RESUMEN
Human gut bifidobacteria rely on ATP-binding cassette (ABC) transporters for oligosaccharide uptake. Multiple oligosaccharide-specific solute-binding protein (SBP) genes are occasionally associated with a single ABC transporter, but the significance of this multiplicity remains unclear. Here, we characterize BlMnBP1 and BlMnBP2, the two SBPs associated to the ß-manno-oligosaccharide (MnOS) ABC transporter in Bifidobacterium animalis subsp. lactis. Despite similar overall specificity and preference to mannotriose (Kd ≈80 nM), affinity of BlMnBP1 is up to 2570-fold higher for disaccharides than BlMnBP2. Structural analysis revealed a substitution of an asparagine that recognizes the mannosyl at position 2 in BlMnBP1, by a glycine in BlMnBP2, which affects substrate affinity. Both substitution types occur in bifidobacterial SBPs, but BlMnBP1-like variants prevail in human gut isolates. B. animalis subsp. lactis ATCC27673 showed growth on gluco and galactomannans and was able to outcompete a mannan-degrading Bacteroides ovatus strain in co-cultures, attesting the efficiency of this ABC uptake system. By contrast, a strain that lacks this transporter failed to grow on mannan. This study highlights SBP diversification as a possible strategy to modulate oligosaccharide uptake preferences of bifidobacterial ABC-transporters during adaptation to specific ecological niches. Efficient metabolism of galactomannan by distinct bifidobacteria, merits evaluating this plant glycan as a potential prebiotic.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Bifidobacterium animalis/metabolismo , Mananos/metabolismo , Transportadoras de Casetes de Unión a ATP/fisiología , Proteínas Bacterianas/metabolismo , Bifidobacterium/genética , Bifidobacterium/metabolismo , Bifidobacterium animalis/genética , Proteínas de Unión al ADN/metabolismo , Galactosa/análogos & derivados , Oligosacáridos/metabolismoRESUMEN
The effect of aerosolised adrenomedullin (ADM), a potent vasodilator peptide, on pulmonary artery pressure was studied for 24 h in a surfactant-depleted piglet model. Animals received either aerosolised ADM (50 ng.kg(-1).min(-1), ADM, n=6), or aerosolised normal saline solution (control, n=6). Aerosol therapy was performed for a 2 h treatment period followed by a 22 h observation period. Ventilator settings were adapted to keep arterial oxygen tension and carbon dioxide arterial tension between 13.3-14.6 kPa and 4.9-5.7 kPa, respectively. Aerosolised ADM reduced mean pulmonary artery pressure (MPAP) compared with the control group (end-point median 24 h after therapy start: DeltaMPAP -14.0 versus -8.0 mmHg; 23.5 h after therapy start). After therapy start, mean systemic arterial pressure (MAP) was not significantly different between the groups (end-point median: MAP ADM 70 (61/74) versus control 72 (54/81) mmHg). Endothelin-1, a potent pulmonary vasoconstrictor, is regulated by ADM via cAMP. Twenty two hours after inhalation of aerosolised ADM, endothelin-1 mRNA in lung tissue and endothelin-1 protein expression in pulmonary arteries was reduced compared with controls (median semi-quantitative immunhistochemical score: ADM 0.21, control 0.76). Aerosolised adrenomedullin significantly reduced mean pulmonary artery pressure independently of arterial oxygen tension.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Péptidos/administración & dosificación , Arteria Pulmonar/efectos de los fármacos , Vasodilatadores/administración & dosificación , Administración por Inhalación , Adrenomedulina , Animales , Presión Sanguínea/fisiología , Dióxido de Carbono/sangre , Modelos Animales , Oxígeno/sangre , Arteria Pulmonar/fisiología , PorcinosRESUMEN
OBJECTIVE: Adipose tissue displays depot-specific metabolic properties and a predominant gene expression of leptin in subcutaneous tissue. The aim of the study was to evaluate leptin mRNA expression in various adipose tissues and to relate it to plasma leptin concentrations. Furthermore, developmental changes in leptin gene expression from childhood to adulthood were examined. DESIGN AND METHODS: Thoracic subcutaneous and intrathoracic adipose tissue specimens were obtained in 22 adults (51-81 years) and 23 children (0.1-17 years) undergoing cardiac surgery, and abdominal subcutaneous, omental and mesenterial fat specimens were collected from 21 adults (38-79 years) and 22 children (0.2-17 years) before abdominal surgery. Preoperative plasma leptin concentrations were measured by RIA. Leptin mRNA expression was quantified by TaqMan real-time PCR. RESULTS: In adults, there was no difference between leptin gene expression in subcutaneous and intrathoracic fat, whereas in children leptin mRNA expression was significantly higher in subcutaneous adipose tissue. In omental fat, leptin mRNA levels were significantly lower compared with subcutaneous and mesenterial sites in both children and adults. Adults revealed a significantly higher leptin gene expression in subcutaneous, omental and mesenterial adipose tissues than children. Subcutaneous and omental leptin gene expression are independent factors for plasma leptin concentrations in children and adults. CONCLUSION: Leptin is differentially expressed at different adipose tissue sites, a situation which is even more pronounced in children. There is a developmental increase in leptin mRNA expression in adipose tissue during childhood, reaching maximal capacity in adulthood.
Asunto(s)
Tejido Adiposo/fisiología , Leptina/genética , Abdomen , Tejido Adiposo/crecimiento & desarrollo , Adolescente , Factores de Edad , Anciano , Niño , Preescolar , Femenino , Expresión Génica/fisiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , ARN Mensajero/análisisRESUMEN
OBJECTIVE: We investigated the influence of acute hypoxia on the placental vascular endothelial growth factor system in vitro and in vivo in acute birth asphyxia compared with pregnancies that were complicated by preeclampsia and with healthy control subjects. STUDY DESIGN: Messenger RNA levels for vascular endothelial growth factor, flt-1, and KDR were measured by TaqMan real-time polymerase chain reaction in human placental choriocarcinoma cells (BeWo) that were exposed to hypoxia (1% oxygen, 5% carbon dioxide, 94% nitrogen) and in placental tissue of neonates with birth asphyxia (n = 20), newborn infants of mothers with preeclampsia (n = 20), and gestational age-matched control subjects. Immunhistologically, placental vascular endothelial growth factor protein expression was compared among the groups. RESULTS: In BeWo cells, vascular endothelial growth factor, flt-1 and KDR messenger RNA increased in a time-dependent manner in response to hypoxia. In vivo, vascular endothelial growth factor/beta-actin and KDR/beta-actin messenger RNA were significantly higher in placental tissue of newborn infants with severe hypoxic-ischemic encephalopathy than with newborn infants with mild or no hypoxic-ischemic encephalopathy and control subjects. In chronic placental hypoxia (preeclampsia), vascular endothelial growth factor and both receptors were found to be up-regulated. Increased placental vascular endothelial growth factor expression was confirmed by immunohistologic examination. CONCLUSION: The vascular endothelial growth factor system is up-regulated in response to placental hypoxia and is assumed to be a potential early indicator of severe birth asphyxia.
Asunto(s)
Asfixia Neonatal/metabolismo , Factores de Crecimiento Endotelial/metabolismo , Hipoxia/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Isquemia/metabolismo , Linfocinas/metabolismo , Placenta/metabolismo , Actinas/genética , Grupos Control , Factores de Crecimiento Endotelial/genética , Femenino , Humanos , Recién Nacido , Péptidos y Proteínas de Señalización Intercelular/genética , Linfocinas/genética , Preeclampsia/metabolismo , Embarazo , ARN Mensajero/metabolismo , Factores de Tiempo , Células Tumorales Cultivadas , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Factores de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: The aim of the present study was to investigate the role of adrenomedullin (ADM) as a hypoxia-inducible marker of clinically relevant tIssue hypoxia in acute birth asphyxia of term newborn infants. METHODS: For this purpose, ADM mRNA was determined in human placental tIssue of 20 term pregnancies complicated by birth asphyxia (pH and base deficit values, clinical score). In addition, ADM mRNA was measured in leukocytes of the asphyxiated newborn infants during the first 12 h of life (n=12). Controls were available from ten healthy term pregnancies. In vitro, hypoxia-inducible expression of ADM mRNA was evaluated in human choriocarcinoma cells (BeWo) and human leukocytes exposed to hypoxia (1% O(2)) for 1-24 h. mRNA levels were measured by TaqMan real-time PCR. RESULTS: In vitro, ADM mRNA related to porphobilinogen deaminase (PBGD) mRNA levels significantly increased in response to hypoxia within a period of 4 h in leukocytes and 12 h in BeWo cells. In human placental tIssue, significantly higher levels of ADM/PBGD mRNA were present in asphyxiated newborn infants with severe hypoxic-ischemic encephalopathy (HIE) (n=5) compared with patients with mild or no HIE (n=15). Increased levels of ADM/PBGD mRNA levels were found during the first hours of life in leukocytes of neonates with severe HIE compared with controls. CONCLUSIONS: Our results indicate an upregulation of ADM gene expression in human placenta and leukocytes in clinically relevant hypoxic-ischemic birth complications and suggest ADM gene expression as a promising marker for severe complications due to perinatal asphyxia such as HIE.
Asunto(s)
Asfixia Neonatal/metabolismo , Expresión Génica , Leucocitos/fisiología , Péptidos/genética , Placenta/fisiología , ARN Mensajero/metabolismo , Adrenomedulina , Biomarcadores/análisis , Hipoxia de la Célula/fisiología , Femenino , Humanos , Hidroximetilbilano Sintasa/genética , Hipoxia-Isquemia Encefálica/metabolismo , Recién Nacido , Embarazo , Valores de Referencia , Células Tumorales CultivadasRESUMEN
Adrenomedullin, a peptide with vasorelaxant activity, stimulates nitric oxide (NO) synthesis. We tested whether or not NO regulates the function of the adrenomedullin system. Human umbilical vein endothelial cells (HUVEC) were incubated with the NO donors sodium nitroprusside (SNP), morpholinosydnonimine (SIN-1) and the phospodiesterase V inhibitor zaprinast. In HUVEC, adrenomedullin concentration in the supernatant was measured by radioimmunoassay and mRNA expression was studied by Northern blot and competitive quantitative PCR. SNP, SIN-1, and zaprinast (100 micromol/l each) significantly increased adrenomedullin concentration in the supernatant of HUVEC twofold. The same concentrations increased adrenomedullin mRNA expression four- to tenfold. Similar results were obtained by both quantitative PCR and Northern blot. Thus, NO donor exposure in vitro increases both adrenomedullin secretion and mRNA expression in a dose-dependent manner.
Asunto(s)
Endotelio Vascular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico/fisiología , Péptidos/genética , Péptidos/metabolismo , Adrenomedulina , Northern Blotting , Células Cultivadas , Endotelio Vascular/citología , Humanos , ARN Mensajero/metabolismo , Radioinmunoensayo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Venas Umbilicales/citologíaRESUMEN
Leptin is produced predominantly in adipose tissue but has recently also been found in gastric mucosa. It has been shown that the oral application of leptin induces neuronal activity in the brain stem of rodents. The objective of the present study was to identify this hormone in human saliva and to examine the production and stability of salivary leptin. We have demonstrated production of leptin in salivary glands and oral mucosa by RT-PCR, its storage by immunocytochemistry, and the release of the peptide by RIA. Chromatographic analysis and immunoblotting confirmed the identity of leptin. There is a strong linear correlation (r2 = 0.78) between leptin concentrations from simultaneously collected saliva and plasma samples (n = 61). Stimulation of saliva flow increases total leptin secretion up to 3-fold (P < 0.001). As to the stability of leptin in gastric fluid, we found the peptide was not degraded above pH 3.5. Additionally, salivary leptin remains stable up to 5 d at 4 C. With regard to the presence of leptin receptors in gastric mucosa, we suggest salivary leptin as being a possible ligand for gastric leptin receptors. Furthermore, the determination of leptin in saliva allows for noninvasive sample collection.
Asunto(s)
Leptina/metabolismo , Saliva/química , Adulto , Anciano , Anciano de 80 o más Años , Cromatografía en Gel , Humanos , Immunoblotting , Inmunohistoquímica , Leptina/análisis , Leptina/sangre , Masculino , Persona de Mediana Edad , ARN Mensajero/biosíntesis , Valores de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Glándulas Salivales/metabolismo , Salivación/fisiologíaRESUMEN
The aim of this study was to assess human intracranial tumours for their gene expression pattern of the vasoactive peptide adrenomedullin (AM), its receptor (AM-R) and leptin, which exerts multiple biological effects including proliferation and angiogenesis via the leptin receptor (OB-Rb). Gene activity of neuropeptide Y (NPY) was monitored additionally. We investigated whether there was a characteristic gene expression pattern of AM and leptin in different intracranial tumours, depending on their proliferation activity and biological behaviour. We investigated 35 non-functioning pituitary adenomas (including eight null cell, four silent plurihormonal, 23 silent gonadotroph adenomas), seven somatotropinomas, seven prolactinomas, eight meningiomas, five astrocytomas, two glioblastoma multiformes and unaffected temporal lobe (n = 8). Quantitative reverse transcriptase-polymerase chain reaction (TaqMan RT-PCR) was performed. AM mRNA was detectable in all tumour specimens. AM/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio was significantly higher in somatotropinomas, as was AM/CD31 ratio in prolactinomas, compared with inactive adenomas (P < 0.05). AM-R mRNA was found in all tumour subgroups in small quantities but, in general, higher in tumours than in temporal lobe tissue, respectively. AM-R/CD31 ratio was significantly higher in prolactinomas than in inactive adenomas (P < 0.05). Leptin was detectable in very low quantities in each subgroup. OB-Rb gene expression was found in all tumour subgroups, OB-Rb/GAPDH ratio was highest for meningiomas (P < 0.0001, compared with temporal lobe). NPY mRNA was detectable in temporal lobe in higher quantities than in tumours (P < 0.0001), and almost undetectable in prolactinomas and astrocytomas. Our data demonstrate that AM and AM-R, NPY, as well as leptin and OB-Rb, are expressed in various intracranial tumours in humans but their particular function has to be elucidated further. At present, there is no evidence for a cross-talk on transcriptional level between the peptidergic vasodilative system AM and the putative angiogenic and proliferation affecting factor leptin.
Asunto(s)
Adenoma/genética , Neoplasias Encefálicas/genética , Expresión Génica , Hormonas/metabolismo , Neuropéptidos/genética , Neoplasias Hipofisarias/genética , Receptores de Superficie Celular , Adenoma/metabolismo , Adrenomedulina , Adulto , Anciano , Proteínas Portadoras/genética , Femenino , Humanos , Leptina/genética , Masculino , Persona de Mediana Edad , Neuropéptido Y/genética , Péptidos/genética , Neoplasias Hipofisarias/metabolismo , Receptores de Adrenomedulina , Receptores de Leptina , Receptores de Péptidos/genéticaRESUMEN
BACKGROUND: During human pregnancy, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays an important role in protecting the fetus from high maternal glucocorticoid concentrations by converting cortisol to inactive cortisone. Furthermore, 11beta-HSD2 is indirectly involved in the regulation of the prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), because cortisol reduces the gene expression and enzyme activity of PGDH in human placental cells. OBJECTIVE: To examine developmental changes in placental 11beta-HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human pregnancies. METHODS: In placental tissue taken from 20 healthy women with normal pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11beta-HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR. RESULTS: Placental mRNA expression of 11beta-HSD2 and PGDH increased significantly with gestational age (r=0.55, P=0.0002 and r=0.42, P=0.007). In addition, there was a significant correlation between the two enzymes (r=0.58, P<0.0001). CONCLUSIONS: In the course of pregnancy there is an increase in 11beta-HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of 11beta-HSD2 prevents increasing maternal cortisol concentrations from transplacental passage and is exerted at the gene level. 11beta-HSD2 up-regulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins.
Asunto(s)
Hidroxiprostaglandina Deshidrogenasas/genética , Hidroxiesteroide Deshidrogenasas/genética , Placenta/enzimología , Embarazo/metabolismo , ARN Mensajero/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2 , Adolescente , Adulto , Peso al Nacer , Femenino , Regulación Enzimológica de la Expresión Génica/genética , Humanos , Hidroxiprostaglandina Deshidrogenasas/biosíntesis , Hidroxiesteroide Deshidrogenasas/biosíntesis , Recién Nacido , Trabajo de Parto Prematuro/enzimología , Placenta/fisiología , Segundo Trimestre del Embarazo/genética , Tercer Trimestre del Embarazo/genética , ARN Mensajero/biosíntesis , Análisis de Regresión , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The effect of aerosolized perfluorocarbon (PFC) (FC77) on pulmonary gas exchange and lung mechanics was studied in a surfactant depleted piglet model. Sixty minutes after induction of lung injury by bronchoalveolar lavage, 20 piglets were randomized to receive aerosolized PFC (Aerosol-PFC, 10 ml/kg/h, n = 5), partial liquid ventilation (PLV) at FRC capacity volume (FRC-PLV, 30 ml/kg, n = 5) or low volume (LV-PLV, 10 ml/kg/h, n = 5), or intermittent mandatory ventilation (IMV) (Control, n = 5). After 2 h, perfluorocarbon application was stopped and IMV was continued for 6 h. Sixty minutes after the onset of therapy, PaO2 was significantly higher and PaCO2 was significantly lower in the Aerosol-PFC and the FRC-PLV groups than in the LV-PLV and the Control groups; p < 0.001. Six hours after treatment, maximum PaO2 was found in the Aerosol-PFC group: 406.4 +/- 26.9 mm Hg, FRC-PLV: 217.3 +/- 50.5 mm Hg, LV-PLV: 96.3 +/- 18.9 mm Hg, Control: 67.6 +/- 8.4 mm Hg; p < 0.001. PaCO2 was lowest in the Aerosol-PFC group: 24.2 +/- 1.7 mm Hg, FRC-PLV: 35.9 +/- 2.8 mm Hg, LV-PLV: 56.7 +/- 12.4 mm Hg, Control: 60.6 +/- 5.1 mm Hg; p < 0.01. Dynamic compliance (C20/c) was highest in the Aerosol-PFC group; p < 0.01. Aerosolized perfluorocarbon improved pulmonary gas exchange and lung mechanics as effectively as PLV did in surfactant-depleted piglets, and the improvement was sustained longer.
Asunto(s)
Fluorocarburos/farmacología , Ventilación Liquida/métodos , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Aerosoles , Análisis de Varianza , Animales , Animales Recién Nacidos , Fluorocarburos/administración & dosificación , Fluorocarburos/uso terapéutico , Surfactantes Pulmonares/deficiencia , Síndrome de Dificultad Respiratoria/terapia , PorcinosRESUMEN
Cortisol reduces the activity of the PG-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) in human placental cells. The objective was to investigate a possible relation between 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), converting cortisol to cortisone, and PGDH gene expression in the placenta of patients with preeclampsia. In placental tissue taken from 20 healthy women with normal pregnancy, 20 premature babies born after labor before term, and 18 neonates after preeclamptic pregnancy, 11beta-HSD2 and PGDH messenger RNA (mRNA) expression was determined using quantitative TaqMan real-time PCR and quantitative competitive PCR. When comparing matched pairs, there were 3-fold lower 11beta-HSD2/glyceraldehyde-3-phosphate dehydrogenase (11beta-HSD2/GAPDH) mRNA levels in placentas of patients with preeclampsia than in controls [0.18 +/- 0.04 relative units (RU) and 0.61 +/- 0.10 RU, P = 0.0003]. We also found a 2-fold reduction in placental PGDH/GAPDH mRNA concentrations (0.28 +/- 0.15 RU and 0.50 +/- 0.18 RU, P = 0.0003). PGDH and 11beta-HSD2 mRNA levels correlated significantly (r = 0.66, P < 0.0001). In term placenta, 11beta-HSD2/GAPDH, but not PGDH, showed a significant correlation to birth weight (r = 0.43, P = 0.01) and to placental weight (r = 0.47, P = 0.01). Results could be confirmed by competitive PCR. We conclude that, in preeclampsia, 11beta-HSD2 mRNA expression is reduced, leading to the known decrease of 11beta-HSD2 activity. By means of an autocrine or paracrine mechanism, the diminished conversion of placental cortisol may lead to reduced PGDH mRNA expression as found in the present study.
Asunto(s)
Expresión Génica , Hidroxiprostaglandina Deshidrogenasas/genética , Hidroxiesteroide Deshidrogenasas/genética , Placenta/enzimología , Preeclampsia/enzimología , 11-beta-Hidroxiesteroide Deshidrogenasas , Adolescente , Adulto , Peso al Nacer , Cortisona/metabolismo , Femenino , Edad Gestacional , Humanos , Hidrocortisona/metabolismo , Recién Nacido , Recien Nacido Prematuro , Reacción en Cadena de la Polimerasa , Embarazo , Proteinuria , ARN Mensajero/análisisRESUMEN
Studies which evaluate the psychosocial development and integration of adult female congenital adrenal hyperplasia (CAH) patients are rare but show that patients with the salt wasting form are significantly more virilized and more frequently single and childless. Major complaints are irregular menstruation, hirsutism, acne, obesity, deep voice, and cushingoid features. Surprisingly, a higher prevalence of psychosomatic disorders has not yet been described. Since anorexia nervosa (AN) has not yet been described in patients with CAH, we here report 4 cases of female CAH patients who developed AN during adolescence. Diagnosis of CAH was made between the age of 10 days and 3 years. Three patients suffer from the simple-virilizing form of CAH, one patient has a mild salt wasting CAH. Genital malformation varied from Prader stage II to IV. All 4 patients were compound heterozygotes for mutations/deletions of the CYP21B gene. Control of substitution therapy consisting of hydrocortisone and fluorocortisone was good. AN developed at ages 12, 13, 17, and 21 years (ICD 10 criteria for AN are BMI below 17.5 kg/m2, deliberate weight loss, body image disturbance, and primary or secondary amenorrhoea). Diagnosis of AN was established by psychiatrists and/or psychologists. All four patients showed an impressive and deliberate weight loss between 13 and 20 kg within 6 months, had primary or secondary amenorrhoea, and presented with BMI between 13 and 17.9 kg/m2. All patients received psychological treatment and recovered. However, one patient had a severe relapse of AN. Two patients are now married and one has a healthy son. These cases demonstrate that the diagnosis of CAH is compatible with the development of AN and illustrate the importance of providing treatment for CAH patients that encompasses not only medical but also psychological and social care.
Asunto(s)
Hiperplasia Suprarrenal Congénita/complicaciones , Anorexia Nerviosa/complicaciones , Hiperplasia Suprarrenal Congénita/genética , Adulto , Amenorrea/complicaciones , Anorexia Nerviosa/genética , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Heterocigoto , Humanos , Esteroide 21-Hidroxilasa/genéticaRESUMEN
Fanconi's anaemia (FA) shows great variability in phenotypic symptoms. We report on two FA siblings of German ancestry with the very rare form of the complementation group FA-D. Both presented with a similar phenotype and mild disease severity but with different growth. In the sister, growth velocity was normal, puberty and menarche occurred spontaneously. Her final height was within her parental target height. The younger brother had a reduced growth velocity, height SDS values below -5.5 SDS, a markedly retarded bone age, and delayed puberty. At the age of 12.9 years, growth hormone deficiency (GHD) was diagnosed and treatment with growth hormone was initiated. Our cases emphasize the heterogeneity of symptoms in FA even in siblings with the same genotype. In FA-children with severe growth retardation, GHD must also be considered.
Asunto(s)
Anomalías Múltiples/genética , Anemia de Fanconi/genética , Trastornos del Crecimiento/genética , Hormona de Crecimiento Humana/deficiencia , Determinación de la Edad por el Esqueleto , Femenino , Estudios de Seguimiento , Prueba de Complementación Genética , Alemania/etnología , Humanos , Lactante , Recién Nacido , Masculino , Países Bajos , Núcleo Familiar , Fenotipo , Pubertad TardíaRESUMEN
Patients with Gitelman syndrome are usually diagnosed by chance or present with muscular weakness, constipation, or tetanies due to hypokalemia and hypomagnesemia. We present a short statured boy with a clear history of familial short stature, normal growth and a final height prognosis within the target height range. However, routine laboratory studies led to the diagnosis of Gitelman syndrome. If a baseline laboratory analysis had not been performed, this diagnosis would have been missed.
Asunto(s)
Estatura/genética , Discapacidades del Desarrollo/diagnóstico , Niño , Discapacidades del Desarrollo/genética , Humanos , Masculino , SíndromeRESUMEN
This is the case report of a girl who was diagnosed as having Ullrich-Turner mosaic at the age of 12 years. She had normal pubertal development and menarche at the age of 15 years. The patient had regular menstrual cycles for 12 months before developing secondary amenorrhea. She was started on estrogen/gestagen replacement therapy by her gynecologist. Several months later a prolactinoma was diagnosed by laboratory and imaging techiques. A second-generation dopamine agonist led to almost regular cycles. Therefore, even in patients with susceptibility to ovarian failure secondary amenorrhea necessitates thorough diagnostic investigation. Copyrightz1999S.KargerAG,Basel
Asunto(s)
Amenorrea/etiología , Mosaicismo , Neoplasias Hipofisarias/complicaciones , Prolactinoma/complicaciones , Aberraciones Cromosómicas Sexuales , Síndrome de Turner/complicaciones , Aminoquinolinas/uso terapéutico , Niño , Agonistas de Dopamina/uso terapéutico , Femenino , Humanos , Imagen por Resonancia Magnética , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactinoma/diagnóstico , Prolactinoma/tratamiento farmacológicoRESUMEN
BACKGROUND: Craniospinal radiotherapy for malignant brain tumors can result in a variety of neuroendocrine disturbances, among which are the development of growth hormone deficiency and early puberty, which can markedly reduce adult height. METHODS: The authors report the case of a girl who received craniospinal radiotherapy for a medulloblastoma at the age of 3.4 years. At 9.1 years, growth hormone therapy was started, and spontaneous onset of puberty (Tanner stage B2) occurred at age 10.3 years. Interval until menarche was short, at only 0.9 years. RESULTS: Although chronologic age at appearance of Tanner stages was within the normal range, the patient showed a rapid acceleration in skeletal maturation, resulting in adult short stature. CONCLUSION: Bone age seems to be a more precise parameter for biologic maturation in some patients after craniospinal irradiation than is clinical assessment of pubertal stages. Thus, if progression of bone age and decreasing final height predictions are noted, puberty should be stopped with gonadotropin-releasing hormone analogs, even if pubertal development seems to be adequate for chronologic age, because this increases the remaining time for growth hormone treatment.
Asunto(s)
Determinación de la Edad por el Esqueleto , Neoplasias Cerebelosas/radioterapia , Irradiación Craneana/efectos adversos , Trastornos del Crecimiento/etiología , Meduloblastoma/radioterapia , Pubertad Precoz/etiología , Estatura/efectos de la radiación , Niño , Femenino , Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento/uso terapéutico , Humanos , Pubertad Precoz/tratamiento farmacológicoRESUMEN
BACKGROUND: On clinical grounds, arachnoid cysts are usually associated with neurological dysfunction. There is little information concerning their involvement in endocrinological disorders. PATIENTS: The experience in 6 children (birth to 12 years) with hypothalamic-pituitary disturbances secondary to the presence of intracranial arachnoid cysts is reported and the literature is reviewed. RESULTS: Three of our children were diagnosed with isolated hormone abnormalities (2 children with precocious puberty and 1 child with growth hormone, GH deficiency). One child presented the unusual combination of GH deficiency and precocious puberty. The remaining 2 children developed panhypopituitarism associated with diabetes insipidus. CONCLUSION: Arachnoid cysts may cause a wide spectrum of endocrinological disorders. Periodical and complete follow-up of every patient is recommended.
Asunto(s)
Quistes Aracnoideos/complicaciones , Quistes Aracnoideos/diagnóstico , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Enfermedades del Sistema Endocrino/complicaciones , Sistema Hipotálamo-Hipofisario/fisiopatología , Sistema Hipófiso-Suprarrenal/fisiopatología , Quistes Aracnoideos/cirugía , Encéfalo/cirugía , Niño , Enfermedades del Sistema Endocrino/fisiopatología , Femenino , Hormona de Crecimiento Humana/deficiencia , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Pruebas de Función de la Tiroides , Glándula Tiroides/fisiopatología , Hormonas Tiroideas/sangre , Hormonas Tiroideas/orina , Tomografía Computarizada por Rayos XRESUMEN
We describe a new simple solid-phase competitive luminescence immunoassay (LIA) for the determination of immunoglobulin A (IgA) in faeces. The assay utilizes an anti-alpha-chain IgA antibody which is coated to polystyrene beads and acridinium ester-labelled human IgA as tracer and, therefore, measures both monomeric and polymeric IgA. Dilution recovery of an internal standard was 96, 100 and 103%. Interassay and intra-assay coefficients of variation (C.V.) ranged from 4.5 to 12.9%. The upper limit of normal of faecal IgA in 122 healthy controls was found to be 300 mg/l IgA (mean 73 mg/l, specificity of 99.2%). Patients with inactive Crohn's disease (Crohn's disease activity index (CDAI < 150, n = 14) had faecal IgA values up to 3317 mg/l (mean 1073 mg/l; P < 0.0001). In the active group (CDAI > 150, n = 26) faecal IgA values ranged from 49 to 4094 mg/l (mean 1253 mg/l; P < 0.0001). Patients with ulcerative colitis were divided into a group with active disease (n = 18) and a remission group (n = 16) with values up to 1843 mg/l faecal IgA (man 486 mg/l; P < 0.0032) and up to 602 mg/l faecal IgA (mean 176 mg/l; P < 0.4833), respectively. We also studied patients with non-inflammatory diseases of the gut with this assay. This LIA has proved to be a reliable method for the determination of elevated faecal IgA concentrations and for the detection of pathological findings in the gastrointestinal tract, especially in Crohn's disease.
Asunto(s)
Heces/química , Inmunoensayo/métodos , Inmunoglobulina A/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Unión Competitiva , Colitis Ulcerosa/inmunología , Pólipos del Colon/inmunología , Neoplasias Colorrectales/química , Neoplasias Colorrectales/inmunología , Enfermedad de Crohn/inmunología , Divertículo/inmunología , Hemorroides/inmunología , Humanos , Inmunoensayo/estadística & datos numéricos , Mediciones Luminiscentes , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
We showed earlier that the memory-improving substance, methylglucamine orotate, a precursor of pyrimidine nucleotide synthesis, improved memory retention and enhanced the postconditioning potentiation of field potentials in a special learning task. Since long-term potentiation (LTP) is frequently regarded as a mechanism of memory formation, we decided to test whether it can be influenced in a similar manner. The present study shows that the same dose of methylglucamine orotate (225 micrograms i.c.v.) prolongs LTP but has only a slight effect on the field potential recorded in the dentate gyrus. In controls, LTP of the population spike returned to 154% of the control value 24 h after tetanization and to 126% after 48 h. However, in drug treated animals LTP of the population spike remained at 246 and 216% of the control, respectively. The results support the assumption that LTP is at least a component of memory formation.