RESUMO
CONTEXT AND PURPOSE: Hypocalcemia and low parathyroid hormone levels have been commonly suggested as factors able to induce central nervous system disturbances. However, evidences on the occurrence of cognitive impairment are limited or underestimated. The aim of this review is, therefore, to systematically summarize the available evidence concerning the occurrence of cognitive impairment among subjects suffering from idiopathic or secondary hypoparathyroidism. METHODS: A systematic selection of the available literature was performed by searching the online databases PubMed, Scopus and Web of Knowledge. RESULTS: The present systematic review included sixteen case report articles and one cross-sectional controlled study. Case reports were the most representative literature sources and involved ten women and seven men. The presence of cognitive impairment was mostly discussed in association with idiopathic hypoparathyroidism (HPT); five articles described the occurrence of cognitive impairment following postsurgical HPT. The case-controlled study reported a significant presence of peculiar cognitive deficits (e.g. reduced inhibitory control, impairment in visuo-spatial functioning among, and psychomotor retardation) among HPT subjects compared to healthy controls, with serum total calcium and its product with phosphorus as independent predictors of neuropsychological dysfunctions. CONCLUSION: Even though mostly based on single case reports, the presence of neuropsychological dysfunctions in the context of HPT appears to be a consistent core finding.
Assuntos
Disfunção Cognitiva , Hipoparatireoidismo , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/etiologia , Hipoparatireoidismo/sangue , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/psicologia , Testes Neuropsicológicos , Hormônio Paratireóideo/análiseAssuntos
Pacientes Internados/estatística & dados numéricos , Deficiência de Magnésio/epidemiologia , Magnésio/sangue , Pacientes Ambulatoriais/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Deficiência de Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Desequilíbrio Hidroeletrolítico , Adulto JovemRESUMO
BACKGROUND: Proton-pump inhibitors (PPI) are extensively prescribed in older patients. However, little information is available on factors associated to PPI prescribing patterns among older patients discharged from hospital. OBJECTIVE: To evaluate the appropriateness and clinical correlates of PPI prescription at discharge in a population of 1081 older patients discharged from acute care Italian hospitals. DESIGN: We used data from the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) study, a multicenter observational study. The appropriateness of PPI prescriptions was defined according to the Italian Medicines Agency (AIFA) rules. Correlates of overprescribing (i.e prescribing without recognized AIFA indications) and underprescribing (i.e. not prescribing despite the presence of recognized AIFA indications) were investigated by logistic regression analysis. RESULTS: Overprescribing was observed in 30% of patients receiving PPIs at discharge. Underprescribing was observed in 11% of patients not receiving PPIs at discharge. Overprescribing of PPIs at discharge was negatively associated with age (OR=0.88, 95%CI=0.85-0.91), depression (OR=0.58, 95%CI=0.35-0.96), use of aspirin (OR=0.03, 95%CI=0.02-0.06) and systemic corticosteroids (OR=0.02, 95%CI=0.01-0.04). The negative association with number of medications (OR=0.95, 95%CI=0.88-1.03) and overall comorbidities (OR=0.92, 95%CI=0.83-1.02) was nearly significant. Conversely, older age (OR=1.09, 95%CI=1.04-1.14), use of aspirin (OR=24.0, 95%CI=11.5-49.8) and systemic corticosteroids (OR=19.3, 95%CI=11.5-49.8) and overall comorbidities (OR=1.22, 95%CI=1.04-1.42) were independent correlates of underprescribing. CONCLUSION: Overprescribing of PPIs is more frequent in younger patients with lower burden of depression, whilst underprescribing is characterized by older age and greater burden of comorbidity and polypharmacy. Hospitalization should be considered as a clue to identify inappropriate use of PPIs and improve appropriateness of prescribing.
Assuntos
Prescrição Inadequada/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Alta do Paciente , Polimedicação , Inibidores da Bomba de Prótons/administração & dosagemRESUMO
OBJECTIVE: We aimed to investigate the association of the clinical variables of the metabolic syndrome (MS) and psychological parameters on health-related quality of life (HRQL) in obesity. In particular, our aim was to investigate the relative impact of physical symptoms, somatic diseases and psychological distress on both the physical and the mental domains of HRQL. DESIGN: Cross-sectional study. SUBJECTS: A cohort of 1822 obese outpatients seeking treatment in medical centers. MEASUREMENTS: HRQL was measured by the standardized summary scores for physical (PCS) and mental (MCS) components of the Short Form 36 Health Survey (SF-36). Patients were grouped according to tertiles of PCS and MCS. Metabolic and psychological profiles of PCS and MCS tertiles were compared by discriminant analysis. RESULTS: The profile of metabolic and psychological variables was tertile-specific in 62.4 and 68.3% of patients in the lowest and highest tertiles of PCS, respectively, while concordance was low in the mid-tertile (32.8%). Concordance was very high in the lowest (74.4%) and in the highest (75.5%) tertiles of MCS, and was fair in the mid-tertile (53.2%). The main correlates of PCS were obesity-specific and general psychological well-being, BMI, body uneasiness, binge eating, gender and psychiatric distress. Only hypertension and hyperglycemia qualified as correlates among the components of MS. The components of MS did not define MCS. CONCLUSIONS: Psychological well-being is the most important correlate of HRQL in obesity, both in the physical and in the mental domains, whereas the features of MS correlate only to some extent with the physical domain of HRQL.
Assuntos
Nível de Saúde , Síndrome Metabólica/psicologia , Obesidade/psicologia , Qualidade de Vida , Adulto , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To verify whether platelet responsiveness to leptin is associated with metabolic syndrome risk factors. DESIGN: Cross-sectional study. SUBJECTS: We studied 169 consecutive patients, mean age=43.6+/-9.9 years, with overweight (N=57) or obesity (N=112). MEASUREMENTS: Cluster analysis was used to generate three clusters based on platelet responsiveness to increasing doses of leptin. Profiles of metabolic syndrome risk factors of the three clusters were compared by discriminant analysis. RESULTS: Platelet responsiveness to leptin was absent in cluster 1, whereas cluster 3 had the greatest platelet aggregation response to leptin pre-incubation. Plasma leptin levels significantly decreased from cluster 1 to cluster 3 in both gender. Patients in cluster 2 had an intermediate profile of leptin responsiveness. Highest body mass index (BMI) values were more frequent in non-responders, whereas the prevalence of high waist circumference, as well as hypertriglyceridemia and hypertension, increased with increasing responsiveness to leptin from cluster 1 to cluster 3. Pattern of metabolic syndrome risk factors qualified as group specific in 69.0% of the cluster 1, 54.9% of the cluster 2 and 55.8% of the cluster 3. Circulating leptin, waist circumference, plasma triglycerides and BMI defined distinctive patterns of metabolic syndrome risk factors in the clusters. CONCLUSIONS: In overweight and obese outpatients, metabolic syndrome risk factors parallel to some extent platelet responsiveness to leptin. Such a correlation involves plasma leptin levels, waist circumference, plasma triglycerides and BMI, and may contribute to the excess risk of cardiovascular events in overweight and obese patients.
Assuntos
Leptina/farmacologia , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Sobrepeso/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Adulto , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Leptina/sangue , Leptina/fisiologia , Masculino , Síndrome Metabólica/complicações , Obesidade/complicações , Sobrepeso/complicações , Fatores de Risco , Triglicerídeos/sangueRESUMO
Fatty liver at ultrasounds, with/ without raised plasma levels of hepatic enzymes, is common in obesity. In most cases, it is the hallmark of non-alcoholic fatty liver disease (NAFLD), a potentially progressive disease associated with insulin resistance and the metabolic syndrome (MS). We tested the hypothesis that insulin resistance per se might be associated with hepatocellular necrosis. Alanine and aspartate aminotransferases (ALT and AST; no.=799) and gamma-glutamyltranspeptidase (GGT; no.=459) were analyzed in a group of treatment-seeking obese patients recruited in 12 Italian medical centers. Insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR; no.=522). Median ALT and AST increased with increasing obesity class (p=0.001 and p=0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased with the obesity class (p<0.0001), and was higher in subjects with elevated ALT (median, 4.93 vs 2.89; p<0.0001). A significant correlation was observed between HOMA-IR and ALT (R2=0.208; p<0.0001), as well as between HOMA-IR and AST or GGT (R2=0.112 and R2=0.080; p<0.0001). The correlation was maintained when cases with elevated enzyme levels were omitted from analysis. Diabetes and hypertriglyceridemia were the features of the MS most commonly associated with raised liver enzymes. In logistic regression, after correction for age, gender, BMI and features of the MS, HOMA-IR maintained a highly predictive value for raised ALT, AST and GGT. We conclude that in obesity insulin resistance is a risk factor for raised liver enzyme levels, possibly related to NAFLD.
Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/fisiopatologia , Resistência à Insulina , Síndrome Metabólica/fisiopatologia , Obesidade/complicações , gama-Glutamiltransferase/sangue , Adulto , Idoso , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Fígado/enzimologia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Obesidade/fisiopatologia , Análise de Regressão , Fatores de RiscoRESUMO
Magnesium sulphate has well known antiplatelet properties. Its effect on leptin-dependent platelet aggregation has not been studied previously. Thus, we performed this ex vivo study to investigate whether magnesium sulphate is able to inhibit leptin-dependent aggregation of human platelets. We obtained platelet rich plasma (PRP) from venous blood samples of 16 healthy male volunteers, and we measured ADP-induced platelet aggregation in the presence of leptin alone (5-500 ng/mL) or leptin and magnesium sulphate (0.25-8 mM). Platelet pre-incubation with leptin led to a significant and dose-dependent increase in ADP-induced platelet aggregation. Magnesium sulphate was able to inhibit the pro-aggregating effect of leptin in a dose-dependent manner. The inhibitory effect was apparent at 1 mM of magnesium sulphate concentration (% maximal aggregation=38.1 +/- 12.2) and reached its maximum at 8 mM (% maximal aggregation=20.0 +/- 7.8). Our results demonstrate that leptin-dependent platelet aggregation is inhibited by magnesium sulphate in a dose-dependent manner. It seems conceivable that the blocking of hydrolysis of phosphoinositide and of intracellular calcium mobilization by magnesium sulphate may be involved in these findings.
Assuntos
Leptina/fisiologia , Sulfato de Magnésio/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Adulto , Humanos , MasculinoRESUMO
OBJECTIVE: To investigate the role of phospholipase C (PLC), phospholipase A(2) (PLA(2)), calcium, and protein kinase C (PKC) in mediating leptin-enhanced aggregation of human platelets. DESIGN: In vitro, ex vivo study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital of Messina, Italy. SUBJECTS: In total, 14 healthy normal-weight male (age 31.4+/-1.9 y; body mass index 22.7+/-0.6 kg/m2) subjects. MEASUREMENTS: Adenosine diphosphate-(ADP-) induced platelet aggregation and platelet free calcium were measured after incubation of platelets with leptin alone (5-500 ng/ml), or leptin (50 and 100 ng/ml) in combination with anti-human leptin receptor long form antibody (anti-ObRb-Ab, 1:800-1:100 dilutions), PLC inhibitor U73122 (3.125-25 microM), PLA(2) inhibitor AACOCF3 (1.25-10 microM), or PKC inhibitor Ro31-8220 (1.25-10 microM). RESULTS: Platelet stimulation with leptin leads to a significant and dose-dependent increase in ADP-induced platelet aggregation and platelet free calcium concentrations. Leptin effects on both platelet aggregation and calcium mobilization were completely abated by the co-incubation with leptin and anti-ObRb-Ab. Leptin-induced platelet aggregation was dose-dependently inhibited by U73122, AACOCF3, or Ro31-8220. The effect of leptin on intracellular calcium was inhibited in a dose-dependent manner by incubation with U73122 and AACOCF3, but not with Ro31-8220. CONCLUSIONS: Our study confirms that leptin is able to enhance ADP-induced aggregation of human platelets, and raise the possibility that PLC, PKC, PLA(2), and calcium could play a relevant role in mediating the proaggregating action of leptin.
Assuntos
Leptina/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Transdução de Sinais , Difosfato de Adenosina/metabolismo , Adulto , Análise de Variância , Anticorpos Monoclonais/farmacologia , Ácidos Araquidônicos/farmacologia , Cálcio/metabolismo , Estrenos/farmacologia , Humanos , Indóis/farmacologia , Leptina/imunologia , Leptina/metabolismo , Masculino , Fosfolipases A/antagonistas & inibidores , Fosfolipases A/metabolismo , Agregação Plaquetária/fisiologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Pirrolidinonas/farmacologia , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/metabolismoRESUMO
INTRODUCTION: The pathogenic mechanisms underlying the increase in peripheral resistance and the contraction of smooth muscular fibre cells in essential hypertension are not yet clearly understood. However, it is now known that immune system activation plays a role in the pathogenesis of some forms of arterial hypertension, and recent data show that the Ca2+ influx in some cells (i.e. red blood cells, leukocytes, platelets, smooth muscular fibre cells) is increased in subjects with essential hypertension, thus revealing a possible alteration in cellular membrane. The end-points of this study were therefore to ascertain whether red blood cells used as a cellular membrane model have a greater Ca2+ dependent K+ flow (Gardos effect) in hypertensive patients than in normotensive controls, to point out a different regulation of ionic channels, and whether IL-8 and the adhesion molecule ICAM-1 influence the membranous outflow. MATERIAL AND METHODS: The study was conducted on 87 Caucasian subjects. Of these, 50 (25 men, 25 women; mean age 43 +/- 3 years, mean body mass index (BMI) 27 +/- 0.5 and 22.3 +/- 0.3 kg/m(2), respectively) had mild-to-moderate hypertension (mean arterial blood pressure 120 +/- 8 mmHg ). The other 37 (18 men, 19 women; mean age 39 +/- 3 years; BMI 23.8 +/- 0.5 kg/m(2) and 22.8 +/- 0.5 kg/m(2), respectively were normotensive healthy volunteers (mean arterial blood pressure 89 +/- 2 mmHg). All the patients and subjects were untreated for at least 4 weeks before blood sampling. RESULTS: Ca2+-dependent K+ outflow was found to be greater in samples from patients with essential hypertension than in those from normotensive controls. lL-8 and ICAM-1 significantly enhanced the Ca2+-dependent K+ outflow in red blood cells from hypertensive subjects but had an inhibitory effect on cells from controls. In the experimental model, the presence of TMB-8, a membrane calcium antagonist, significantly reduced the Ca2+-dependent K+ efflux. CONCLUSION: Vasoconstriction in subjects with essential hypertension may therefore depend on a different regulation of ionic flow that probably supports an increased Ca2+ inflow in smooth muscle fibre cells. Under certain pathological conditions, some immune system components (i.e. interleukins, adhesion molecules) may directly enhance membrane permeability to Ca2+, thus inducing vasoconstriction in the smooth muscle cells.
Assuntos
Cálcio/fisiologia , Membrana Eritrocítica/fisiologia , Ácido Gálico/análogos & derivados , Hipertensão/sangue , Molécula 1 de Adesão Intercelular/fisiologia , Interleucina-8/fisiologia , Potássio/sangue , Adulto , Bloqueadores dos Canais de Cálcio/farmacologia , Feminino , Ácido Gálico/farmacologia , Humanos , Masculino , Canais de Potássio/fisiologia , Vasoconstrição/fisiologiaRESUMO
OBJECTIVE: This study investigated the frequency of the panic-agoraphobic spectrum symptoms in a sample of obese subjects affected by Binge Eating Disorder (BED) vs controls. METHOD: Fifty obese with BED were matched by age, sex and marital status to twenty-five normal weight controls. The Structured Clinical Interview For Panic-Agoraphobic Spectrum--SCI-PAS was administered to all participants. RESULTS: Obese subjects with BED presented significantly higher frequencies of typical and atypical panic symptoms (82% vs 8%, p<0.0001), agoraphobia (58% vs 12%, p=0.002) and reassurance orientation (56% vs 8%, p=0.001) than controls. DISCUSSION: BED frequently co-occurs with other major psychiatric disorders, traditionally assessed using categorical methods of classification of mental disorders. The spectrum of the subthreshold, atypical and partial symptoms of full-blown mental disorders, often neglected by categorical approach, may also affect subjective well-being and functioning as full-blown disorders. The identification of the subthreshold symptomatology may have relevant implications for the response to treatment and the outcome of the eating disorder.
Assuntos
Agorafobia/epidemiologia , Bulimia/epidemiologia , Obesidade/epidemiologia , Transtorno de Pânico/epidemiologia , Adulto , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Itália/epidemiologia , MasculinoRESUMO
OBJECTIVE: To investigate the effects of leptin on platelet aggregation and platelet free calcium (Ca(2+)) concentrations, and the role of the long form of leptin receptor (ObRb) and the phospholipase C (PLC) in mediating leptin effects on platelet function. DESIGN: Cross-sectional, clinical study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital of Messina, Italy. SUBJECTS: A total of 19 healthy, 14 overweight, and 16 obese male subjects. MEASUREMENTS: ADP-induced platelet aggregation and platelet Ca(2+) were measured after incubation of platelet-rich plasma with leptin alone 5-200 ng/ml, leptin 200 ng/ml and anti-human leptin receptor long-form antibody (ObRb-Ab) 5-10 microl, or leptin 200 ng/ml and PLC inhibitor U73122 0.5-1 nmol/l. RESULTS: Platelet stimulation with leptin lead to a significant and dose-dependent increase in platelet aggregation in healthy subjects. This effect was blunted in overweight, and strongly reduced in obese subjects. Similarly, the incubation with leptin induced a significant and dose-dependent increase in platelet free calcium, which was blunted in overweight and obese patients. The effect of leptin on platelet aggregation and platelet Ca(2+) was completely abated by the anti-ObRb-Ab and the PLC inhibitor U73122. CONCLUSIONS: Leptin produces a dose-dependent enhancement of ADP-induced platelet aggregation in humans. Platelet aggregation response to leptin is blunted, but not completely abolished in overweight/obese subjects, thus suggesting that platelet may represent a site of leptin resistance in human obesity. Leptin increases platelet free calcium in a dose-dependent manner. The inhibition of PLC completely abates the effect of leptin on both platelet aggregation and Ca(2+) levels. These findings suggest that signaling pathway other than JAK-STAT tyrosine phosphorylation (ie PLC and calcium) may be involved in mediating the prothrombotic action of leptin.
Assuntos
Plaquetas/efeitos dos fármacos , Leptina/farmacologia , Obesidade/sangue , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/sangue , Adulto , Plaquetas/metabolismo , Índice de Massa Corporal , Cálcio/sangue , Estudos Transversais , Humanos , Masculino , Receptores de Superfície Celular/fisiologia , Receptores para Leptina , Fosfolipases Tipo C/fisiologiaRESUMO
Erythropoietin (Epo) is a hydrophobic sialoglycoproteic hormone produced by the kidney and responsible for the proliferation, maturation, and differentiation of the precursors of the erythroid cell line. Human recombinant erythropoietin (rHuEpo) is used to treat different types of anemia, not only in uremic patients but also in newborns with anemia of prematurity, in patients with cancer-related anemia or myeloproliferative disease, thalassemias, bone marrow transplants, or those with chronic infectious diseases. The pleiotropic functions of Epo are well known. It has been shown that this hormone can modulate the inflammatory and immune response, has direct hemodynamic and vasoactive effects, could be considered a proangiogenic factor because of its interaction with vascular endothelial growth factor, and its ability to stimulate mitosis and motility of endothelial cells. The multifunctional role of Epo has further been confirmed by the discovery in the central nervous system of a specific Epo/Epo receptor (EpoR) system. Both Epo and EpoR are expressed by astrocytes and neurons and Epo is present in the cerebrospinal fluid (CSF). Therefore, novel functions of Epo, tissue-specific regulation, and the mechanisms of action have been investigated. In this review we have tried to summarize the current data on the role of Epo on brain function. We discuss the different sites of cerebral expression and mechanisms of regulation of Epo and its receptor and its role in the development and maturation of the brain. Second, we discuss the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischemia, and subarachnoid hemorrhage, and the consequent possibility that rHuEpo therapy could soon be used in clinical practice to limit neuronal damage induced by these diseases.
Assuntos
Sistema Nervoso Central/fisiologia , Eritropoetina/fisiologia , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/crescimento & desenvolvimento , Eritropoetina/biossíntese , Eritropoetina/uso terapêutico , Regulação da Expressão Gênica/fisiologia , Humanos , Receptores da Eritropoetina/biossínteseRESUMO
Colon diverticular disease is a very common pathology in western countries and represents a risk factor for septic-type complications, especially in peritoneal dialysis patients. We examined both diagnostic procedure and therapeutics options, either pharmacological or surgical. Ultrasonography, which is useful for the diagnosis of diverticulosis and diverticular disease, has been supported in the last few years by new imaging techniques, such as NMR and CT, that also find applications in the treatment of diverticulitis complications like peritoneal abscesses. Our emphasis is on the therapeutic perspective, either dietetic - based on the use of a fibre-rich diet and the infusion of liquids by intravenous injection - or surgical, such as the Hartmann procedure, single anastomosis with stomia conservation and laparoscopic and endoscopic treatment. These therapeutic approaches have reduced both morbidity and mortality rate and have emphasized how the reduction of surgical stress on the mesothelium promotes the recovery of the functional integrity and, consequently, faster resumption of peritoneal dialysis. In conclusion, diverticulosis alone is not a contraindication for peritoneal dialysis, but constitutes a risk factor for the continuation of this alternative treatment.
Assuntos
Divertículo/complicações , Falência Renal Crônica/terapia , Diálise Peritoneal , Peritonite/etiologia , Anastomose Cirúrgica , Colonoscopia , Terapia Combinada , Contraindicações , Diagnóstico por Imagem , Fibras na Dieta/uso terapêutico , Divertículo/diagnóstico , Divertículo/dietoterapia , Divertículo/fisiopatologia , Divertículo/cirurgia , Humanos , Perfuração Intestinal/etiologia , Perfuração Intestinal/prevenção & controle , Falência Renal Crônica/complicações , Laparoscopia , Diálise Peritoneal/efeitos adversos , Peritonite/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
Hemodialysis influences the transport of water through the erythrocytic membrane, and induces morphologic and functional modifications. Recently water channels, called aquaporins (AQP), have been identified on the membrane of red blood cells. The aim of the present study was, therefore, to evaluate any relationships between volumetric changes in erythrocytes (MCV), plasma osmolarity and membrane expression of AQP1 in 22 uremic patients during a hemodialysis session, and compare value with those in a control group of 22 healthy volunteers. Membranal AQP1 expression was evaluated using three methods: indirect immunofluorescence under confocal microscopy, immunoenzymatic method after membrane extraction, and immunoblotting. In uremic subjects, at baseline membrane AQP1 expression was significantly lower, whereas plasma osmolality was higher than in controls. At 1 and 2 h of replacement therapy, a progressive increase was observed in erythrocytic AQP1, values similar to those in controls being attained after 3.5 h. During the session osmolality values reduced progressively, becoming significantly lower than basal values. The mean erythrocytic corpuscular volume in patients with ESRD was significantly lower than in cntrols at baseline. This value increased during hemodialysis, attaining statistical significance with respect to the basal value at 3.5 h of dialysis. Close correlations were found between plasma osmolality and AQP1 values (r = -0.930; p < 0.05), and also between MCV and plasma osmolality trend (r = -0.909; p < 0.05). There was a linear correlation (r = 0.63, p < 0.05) between plasma AVP concentrations and plasma osmolality. The variations found in plasma osmolarity during hemodialysis, may induce AQP1 expression on the membrane of intact red blood cells.
Assuntos
Aquaporinas/sangue , Eritrócitos/metabolismo , Diálise Renal , Uremia/sangue , Adulto , Idoso , Aquaporina 1 , Antígenos de Grupos Sanguíneos , Pressão Sanguínea , Índices de Eritrócitos , Eritrócitos/citologia , Feminino , Hemoglobinas/análise , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Potássio/sangue , Sódio/sangue , Uremia/terapia , Vasopressinas/sangueRESUMO
It is now widely known that erythropoietin (Epo) does not only affect the haematopoietic system, but it can be considered a multifunctional trophic factor with an effect on the general homoeostasis of the entire organism. The recent discovery of a specific Epo/Epo-receptor system in the central nervous system (CNS) and cerebrospinal fluid, independently of the haematopoietic system, has further paved the way for new studies aimed at investigating the different sites of cerebral expression of Epo and its receptor, the regulation of their expression and, finally, the effects that this hormone has on the development and maturation of the brain. A further aim has been to investigate how it influences CNS homoeostasis and neurotransmission in adult brain. Attention has also been focused on the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischaemia and subarachnoid haemorrhage, and therefore on the possibility that human recombinant Epo therapy could soon be used in clinical practice, also to limit neuronal damage induced by these diseases.
Assuntos
Encéfalo/crescimento & desenvolvimento , Eritropoetina/fisiologia , Animais , Lesões Encefálicas/prevenção & controle , Eritropoetina/líquido cefalorraquidiano , Eritropoetina/uso terapêutico , Humanos , Fármacos Neuroprotetores/uso terapêutico , Proteínas RecombinantesRESUMO
PURPOSE: The assessment of hydronephrosis due to chronic partial ureteral obstruction is controversial. We determined whether a new radiographic technique for assessing kidney function, electron beam computerized tomography (CT), can detect altered renal physiology due to chronic partial ureteral obstruction. We also compared and contrasted electron beam CT with standard well tempered diuretic mercaptoacetyltriglycine (MAG-3) urography. MATERIALS ANDS METHODS: Six pigs underwent creation of unilateral partial ureteral occlusion or sham operation. Three weeks after surgery diuretic enhanced MAG-3 renal scan was done and 48 hours later contrast enhanced electron beam CT was performed. RESULTS: Mean differential function plus or minus standard error of mean of the obstructed kidney was 5.6% +/- 2.4% on MAG-3 renography. In contrast, electron beam CT revealed significantly preserved mean renal function at 24.5% +/- 2.7% (p <0.01). Electron beam CT analysis of tubular function revealed persistent glomerular filtration and filtrate flow through the proximal tubules and loop of Henle with a selective decrease in distal tubular flow, which were findings suggestive of proximal tubular sparing that were not demonstrated by nuclear renography. CONCLUSIONS: Renal function on MAG-3 renography is primarily determined by measuring kidney perfusion and tubular secretion of the isotope. In contrast, electron beam CT determines renal function via quantifying the in vivo single kidney glomerular filtration rate and by assessing renal tubular function. This study documents that electron beam CT of differential renal function is significantly different from that of MAG-3 renography. To our knowledge which of these 2 radiographic studies is most clinically applicable is unknown to date.
Assuntos
Taxa de Filtração Glomerular , Hidronefrose/fisiopatologia , Túbulos Renais/fisiopatologia , Rim/diagnóstico por imagem , Rim/fisiopatologia , Tomografia Computadorizada por Raios X , Obstrução Ureteral/fisiopatologia , Animais , Feminino , Suínos , UrodinâmicaRESUMO
BACKGROUND: It is known that hyperhomocysteinemia is associated with an increased risk of vascular disease, yet little is known about the pathogenic mechanisms underlying the action of homocysteine (Hcy) itself. METHODS: We evaluated the effects of Hcy on cell proliferation, apoptosis, and necrosis in smooth muscle cells (SMCs) cultured for 24 h with different amounts of Hcy. The percentage of apoptotic and necrotic cells from the culture was evaluated using two different techniques: annexin V-FITC and propidium iodide (PI) fluorescence and apoptosis TUNEL assay. RESULTS: The addition of 10 microM/l of Hcy to the medium was followed by a significant increase in cell proliferation and death, through apoptosis and necrosis, respectively. Notwithstanding this apparent balance, a significant increase was found in the total number of cells present in Hcy-treated culture, thus demonstrating a positive dose-dependent correlation with Hcy concentrations in the culture medium. The addition of folic acid to the culture medium significantly reduced both Hcy concentrations in media and the effects of Hcy on the proliferation/apoptosis/necrosis balance of cells in culture. The percentages for apoptotic cells and for cells with a necrotic morphology continued to increase as Hcy concentrations increased, although the absolute values were lower in the culture treated than in that not treated with folic acid. CONCLUSIONS: In the presence of folic acid, at increasing concentrations of Hcy, the total number of cells in culture showed increases far less relevant with respect to the control. Also the percentage of apoptotic cells to that of cells with a necrotic morphology, although conserving the tendency to increase to growth of the concentrations of Hcy, have shown absolute values that were lower in the folic acid-treated cultures.
Assuntos
Ácido Fólico/farmacologia , Homocisteína/farmacologia , Músculo Liso Vascular/citologia , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Homocisteína/efeitos dos fármacos , Humanos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , NecroseRESUMO
BACKGROUND: In healthy primiparas the total body water content increases by about 8 liters within the last trimester, with a consequent reduction in plasma arginine-vasopressin (AVP) levels. The aim of the present study was to investigate the effect of normal pregnancy on urinary excretion of AQP2, a vasopressin sensitive water channel. METHODS: Forty-five healthy pregnant primiparas (specify mean age and range) with a physiological single-fetus pregnancy were studied during weeks 12, 24 and 36 of pregnancy and then for 3 to 5 days postpartum. The control group consisted of 14 age-matched women in the early follicular phase of the menstrual cycle (day 5 or 6). The behavior of plasma AVP, ANP, oxytocin, urinary 6-keto-PGF1alpha (a metabolite of prostacyclin) and urinary AQP-2 excretion were evaluated in all subjects. RESULTS: Plasma ANP and oxytocin, and urinary AQP-2 and 6kPGF1alpha excretion increased during all three trimesters, with the highest peaks at the 36(th) week. In the postpartum period, these values markedly decreased. No statistically significant changes were found in plasma AVP levels throughout the study period. CONCLUSIONS: Our findings suggest that a non-AVP factor present in pregnancy plays a role in the control of the excretion of AQP-2 water channels.