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OBJECTIVE: The renin-angiotensin-aldosterone system (RAAS) and glucocorticoids (GCs) are involved in vascular remodeling and fibrosis, but have not been extensively studied in systemic sclerosis (SSc). Our aim was to investigate the RAAS and GC hormones in SSc patients. METHODS: Serum levels of renin (dosage and activity), aldosterone and its precursors (DOC, B, 18-OH-DOC, 18-OH-B), and GCs (cortisol, cortisone, 11-deoxycortisol, 18-OH-F) were assessed in 122 SSc patients and 52 healthy controls. After applying stringent inclusion criteria aimed at ensuring accurate hormone assessments (exclusion of interfering drugs, strict sampling conditions), we analyzed RAAS hormones in 61 patients, and GCs in 96 patients. Hormone levels were compared between patients and controls; and associations with disease characteristics were assessed in patients. RESULTS: Regarding RAAS hormones, SSc patients displayed significantly lower aldosterone levels (although within normal range), similar renin levels, and higher B levels than controls. Abnormal RAAS hormone levels were associated with a more severe SSc phenotype (lung and skin fibrosis, heart and pulmonary vascular involvements, inflammation). Regarding GC hormones, SSc patients had higher levels of cortisol, 11-desoxycortisol (precursor) and 18-OH-F (metabolite) but lower levels of cortisone (inactive counterpart) than controls.RAAS hormone levels were assessed in 5 SSc patients before and during scleroderma renal crisis (SRC): concentrations varied considerably between patients, but consistently included normal/increased aldosterone levels and elevated renin levels. CONCLUSION: RAAS and GC hormones are abnormally produced in SSc patients, especially in patients with severe SSc and during SRC. This could suggest a participation of these hormonal systems in SSc pathogenesis.
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Inherited metabolic diseases (IMD) form a heterogeneous group of genetic disorders that surface primarily during childhood and result in significant morbidity and mortality. A prevalence of 1 in 2500-5000 live births is often reported. The transfer of adolescents from pediatric care to adult health facilities is often difficult for patients and their families and can lead to a breakdown in medical follow-up and therefore serious complications. Existing recommendations for the successful transition of patients with chronic disorders do not specifically address patients with IMDs associated with dietary treatment. Here, the French network for rare inherited metabolic diseases (G2M) presents its reflections and recommendations for a successful transition. Preparations for the transfer must be made well in advance. The transfer must aim for adolescents gaining autonomy by making them responsible and providing them with the knowledge that will enable them to manage their care themselves, know how to react appropriately if there is any change in their condition, and move comfortably within the adult healthcare system. This requires the active participation of the patient, his or her family, and pediatric and adult care teams. It involves multidisciplinary management plus the production and maintenance of an educational therapy program. Finally, the identification of physicians and dietitians trained in IMDs, relevant subspecialists, and even expert patients could improve the continuum of complete and appropriate care for these patients within adult medicine.
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INTRODUCTION: Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B). METHODS: Retrospective multicentric analysis of French adult patients with ASMD over the period 1985-March 2015. Clinical, biological, and imaging data were analyzed. RESULTS: Twenty-eight patients (19 males, 9 females) were analyzed. Diagnosis was made before the age of 10 years in 16 cases. Main symptoms at diagnosis were spleen/liver enlargement and interstitial lung disease. Biological abnormalities included: thrombocytopenia (platelet count <150 000/mm3) in 24 cases including 4 patients with platelet count <60 000/mm3, constantly low high-density lipoprotein (HDL) cholesterol, polyclonal hypergammaglobulinemia (n=6), monoclonal gammopathy of unknown significance (n=5), normal prothrombin level discordant with low factor V (n=5), elevated chitotriosidase level (n=11). The diagnosis was confirmed in all cases by deficient acid sphingomyelinase enzyme activity. SMPD1 gene sequencing was performed in 25 cases. The frequent p.R610del mutation was largely predominant, constituting 62% of the non-related alleles. During the follow-up period, three patients died before 50 years of age from cirrhosis, heart failure and lung insufficiency, respectively. CONCLUSION: ASMD in adulthood (NP-B) associates spleen/liver enlargement and interstitial lung disease. Early diagnosis and appropriate management are essential for reducing the risk of complications, improving quality of life, and avoiding inappropriate procedures such as splenectomy. To date, only symptomatic therapy is available. A phase 2/3 therapeutic trial with IV infusion of recombinant enzyme is on-going.
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Enfermedad de Niemann-Pick Tipo B , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Preescolar , Consanguinidad , Femenino , Francia/epidemiología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Enfermedad de Niemann-Pick Tipo B/diagnóstico , Enfermedad de Niemann-Pick Tipo B/epidemiología , Enfermedad de Niemann-Pick Tipo B/genética , Fenotipo , Estudios Retrospectivos , Esfingomielina Fosfodiesterasa/deficiencia , Esfingomielina Fosfodiesterasa/genética , Adulto JovenRESUMEN
INTRODUCTION: Hyperhomocysteinemia is a biological marker that could be identified in the venous thrombotic events and rarely during acute arterial thrombotic events. The consequences can be serious. Effective diagnostic strategy is needed to optimize the management. CASE REPORT: Following bariatric surgery, a 40-year-old patient was admitted with an acute encephalopathy associated with peripheral lower limb arterial ischemia. The diagnostic work-up identified a major hyperhomocysteinemia whose causes were several. Surgical treatment and anticoagulation was associated with vitamins and trace elements supplementation. Correcting deficiencies allowed delirium and hyperhomocysteinemia improvement. Once treatment established, the patient did not present a recurrent thrombotic episode. CONCLUSION: Major hyperhomocysteinemia seems to be associated with an increased risk of acute arterial thrombosis. This marker might be considered in nutritional deficiency situations with appropriate support on the vascular, metabolic and nutrition level.
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Anticoagulantes/uso terapéutico , Hiperhomocisteinemia/complicaciones , Trombosis/etiología , Adulto , Arterias/patología , Suplementos Dietéticos , Femenino , HumanosRESUMEN
Urea cycle disorders (UCDs) are inborn errors of metabolism in which the clinical picture is mostly due to ammonia intoxication. UCD onset may be observed at any age. Acute decompensations of UCDs include neuro-psychiatric symptoms such as headache, confusion, convulsions, ataxia, agitation or delirium, as well as digestive symptoms, namely nausea and vomiting along with abdominal pain. Acute decompensations may lead to an irreversible coma in the absence of specific therapy. The first step is to measure promptly ammonemia in such patients, and start appropriate therapy on an emergency basis.
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Trastornos Innatos del Ciclo de la Urea/diagnóstico , Trastornos Innatos del Ciclo de la Urea/terapia , Adulto , Confusión/diagnóstico , Confusión/etiología , Cefalea/diagnóstico , Cefalea/etiología , Humanos , Náusea/diagnóstico , Náusea/etiología , Convulsiones/diagnóstico , Convulsiones/etiología , Trastornos Innatos del Ciclo de la Urea/complicaciones , Vómitos/diagnóstico , Vómitos/etiologíaRESUMEN
Inborn errors of metabolism (IEM) are rare diseases, most often inherited as an autosomal recessive disorder. They may be associated with endocrine dysfunction, the most frequent of them being disorders of carbohydrate metabolism (hypoglycemia, diabetes). The endocrinologist might be led to screen these complications in a patient whose diagnosis has been done during childhood. In some rare cases, he should evoke the diagnosis in front of an endocrine disorder most often associated to a multisystemic involvement. This spreading field is new, not yet very well known in adulthood. Long-term consequences of IEM on fertility and bone metabolism are still poorly understood. Diagnosis orientation relies on a few specific lab investigations encompassing blood lactate, free fatty acids and 3-hydroxy-butyrate, ammoniemia, carnitine and acylcarnitines, aminoacid and urinary organic chromatography. Hyperinsulinism, glycogenosis, fatty acid ss-oxydation, carnitine cycle and glycosylation (CDG syndrome) disorders, fructose intolerance, tyrosinemia, organic aciduria may explain hypoglycemia. These diagnosis should be evoked in front of unexplained adult hypoglycemia. Diabetes is related to iron overload, mitochondriopathy and thiamine sensitive diabetes. Clinical spectrum of some forms of IEM switch from hypoglycemia in childhood to diabetes in adulthood. Mitochondriopathies can be associated to all types of endocrine disorders, the most frequent being diabetes and dysthyroidism. Hypothyroidism is encountered in mitochondriopathies, cystinosis and primary hyperoxaluria. Hypogonadism is almost constant in galactosemia, frequent in CDG syndromes, cystinosis and iron overload. Most of the time, a specialized advice is required, which is one of the mission of reference centres.
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Hormonas/sangre , Hipoglucemia/etiología , Errores Innatos del Metabolismo/metabolismo , Insuficiencia Suprarrenal/fisiopatología , Adulto , Femenino , Fertilidad , Enfermedad del Almacenamiento de Glucógeno/clasificación , Enfermedad del Almacenamiento de Glucógeno/metabolismo , Humanos , Hipoparatiroidismo/fisiopatología , Masculino , Errores Innatos del Metabolismo/fisiopatología , Mitocondrias/metabolismo , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/fisiopatologíaRESUMEN
UNLABELLED: The obese patients adhere weakly to rehabilitation programs; therefore the expected gains are often disappointing. This is possibly linked to the monotony of constant velocity exercises frequently proposed. Consequently, other less monotonous exercises such as the intermittent walk may be more appropriated. OBJECTIVES: The main objectives of this study were to determine if the obese women prefer a constant velocity walk or an intermittent walk, and to analyze the effects of a rehabilitation program based on the intermittent walk. MATERIALS AND METHODS: Twenty obese women were recruited. To determine the preferred walk modality, 10 obese women performed a constant velocity walk and an intermittent walk (with a similar duration and velocity) on a treadmill. The preferred walk modality was determined by lower ratings of perceived exertion. Then, these same 10 women participated in a rehabilitation program of 10 weeks (three days per week) consisting of intermittent walks. The 10 other women did not participate in a training program. RESULTS: The ratings of perceived exertion were not significantly different between the two walk modalities. However, the women who participated in a training program increased their maximal distance during a 6 min walking test and they have stabilized theirs anthropometric data. Meanwhile, the untrained women have increased their body mass, body mass index and percentage of body fat. CONCLUSION: The obese patients preferred similarly the constant velocity walk and the intermittent walk, and a rehabilitation program based on an intermittent walk is effective in avoiding the obesity aggravation.
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Composición Corporal , Índice de Masa Corporal , Obesidad/rehabilitación , Caminata , Adulto , Femenino , Humanos , Persona de Mediana Edad , Obesidad/psicología , Percepción , Esfuerzo FísicoRESUMEN
We present the case of a 17-year-old male who was diagnosed at birth with hereditary fructose intolerance (HFI). The patient complained of morning-time asthenia and post-prandial drowsiness despite a correct sleep pattern. The physical examination and biological check-up only showed severe vitamin C deficiency (<10 mol/l; normal range: 26-84). The patient's tiredness was attributed to this vitamin C deficiency, which is a frequent side-affect of the fructose-free diet. A change in diet associated with a supplementation in vitamin C was advised, with an increase in vegetable intake, principally avoiding carrots, onions, leaks and tinned sweet-corn. This case offers the opportunity for a review of this rare disease. Two kinds of fructose metabolism disorders (both autosomal recessive) are recognized: 1) essential fructosuria caused by a deficiency of fructokinase, which has no clinical consequence and requires no dietary treatment; 2) HFI, linked to three main mutations identified in aldolase B gene that may be confirmed by fructose breath test, intravenous fructose tolerance test, and genetic testing. In HFI, fructose ingestion generally induces gastro-intestinal (nausea and vomiting, abdominal pain, meteorism) and hypoglycemic symptoms. Fasting is well tolerated. If the condition remains undiagnosed, it leads to liver disease with hepatomegaly, proximal tubular dysfunction, and slow growth and weight gain. In conclusion, endocrinologists should be aware of this rare metabolic disease in order to provide careful follow-up, particularly important when the patient reaches adulthood. Moreover, hypoglycemia induced by fructose absorption, unexplained liver disease, irritable bowel syndrome or familial gout in an adult is suggestive of the diagnosis.
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Intolerancia a la Fructosa/diagnóstico , Intolerancia a la Fructosa/genética , Adolescente , Ácido Ascórbico/uso terapéutico , Astenia/etiología , Diagnóstico Diferencial , Dieta , Fructosa/metabolismo , Intolerancia a la Fructosa/dietoterapia , Intolerancia a la Fructosa/fisiopatología , Fructosa-Bifosfato Aldolasa/deficiencia , Glucógeno/metabolismo , Humanos , MasculinoRESUMEN
Recent studies have focused on the occurrence of concomitant medullary-papillary thyroid carcinomas (MTC-PTC). The aims of this report were to compare the frequency of occult PTC in a population with MTC versus a control population that had undergone thyroidectomies and to check whether differences could be related to particular phenotype or genotype. To achieve these goals, we determined the frequency of occult PTC among patients operated for MTC (n = 82) or undergoing total thyroidectomy mainly for goiter and/or nodules (n = 7313) between 1994-2001. We then examined the clinical, histologic, and genetic characteristics (using a bio-chemical family inquiry and screening for RET germline mutations) of patients with associated PTC-MTC. Results show a significantly higher frequency of occult PTC in MTC (14.7%) than in total thyroidectomy (6.8%; p < 0.01). Seventeen cases of MTC or bilateral C-cell hyperplasia (CCH) and separate occult PTC were identified from 16 different families. Although common RET mutations providing evidence of familial forms of MTC were identified in only 3 of 16 families, clinical and histologic features usually seen in inherited forms of MTC such as young age of occurrence, bilateral CCH or associated case in family were found in 11 of the remaining 14 patients. In conclusion, results suggest that the association of MTC-PTC is not only a coincidence. Surprisingly, 11 of 17 MTC-PTC patients exhibited clinical, histologic, and/or family features usually encountered in familial forms despite the fact that no RET defect were present. This suggests the possible involvement of another gene or uncommon abnormality of RET gene.
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Carcinoma Medular/genética , Carcinoma Papilar/genética , Proteínas Oncogénicas/genética , Lesiones Precancerosas/genética , Proto-Oncogenes , Proteínas Tirosina Quinasas Receptoras/genética , Neoplasias de la Tiroides/genética , Adulto , Anciano , Carcinoma Medular/patología , Carcinoma Papilar/patología , Humanos , Hiperplasia , Persona de Mediana Edad , Mutación , Lesiones Precancerosas/patología , Proteínas Proto-Oncogénicas c-ret , Neoplasias de la Tiroides/patologíaRESUMEN
The typical manifestations of severe hypercalcemia with osteitis fibrosa cystica have become exceedingly rare. We describe the case of a woman hospitalized for a tibial tumor with functional impotence, leading to a diagnosis of primary hyperparathyroidism (HPT I) associated with profound vitamin D deficiency. This 31-year-old woman was admitted, after two pregnancies complicated by the HELLP syndrome. Preoperative laboratory values were as follows: calcemia 4.05 mmol/l (2.2-2.6); urinary calcium 30 mmol/24 h (1.25-7.5); parathormone (PTH) 1 195 pg/ml (10-60); and 25 OH-vitamin D 13 nmol/l (22-120). Specific MIBI uptake by the tibial lesion oriented the diagnosis towards a brown tumor. After surgical excision of a parathyroid adenoma and the brown tumor (associated with tibial fracture), calcemia fell to 1.55 mmol/l and normalized after three months. Urinary calcium fell to 0.1 mmol/24 h and remained low during the 2 years following surgery. Vitamin D levels rapidly normalized on supplementation (87 nmol/l). PTH levels fell markedly after surgery but remained higher than normal till 2 years after surgery despite normalization of calcemia three months after. Bone repair, estimated by means of bone densitometry, improved from preoperative Z-score values of - 6.54, - 5.20 and - 3.50 in the left femoral neck, right femoral neck and lumbar spine, respectively, to - 0.20, - 1.55 and - 0.28, respectively, one year after surgery. In conclusion, this case illustrates: 1) the severe osseous expression of HPT probably related to vitamin D deficiency; 2) specific MIBI uptake by the bone lesion, orientating the diagnosis towards a brown tumor; 3) the consequences of vitamin D deficiency on postoperative outcome, with transient severe initial hypocalcemia related to bone calcium avidity; 4) a possible link between HPT and the HELLP syndrome.
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Neoplasias Óseas/diagnóstico , Hiperparatiroidismo/diagnóstico , Deficiencia de Vitamina D/diagnóstico , Adulto , Neoplasias Óseas/cirugía , Femenino , Estudios de Seguimiento , Francia , Humanos , Hiperparatiroidismo/complicaciones , Osteólisis/etiología , Osteólisis/cirugía , Factores de Tiempo , Deficiencia de Vitamina D/complicaciones , Población BlancaRESUMEN
We describe an unusual clinical case in which a non functional cervical thyroid coexisted with a functional ectopic lingual thyroid. A twenty-year-old woman was referred for hypothyroidism treated with L-thyroxin related to a basilingual tumor diagnosed 8 years previously. Oropharyngeal examination showed a spherical basilingual tumor 2.5 cm in diameter. Laboratory findings during treatment with 50 microgram of L-thyroxin daily showed: TSH 6,280 microIU/ml (N: 4,4 to 3.6), FT3 4,2 pmol/l (N: 3.3 to 5.1), and FT4 15.4 pmol/l (N: 10,5 to 25,5). Antithyroid antibodies were absent. Cervical ultrasonography showed a small hypoechogenic, heterogeneous orthotopic thyroid gland confirmed by cervical computed tomography thyroid. An I(123) scan revealed uptake above the chin on the profile, and no significant uptake is the area of the normal thyroid. The lack of iodine uptake by the cervical thyroid remains unexplained. In conclusion, this report of an ectopic thyroid location in unusual because of the coexistence of non functional cervical thyroid and of a partially functional lingual thyroid tissue. The pathogenesis of this association remains unclear.
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Coristoma/patología , Glándula Tiroides , Enfermedades de la Lengua/patología , Adulto , Trastornos de Deglución/etiología , Femenino , Humanos , Hipotiroidismo/etiología , Radioisótopos de Yodo , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/metabolismo , Tiroxina/uso terapéutico , UltrasonografíaRESUMEN
UNLABELLED: Oxidative stress has been implicated in the pathogenesis of the chronic complications of diabetes mellitus but little is known in diabetic ketoacidosis (DKA). The aim of this work was to determine whether lipid peroxidation, as assessed by measuring malondialdehyde (MDA, a prooxidant) and antioxidant status (TAS, an index of antioxidant defenses), is modified in DKA, and also whether any observed abnormalities were related to metabolic disturbances. METHODS: four groups of patients were studied, comprising 19 patients with DKA, massive ketonuria and plasma standard bicarbonate levels below 16 mmol/l (group 1); 20 patients with poorly controlled diabetes, glycated hemoglobin (HbA1c) above 8% and plasma bicarbonate levels above 16 mmol/l (group 2); 11 patients with well-controlled diabetes and HbA1c below 8% (group 3); and 10 non-diabetic, non-obese control subjects (group 4). Metabolic parameters, MDA levels and TAS were assessed in the plasma of the four groups of subjects. RESULTS: mean plasma MDA and TAS values were significantly different among the four groups (respectively p < 0.001 and p < 0.01). Mean plasma MDA value was significantly higher in group 1 than in group 3 (p < 0.02) and group 4 (p < 0.001) but was not different from that in group 2. Mean plasma MDA value in group 2 was significantly lower than that in group 4 (p = 0.002). Mean plasma TAS value in group 1 was significantly lower than in groups 3 (p < 0.002) and 4 (p < 0.05). Mean plasma TAS value was significantly lower in group 2 than in group 4 (p<0.05). Plasma MDA values in the diabetic patients (groups 1+2+3) were not related to any clinical characteristics (BMI, age, duration of the disease) or metabolic parameters (glycemia, HbA1c bicarbonates, blood urea nitrogen, phosphatemia, lipids), while plasma TAS values correlated negatively with glycemia, osmolality and HbA1c. A significant relationship was also found between TAS and HbA1c in group 1 (p < 0.05) and between MDA and HbA1c in group 3 (p < 0.05). Correlations were also found between TAS and phosphatemia in group 1 (p < 0.01) and between MDA and phosphatemia in group 2 (p < 0.01). A positive relationship between MDA and cholesterol levels was found in group 1 (p < 0.01). In conclusion, MDA values are increased and TAS values decreased in DKA and poorly controlled diabetes, and tend to correlate more with markers of diabetic imbalance than with markers of acute metabolic disturbances of DKA.
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Biomarcadores/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Cetoacidosis Diabética/sangre , Estrés Oxidativo , Adulto , Antioxidantes/análisis , Bicarbonatos/sangre , Glucemia/análisis , Nitrógeno de la Urea Sanguínea , Femenino , Hemoglobina Glucada/análisis , Humanos , Peroxidación de Lípido , Lípidos/sangre , Masculino , Malondialdehído/sangre , Fosfatos/sangreRESUMEN
VASOPRESSIN: The action of vasopressin (AVP) is not limited to regulating water excretion but also plays an essential role in regulating the corticotropic axis during stress. PHYSIOLOGY: Vasopressin is synthesized in the hypothalamus and stored in the posterior pituitary. It acts on 3 types of receptors (RV). RV1a are vascular receptors mediating the vasoconstrictor and glycogenolytic effects of the hormone. Anterior pituitary RV1b or V3 mediate stimulating effects on the corticotropic axis. Renal RV2 regulate water and urea excretion. Hypothetical extrarenal RV2 would be responsible for the vasodilator and procoagulant effects of the hormone. MODIFICATIONS IN ENDOCRINE DISEASES: Pituitary or adrenal hypocorticism syndromes include hyponatremia with secondary plasma hypoosmolality and reduced glomerular filtration due to the direct effect of glucocorticoids and also the effect of vasopressinism. Certain endogenous hypercorticisms appear to be related to an overexpression of RV: in ACTH-independent Cushingís syndrome, adrenal overexpression of eutopic RV1a, and in ACTH-dependent Cushingís syndrome, pituitary overexpression of eutopic RV1b or ectopic RV2. In addition, inappropriate secretion of antidiuretic hormone is frequent after transphenoidal surgery, particularly for corticotropic adenomas. DYNAMIC TESTS: The physiological response of ACTH and also AVP to corticotropin releasing hormone (CRH) in the petrous sinus, the unusual responses of certain corticotropic tumors to dDAVP, or certain forms of ACTH-independent hypercortisolism to lysine vasopressin (LVP) suggest excessive or ectopic expression of RV in corticotropic or adrenal cells: tumorgenesis of these cells could also depend, at least partially, on AVP.
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Hormona Adrenocorticotrópica/metabolismo , Arginina/metabolismo , Enfermedades del Sistema Endocrino/metabolismo , Vasopresinas/metabolismo , Aminoácidos/metabolismo , HumanosRESUMEN
We describe simplified and rapid methods to assess islet function with the aim to develop better protocols for islet isolation and to determine islet characteristics before transplantation. These methods are also useful in the assessment of the potentially beneficial or deleterious effects of compounds added to the culture media in stimulation experiments. To this end, we took advantage of the multiscreen assay system produced by Millipore SA. This 96-well unit allowed the free-floating culture of islets on filter membranes, the rapid vacuuming and collection of conditioned media or reaction buffer and thus successive testing of the same number of islets, possibly at different culture times. We estimated islet viability by determination of the metabolic activity of cells, normal function of islets by their ability to metabolize glucose and to synthesize and secrete insulin and of nitrite release, a reflection of nitric oxide (NO) status of cells, which may be involved in a signaling pathway during glucose-stimulated insulin secretion or in cytokine inducible pathway. Assays may be performed either on selected islets or on aliquots of semi-purified preparations designated for grafting, allowing thus the rapid estimation of graft function of the entire preparation. This herein described system may be also extended to many other functional tests.
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Trasplante de Islotes Pancreáticos/normas , Islotes Pancreáticos/citología , Islotes Pancreáticos/fisiología , Automatización , Separación Celular , Supervivencia Celular , ADN/análisis , Humanos , Insulina/análisis , Nitritos/análisis , Control de CalidadRESUMEN
Bartter syndromes are defined as a family of inherited recessive autosomal tubulopathies. They are characterized by hypochloremia, hypokalemia, metabolic alkalosis associated with potassium renal leakage and normal blood pressure despite increased plasma renin activity. Three forms of the disease are identified as followed: 1) Gitelman syndrome or hypocalciuria hypomagnesemia syndrome is a mild form often discovered in childhood or teenagers in reason of tetany. It is an homogeneous disorder related to mutations of the genes encoding the thiazide-sensitive Na-Cl cotransporter located in the distal convoluted tubule. 2) Antenatal Bartter syndrome with hypercalciuria and nephrocalcinosis or hyperprostaglandin E syndrome is a severe form, often revealed by hydramnios, prematurity and growth delay. It is related to mutations of two types of genes encoding for transporters of Henle's loop: the bumetanide-sensitive cotransporter Na-K-2Cl (NKCC2) [type I] or the inwardly-rectifying potassium channel (ROMK) [type II]. 3) the classical form or type III Bartter syndrome, often revealed by dehydration in the first year of life, is associated with hypomagnesemia in 20% of cases and normal or increased calciuria. This form is related to mutations of CLCNKB gene encoding for a chloride channel in Henle's loop. This classification, in part related to the demonstration of mutations in the genes encoding for tubular chloride or potassium channels, does not fit all cases, overlapping syndromes are frequent. Moreover some endocrinological (diabetes) and neurological (deafness) abnormalities are sometimes associated with Bartter syndromes. Both phenotypic and genetic approach must help to the diagnosis of these tubulopathies.