelae and health-related quality of life (HRQoL) in survivors of EN. What does this study add? Survivors of EN, particularly those admitted to the intensive care unit, had poorer physical HRQoL than the French reference population but had comparable HRQoL to survivors of septic shock. Survivors of EN exhibited symptoms of anxiety, depression and post-traumatic stress syndrome. The most frequent sequelae were cutaneous, ocular and psychological, with visual analogue scale scores of 5/10 and 6/10. These results confirm the burden of EN on quality of life.

Developing reference criteria for the ecological status of West African rivers.

Awareness of sustainable management of water and its biological resources is rising in West Africa, but application of effective tools for biomonitoring and detecting habitats at risk in aquatic ecosystems is limited. In this study, we provide key environmental descriptors to characterize reference sites by applying the following "a priori criteria" (physical and chemical, hydro-morphological, and land use parameters) by exploring their potential to determine suitable reference sites. Using data collected from 44 sites, we identified 37 criteria that reliably identify reference conditions in semi-arid rivers by reflecting the impacts of multiple pressures ranging from low to very high intensity of human uses and impairments. We integrated all these impacts in an overall pressures index, which showed that protected areas can reasonably be considered as credible reference sites as far as they show low overall impact levels from cumulative pressures. We recommend that development of bio-indicator standards should be based on the collection and integration of all the available information, especially quantitative, spatially-explicit data, from benthic macroinvertebrates and fish. Rigorous standardization of bio-indicator protocols will make them more easily applicable for management and conservation of aquatic ecosystem resources in semi-arid zones of Africa.

Enabling sustainable pastoralism: policies and investments that optimise livestock production and rangeland stewardship.

Pastoralism is a system of dynamically managing livestock and land for economic, social and environmental benefit. To a large extent, pastoralism is an adaptation to ecological and climatic variability and is not simply a livestock production system but provides significant environmental services to humanity. Evidence from a range of national contexts shows that sustainable pastoralist development requires an understanding of the dual environmental and economic roles of pastoralism and an adaptation of policies and investments to support both. The current paper examines three cornerstones that have proven to be crucial for sustainable pastoralist development and for maximising the links between livestock production and environmental stewardship: strengthening pastoral capabilities and institutions, securing land tenure and natural resource governance, and ensuring equitable markets for pastoral diversity. To effectively support the dual economic-environmental roles of pastoralism requires not only optimisation of the production of ecosystem services through extensive livestock production, but also a major overhaul of the way we approach pastoralist development, and major investment in the people who are central to the system. As long as pastoralists remain marginalised, with weak rights and little access to services, their future will remain uncertain.

Le pastoralisme est un système de gestion dynamique du bétail et des terres qui génère des bénéfices économiques, sociaux et environnementaux. Dans une large mesure, le pastoralisme est le fruit d'une adaptation à la variabilité écologique et climatique ; de ce fait, il n'est pas simplement un système de production animale mais fournit d'importants services écologiques à l'humanité. Des données probantes obtenues dans plusieurs contextes nationaux montrent que l'évolution durable du pastoralisme passe par la prise en compte de la double fonction environnementale et économique du pastoralisme et par une adaptation des politiques et des investissements afin de soutenir chacune de ces fonctions. Les auteurs de cet article examinent trois facteurs éprouvés qui contribuent de manière déterminante au développement durable du pastoralisme et à l'optimisation des liens entre la production animale et la gestion de l'environnement : le renforcement des capacités et des institutions pastorales ; la protection de la jouissance des terres et la gouvernance des ressources naturelles ; la garantie de marchés équitables tenant compte de la diversité pastorale. Pour apporter un véritable soutien à cette double fonction économique et environnementale du pastoralisme, il convient non seulement d'optimiser la production de services écosystémiques grâce à l'élevage extensif, mais aussi de procéder à une refonte majeure de notre approche du développement pastoral et d'investir massivement dans les populations au coeur de ce système. Tant que les pasteurs demeureront marginalisés, dotés de peu de droits et d'un accès limité aux services, leur avenir restera incertain.

El pastoreo es un sistema que reposa en una gestión dinámica del ganado y las tierras para obtener un beneficio económico, social y ambiental. Lejos de ser un mero sistema de producción ganadera, constituye en gran medida una adaptación a la variabilidad ecológica y climática que presta a la humanidad importantes servicios ambientales. Los datos empíricos obtenidos en muy distintos contextos nacionales demuestran que el desarrollo sostenible del pastoreo pasa por entender su doble función, a la vez ambiental y económica, y por adaptar políticas e inversiones que vayan en apoyo de ambas dimensiones. Los autores examinan tres líneas básicas de trabajo que, según se ha comprobado, son cruciales para el desarrollo sostenible del pastoreo y para lograr que, en la mayor medida posible, producción ganadera y administración del medio ambiente vayan de la mano: reforzar las instituciones y capacidades pastorales; asegurar la propiedad de la tierra y la buena administración de los recursos naturales; y proporcionar mercados equitativos para la diversidad pastoral. Para respaldar eficazmente la doble función (económica y ambiental) del pastoreo es preciso no solo optimizar la producción de los servicios ecosistémicos mediante una producción ganadera extensiva, sino también reconsiderar a fondo la manera en que entendemos el desarrollo del pastoreo e invertir cuantiosamente en las personas que constituyen el núcleo del sistema. Mientras las sociedades pastorales sigan estando relegadas, disfruten de derechos endebles y gocen de un acceso deficiente a los servicios, su futuro seguirá rodeado de incertidumbre.

[Epidemiology of maxillo-facial traumatism s sequels at stomatology and maxillo-facial surgery service of Yalgado Ouedraogo University Hospital Center]. / Epidémiologie des séquelles de traumatismes maxillo-faciaux au service de stomatologie et chirurgie maxillo-faciale du Centre Hospitalier Universitaire Yalgado Ouedraogo (Burkina Faso).

Introduction: Our study brings back the epidemiological and anatomo-clinical characteristics of the maxillo-facial traumatisms sequels at Yalgado Ouedraogo University Hospital Center of Ouagadougou. Methodology: It was a transversal descriptive study going from May 2013 to April 2015. Results and Discussion: In all, 152 cases of post traumatisms sequels were collected. The masculine sex was more affected with a sex-ratio of 2,53. The mean age was 30,80 years. The public road accidents (73,68%) were the main etiology of initial lesions. The isolated functional and morphological sequels respectively represented 1/3 and 1/6 of cases. Half of patients had mixed sequels. The odontological sequels (41,45%), the disgracious scars (93,68%), the neurological sequels (15,79%), the ocular sequels (11,18%), and the temporo-mandibular ankylosis were the main sequels found in our study. These sequels could be explained by the nature of initial lesions and the lateness of consultations. Conclusion: Development of population's awareness and close interdisciplinary collaboration helped to reduce the frequency of these sequels.

High prevalence of high-risk human papillomavirus (HPV) infection among sexually active women in Ouagadougou.

Human papillomavirus (HPV) is the leading cause of cervical cancer, which in turn is the leading cause of cancer death in women in Africa. The objective of this study was to determine the prevalence of high-risk HPV infection (HR-HPV) and the distribution of genotypes encountered in the sexually active female population of Ouagadougou. In four level-two health centers, we recruited 234 women who agreed to undergo an endocervical swab. HR-HPV genotypes were identified by real-time PCR. The Chi-square test was used for comparisons, with significance defined by a P-value < 0.05. The prevalence of HR-HPV infection was 52.56%. Fourteen genotypes corresponding to 216 infections were characterized: HPV 59 (42/216), HPV 66 (30/216), HPV 56 (20/216), HPV 45 (20/216), HPV 58 (18/216), HPV 39 (18/216), HPV 51 (16/216), HPV 68 (14/216), HPV 52 (12/216), HPV 18 (12/216), HPV 35 (6/216), HPV 31 (5/216), HPV 16 (3/216), HPV 33 (0/216). HPV infection was statistically associated with age (P = 0.033) and with some specific sexual practices, such as oral sex (P = 0.001). The prevalence of HR-HPV infection among women without lesions in our study is higher than that reported previously in studies conducted in Ouagadougou among women in the general population and those found in the rest of the world. Moreover, HPV16 and 18 were not the genotypes most frequently encountered.

Emergence and spread of antibiotic resistance in West Africa : contributing factors and threat assessment.

The emergence and spread of antibiotic resistance present a major public health issue in both developed (DC) and less developed countries (LDC). Worldwide, its main cause is the uncontrolled and unjustified use of antibiotics. In countries with limited resources, such as West African nations, other features, more specifically socioeconomic and behavioral factors, contribute to exacerbate this problem. The objective of this review is to give an update of the common and specific factors involved in the amplification of antibiotic resistance phenomena in LCD, particularly in West African countries. In particular, some frequent societal behaviors (such as self-medication), inadequate healthcare infrastructure (insufficiently trained prescribers and inadequate diagnostic tools), and an uncontrolled drug sector (antibiotics sold over-the-counter, improperly stored, counterfeit, and/or expired) all strongly promote the emergence of antibiotic resistance. This risk is particularly worrisome for enterobacteriaceae producing extended spectrum beta-lactamases (10 to 100 % of colonizations and 30 to 50 % of infections). A similar trend has been observed for carbapenem resistance in enterobacteriaceae with rates ranging from 10 to 30 % and for methicillin resistance in Staphylococcus aureus, which now exceeds 30 %. These troubling observations call for effective health policies in these regions. These intervention strategies must be integrated and simultaneously target policy makers, prescribers, and users.

[Factors for non-observance of the extended program timetable for vaccination in health districts: the case of Boussé in Burkina Faso]. / Déterminants du non-respect du calendrier vaccinal du programme élargi de vaccination au niveau district sanitaire: cas du district sanitaire de Boussé, Burkina Faso.

UNLABELLED: Prevention through vaccination is a strong means to fight pediatric lethal diseases. In Burkina Faso, one of the main problems for vaccination is the non-respect of the vaccination timetable bringing about a significant reduction of validity of administered doses. OBJECTIVES: The authors had for aim to assess reasons for the non-compliance to the timetable. A transversal study was carried out in the Boussé health district to: 1) analyze the qualitative and organizational factors of the vaccination services linked to this non compliance; 2) analyze community factors accounting for this situation. POPULATION AND METHOD: The study target group included mothers of children aged 0 to 11 months vaccinated by the vaccination team of the Boussé health district from August 1st, 2003 to June 30th, 2004, and the vaccination team. Variables covered in this study included sociodemographic factors, the organization of vaccination campaigns, the mothers' perception of health service organization, the vaccination team's experience, vaccinal safety, knowledge of vaccination timetable. RESULTS: The following were identified as key factors for the non-observance of the vaccination timetable: poor organization of the vaccination services, inadequate competence of the vaccination team, poor educational level of mothers, poor communication level with mothers, postvaccination side effects. CONCLUSION: The study recommends the following: training of vaccination providers, a better organization of vaccination services, and the implementation of a communication plan.

[Perinatal asphyxia and acute renal insufficiency in Ouagadougou]. / Asphyxie périnatale et insuffisance rénale aiguë à Ouagadougou.

AIM: This study aimed to analyze acute renal failure in perinatal asphyxia (PNA) of term newborns in a sub-Saharan urban health center. PATIENTS AND METHODS: The study was prospective, conducted from 1st June to 30th November 2013 on term newborns hospitalized at the centre hospitalier universitaire pédiatrique Charles-de-Gaulle for PNA. Renal insufficiency (RI) was defined by a serum creatinine greater than or equal to 90 µmol/L. RESULTS: Eighty-five PNA cases were included, or 19.8% of newborns hospitalized in the study period. The sex ratio was 2.1. Thirty-eight newborns (44.7%) had RI. Their creatinine averaged 153.8±96.6 µmol/L. Twenty-six of 38 (68.4%) had brain damage in Sarnat stage 2 and 12 (31.6%) stage 3. Twelve newborns with RI (31.6%) had seizures. Transfontanellar echography revealed an abnormality in 30 cases (78.9%) of RI. Of the 38 newborns with renal failure, albuminuria was found in 21 cases (65.2%) and leukocyturia in 28 cases (73.7%). Renal function improved in 86.1% of cases. Newborns with initially normal serum creatinine had no RI during hospitalization. Six newborns (7.1%) died. CONCLUSION: This study showed that acute RI is common during PNA most particularly in newborns with severe neurological impairment. In our context, earlier support for women in labor could help prevent PNA and therefore newborn acute RI.

[Respiratory syncytial virus (RSV) infections in the pediatric teaching hospital Charles de Gaulle of Ouagadougou, Burkina Faso]. / Infections à virus respiratoire syncytial (VRS) au CHU pédiatrique Charles de Gaulle de Ouagadougou, Burkina Faso.

Human respiratory syncytial virus (RSV) infections are little known in Burkina Faso. The objective of our work is to study the epidemiological and clinical aspects of RSV infections in infants in the Pediatric Teaching Hospital Charles de Gaulle of Ouagadougou. Between July 1(st) 2010 and June 30(th) 2011, we analyzed by direct immunofluorescence and PCR nasopharyngeal swabs from children from 0 to 36 months old. All in all, 210 patients among whom 74 from the external consultation (35.2%) and 136 hospitalized (64.7%) benefited from a nasopharyngeal aspiration. The motives for consultation were cough (91.7%), rhinitis (79.2%), fever (79.2%) and respiratory distress syndrome (66.7%). The evoked diagnoses were predominantly the acute bronchiolitis in 14 cases (58.3%) followed by the acute pulmonary disease in 7 patients (26.2%) then flue in 1 patient (16.7%). We detected by direct immunofluorescence the antigens of the respiratory viruses in 21 nasopharyngeal aspirations with 10 cases of respiratory syncytial virus (RSV) infections (47.6%). The PCR realized on 208 samples allowed to identify 153 positive samples (73.2%) with 24 RSV, i.e. a global prevalence of 16.1% with a peak of 18 cases (75%). In October, all the patients benefited from an often multiple antibiotic treatment of at least 10 days which was not still necessary. The evolution was favorable for all patients. This study confirms the important place of the viruses which are detected in 70% of the cases. The PCR multiplex, certainly expensive but effective and successful, deserves to be used in our developing countries to avoid the irrational prescription of antibiotic.

[Positive impact on the Expanded Program on Immunization when sending call-back SMS through a Computerized Immunization Register, Bobo Dioulasso (Burkina Faso)]. / Impact positif sur le Programme élargi de vaccinations de l'envoi de SMS de rappel à partir d'un registre informatisé, Bobo-Dioulasso (Burkina Faso).

The impact of a Computerized Immunization Register (CIR) on Expanded Program on Immunization (EPI), with sending SMS to parents before immunization sessions, has never been studied in sub-Saharan Africa. The objective of this study is to measure EPI quickness and completeness of vaccinations after sending call-back SMS to parents through CIR put in place in a health center. In a health center, chosen at random (Colma 1) in the city of Bobo Dioulasso, Burkina Faso, West Africa, mothers, at first EPI session, if they had a mobile phone available at hand or in her surrounding, were randomized for receiving, or not, a call-back SMS before following EPI sessions, after child registration on a Francophone CIR (Siloxane's Intervax ©). Mothers, which were sent SMS and did not correctly followed sessions were asked through mobile phone why their child was late for EPI. 523 newborns were included in the study, with 253 whose parents were sent SMS, and 268 being informed of sessions only by ordinary methods. At second EPI session at 2 months of age, there was a statistical significant increase of coverage for children whose parents received SMS (p<0.001). Quickness to come also to this session was significantly shorter when parents received SMS (p=0.03). At third EPI session at 3 months of age, attendance to EPI for children whose parents were sent SMS was significantly better (p<0.001). Quickness to come to this session was shorter for children with SMS (p=0.02). At fourth EPI session at 4 months of age, attendance for children with SMS was significantly better for children whose parents were sent SMS (p<0.001). Quickness to come to this session was better but not significantly different (p=0.49). Out of 101 children registered as late for EPI sessions in Colma 1 CIR, even with call-back SMS, 19 (19%) parents could not be reached on the telephone. 31/82 (38%) mothers had shifted for EPI to a more proximate vaccination center (Colma 2), and 5 (6%) to private or civil servants clinic. 14/82 (17%) mothers had been travelling far from health center. Ten (12%) admitted neglect of EPI sessions. Two (2%) children had deceased, and one mother did not come back to Colma 1 after her child's AEFI. One child has been dismissed two times of vaccination following recommendation not to open a measles multi-dose vial for a single child, and did not come back. Of 523 children registered in CIR, 77 (14.7%) could not be found in the paper registers of Colma 1. Quickness and completeness for EPI is increased by sending SMS with help of CIR. An official number should be given for each child registered in CIR, consulted by health staff admitting children in urgency, allowing EPI vaccinations completion. With CIR safeguards, CIR should replace paper registers and should be used to send EPI reports by internet at central levels, helping MOH coverage determination and MAPI surveillance. The fall of coverage due to restriction policy not to open a multidose vial for a single child is low. Health staff should institute telephone call-back for badly immunized children registered on CIR and incorporate in it, with SMS call-back, pregnant women, to better complete prenatal sessions and tetanus vaccination.

3-Alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to diazoxide and pinacidil as potassium channel openers acting on vascular smooth muscle cells: design, synthesis, and pharmacological evaluation.

A series of 3-alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides structurally related to diazoxide and pinacidil were synthesized and tested as possible K(ATP) channel openers on isolated pancreatic endocrine tissue as well as on isolated vascular, intestinal, and uterine smooth muscle. In contrast to previously described 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1, 1-dioxides, most of the new compounds were found to be poorly active on B-cells but exhibited clear vasorelaxant properties. 3-(3, 3-Dimethyl-2-butylamino)-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxide (4d) and 7-chloro-3-(3, 3-dimethyl-2-butylamino)-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxide (5d), two compounds bearing the alkyl side chain of pinacidil, were found to be the most active representatives of their respective series on rat aorta rings. 3-Cycloalkylalkylamino- and 3-aralkylamino-7-chloro-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides also expressed myorelaxant activity on electrically stimulated guinea pig ileum and on oxytocin-induced contractions of the rat uterus. Further biological investigations ((86)Rb efflux measurements, vasodilator potency on 30 and 80 mM KCl-induced contractions in the absence and presence of glibenclamide) revealed that compounds 4d and 5d, but not compound 5f, expressed the pharmacological profile of classical K(ATP) channel openers. In conclusion, by changing the position of the nitrogen atom in the pyridine ring, we now have obtained a family of drugs expressing an opposite tissue selectivity. Taken as a whole, the present findings also suggest that 3-alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides such as 4c, 4d, 5c, and 5d may be considered as new examples of K(ATP) channel openers expressing a pharmacological profile similar to that of pinacidil and diazoxide.

Original 2-alkylamino-6-halogenoquinazolin-4(3H)-ones and K(ATP) channel activity.

A series of 6-substituted 2-alkylaminoquinazolin-4(3H)-ones structurally related to 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested as putative K(ATP) channel openers on isolated pancreatic endocrine tissue as well as on isolated vascular, intestinal, and uterine smooth muscle. Most of the 6-halogeno-2-alkylaminoquinazolin-4(3H)-ones were found to inhibit insulin release from pancreatic B-cells and to exhibit vasorelaxant properties. In contrast to their pyridothiadiazine dioxide isosteres previously described as more active on the endocrine than on the smooth muscle tissue, quinazolinones cannot be considered as tissue selective compounds. Biological investigations, including measurements of (86)Rb, (45)Ca efflux from pancreatic islet cells and measurements of vasodilator potency in rat aortic rings exposed to 30 or 80 mM KCl in the presence or the absence of glibenclamide, were carried out with 6-chloro- and 6-iodo-3-isopropylaminoquinazolin-4(3H)-ones. Such experiments showed that, depending on the tissue, these new compounds did not always express the pharmacological profile of pure K(ATP) channel openers. Analyzed by X-ray crystallography, one example of quinazolinones appeared to adopt a double conformation. This only suggests a partial analogy between the 2-alkylaminoquinazolin-4(3H)-ones and the 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides. In conclusion, the newly synthesized quinazolinones interfere with insulin secretion and smooth muscle contractile activity. Most of the compounds lack tissue selectivity, and further investigations are required to fully elucidate their mechanism(s) of action.

3-and 4-substituted 4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides as potassium channel openers: synthesis, pharmacological evaluation, and structure-activity relationships.

4-N-Substituted and -unsubstituted 3-alkyl- and 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested vs diazoxide and selected 3-alykl- and 3-(alkylamino)-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxides as potassium channel openers on pancreatic and vascular tissues. Several 4-N-unsubstituted 3-(alkylamino)pyridothiadiazines and some 3-(alkylamino)-7-chlorobenzothiadiazines were found to be more potent than diazoxide for the inhibition of the insulin-releasing process. Moreover, the 3-(alkylamino)pyridothiadiazines appeared to be more selective for the pancreatic than for the vascular tissue. By means of the pharmacological results obtained on pancreatic B-cells, structure--activity relationships were deduced and a pharmacophoric model for the interaction of these drugs with their receptor site associated to the pancreatic K(ATP) channel was proposed. According to their selectivity for the B-cell (endocrine tissue) vs the vascular (smooth muscle tissue) ionic channel, selected 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4,-thiadiazine 1,1-dioxides may serve as pharmacological tools in studying the K(ATP) channels ("pancreatic-like" K(ATP) channels) in other tissues.

3-Morpholinosydnonimine as instigator of a glibenclamide-sensitive reduction in the insulin secretory rate.

The nitric oxide (NO) donor SIN-1 (3-morpholinosydnonimine) induced a concentration-dependent inhibition of the secretory response to glucose. The negative insulinotropic action of SIN-1 was attenuated by the hypoglycemic sulfonylurea glibenclamide. Moreover, the NO donor enhanced 86Rb outflow from perfused islets and reduced the glucose-induced increase in 45Ca outflow. The present data provide further evidence that NO donors impair the secretory response to glucose, at least in part, by activating the ATP-sensitive K+ channels.

Hydroxylamine, a nitric oxide donor, inhibits insulin release and activates K+ATP channels.

The present study was undertaken to assess the effects of hydroxylamine, a nitric oxide (NO) donor, on ionic and secretory events in rat pancreatic islets. Hydroxylamine provoked a concentration-dependent inhibition of the glucose-induced insulin release. This inhibitory action was counteracted by glibenclamide. Moreover, hydroxylamine increased the rate of 86Rb outflow from perifused islets. This effect persisted in the absence of external Ca2+ but was impaired by glibenclamide. Hydroxylamine decreased 45Ca outflow, [Ca2+]i and insulin output from islets exposed to 16.7 mM glucose and extracellular Ca2+. By contrast, hydroxylamine did not affect the increase in 45Ca outflow and [Ca2+]i evoked by K+ depolarization. These experimental results suggest that the negative insulinotropic action of the NO donor results, at least in part, from the activation of ATP-sensitive K+ channels leading to a decrease in Ca2+ influx and [Ca2+]i. Additional mechanisms, however, could also be involved in the NO donor modulation of the secretory process.

[Progressive noma: apropos of 27 cases seen at the National Hospital Center of Ouagadougou]. / Le noma évolutif: à propos de 27 cas observés au Centre Hospitalier National de Ouagadougou.

This retrospective study objects to report epidemiological profile, clinical display and take care of progressive noma at the National Hospital Center of Ouagadougou. We assign the term noma to the gangrenous gingivo-stomatitis occurring in a prone environment, leading in a few days into a sharp ulcer in the soft parts, accompanied by halitosis. This definition excludes noma like-lesions. 27 cases have been observed in the ENT department and the Paediatrics between 1991 and 1995. They were 17 boys and 10 girls aging between 2 and 8 years and most of them coming from families with modest income (76%). The consultation delay averaged 8 days. The research for associated pathologies showed 63% energizing and protein malnutrition. We only observed unilateral localisations and no case of extra-facial one. At the stage we received our patients, the gangrenous was formed and the aspect evoked noma right away. Quite a lot needs to be done for precocious diagnosis because it is at the beginning phase that best evolution is obtained. Even though no evidence of the responsibility of a specific pathogenic germ was established so far, nevertheless, the assumption that has more support remains that of a bacterial infection in a prone environment. The vital prognosis of the progressive noma appears to be much linked with intensive care and feeding again. The hope to see this poverty-linked pathology under control is essentially based on prevention: medical population information, medical personnel's awareness for early diagnosis and best take care of these patients, improvement of the living conditions of the people and the health care services.