RESUMEN

BACKGROUND AND AIM: The Danish Health and Medicines Authority assembled a group of experts to develop a national clinical guideline for patients with schizophrenia and complex mental health needs. Within this context, ten explicit review questions were formulated, covering several identified key issues. METHODS: Systematic literature searches were performed stepwise for each review question to identify relevant guidelines, systematic reviews/meta-analyses, and randomized controlled trials. The quality of the body of evidence for each review question was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Clinical recommendations were developed on the basis of the evidence, assessment of the risk-benefit ratio, and perceived patient preferences. RESULTS: Based on the identified evidence, a guideline development group (GDG) recommended that the following interventions should be offered routinely: antipsychotic maintenance therapy, family intervention and assertive community treatment. The following interventions should be considered: long-acting injectable antipsychotics, neurocognitive training, social cognitive training, cognitive behavioural therapy for persistent positive and/or negative symptoms, and the combination of cognitive behavioural therapy and motivational interviewing for cannabis and/or central stimulant abuse. SSRI or SNRI add-on treatment for persistent negative symptoms should be used only cautiously. Where no evidence was available, the GDG agreed on a good practice recommendation. CONCLUSIONS: The implementation of this guideline in daily clinical practice can facilitate good treatment outcomes within the population of patients with schizophrenia and complex mental health needs. The guideline does not cover all available interventions and should be used in conjunction with other relevant guidelines.(AU)

Asunto(s)

Humanos , Esquizofrenia/terapia , Antipsicóticos/uso terapéutico , Terapia Cognitivo-Conductual , Terapia Familiar , Accesibilidad a los Servicios de Salud , Resultado del Tratamiento , Diagnóstico Dual (Psiquiatría) , Enfoque GRADE

RESUMEN

BACKGROUND: Tuberculosis (TB) is associated with high morbidity and mortality in solid organ transplant (SOT) recipients. Also, SOT patients have a 20- to 74-fold increase in the chance of developing TB compared to the general population. Here we evaluated the incidence of hepatotoxicity in SOT recipients on treatment for TB and determined risk factors for liver toxicity in these patients. PATIENTS AND METHODS: Retrospective cohort conducted in a reference hospital for SOT in Southern Brazil. All SOT recipients who underwent TB treatment during the years 2000-2012 were considered for the study. RESULTS: A total of 69 patients were included in the study and 23 had liver toxicity (incidence 33.3%). Independent risk factors for hepatotoxicity were rifampin use at doses of ≥600 mg daily (P = .016; OR 2.47; 95% CI, 1.18-5.15) and lung transplantation (P = .017; OR 2.05; 95% CI, 1.14-3.70). Kidney transplantation appeared as a protective factor (P = .036; OR 0.50; 95% CI, 0.26-0.96). Mortality was higher in the patients who had hepatotoxicity (43.5%), compared with those who did not (19.6%). CONCLUSION: In this study, the use of rifampin at doses of 600 mg daily or higher was found to be an independent risk factor for liver toxicity in SOT recipients. The importance of additional risk factors for hepatotoxicity, such as lung transplantation as well as the protective role of kidney transplantation, should be better investigated in SOT recipients being treated for TB.

Asunto(s)

Antituberculosos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Trasplante de Órganos , Tuberculosis/tratamiento farmacológico , Antituberculosos/uso terapéutico , Brasil/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Tuberculosis/epidemiología , Tuberculosis/microbiología

RESUMEN

Insulin secretion from glucose-stimulated pancreatic beta-cells is oscillatory, and this is thought to result from oscillations in glucose metabolism. One of the primary metabolic stimulus-secretion coupling factors is the ATP/ADP ratio, which can oscillate as a result of oscillations in glycolysis. Using a novel multiwell culture plate system, we examined oscillations in insulin release and the ATP/ADP ratio in the clonal insulin-secreting cell lines HIT T-15 and INS-1. Insulin secretion from HIT cells grown in multiwell plates oscillated with a period of 4 min, similar to that seen previously in perifusion experiments. Oscillations in the ATP/ADP ratio in cells grown under the same conditions also occurred with a period of 4 min, as did oscillations in [Ca(2+)](i) monitored by fluorescence microscopy. In INS-1 cells oscillations in insulin secretion, the ATP/ADP ratio, and [Ca(2+)](i) were also seen, but with a shorter period of about 1.5 min. These observations of oscillations in the ATP/ADP ratio are consistent with their proposed role in driving the oscillations in [Ca(2+)](i) and insulin secretion. Furthermore, these data show that, at least in the clonal beta-cell lines, cell contact or even circulatory connection is not necessary for synchronous oscillations induced by a rise in glucose.

Asunto(s)

Calcio/metabolismo , Glucosa/farmacología , Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Cricetinae , Islotes Pancreáticos/metabolismo , Células Tumorales Cultivadas

RESUMEN

Administration of dehydroepiandrosterone (DHEA), or its sulfated form (DHEAS), controls hyperglycemia in diabetic rodents without directly altering insulin sensitivity. We show that DHEAS enhanced glucose-stimulated insulin secretion when administered in vivo to rats or in vitro to beta-cell lines, without changing cellular insulin content. Insulin secretion increased from 3 days of steroid exposure in vitro, suggesting that DHEAS did not directly activate the secretory processes. DHEAS selectively increased the beta-cell mRNA expression of acyl CoA synthetase-2 and peroxisomal acyl CoA oxidase in a time-dependent manner. Although DHEAS is a peroxisomal proliferator, it did not alter the mRNA expression of peroxisomal proliferator-activated receptor (PPAR) alpha or beta, or enhance the activity of transfected PPAR alpha, beta, or gamma in vitro. Thus, DHEAS directly affected the beta-cell to enhance glucose-stimulated insulin secretion and increased the mRNA expression of specific beta-cell mitochondrial and peroxisomal lipid metabolic enzymes. This effect of DHEAS on insulin secretion may contribute to the amelioration of hyperglycemia seen in various rodent models of diabetes.

Asunto(s)

Sulfato de Deshidroepiandrosterona/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/fisiología , Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/fisiología , Acil-CoA Oxidasa , Animales , Línea Celular , Coenzima A Ligasas/genética , Secreción de Insulina , Masculino , Proteínas Mitocondriales , Oxidorreductasas/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Tiempo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transfección

RESUMEN

We have previously shown that the serum parathyroid hormone (PTH) concentration in lactating (L) rats is not suppressed by high serum Ca2+ to the same extent as in nonmated (NM) rats. To investigate further Ca2+ regulation of PTH secretion, parathyroid cells from NM rats and rats in late pregnancy and at peak lactation were dispersed and incubated for 2 h in medium containing 0.52-2.05 mM Ca2+. Medium PTH was assayed with a homologous immunoradiometric assay (IRMA). At the two highest Ca2+ levels (1.81 and 2.05 mM), medium PTH was significantly higher (p = 0.031) for cells from L rats than for cells from NM rats. In contrast, significantly less (p < 0.001) PTH was secreted for the L group versus the NM group at medium Ca2+ values of 1.27 and 1.46 mM. Estimated set points for L and NM groups were 1.17 mM and 1.35 mM, respectively, corresponding closely to the prevailing serum Ca2+ for these two groups. Consistent with the present in vitro data, high serum PTH (> 40 pg/ml) in L rats occurred only at serum Ca2+ values below 1.27 mM. Elevated serum PTH at lower serum Ca2+ levels was also seen in pregnant rats. Dispersed parathyroid cells from 20- to 21-day pregnant rats secreted significantly more PTH (p = 0.028) than cells from NM rats at all Ca2+ levels tested (1.1-1.6 mM). In conclusion, the relationship between extracellular Ca2+ and PTH secretion is altered in rats during late pregnancy and at peak lactation, perhaps as part of the adaptation to the demands for calcium for pre- and postnatal growth.

Asunto(s)

Calcio/farmacología , Lactancia/fisiología , Hormona Paratiroidea/metabolismo , Preñez/fisiología , Animales , Volumen Sanguíneo , Calcio/sangre , Calcio de la Dieta/administración & dosificación , Femenino , Técnicas In Vitro , Lactancia/sangre , Glándulas Paratiroides/citología , Glándulas Paratiroides/efectos de los fármacos , Glándulas Paratiroides/metabolismo , Hormona Paratiroidea/sangre , Embarazo , Preñez/sangre , Ratas

RESUMEN

Serum calcitriol concentrations in rats follow a biphasic pattern during reproduction, with elevated levels during late pregnancy, a decline after parturition, and a rise to even higher levels during peak lactation. We have previously shown that serum calcitriol in rats at peak lactation correlates significantly with, and appears to be regulated by, serum ionized Ca (Ca2+), with parathyroid hormone (PTH) serving a permissive role. We have extended this study by determining if serum calcitriol also correlates with serum Ca2+ during late pregnancy, when calcitriol levels are clearly elevated, and during early lactation, when only modest increases in serum calcitriol are observed. Analyses of data combined from nonmated, 21-day pregnant (P), and 1-day lactating rats (L) revealed a significant regression (p < 0.001) of calcitriol on Ca2+, but a nonsignificant regression (p = 0.34) of calcitriol on serum PTH. An even stronger correlation (p < 0.001) between calcitriol and Ca2+ was found for the combined data for 5-, 8-, and 14-day L rats. The partial correlation coefficient for calcitriol versus Ca2+, with PTH as the independent variable, was highly significant (p < 0.01) for the data from both combined groups. However, the coefficient for calcitriol versus PTH, with Ca2+ as the independent variable, was not significant (p > 0.05). Fetal weights (uterus and contents) correlated significantly with both maternal calcitriol and Ca2+ concentrations (p < 0.01), but not with maternal PTH levels. Litter weights for 14-day-old pups likewise correlated significantly with maternal calcitriol and Ca2+ (p < 0.001). We conclude that hypocalcemia, induced by the demands for Ca for fetal calcification and milk production, appears to be a controlling factor in serum calcitriol elevation in late pregnancy and throughout lactation, whereas PTH may be important for calcitriol synthesis without playing a direct regulatory role.

Asunto(s)

Calcitriol/sangre , Calcio/sangre , Lactancia/sangre , Preñez/sangre , Animales , Peso Corporal , Femenino , Feto/anatomía & histología , Homeostasis , Hormona Paratiroidea/sangre , Embarazo , Ratas , Factores de Tiempo

RESUMEN

Stimulation of insulin release by glucose requires increased metabolism of glucose and a rise in cytosolic free Ca2+ in the pancreatic beta-cell. It is accompanied by increases in respiratory rate, pyridine and flavin nucleotide reduction state, intracellular pH and the ATP/ADP ratio. To test alternative proposals of the regulatory relationships among free Ca2+, mitochondrial metabolism and cellular energy state, we determined the temporal sequence of these metabolic and ionic changes following addition of glucose to clonal pancreatic beta-cells (HIT). Combined measurements of the native fluorescence of reduced pyridine nucleotides and oxidized flavin, intracellular pH, and free Ca2+ were performed together with simultaneous measurement of O2 tension or removal of samples for assay of the ATP/ADP ratio. The initial changes were detected in three phases. First, decreases occurred in the ATP/ADP ratio (<3 s) and increases in pyridine (2 +/- 1 s) and flavin (2 +/- 1 s) nucleotide reduction. Next, increases in the O2 consumption rate (20 +/- 5 s), the ATP/ADP ratio (29 +/- 12 s) and internal pH (48 +/- 5 s) were observed. Finally, cytosolic free Ca2+ rose (114 +/- 10 s). Maximal changes in the ATP/ADP ratio, O2 consumption and pyridine and flavin nucleotide fluorescence preceded the beginning of the Ca2+ change. These relationships are consistent with a model in which phosphorylation of glucose is the initial event which generates the signals that lead to an increase in respiration, a rise in the ATP/ADP ratio and finally influx of Ca2+. Our results indicate that Ca2+ does not function as the initiator of increased mitochondrial respiration.

Asunto(s)

Glucosa/farmacología , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Calcio/metabolismo , Células Clonales , Cricetinae , Citosol/metabolismo , Flavina-Adenina Dinucleótido/metabolismo , Concentración de Iones de Hidrógeno , Insulina/metabolismo , Secreción de Insulina , Cinética , Mitocondrias/metabolismo , NAD/metabolismo , NADP/metabolismo , Consumo de Oxígeno , Fosforilación , Transducción de Señal

RESUMEN

Closure of ATP-sensitive K+ (K(ATP)) channels is part of the stimulus-secretion coupling mechanism in the pancreatic beta-cell, leading to membrane depolarization and influx of Ca2+ through voltage-sensitive L-type Ca2+ channels. The elevated ATP/ADP ratio seen in the presence of high levels of glucose has been postulated to mediate the glucose-induced closure of the K(ATP) channels and rise in cytoplasmic free Ca2+ concentration ([Ca2+]i), or alternatively to be a consequence of activation of mitochondrial dehydrogenases by the increase in [Ca2+]i. To distinguish between these two possibilities, the time course of the change in the ATP/ADP ratio was determined in comparison with that of [Ca2+]i. We here show that a severalfold rise in the ATP/ADP ratio occurs rapidly on stimulation of suspensions of mouse pancreatic beta-cells with glucose. The change in the ATP/ADP ratio is an early event that begins within 20-40 s and precedes the rise in [Ca2+]i. The temporal relationship indicates that the adenine nucleotide changes cannot be a consequence of the [Ca2+]i changes and may indeed be the connecting link between glucose metabolism and [Ca2+]i changes. When the cells were sequentially treated with high glucose concentration, clonidine and finally high extracellular Ca2+ concentration to induce synchronized oscillations in [Ca2+]i in the cell suspension, corresponding oscillations in the ATP/ADP ratio were observed. Glucose 6-phosphate levels oscillated out of phase with the ATP/ADP ratio. These results support the hypothesis that the Ca2+ oscillations previously observed in glucose-stimulated single islets or beta-cells may reflect oscillations in the ATP/ADP ratio that accompany oscillatory glycolysis.

Asunto(s)

Adenosina Trifosfato/metabolismo , Calcio/metabolismo , Glucosa/farmacología , Glucofosfatos/metabolismo , Islotes Pancreáticos/metabolismo , Adenosina Difosfato/metabolismo , Agonistas alfa-Adrenérgicos/farmacología , Animales , Células Cultivadas , Clonidina/farmacología , Glucosa-6-Fosfato , Glucólisis , Cinética , Ratones , Ratones Obesos , Canales de Potasio/metabolismo

RESUMEN

Normal insulin secretion is oscillatory in vivo, and the oscillations are impaired in type II diabetes. We and others have shown oscillations in insulin secretion from isolated perifused islets stimulated with glucose, and in this study we show oscillations in insulin secretion from the glucose-sensitive clonal beta-cell line INS-1. We have proposed that the oscillatory insulin secretion may be caused by spontaneous oscillations of glycolysis and the ATP:ADP ratio in the beta-cell, analogous to those seen in glycolyzing muscle extracts. The mechanism of the latter involves autocatalytic activation of the key regulatory enzyme, phosphofructokinase (PFK), by its product fructose 1,6-bisphosphate (F16BP). However, of the three PFK subunit isoforms (M-[muscle], L-[liver], and C-type, predominant in fibroblasts), only M-type is activated by micromolar F16BP at near-physiological conditions. We therefore studied PFK isoforms in the beta-cell. Western analysis of PFK subunits in isolated rat islets and INS-1 cells showed the presence of M-type, as well as C-type and perhaps lesser amounts of L-type. Kinetic studies of PFK activity in INS-1 cell extracts showed strong activation by micromolar concentrations of F16BP at near-physiological concentrations of ATP (several millimolar) and AMP and fructose 6-phosphate (micromolar), indicative of the M-type isoform. Activation by submicromolar concentrations of fructose 2,6-bisphosphate (F26BP) and potent inhibition by citrate were also observed. The F16BP-stimulatable activity was about one-half of the F26BP-stimulatable activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Insulina/metabolismo , Islotes Pancreáticos/enzimología , Islotes Pancreáticos/metabolismo , Isoenzimas/metabolismo , Fosfofructoquinasa-1/metabolismo , Adenosina Monofosfato/farmacología , Adenosina Trifosfato/farmacología , Animales , Western Blotting , Células Clonales , Activación Enzimática , Fructosadifosfatos/farmacología , Fructosafosfatos/farmacología , Glucosa/farmacología , Técnicas In Vitro , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Isoenzimas/aislamiento & purificación , Cinética , Sustancias Macromoleculares , Masculino , Oscilometría , Fosfofructoquinasa-1/aislamiento & purificación , Ratas , Ratas Sprague-Dawley , Factores de Tiempo

RESUMEN

The effects of anesthetics on serum parathyroid hormone (PTH) concentrations were determined by a new homologous two-site immunoradiometric assay for rat PTH. Serum PTH concentrations (mean +/- SE) from ether-anesthetized rats (14.7 +/- 1.5 pg/ml, n = 22) were not significantly different from those of decapitated unanesthetized female rats (13.0 +/- 1.8 pg/ml, n = 21). Serum PTH concentrations in pg/ml (n = 4-14) for other anesthetics tested were: ketamine, 12.5 +/- 1.1; Na pentobarbital, 23.3 +/- 2.4; methoxyflurane (inhalation), 42.2 +/- 6.8; and xylazine combined with ketamine, 51.4 +/- 11.3 pg/ml. The latter two concentrations were significantly (p < 0.001) higher than the values for all other anesthetics and decapitation. Elevation of serum PTH induced by pentobarbital or ketamine + xylazine increased with time under anesthesia. Neither serum Ca2+ concentrations nor pH differed among any of the groups. We conclude that anesthesia induced by pentobarbital, methoxyflurane, or ketamine + xylazine in rats leads to a marked elevation of serum PTH levels that appears to be related to the duration of anesthesia and not due to any measurable fall in serum Ca2+.

Asunto(s)

Anestésicos/farmacología , Éter/farmacología , Hormona Paratiroidea/sangre , Animales , Calcio/sangre , Combinación de Medicamentos , Femenino , Concentración de Iones de Hidrógeno , Hipnóticos y Sedantes/farmacología , Ensayo Inmunorradiométrico , Ketamina/farmacología , Lactancia/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Estadística como Asunto

RESUMEN

The Danish law concerning commitment and compulsory procedures in psychiatry was reformed in October 1989, and for the first time laid down regulations for compulsory treatment of somatic disease in psychotic patients. The aim of the study was to evaluate whether the law is useful in clinical practice. The course of 28 psychotic patients who were committed and/or compulsorily treated due to severe somatic disease is described. We conclude that the law is a useful tool in the acute treatment of life-endangering somatic disease in psychotic patients.

Asunto(s)

Internamiento Obligatorio del Enfermo Mental/legislación & jurisprudencia , Trastornos Psicóticos/complicaciones , Adulto , Anciano , Dinamarca , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/terapia , Estudios Retrospectivos , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico

RESUMEN

A three-month-old, male Chihuahua puppy with congenital absence of the distal 40% of the right thoracic limb was examined. The limb ended as a short, rounded, skin-covered stump. Radiography revealed a 40% shortened humerus tapered to a blunt end without its distal extremity. Dissection of the left thoracic limb identified luxation of the elbow joint and absence of the fourth digital pad. Alizarin-red staining and clearing demonstrated syndactylous fourth and fifth digits in the left thoracic limb and an anomalous eighth lumbar vertebra. This additional vertebra was unilaterally sacralized and constituted a lumbosacral transitional vertebra.

Asunto(s)

Anomalías Múltiples/veterinaria , Perros/anomalías , Miembro Anterior/anomalías , Vértebras Lumbares/anomalías , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/patología , Animales , Miembro Anterior/diagnóstico por imagen , Miembro Anterior/patología , Húmero/anomalías , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Masculino , Radiografía , Dedos del Pie/anomalías

RESUMEN

A new homologous 2-site assay for rat parathyroid hormone (IRMA), developed by Immutopics, Inc., has been evaluated and compared with a bone cell cAMP bioassay. Circulating PTH for adult rats assayed with this IRMA are in the range 10-15 pg/ml, and of the same order of magnitude as published values for biologically active PTH. The standard curve for the IRMA was linear over the range 3.4-240 pg/ml of rPTH 1-34, and serum samples diluted in parallel with the standard curve. The within-assay and between-assay coefficients of variation ranged from 5.2% (n = 18) to 7.6% (n = 24) and 8.3% (n = 16) to 26.4% (n = 10), respectively. Serum PTH values (mean +/- S.E.) for parathyroidectomized rats were 3.5 +/- 0.6 pg/ml (n = 18) versus 10.3 +/- 1.4 pg/ml (n = 16) for intact non-mated rats. Calcium injections suppressed circulating PTH by 50%. Lactating rats had serum PTH levels 5-fold higher and vitamin D deficient rats 60-fold higher than non-mated controls. PTH secreted from parathyroid cells in vitro was in the range 60-490 pg/ml as determined by the IRMA. These values represented 86.0 +/- 9.0% of the comparable bioassay values, indicating that the IRMA detects only bioactive PTH.

Asunto(s)

AMP Cíclico/metabolismo , Glándulas Paratiroides/citología , Hormona Paratiroidea/sangre , Animales , Células Cultivadas , AMP Cíclico/análisis , Femenino , Ensayo Inmunorradiométrico , Glándulas Paratiroides/metabolismo , Hormona Paratiroidea/análisis , Hormona Paratiroidea/metabolismo , Paratiroidectomía , Embarazo , Ratas , Ratas Sprague-Dawley , Análisis de Regresión

RESUMEN

The temporal relationship of glucose-induced increases in cytoplasmic pH (pHi) and cytoplasmic free Ca2+ was studied in single mouse pancreatic beta-cells and suspensions of clonal beta-cells (HIT). In both preparations of cells the increase in pHi preceded the cytoplasmic free Ca2+ increase. Therefore the alkalinization cannot be a consequence of the Ca2+ influx. A potential metabolic mechanism for the increase in pHi, involving stimulation of pyruvate transport and oxidation, was demonstrated in a model system of liver mitochondria incubated with pyruvate, ATP, and hexokinase to which glucose was then added to initiate ATP use. The involvement of this mechanism in beta-cells is suggested by the observation that the alkalinization was prevented in most cells by incubation with 3-hydroxycyanocinnamate, a mitochondrial pyruvate transport inhibitor. On the other hand, the inhibited cells exhibited normal Ca2+ responses to glucose stimulation. This indicates that neither pyruvate metabolism nor the alkalinization is of critical importance for the Ca2+ signal, though pyruvate oxidation or its metabolites may be important in downstream regulation of secretion.

Asunto(s)

Calcio/metabolismo , Glucosa/farmacología , Concentración de Iones de Hidrógeno , Islotes Pancreáticos/metabolismo , Piruvatos/metabolismo , Animales , Dióxido de Carbono/análisis , Células Clonales , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Fluoresceínas , Colorantes Fluorescentes , Fura-2 , Técnicas In Vitro , Islotes Pancreáticos/efectos de los fármacos , Cinética , Ratones , Ratones Obesos , Modelos Biológicos , Espectrometría de Fluorescencia , Factores de Tiempo

Asunto(s)

Adenosina Difosfato/análisis , Adenosina Trifosfato/análisis , Sulfato Adenililtransferasa/metabolismo , Animales , Bovinos , Células Cultivadas , Escarabajos/enzimología , Endotelio Vascular/química , Guanosina Monofosfato/análisis , Guanosina Trifosfato/análisis , Islotes Pancreáticos/química , Islotes Pancreáticos/citología , Luciferasas/química , Mediciones Luminiscentes , Ratones

RESUMEN

Isolated bovine cerebral microvessels (ICMV) were incubated with different metabolic fuels to determine their ability to support microvessel Na(+)-K(+)-ATPase (quantitated as ouabain-sensitive 86Rb+ uptake) and the ATP/ADP ratio. In comparison with ICMV incubated with glucose, Na(+)-K(+)-ATPase activity was reduced by 55% after a 3-h incubation in fuel-free medium and by 30-40% after incubation with beta-hydroxybutyrate, acetoacetate, or glutamate. However, Na(+)-K(+)-ATPase activity was not significantly decreased in ICMV incubated with pyruvate or oleate plus carnitine. In contrast, only glucose was able to maintain the ATP/ADP ratio. To evaluate the effect of endogenous fatty acid metabolism on these parameters, ICMV were incubated with bromostearate, an inhibitor of fatty acid oxidation. Bromostearate decreased both Na(+)-K(+)-ATPase activity and the ATP/ADP ratio, even in the presence of glucose. These results indicate that the varying effects of different fuels on Na(+)-K(+)-ATPase in ICMV cannot be explained solely by their effects on the ATP/ADP ratio or on glycolytic ATP generation. They suggest that other fuel-modulated factors play a key role in regulating this enzyme.

Asunto(s)

Circulación Cerebrovascular , Metabolismo Energético/efectos de los fármacos , Microcirculación/metabolismo , Músculo Liso Vascular/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Ácido 3-Hidroxibutírico , Acetoacetatos/farmacología , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Carnitina/farmacología , Bovinos , Glucosa/farmacología , Glutamatos/farmacología , Ácido Glutámico , Hidroxibutiratos/farmacología , Técnicas In Vitro , Cinética , Microcirculación/efectos de los fármacos , Microcirculación/enzimología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/enzimología , Ácido Oléico , Ácidos Oléicos/farmacología , Ouabaína/farmacología , Piruvatos/farmacología , Ácido Pirúvico , Rubidio/metabolismo

RESUMEN

A case of full-blown neurosyphilis in a 40 year old university man is demonstrated. The disease was initially misdiagnosed as Creutzfeldt-Jakob disease. Nuclear magnetic resonance scanning supported this diagnosis. One year later the patient was hospitalized owing to increasing neurological deficits. For the first time he was examined for syphilis, and the disease was confirmed by a WR test. Despite lege artis penicillin treatment the patient was left with severe deficits, particularly of the intellect. The old phrase that syphilis can mimic any form of psychopathology is still true, and WR is still the test of choice whenever a neuropsychiatric diagnosis is unclear.

Asunto(s)

Trastornos Mentales/etiología , Neurosífilis/complicaciones , Adulto , Diagnóstico Diferencial , Errores Diagnósticos , Humanos , Masculino , Trastornos Mentales/diagnóstico , Neurosífilis/diagnóstico , Neurosífilis/tratamiento farmacológico , Factores de Tiempo

RESUMEN

Forty relatives of young psychotic patients participated in psychoeducative groups for eight sessions and filled in questionnaires at the first and the last session. They were questioned about user satisfaction, degree of strain, knowledge, attitude and behaviour in relation to mental illness, and the emotional climate in the family. The emotional climate in the family was investigated by means of the Family Questionnaire and divided in subscales, measuring criticism and over-involvement. The relatives had experienced strain in relation to the patient's behaviour. Aggression, unpredictability, dependence/helplessness were factors which the relatives felt most straining. The relatives' burden of care had consequences in economy, private life and working life. The relatives complained of lack of continuity in the treatment of the patient. Information about the condition, diagnosis and prognosis of the patient was criticized for being unsatisfactory, too vague or too scarce. After the psychoeducative group sessions, both criticism and over-involvement tended to fall (non-significant). The relatives were very satisfied with the group sessions. It is concluded that psychoeducative group sessions with relatives of psychotic patients are effective in influencing the emotional climate in the families in a desirable way. Better cooperation between psychiatric department/community mental health care centre, patient and relative can increase compliance with medical treatment and increase the relatives' ability to handle problems related to the patient's disease.

Asunto(s)

Terapia Familiar/métodos , Familia/psicología , Psicoterapia de Grupo/métodos , Trastornos Psicóticos/psicología , Adolescente , Adulto , Actitud Frente a la Salud , Emociones , Femenino , Humanos , Masculino , Trastornos Psicóticos/terapia , Factores Socioeconómicos , Encuestas y Cuestionarios

Asunto(s)

Adenosina Difosfato/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Piruvato Quinasa/metabolismo , Animales , Bovinos , Células Cultivadas , Creatina Quinasa/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Guanosina Difosfato/metabolismo , Lactatos/metabolismo , Ácido Láctico , Fosfocreatina/metabolismo , Fosforilación , Piruvatos/metabolismo , Ácido Pirúvico , Espectrofotometría Ultravioleta/métodos

RESUMEN

In 103 schizophrenic patients we investigated the extent of practice needed in the use of the Brief Psychiatric Rating Scale (BPRS) to enable its reliability to be assessed. The agreement level of the 7 raters was analysed. Generally, the lowest mean agreement found was for the negative symptoms of the BPRS schizophrenia subscale. A high degree of agreement was attained both for the positive symptoms of the BPRS schizophrenia subscale and for the symptoms of the depression--and of the mania subscale. The degree of disagreement observed was due to both individual differences in assessment ability and the rating procedure. These results indicate that it is necessary to state the degree of agreement achieved in studies in which several raters are taking part.

Asunto(s)

Escalas de Valoración Psiquiátrica , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Adulto , Competencia Clínica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados