RESUMO
In the last few years, polymerase chain reaction analysis is frequently required to improve the detection of pathogen infections in central nervous system as a potential cause of neurological disorders and neuropsychiatric symptoms. The goal of this paper is to set up a fast, cheap and reliable molecular approach for qualitative detection of six neurotropic pathogens. A method based on PCR has been designed and implemented to guarantee the qualitative DNA detection of herpes simplex virus types 1 and 2 (HSVI/II), Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella-zoster virus (VZV), rubella virus (RUBV) and Toxoplasma gondii in the cerebrospinal fluid, where otherwise they are barely detectable. Each PCR assay was tested using dilutions of positive controls, which demonstrated a sensitivity allowing to detect up to 102 copies/ml in PCR and 10 copies/ml in real-time PCR for each pathogen. Once been set up, the protocol was applied to evaluate the cerebrospinal fluid from 100 patients with suspected infectious diseases of the central nervous system and 50 patients without any infection. The method allowed to identify 17 positive cerebrospinal fluid with polymerase chain reaction and 22 with real-time PCR (RT-PCR), respectively. Therefore, application of RT PCR allows a fast and sensitive evaluation of neurotropic DNA pathogens in the course of diagnostic routine within neurological units.
Assuntos
Infecções do Sistema Nervoso Central/virologia , Sistema Nervoso Central/virologia , Viroses/virologia , Estudos de Avaliação como Assunto , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Vírus/genéticaRESUMO
The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blue, immune- histochemistry and immune-gold electron microscopy. To analyze whether METH administration produces PrPsc aggregates we used antibodies directed against PrP following exposure to proteinase K or sarkosyl which digest folded PrPc but misfolded PrPsc. We fond that METH triggers PrPsc aggregates in DA-containing cells while METH is not effective in primary striatal neurons which do not produce DA. In the latter cells exogenous DA is needed to trigger PrPsc accumulation similarly to what happens in DA containing cells under the effects of METH. The present findings, while fostering novel molecular mechanisms involving prion proteins, indicate that, cell pathology similar to prion disorders can be mimicked via a DA-dependent mechanism by a drug of abuse.
Assuntos
Dopaminérgicos/farmacologia , Metanfetamina/farmacologia , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas PrPSc/efeitos dos fármacos , Proteínas Priônicas/efeitos dos fármacos , Neoplasias das Glândulas Suprarrenais , Animais , Linhagem Celular Tumoral , Dopamina/metabolismo , Eletroforese em Gel de Poliacrilamida , Endopeptidase K/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Neostriado/citologia , Neurônios/metabolismo , Feocromocitoma , Proteínas PrPSc/metabolismo , Proteínas Priônicas/metabolismo , Ratos , Sarcosina/análogos & derivados , Sarcosina/farmacologiaRESUMO
One of the most successful applications of pharmacogenetics research is the genetic screening for HLA-B*57:01, strongly associated with an increased risk to develop hypersensitivity reaction in HIV-positive patients following abacavir administration. Taking into consideration the limits of current genotyping methodologies, we have developed and validated (150 buccal swabs) an inexpensive pharmacogenetic approach for HLA-B*57:01 typing. In our assay DNA extraction and amplification are combined in one single step (direct PCR protocol), which is performed directly on the biological sample without the need of extraction and sequencing passages. The amplicons obtained by direct PCR can be easily separated on the agarose gel under ultraviolet. As per our results, the direct PCR represents a good alternative to the traditional methods of HLA-B*57:01 pharmacogenetic test, especially for those laboratories or countries where currently available approaches are often not available or not affordable. Furthermore it is an innovative approach, promoting a personalized, safer and cost-effective therapy.
Assuntos
Antígenos HLA-B/genética , Farmacogenética/economia , Farmacogenética/métodos , Reação em Cadeia da Polimerase/economia , Reação em Cadeia da Polimerase/métodos , Análise Custo-Benefício/economia , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/genética , Testes Genéticos/economia , Testes Genéticos/métodos , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Humanos , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
PurposeThe goal was to develop a simple model for predicting the individual risk profile for age-related macular degeneration (AMD) on the basis of genetic information, disease family history, and smoking habits.Patients and methodsThe study enrolled 151 AMD patients following specific clinical and environmental inclusion criteria: age >55 years, positive family history for AMD, presence of at least one first-degree relative affected by AMD, and smoking habits. All of the samples were genotyped for rs1061170 (CFH) and rs10490924 (ARMS2) with a TaqMan assay, using a 7500 Fast Real Time PCR device. Statistical analysis was subsequently employed to calculate the real individual risk (OR) based on the genetic data (ORgn), family history (ORf), and smoking habits (ORsm).Results and conclusionThe combination of ORgn, ORf, and ORsm allowed the calculation of the Ort that represented the realistic individual risk for developing AMD. In this report, we present a computational model for the estimation of the individual risk for AMD. Moreover, we show that the average distribution of risk alleles in the general population and the knowledge of parents' genotype can be decisive to assess the real disease risk. In this contest, genetic counseling is crucial to provide the patients with an understanding of their individual risk and the availability for preventive actions.
Assuntos
Aconselhamento Genético , Testes Genéticos , Degeneração Macular/etiologia , Anamnese , Idoso , Alelos , Feminino , Humanos , Degeneração Macular/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Fumar/efeitos adversosRESUMO
Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis conductance transmembrane regulator (CFTR). Symptoms are pancreatic insufficiency, chronic obstructive lung disease, liver disease, chronic sinusitis and infertility in male patients. The phenotypic variability may be explained only in part by the more than 1200 CFTR mutations, which are grouped into six different classes, according to their effect on the protein ranging from a severe (no synthesis or blocked processing) to mild mutation (altered conductance or reduced synthesis). However, it is now accepted that other genes (CF modifiers) influence the phenotypic spectrum of the disease. In order to identify CF modifier genes, we built a low-density home-made oligoarray containing 144 genes selected according to biochemical criteria and evaluated their expression in two CF bronchial epithelial cell lines (CuFi1 F508del/F508del; CuFi3 F508del/R553X). If we consider both cell lines, 38 genes (26.3%) show an altered expression pattern with a threshold > +/-1.5. Of these 38 genes, 12 are altered in CuFi1, and 26 in CuFi3. Some of these genes share the same expression pattern in both cell lines, while others have a different behaviour. These results were validated by a QRT-PCR assay (R2 CuFi1 = 0.81 and R2 CuFi3 = 0.91). These data could suggest that the presence of a class I allele (R553X) determines a more profound alteration of gene expression pattern than the presence of a class II allele (F508del). The identification of the genes altered by a specific CF mutation could lead to the development of a pharmacological approach specific for different CFTR genotypes.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Mucosa Respiratória/metabolismo , Alelos , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/análise , RNA Mensageiro/genética , Mucosa Respiratória/citologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
In diabetic autonomic neuropathy, abnormal circadian patterns of blood pressure and sympathovagal balance with reduced fall of blood pressure and prevalence of sympathetic activity during the night have been described. To correlate the abnormalities of blood pressure to those of sympathovagal balance, we simultaneously performed 24-h noninvasive monitoring of blood pressure and ECG in 25 diabetic patients (45.6 +/- 13.6 yr of age with a 17.6 +/- 9.1 yr duration of diabetes) with various degrees of cardiovascular reflex impairment. Autoregressive power spectrum analysis of RR interval variability was applied to 24-h ECG recordings to obtain for day and night periods the mean power of low- (0.03-0.15 Hz) and high-frequency (0.18-0.40 Hz) components, which are relative markers of sympathetic and vagal activity, respectively, and their ratio (low frequency/high frequency), assumed as index of sympathovagal balance. Diabetic patients showed a lower percentage of day-night change in systolic blood pressure (9 +/- 5.48 vs. 11.6 +/- 4.78%, P < 0.037), a lower day low frequency (5.9 +/- 0.81 vs. 6.62 +/- 0.73 In-ms2, P < 0.001), a lower night high frequency (6.06 +/- 0.71 vs. 6.52 +/- 0.85 In-ms2, P < 0.05), a lower day low frequency:high frequency ratio (1.82 +/- 1.77 vs. 3.05 +/- 1.82, P < 0.01), and a lower percentage of day-night change in low-frequency:high frequency ratio (-13.4 +/- 109.9 vs. 28.7 +/- 29.7%, P < 0.05), when compared with control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Pressão Sanguínea , Ritmo Circadiano , Neuropatias Diabéticas/fisiopatologia , Nervo Vago/fisiopatologia , Adulto , Monitores de Pressão Arterial , Diástole , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , SístoleRESUMO
We have studied the functional importance of renal eicosanoids in renal hemodynamics of seven newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients by treatment with two structurally unrelated inhibitors of cyclooxygenase (i.e., piroxicam and sulindac). Glomerular filtration rate (GFR), renal plasma flow (RPF), daily urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, the stable hydrolysis product of prostacyclin), and thromboxane B2 (TXB2, the stable hydrolysis product of thromboxane A2) were measured before, during, and after piroxicam (all patients) or sulindac (3 patients) treatment. Urinary excretion of 6-keto-PGF1 alpha was significantly increased (P less than .01) in diabetic patients compared with seven healthy subjects, whereas urinary excretion of TXB2 was unchanged. The baseline value of GFR was significantly (P less than .01) higher in diabetic compared with normal volunteers, whereas baseline RPF was comparable in both groups. Piroxicam (20 mg/day) reduced urinary excretion of 6-keto-PGF1 alpha and TXB2 by 65.7 +/- 26 and 64.6 +/- 33%, respectively. These biochemical changes were temporally associated with the approximately 19% decrease in GFR (P less than .01). A week after discontinuation of the drug, GFR and urinary excretion of 6-keto-PGF1 alpha were still significantly (P less than .05) reduced, whereas urinary excretion of TXB2 returned to control values. In contrast, urinary excretion of eicosanoids and renal function were not affected by sulindac (0.4 g/day) treatment. No functional changes were detected in healthy subjects despite a similar suppression of renal cyclooxygenase activity when they were treated with piroxicam.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
6-Cetoprostaglandina F1 alfa/urina , Diabetes Mellitus Tipo 1/urina , Tromboxano A2/urina , Adolescente , Adulto , Creatinina/urina , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Rim/fisiopatologia , Masculino , Piroxicam/uso terapêutico , Sulindaco/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the relationship between autonomic neuropathy, nephropathy, and 24-h blood pressure (BP) pattern in insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: We studied 30 normotensive IDDM patients without overt nephropathy, divided into two groups and matched for age, duration of diabetes, and HbA1, according to the presence of cardiovascular autonomic neuropathy. We simultaneously measured 24-h BP and urinary albumin excretion rate (UAE) on urine collections timed overnight and at 2-h intervals during the day. RESULTS: Mean day and night systolic and diastolic BP values did not significantly differ between the groups. Mean night albuminuria was significantly higher in patients with autonomic neuropathy than in those without (61.4 +/- 104.6 [mean +/- SD] vs. 16 +/- 25.2 micrograms/min, P < 0.04). The percentages day-night changes in systolic BP, diastolic BP, and UAE were significantly lower in neuropathic patients (systolic BP: 2.4 +/- 7.7 vs. 9.6 +/- 4.2%, P < 0.001; diastolic BP: 8.4 +/- 6.9 vs. 15.5 +/- 5.4%, P < 0.002; UAE: -8 +/- 99.4 vs. 49.3 +/- 29.4%, P < 0.02) and were inversely related to autonomic score, index of autonomic neuropathy degree (r = -0.54, P < 0.002; r = -0.58, P < 0.001; and r = -0.53, P < 0.005, respectively). In patients with autonomic neuropathy, 2-h day periods and day and night UAE were more strongly related, respectively, to mean 2-h day periods (r = 0.58, P < 0.0001), day systolic BP (r = 0.67, P < 0.04), and night systolic BP (r = 0.69, P < 0.04) than in patients without autonomic neuropathy (2-h day periods: r = 0.32, P < 0.001; day: r = 0.37, NS; night: r = 0.35, NS). CONCLUSIONS: Autonomic neuropathy in IDDM patients is associated with reduced nocturnal falls in BP and UAE and with a stronger relationship of UAE to systolic BP. We suggest a pathogenetic role of autonomic neuropathy in the development of diabetic nephropathy through changes in nocturnal glomerular function and by enhanced kidney vulnerability to hemodynamic effects of BP.
Assuntos
Pressão Sanguínea , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Creatinina/sangue , Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/sangue , Neuropatias Diabéticas/sangue , Retinopatia Diabética/sangue , Retinopatia Diabética/fisiopatologia , Diástole , Feminino , Humanos , Masculino , Postura , Valores de Referência , Análise de Regressão , Respiração , Sístole , Manobra de ValsalvaRESUMO
OBJECTIVE: To evaluate the effects of intensive insulin therapy and subsequent optimized metabolic control on daily urinary mevalonic acid (MVA) excretion, an index of whole-body cholesterol synthesis, and the acute effects of insulin on plasma MVA concentrations in type II diabetes. RESEARCH DESIGN AND METHODS: Ten (five men and five postmenopausal women) nonobese, normolipidemic (total cholesterol < 6.2 mmol/l, triglycerides < 2.82 mmol/l), type II diabetic patients in poor metabolic control (HbA1c > 10%, fasting plasma glucose > 11 mmol/l) and receiving sulfonylurea treatment were selected. The 24-h urinary MVA excretion and plasma lipid values were determined before and after intensive insulin therapy. The acute effects of insulin on plasma MVA concentrations were also evaluated during a 3-h euglycemic hyperinsulinemic clamp study. RESULTS: Urinary MVA excretion rates (mumol/24h) were 1.82 +/- 0.21 in control subjects and 2.49 +/- 0.35 (P < 0.01 vs. control subjects) and 1.78 +/- 0.28 in patients before and after intensive insulin therapy, respectively. Total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides decreased by 9, 8, and 12%, respectively, after blood glucose optimization. Acute insulin infusion during the euglycemic clamp studies reduced mean plasma MVA concentrations at 120 and 180 min by 29 and 38%, respectively (P < 0.01 for both vs. baseline). CONCLUSIONS: Our study demonstrates that in nonobese, normolipidemic, type II diabetic patients under poor metabolic control, an increased cholesterol synthesis is normalized by insulin therapy. Hyperinsulinemia in the presence of euglycemia acutely decreases the circulating levels of MVA, the immediate product of hydroxymethylglutaryl-CoA reductase activity and an index of whole-body cholesterol synthesis.
Assuntos
Colesterol/biossíntese , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Ácido Mevalônico/sangue , Apolipoproteína A-I/sangue , Apolipoproteína B-100 , Apolipoproteínas B/sangue , Glicemia/metabolismo , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta para Diabéticos , Ingestão de Alimentos , Ingestão de Energia , Jejum , Ácidos Graxos não Esterificados/sangue , Feminino , Técnica Clamp de Glucose , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/farmacologia , Insulina/sangue , Insulina/farmacologia , Masculino , Ácido Mevalônico/urina , Pessoa de Meia-Idade , Valores de Referência , Triglicerídeos/sangueRESUMO
In 3 normal subjects and in 4 acromegalic patients pretreatment with an alcohol infusion for 4 hours at a constant rate reduced the GH response to Arginine, when comparison was made with pretreatment with saline. The reduction in acromegalics was more marked and sustained than in normals. Though it is likely that the effect of alcohol is exerted on hypothalamic centers, a direct influence on the pituitary cannot be excluded.
Assuntos
Acromegalia/sangue , Etanol/farmacologia , Hormônio do Crescimento/sangue , Acromegalia/fisiopatologia , Arginina , Jejum , Hormônio do Crescimento/metabolismo , Humanos , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiologia , Hipotálamo/fisiopatologiaRESUMO
OBJECTIVE: To evaluate the impact of beta-adrenergic blockade in spontaneously hypertensive rats (SHR) and in their normotensive controls, Wistar-Kyoto (WKY) rats, on whole-body glucose disposal under metabolic steady state conditions, in unrestrained and conscious animals. METHOD: SHR (n = 13) and WKY rats (n = 12) underwent a 240 min insulinaemic clamp study with or without a super-infusion (120th to 240th minutes; second step) of propranolol. RESULTS: From 0 to 120 min (the first step) SHR showed significantly increased glucose uptake, muscle glycogen synthesis and glycogen synthase activity compared with WKY rats. When propranolol was superinfused, glucose uptake and muscle glycogen synthesis in SHR returned to levels similar to those observed in WKY rats during the first step. No significant differences were found for whole-body glycolysis in SHR and WKY in the first and second steps. CONCLUSION: Hypertensive rats display an increased insulin sensitivity compared with controls. Beta-Blockade is associated with a reduction in overall glucose metabolism in SHR, but not in WKY rats.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Glucose/metabolismo , Hipertensão/metabolismo , Insulina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Glicogênio Sintase/metabolismo , Propranolol/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
In patients with insulin-dependent diabetes, antihypertensive treatment has a beneficial effect on the rate of progression toward uremia of overt diabetic nephropathy (albumin excretion rate [AER] greater than 300 mg/24 hour). The influence of hypertension on the progression of "incipient" nephropathy (AER ranging between 30 and 300 mg/24 hours) is not well defined, particularly in patients with noninsulin-dependent diabetes. In this study, 21 patients with noninsulin-dependent diabetes and hypertension (11 with normoalbuminuria and 10 with microalbuminuria), who were comparable for age, duration of diabetes and hypertension, were treated with indapamide, 2.5 mg once daily, and followed up for 24 months. Blood pressure, glomerular filtration rate (GFR), albumin excretion rate and subclass 4 of urinary immunoglobulin G (IgG4) were indicated. In normoalbuminuric patients, blood pressure was significantly reduced, whereas AER, IgG4 and GFR did not show any variation throughout the study. In microalbuminuric patients, blood pressure, AER and IgG4 were significantly reduced, and GFR remained unchanged. In patients with noninsulin-dependent diabetes, antihypertensive treatment, which is begun during incipient diabetic nephropathy, may have a beneficial effect on the progression of the disease, although a long-term follow-up study is needed to confirm this.
Assuntos
Albuminúria/fisiopatologia , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas/fisiopatologia , Diuréticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Imunoglobulina G/urina , Indapamida/uso terapêutico , Adulto , Albuminúria/urina , Glicemia/análise , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/urina , Dieta para Diabéticos , Seguimentos , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Pessoa de Meia-Idade , Potássio/sangue , Sódio/sangueRESUMO
Several studies on both humans and animal models have reported a pathogenetic relationship among hyperinsulinism, insulin resistance, and hypertension. We have previously evaluated whole body glucose disposal and insulin sensitivity in different models of hypertensive rats, showing an increase rather than an impairment of glucose metabolism, which in turn was due to an improved ability of insulin to channel the absorbed glucose towards the nonoxidative disposal. Aiming to confirm our previous findings we performed the direct assay of skeletal muscle glycogen synthase on tissue samples from the previous clamp studies, as a rate limiting step enzyme of glycogen synthesis, under conditions of physiologic hyperinsulinemia and euglycemia. Glycogen synthase was assayed on samples from rectus muscle tissues of spontaneously hypertensive rats and high sodium, one kidney, one figure-8 hypertensive rats. Compared to controls, our data show an increased activity of glycogen synthase in the hypertensive animals, which is consistent with the increased glycogen synthesis previously reported. In conclusion, under our experimental conditions, hypertension and chronic hyperadrenergism are associated with an increased ability of insulin to stimulate glucose uptake and disposal. These latter effects are mainly due to an increase in nonoxidative disposal and glycogen synthase activity.
Assuntos
Glicogênio Sintase/metabolismo , Glicogênio/biossíntese , Hipertensão/metabolismo , Músculo Esquelético/metabolismo , Animais , Modelos Animais de Doenças , Glucose/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
The possible relationship between diabetic autonomic neuropathy, circadian blood pressure changes, and echocardiographic parameters was investigated in 27 normotensive diabetic patients (10 with and 17 without autonomic neuropathy) who underwent 24 h noninvasive ambulatory blood pressure monitoring and M-mode echocardiographic recording. The two groups were comparable for age, sex, duration of diabetes, body mass index, and metabolic control. There were no significant differences in 24 h average and diurnal values of systolic, diastolic, or mean blood pressure. The percent changes from day to night of systolic, diastolic, and mean blood pressures were significantly lower in diabetics with neuropathy than in those without (P < .04 or less). Increased left ventricular mass index (LVMI) (135.4 +/- 10.2 v 102.9 +/- 6.3; P < .005), septal wall thickness, and posterior wall width were observed in neuropathic patients. Fractional shortening, peak velocity of early left ventricular filling (E), peak velocity of late ventricular filling (A), and their ratio (E/A) were similar in the two groups. The increased LVMI we observed may represent a possible link between diabetic autonomic neuropathy, nocturnal blood pressure levels, and higher cardiovascular mortality rate.
Assuntos
Doenças do Sistema Nervoso Autônomo/complicações , Angiopatias Diabéticas/etiologia , Neuropatias Diabéticas/complicações , Hipertrofia Ventricular Esquerda/etiologia , Adulto , Idoso , Envelhecimento/patologia , Envelhecimento/fisiologia , Doenças do Sistema Nervoso Autônomo/patologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/fisiopatologia , Ecocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Caracteres SexuaisRESUMO
Some controversy still exists about factors involved in the abnormal circadian pattern of blood pressure (BP) in diabetes, while prognostic value of non-dipping condition is being increasingly recognised. This study was aimed at evaluating the relative influence of autonomic neuropathy (AN) and albumin excretion on 24-h BP profile in type 1 and type 2 diabetes. We measured AN cardiovascular tests, 24-h ambulatory BP, and urinary albumin excretion rate (UAE) in 47 type 1 and 34 type 2 normotensive non-proteinuric diabetic patients. In type 1 diabetic patients day-night differences (Delta) in systolic and diastolic BP were lower in those with AN than in those without (3 +/- 9 vs 10 +/- 6%, P < 0.01, and 8 +/- 9 vs 16 +/- 6%, P < 0.001), and in univariate regression analysis they were inversely related to both autonomic score, index of degree of AN (r = -0.61, P < 0.001 and r = -0.65, P < 0.001), and to 24-h UAE (r = -0.39, P < 0.01 and r = -0.46, P < 0.001). In type 1 diabetic patients AN was also associated with lower nocturnal decrease in UAE (patients with AN vs without AN: -37 +/- 214 vs 49 +/- 37%, P < 0.05), and with a stronger relationship between simultaneous 24-h UAE and 24-h BP (for systolic BP patients with AN vs without AN: r = 0.62, P < 0.01 vs r = 0.28, NS). In type 2 diabetic patients Delta systolic BP was reduced in patients with AN compared to those without (4 +/- 7 vs 10 +/- 4%, P < 0.01), and it was related only to autonomic score (r = -0.42, P < 0.01). Using a stepwise regression analysis, in type 1 diabetic patients autonomic score was the variable of primary importance for Delta BP, while in type 2 diabetic patients it was the unique determinant not only of Delta systolic BP but also of 24-h systolic BP. In conclusion, AN is the pivotal factor of blunted nocturnal fall in BP in both type 1 and type 2 diabetic patients. In type 1 diabetic patients AN is associated with attenuated circadian pattern of albuminuria and with a steeper relationship between albuminuria and BP, in type 2 diabetic patients AN is the only factor related to elevated 24-h BP levels. Longitudinal studies are needed to establish the potential role of autonomic dysfunction as a progression promoter for nephropathy and hypertension in type 1 and type 2 diabetes respectively.
Assuntos
Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Hipertensão/fisiopatologia , Adulto , Albuminúria/complicações , Albuminúria/fisiopatologia , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Previous studies have shown an increased incidence of sudden deaths and lower survival in diabetics with autonomic neuropathy. In hypertensive non diabetic patients a direct correlation has been found between nocturnal blood pressure levels and left ventricular hypertrophy. We have shown in diabetics with autonomic neuropathy a flattening in nocturnal blood pressure reduction and increased 24 hours blood pressure values compared to diabetics without autonomic neuropathy and controls. Our results suggest that abnormalities in 24 hours blood pressure profile might play a role in the increased incidence of cardiovascular morbidity and mortality in diabetics with autonomic neuropathy.
Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Monitores de Pressão Arterial , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Neuropatias Diabéticas/fisiopatologia , Frequência Cardíaca/fisiologia , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The aim of this study was to evaluate if dipyridamole-atropine stress echocardiography (DASE) performed between the third-fifth day in uncomplicated acute myocardial infarction allows for an effective risk stratification with an early discharge in some cases. METHODS: Between February 1997 and September 1998, 190 patients (138 males and 52 females, mean age 59 +/- 10.3 years), with acute myocardial infarction, were enrolled in the study. DASE was performed between the third-fifth day with a dipyridamole infusion of 0.84 mg/kg over 10 min followed by 1 mg of atropine from the twelfth to the fifteenth minute. DASE was considered positive in the presence of a new or worsening dyssynergy. Patients with heart failure, angina, major arrhythmias, and poor acoustic window were excluded. In the follow-up spontaneous events were defined as cardiac death, non-fatal myocardial reinfarction, unstable angina or heart failure (with hospitalization). RESULTS: DASE was performed in 92 patients (48.4%), all without complications: 29 patients (31.5%) had a negative DASE result, and 63 patients (68.5%) had a positive DASE. The average hospital stay of patients with a negative test was significantly lower in comparison with that of patients with a positive test (7.55 +/- 1.32 vs 9.29 +/- 1.61 days, p < 0.0001). Events occurred in 19 patients (20.6%), 2/29 patients with a negative DASE (6.9%), 17/63 patients with a positive DASE (27%), 6/43 patients with homozonal positivity after atropine or high-dose dipyridamole (14%), 11/20 patients with heterozonal positivity or homozonal positivity after low-dose dipyridamole (55%). On univariate analysis the variables significantly associated with spontaneous events were: age (chi 2 = 6.41, p = 0.019), left ventricular ejection fraction at rest (chi 2 = 8.89, p = 0.004), number of asynergic segments after stress (chi 2 = 6.87, p = 0.010), increase in the number of asynergic segments after stress (chi 2 = 4.01, p = 0.039), wall motion score index after stress (chi 2 = 9.60, p = 0.003), increase in wall motion score index after stress (chi 2 = 3.60, p = 0.049), DASE positivity (chi 2 = 4.89, p = 0.029), homozonal positivity after low-dose dipyridamole (chi 2 = 8.57, p = 0.013), heterozonal positivity (chi 2 = 13.10, p = 0.001). On Cox's multivariate analysis independent predictors of events were: age (relative risk 3.92, p = 0.0146), DASE positivity (relative risk 1.79, p = 0.0054). CONCLUSIONS: DASE between the third-fifth day in uncomplicated acute myocardial infarction is feasible, tolerable, safe, and effective for early risk stratification. A negative DASE detects a "very low-risk" patient group, and allows for an earlier hospital discharge, without an increased risk of events. The heterozonal positivity or the homozonal positivity after low-dose dipyridamole indicates the need for a coronarography, due to the high risk of events at follow-up.
Assuntos
Antiarrítmicos , Atropina , Dipiridamol , Ecocardiografia/métodos , Teste de Esforço/métodos , Infarto do Miocárdio/diagnóstico , Alta do Paciente , Vasodilatadores , Idoso , Ecocardiografia/estatística & dados numéricos , Eletrocardiografia/efeitos dos fármacos , Eletrocardiografia/estatística & dados numéricos , Teste de Esforço/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de TempoRESUMO
This article describes how mobile radiography was used to examine a mummified cadaver exhumed in 1875 and stored in the Smithsonian Museum. Radiographs revealed artifacts imbedded in the cadaver, indicating 1824 as the earliest possible interment. Through radiographic assessment of the skeleton, researchers were able to approximate the individual's age at death. In addition, evidence of pathology, possibly ideopathic skeletal hyperostosis, suggested the individual may have been employed in manual labor. The radiographs, when compared to x-rays of another cadaver exhumed at the same time and place, refuted information in museum records.