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This paper presents the first experimental results obtained with the four cameras backward gazing method for measuring the optomechanical errors of solar concentrating surfaces in operation. It consists in combining the images simultaneously acquired by four cameras placed near the solar receiver in order to reconstruct the slope errors of the mirrors digitally. New algorithms adapted to real acquired images are described. The experiment has been conducted on a sun-tracking heliostat of the experimental solar tower THEMIS with canting error measurement accuracy estimated as 0.2 mrad. The main experimental error sources are analyzed, and possible ways of mitigation are proposed, giving reasonable hope of reaching an ultimate measurement accuracy of 0.1 mrad.
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We report a large improvement in the collection and slope efficiency of an Nd:YAG solar laser pumped by a heliostat-parabolic mirror system. A conical fused silica lens was used to further concentrate the solar radiation from the focal zone of a 2 m diameter primary concentrator to a Nd:YAG single-crystal rod within a conical pump cavity, which enabled multipass pumping to the active medium. A 56 W cw laser power was measured, corresponding to 21.1 W/m2 record-high solar laser collection efficiency with the heliostat-parabolic mirror system. 4.9% slope efficiency was calculated, corresponding to 175% enhancement over our previous result.
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BACKGROUND: The role of nipple-sparing mastectomy (NSM) for breast cancer is controversial as there is concern regarding its oncological safety and complication rate. We carried out a review of the literature to quantify the incidence of occult nipple malignancy in breast cancer, identify the factors influencing occult nipple malignancy, quantify locoregional recurrence rates and quantify NSM complication rates. METHODS: A search of the literature was performed using PubMed. Keywords used were "mastectomy", "nipple involvement", "nipple-sparing mastectomy", "skin-sparing mastectomy" "occult nipple malignancy" "occult nipple disease" "breast cancer recurrence". Articles were analyzed regarding incidence of occult nipple malignancy, potential factors influencing the incidence of occult malignancy and recurrence/complications following NSM. The incidence of occult nipple disease was compared between groups using Chi(2) or Fisher's exact tests for categorical variables and Student's t-tests for continuous variables. P values were considered significant<0.05. We identified nearly 30 studies compiling nearly 10 000 cases examining the rate of occult nipple malignancy and 23 studies compiling 2300 cases providing information on the rate of local recurrence after NSM. RESULTS: The overall rate of occult nipple malignancy was 11.5 %. Primary tumour characteristics influencing occult nipple malignancy were tumour-nipple distance<2cm, grade, lymph node metastasis, lymphovascular invasion, HER2 positive, ER/PR negative, tumour size>5cm, retro-areolar/central location and multicentric tumours. The overall nipple recurrence rate following NSM was 0.9 %, skin flap recurrence rate was 4.2 %. Full and partial thickness nipple necrosis rates were 2.9 % and 6.3 % respectively. CONCLUSION: NSM for primary breast cancer is appropriate in carefully selected patients. All patients should have retro-areolar sampling. There is strong evidence to suggest that suitable cases are well circumscribed single or multifocal lesions that have a TND>2cm. Tumours should be graded 1-2 and not have LVI, axillary node metastasis or HER2 positivity.
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Neoplasias de la Mama/cirugía , Mastectomía/métodos , Pezones , Tratamientos Conservadores del Órgano , Femenino , HumanosRESUMEN
The data presented in this article were collected in the field at an experimental station in southern France under a Mediterranean climate. Experiments were conducted under three plastic walk-in tunnels used as blocks with organic farming practices over two successive years in a completely randomized design. The aim was to compare the intercropping of sweet pepper with basil, onion, lettuce, parsley or French bean to a sole crop of sweet pepper used as a control. The dataset provides information on cultural practices with details on inputs and working times used to estimate economic costs. The data also describe the climatic conditions under tunnels as well as the dynamics of soil nitrate concentration and water tension over time through treatments. Yields, economic benefits and the rates of products with visual defects are presented. In addition, some variables applied exclusively to sweet pepper crops, namely nitrate concentration in petiole sap, growth parameters, abundance of aerial pests and beneficials, incidence of root necrosis, arbuscular mycorrhizal fungi colonization rates and diversity in roots. The field dataset is made publicly available to allow free and easy access for the scientific and professional community to enable analysis and reuse. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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OBJECTIVES: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). ANIMALS: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. METHODS: Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. RESULTS: Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. CONCLUSIONS: Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.
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Enfermedades de los Perros , Insuficiencia Cardíaca , Animales , Biomarcadores , Muerte , Enfermedades de los Perros/diagnóstico por imagen , Perros , Ecocardiografía/veterinaria , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/veterinaria , Válvula Mitral/diagnóstico por imagen , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Estudios ProspectivosRESUMEN
Historically, aldosterone receptor antagonists (ARA) have been classified as 'potassium sparing diuretics'. However, the positive effect of spironolactone, the most extensively studied ARA, on morbidity and mortality observed in humans suffering cardiac insufficiency could not be explained by the renal effect of the drug alone, and a pivotal clinical study has led to extensive research. Many experimental studies have demonstrated that ARA have previously unexpected beneficial effects on the cardiovascular system including reduction in remodelling of the vascular smooth muscle cells and myocytes and improvement of endothelial cell dysfunction in heart failure. These effects improve vascular compliance and slow down the progression of left ventricular dysfunction and end-organ damage. Furthermore, aldosterone receptor blockade also restores the baroreceptor reflex, improving heart rate variability in heart failure in humans. Some of these effects have been demonstrated in dog models of cardiac disease and so justified further investigation of the potential benefit of ARA in dogs with congestive heart failure (CHF). Positive effects of spironolactone on morbidity and mortality appear to have been seen in studies conducted in dogs suffering from naturally occurring CHF. In addition, eplerenone has been shown to have benefits in canine models of heart failure. The precise mechanisms by which ARA produce these beneficial effects in dogs remain to be determined but this group of drugs clearly provide therapeutic actions out-with their diuretic effects.
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Enfermedades de los Perros/tratamiento farmacológico , Insuficiencia Cardíaca/veterinaria , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Espironolactona/análogos & derivados , Espironolactona/uso terapéutico , Animales , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Cardiovascular/efectos de los fármacos , Perros , Eplerenona , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/farmacología , Espironolactona/farmacologíaRESUMEN
INTRODUCTION: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial. HYPOTHESIS: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). ANIMALS: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) ≥1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) ≥1.7. METHODS: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations. RESULTS: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group. CONCLUSIONS: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance.
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Benzazepinas/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/veterinaria , Espironolactona/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina , Animales , Perros , Ecocardiografía/veterinaria , Femenino , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Masculino , Válvula Mitral , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Estudios Prospectivos , Troponina IRESUMEN
OBJECTIVE: To evaluate the reproducibility, the feasibility and the functional results of the HydroThermAblator (HTA) technique. PATIENTS AND METHODS: This is a retrospective multicenter study in which 143 patients were enrolled in six French medical centers. Patients suffering from dysfunctional and heavy uterine bleeding were treated using the HTA technique between June 2003 and June 2005. A preoperational questionnaire describing the symptoms as well as a qualitative assessment of bleeding was filled. We report the surgical conditions as well as the per- and postoperative complications. We analyzed the level of patient's satisfaction with this technique using a postoperative questionnaire. RESULTS: The average patient's age was 48 years (37-67 years). Patients described their bleeding as being very significant in 46% of the cases, significant in 36%, normal but postmenopausal in 11% of the cases and unknown in 7% of the cases. Previous treatment for bleeding was prescribed in 42.4% of cases. Forty-two decimal four percent of the patients had myomas on preoperative ultrasound examinations. Four minor operative complications were encountered. Thirteen patients had postoperative complications, most of which were described as pelvic pain. Mean postoperative follow-up time was nine months. There were 72.7% of the patients who were satisfied with the procedure. Forty-four percent of the patients were amenorrheic, 37% were oligomenorrheic and 13% were eumenorrheic. Seven patients underwent hysterectomy. The indication for hysterectomy in half of these patients was persistent menorrhagias. DISCUSSION AND CONCLUSION: The hydrothermablator is a simple and efficient endometrial ablation technique for patients suffering from menometrorrhagias. This technique can be used in patients with uterine myomas and irregular uterine cavity. Hydrothermablation must be carried out under hysteroscopic control, which allows to assess treatment success at the end of the intervention. Histology is compulsory (with the exception of patients with metrorrhagia only), all the more so as cancer cases can remain undiscovered.
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Ablación por Catéter , Histeroscopía/métodos , Leiomioma/cirugía , Trastornos de la Menstruación/cirugía , Neoplasias Uterinas/cirugía , Adulto , Anciano , Ablación por Catéter/métodos , Ablación por Catéter/normas , Femenino , Humanos , Histeroscopía/normas , Trastornos de la Menstruación/etiología , Persona de Mediana Edad , Satisfacción del Paciente , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Pregnancy in the rudimentary horn of a unicornuate uterus is an extremely rare form of ectopic gestation associated with a high risk of uterine rupture. We report the case of a pregnancy developed in a non communicating rudimentary horn of a unicornuate uterus complicated by horn rupture at 23 weeks of amenorrhea showing as an acute abdominal pain and massive hemoperitoneum. This patient's uterine abnormality was known before, as this woman has delivered two years before at term a healthy boy by cesarean section. This past pregnancy was located in the normal horn and the non communicating rudimentary horn seemed at this time normal. This uterine malformation is presented with its gynecological and obstetrical entailments as well as methods that could prevent such outcome.
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Abdomen Agudo/etiología , Trompas Uterinas/anomalías , Hemoperitoneo/etiología , Embarazo Tubario/patología , Rotura Uterina , Útero/anomalías , Adulto , Trompas Uterinas/patología , Femenino , Humanos , Embarazo , Factores de Riesgo , Rotura Uterina/prevención & controlRESUMEN
Ovarian and peritoneal sarcoidosis is a very rare condition, with an atypical clinical presentation close to that of ovarian cancer. An erroneous diagnosis could induce a definitive castration. A 38-year-old woman was admitted because of ascites and weight loss. A computerized tomography scan revealed multiple soft tissue nodules in the pelvis, on the ovaries as well as peritoneal deposits. Histological examination after laparoscopic biopsy was indicative of sarcoidosis. Corticosteroids were given to the patient and the symptoms quickly subsided. This case with its clinical presentation is discussed in comparison with previously reported cases.
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Corticoesteroides/uso terapéutico , Enfermedades del Ovario/diagnóstico , Enfermedades Peritoneales/diagnóstico , Sarcoidosis/diagnóstico , Adulto , Biopsia/métodos , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades del Ovario/tratamiento farmacológico , Enfermedades del Ovario/patología , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Enfermedades Peritoneales/tratamiento farmacológico , Enfermedades Peritoneales/patología , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/patología , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate fertility outcome after laparoscopic management of endometriosis in an infertile population. MATERIALS AND METHODS: A retrospective analysis of 64 patients presenting more than one year infertility and a pregnancy-wish associated with minimal to severe endometriotic lesions (stage I to IV according to the revised American Fertility Society (rAFS) classification), treated using laparoscopic surgery in order to remove the entire lesions. We excluded women under 20 years and over 40, as well as those with other infertility factors (tubal non endometriosis-related, hormonal or sperm). Fertility of the remaining 34 patients was studied in relation to endometriosis stage and to pregnancy's mode (spontaneous or induced). RESULTS: Pregnant women percentage was 65% (22 patients) within a 8.5 months (quartiles: 3; 15.5) [range: 1; 52] post-surgical time, and 86.5% pregnancies issued with a delivery. The rate of pregnant women depended on stage of endometriosis (89% for stages I-II, and 56% for stages III-IV). Sixty percent pregnancies were spontaneous within a 5 months (3; 9) [1; 52] post-surgical time to pregnancy average. When pregnancies were obtained with assisted reproductive techniques, the median post-surgical time to pregnancy was 12 months (9; 22) [2; 31]. Among women with stages I-II endometriosis, the median post-surgical time to pregnancy was 2 months when spontaneous and 20.5 months when induced (P=0.007). In case of stages III-IV endometriosis, pregnancy's delay was 8 and 12 months respectively (P=0.79). Among the 21% women who had had an induced pregnancy failure before surgery, 71% became pregnant and 80% spontaneously. Eighteen patients (53%) had an ovarian endometrioma and 50% of them became pregnant. Among the 4 patients who had colorectal endometriosis requiring colorectal resection, 1 pregnancy was obtained. CONCLUSIONS: These findings suggest that in a context of more than one year infertility only related to endometriosis, it is reasonable to offer these patients a complete operative laparoscopic treatment of their lesions, which enables 65% of them to be pregnant within a 8.5 months post-surgical median time to pregnancy and spontaneously in 60%. In case of stages I-II endometriosis we suggest a spontaneous pregnancy try during 8 to 12 months before starting induced pregnancy therapeutics instead of stages III-IV endometriosis where induced methods should be used after only 6 or 8 months.
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Endometriosis/cirugía , Infertilidad Femenina/cirugía , Laparoscopía , Resultado del Tratamiento , Adulto , Endometriosis/complicaciones , Endometriosis/patología , Femenino , Humanos , Infertilidad Femenina/etiología , Embarazo , Técnicas Reproductivas Asistidas , Estudios Retrospectivos , Factores de TiempoRESUMEN
We report a case of placenta accreta left fully in situ during a cesarean section. Postoperative courses were complicated with a thrombosis of the right external iliac artery after embolization and with a pyometra needing n hysterectomy. We discuss the risks of such conservative treatment of a placenta accreta, compared with classical ablation.
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Embolización Terapéutica , Arteria Ilíaca , Placenta Accreta/cirugía , Adulto , Cesárea , Femenino , Humanos , Histerectomía , Placenta Accreta/terapia , Embarazo , Factores de Riesgo , Insuficiencia del TratamientoRESUMEN
Genetic analysis of 16 deletions obtained in the amiA locus of pneumococcus is described. When present on donor DNA, all deletions increased drastically the frequency of wild-type recombinants in two-point crosses. This effect was maximal for deletions longer than 200 bases. It was reduced for heterologies shorter than 76 bases and did not exist for very short deletions. In three-point crosses in which the deletion was localized between two point mutations, we demonstrated that this excess of wild-type recombinants was the result of a genetic conversion. This conversion extended over several scores of bases outside the deletion. Conversion takes place during the heteroduplex stage of recombination. Therefore, in pneumococcal transformation, long heterologies participated in this heteroduplex configuration. As this conversion did not require an active DNA polymerase A gene it is proposed that the mechanism of conversion is not a DNA repair synthesis but involves breakage and ligation between DNA molecules. Conversion of deletions did not require the Hex system of correction of mismatched bases. It differs also from localized conversion. It appears that it is a process that evolved to correct errors of replication which lead to long heterologies and which are not eliminated by other systems.
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Deleción Cromosómica , Recombinación Genética , Streptococcus pneumoniae/genética , Transformación Genética , Mapeo Cromosómico , Cruzamientos Genéticos , Mutación , TemperaturaRESUMEN
In genetic transformation, long deletions dramatically increase the frequency of wild-type recombinants in 2-point crosses. In 3-point crosses in which the deletion was localized between 2 point mutations we demonstrated that this hyper-recombination was the result of genetic conversion extending over several scores of bases outside the deletion. As this conversion did not require an active DNA polymerase A gene, it was proposed that the mechanism of conversion involves breakage and ligation between DNA molecules. A similar hyper-recombination was observed when donor DNA carried an insertion. These results suggest that long heterologies participated in recombination so that surrounding homologous regions are almost completely paired and that these long heterologies are converted. It appears that it is a process that evolved to correct errors of replication which lead to long deletions and which are not eliminated by other systems.
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Deleción Cromosómica , Recombinación Genética , Streptococcus pneumoniae/genética , Transformación GenéticaRESUMEN
A sensitive and rapid method was developed to detect Cryptosporidium parvum oocysts in drinking water. This molecular assay combined immunomagnetic separation with polymerase chain reaction amplification to detect very low levels of C. parvum oocysts. Magnetic beads coated with anti-cryptosporidium were used to capture oocysts directly from drinking water membrane filter concentrates, at the same time removing polymerase chain reaction inhibitory substances. The DNA was then extracted by the freeze-boil Chelex-100 treatment, followed by polymerase chain reaction. The immunomagnetic separation-polymerase chain reaction product was identified by non-radioactive hybridization using an internal oligonucleotide probe labelled with digoxigenin. This immunomagnetic separation-polymerase chain reaction assay can detect the presence of a single seeded oocyst in 5-100-1 samples of drinking water, thereby assuring the absence of C. parvum contamination in the sample under analysis.
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Cryptosporidium parvum/aislamiento & purificación , Separación Inmunomagnética/métodos , Reacción en Cadena de la Polimerasa/métodos , Microbiología del Agua , Abastecimiento de Agua , Animales , Técnicas Inmunológicas , Microesferas , Sensibilidad y EspecificidadRESUMEN
In order to estimate the rate and seasonal variation of Enterocytozoon bieneusi contamination of surface water, sequential samples of water from the River Seine in France were collected during a 1-year period. Each sample (300-600 l) was submitted to sequential filtrations, and the filters were then examined for microsporidia using light microscopy and nested polymerase chain reaction (PCR) for E. bieneusi. Amplified products were hybridized with a E. bieneusi-specific probe. Twenty-five samples of water were analyzed during 1 year. Microscopic examination of stained filters proved unreliable for the identification of spores. Using nested PCR, 16 of 25 specimens were positive (64%). Unexpectedly, E. bieneusi was identified in only one sample by specific hybridization underlining the lack of specificity of ours primers. Nevertheless, using DNA sequence analysis, unknown microsporidia species were identified in eight cases, which had highest scores of homology with Vittaforma corneae or Pleistophora sp. This study shows a low rate of water contamination by E. bieneusi suggesting that the risk of waterborne transmission to humans is limited.
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Enterocytozoon/aislamiento & purificación , Agua Dulce/parasitología , Microsporidios/aislamiento & purificación , Microbiología del Agua , Animales , Southern Blotting , ADN Protozoario/análisis , Enterocytozoon/genética , Estudios de Seguimiento , Francia , Microsporidios/genética , Pleistophora/genética , Reacción en Cadena de la Polimerasa , Homología de Secuencia de Ácido Nucleico , Vittaforma/genéticaRESUMEN
The effects of the selective alpha 2-adrenoceptor agonist UK 14.304 on glucose, insulin and amylin levels were examined in neonatal streptozotocin-induced diabetic rats. UK 14.304 (0.03 to 0.3 mg/kg i.p.) induced a dose-dependent reduction of both insulin and amylin levels in normal rats while UK 14.304 at 0.03 mg/kg had already a maximal effect in diabetic rats. Amylin/insulin molar ratios rose after UK 14.304 administration in diabetic rats but remainded constant in normal rats. The alpha 2-adrenoceptor antagonist deriglidole (3 mg/kg i.p.) slightly increased insulin and amylin levels in the two groups of rats but glucose levels were more markedly decreased in diabetic rats. Deriglidole completely antagonized UK 14.304 (0.1 mg/kg i.p.)-induced changes thereby normalizing amylin/insulin molar ratios in diabetic rats. These results suggest that insulin and amylin are both under inhibitory control via alpha 2-adrenoceptor though the responses may be differentially regulated. It is further suggested that diabetes in the neonatal streptozotocin-induced rat model is associated with a hypersensitivity of the pancreas to alpha 2-adrenoceptor stimulation.
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Amiloide/sangre , Glucemia/análisis , Diabetes Mellitus Experimental/metabolismo , Insulina/sangre , Receptores Adrenérgicos alfa 2/fisiología , Animales , Tartrato de Brimonidina , Femenino , Polipéptido Amiloide de los Islotes Pancreáticos , Quinoxalinas/farmacología , Ratas , Ratas Sprague-Dawley , EstreptozocinaRESUMEN
The role of afferent sensory nerves in glucose tolerance and glucose stimulated insulin secretion was investigated in normal (N) or neonatal streptozotocin-induced diabetic (D) rats treated with capsaicin (NC and DC, respectively) during the neonatal period. In capsaicin treated animals, oral glucose tolerance was markedly improved both in NC and DC whereas insulin secretion was not affected. The effect of alpha 2-adrenergic blockade was investigated in D and DC rats. The alpha 2-adrenoceptor antagonist deriglidole (3 mg/kg i.p.) administered 30 min before glucose load slightly reduced glucose levels and markedly increased insulin levels both in D and DC rats. Thereafter, the high insulin levels were maintained or further increased following glucose administration. As a consequence, glucose tolerance was further improved in D and in DC, which already expressed an improved glucose tolerance after capsaicin administration. These results suggest that sensory nerves are implicated in the control of glucose tolerance in normal and neonatal streptozotocin-induced diabetic rats through a mechanism independent of insulin release. It is also suggested that afferent sensory nerves are not implicated in the adrenergic control of insulin secretion from pancreatic beta-cells.
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Capsaicina/farmacología , Diabetes Mellitus Experimental/fisiopatología , Prueba de Tolerancia a la Glucosa , Neuronas Aferentes/efectos de los fármacos , Antagonistas de Receptores Adrenérgicos alfa 2 , Antagonistas Adrenérgicos alfa/farmacología , Animales , Diabetes Mellitus Experimental/sangre , Femenino , Imidazoles/farmacología , Indoles/farmacología , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Neuronas Aferentes/fisiología , Ratas , Ratas Sprague-Dawley , EstreptozocinaRESUMEN
The effects of the alpha2-adrenoceptor antagonist SL84.0418 and its two enantiomers, (+) deriglidole and (-)SL86.0714 on glucose and insulin levels were examined in mice and in neonatal streptozotocin-induced diabetic rats. It was recently demonstrated in mouse pancreatic beta-cells that both deriglidole and SL86.0714 inhibit ATP-sensitive K+ channel with similar potency whereas alpha2-adrenoceptors are blocked only by deriglidole. In the present study, we showed, in vivo in mice, that SL84.0418 and deriglidole potently reduced glycemia and antagonized diazoxide-induced hyperglycemia, whereas SL86.0714 and tolbutamide were markedly less potent. In diabetic rats, SL84.0418 and deriglidole (10 mg/kg i.p.) fully normalized glucose tolerance whereas SL86.0714 and tolbutamide only slightly improved it. Five min after deriglidole administration in mice a marked and short lasting rise in insulin levels was observed, followed by a progressive reduction of glycemia. In diabetic rats, insulin and norepinephrine levels rose 15 min after deriglidole administration. Sympathetic outflow blockade by chlorisondamine, beta-adrenoceptor blockade by propranolol or their combination markedly reduced deriglidole-induced rise in insulin levels in a similar manner. Furthermore, in chlorisondamine-treated animals norepinephrine levels were strongly lowered and not modified by deriglidole and propranolol administration. However, in spite of sympathetic outflow and beta-adrenoceptor blockade, a moderate rise in insulinemia was still observed after deriglidole administration. Taken together these data demonstrate that deriglidole is the enantiomer that mediates the antihyperglycemic and insulin secretory effects of SL84.0418. Our study suggests that the major part of deriglidole effects is the consequence of the blockade of prejunctional alpha2-adrenoceptors that have reinforced the release of catecholamines in adrenergic nerve endings and indirectly activated postjunctional beta-adrenoceptors to further potentiate insulin secretion. However, it is also suggested that another undefined mechanism is involved in deriglidole potentiation of insulin secretion.
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Antagonistas Adrenérgicos alfa/farmacología , Hipoglucemiantes/farmacología , Imidazoles/farmacología , Indoles/farmacología , Pirroles/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2 , Animales , Glucemia/análisis , Clorisondamina/farmacología , Diabetes Mellitus Experimental/sangre , Diazóxido/farmacología , Femenino , Prueba de Tolerancia a la Glucosa , Imidazoles/farmacocinética , Indoles/farmacocinética , Insulina/sangre , Insulina/metabolismo , Antagonistas de Insulina/farmacología , Secreción de Insulina , Masculino , Ratones , Norepinefrina/sangre , Propranolol/farmacología , Ratas , Ratas Sprague-Dawley , Especificidad de la EspecieRESUMEN
In the present study, we evaluated the pharmacological characteristics of the functional muscarinic receptors implicated in rabbit detrusor contraction and coupled to inositol phospholipid turnover in rabbit detrusor and parotid gland. The selectivity of several muscarinic antagonists for detrusor vs. salivary gland muscarinic receptors was also examined. The affinities for the muscarinic m1-, m2- and m3-receptor subtypes were determined using membranes from human cloned receptors expressed in CHO-K1 cells using [3H]-N-methyl scopolamine as a radioligand. Anti-muscarinic activity was determined in isolated rabbit detrusor by measuring the displacement of the contractile response to carbachol, and in rabbit detrusor and rabbit parotid by measuring the displacement of inositol phospholipid hydrolysis (total inositol phosphate accumulation) to carbachol. A significant correlation was found between the potencies to antagonize carbachol-induced rabbit detrusor contraction (pK(B)) and the affinities (pKi) for the m3-receptor subtype (r = 0.93, P = 5 x 10(-6)). Lower, but significant, correlations [0.88 (P = 6.3 x 10(-5)), 0.72 (P = 4.6 x 10(-3))] were obtained with m1- or m2-receptor subtypes, respectively. Each muscarinic antagonist tested displayed similar potency to antagonize carbachol-stimulated inositol phospholipid hydrolysis in rabbit detrusor and parotid (r = 0.96, P = 8 x 10(-3)). A significant correlation was found between the potencies to antagonize carbachol-stimulated inositol phospholipid hydrolysis (pK(B)), determined in rabbit detrusor and rabbit parotid, and the affinities (pK(i)) for the m3-receptor subtype [r = 0.96 (P = 0.01), 0.99 (P = 5 x 10(-5)), respectively] and for the m1-receptor subtype [r = 0.98 (P = 3.5 x 10(-3)), 0.94 (P = 0.02), respectively] but not for the m2-receptor subtype [r = 0.33, 0.57, ns, respectively]. In each in vitro assay, methoctramine (preferential M2 selective antagonist) and pirenzepine (preferential M1 selective antagonist) were slightly potent. We suggest that the muscarinic receptor implicated in the response to carbachol in rabbit detrusor and parotid gland corresponds to the M3-subtype. None of the muscarinic antagonists studied in rabbit tissues displayed preferential affinity for the detrusor.