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2.
Parkinsonism Relat Disord ; 95: 103-106, 2022 02.
Article in English | MEDLINE | ID: mdl-35093711

ABSTRACT

INTRODUCTION: Wilson's Disease (WD) is an autosomal recessive disorder caused by excessive copper deposition in liver, brain and other organs. The clinical picture is characterized by hepatic, psychiatric and neurological dysfunction. Movement disorders are the core neurological features, although non-motor symptoms (NMS), as cognitive/affective, autonomic and sleep disorders, may occur over time. We aimed to assess the frequency of NMS in WD patients compared with healthy subjects. METHODS: Twenty-seven patients affected with genetically proven WD (12 F, 15 M) and 35 healthy controls (Ctrl; 17 F, 18 M), comparable for age and education, were enrolled. Eighteen patients presented with the neurological form of the disease (NV) and nine with the non-neurological variant (NNV). NMS were assessed in all subjects by the following clinical scales: Mini-Mental State Examination (MMSE), Non-Motor Symptoms Scale (NMSS), SCOPA-AUT Questionnaire, Apathy Evaluation Scale (AES), Beck Depression Inventory (BDI), Epworth Sleepiness Scale (ESS), Restless Legs Syndrome Rating Scale (RLSRS), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP-RS). RESULTS: We found that the patients showed more severe and frequent NMS and daytime sleepiness, and lower MMSE than Ctrl. In comparison to healthy subjects, NV subjects showed statistically significant higher ESS, NMSS, and RLSRS scores, and a lower MMSE score. Subtle and subclinical extrapyramidal/pyramidal signs and brain MRI signal abnormalities were detected in patients considered as asymptomatic for neurological disturbances. CONCLUSIONS: NMS are common among WD patient, in particular those with NV, likely due to the widespread pathological changes throughout the central nervous system.


Subject(s)
Hepatolenticular Degeneration , REM Sleep Behavior Disorder , Sleep Wake Disorders , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/epidemiology , Humans , Prevalence , Psychiatric Status Rating Scales , REM Sleep Behavior Disorder/diagnosis , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology
3.
Reprod Biomed Online ; 42(4): 835-841, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33549482

ABSTRACT

RESEARCH QUESTION: Wilson's disease (WD) is a disorder of copper metabolism that can cause hormonal alterations. The impact of WD and its therapies on fertility is not well defined. The aim of this study was to evaluate ovarian reserve and sperm parameters in long-term treated WD patients with hepatic onset. DESIGN: WD patients with hepatic onset treated for at least 5 years were compared with healthy controls. Men underwent spermiogram and sperm DNA fragmentation (SDF) analysis. Women were tested for serum FSH, anti-Müllerian hormone (AMH) and sonographic antral follicle count (AFC) in the early follicular phase. Ovulation was monitored with ultrasound and progesterone serum concentrations in the luteal phase. RESULTS: The WD group included 26 patients (12 males), the control group 19 subjects (9 males). All patients apart from four (one male) were responders to WD treatment. Sperm count and morphology were comparable between cases and controls. Sperm motility (total and after 1 h) was significantly lower in cases (44.78 ± 21.65%; 47.85 ± 21.52%) than controls (61.88 ± 11.03; 69.44 ± 11.02%, P = 0.03 and 0.01, respectively). The only non-responder had severe oligo-astheno-teratozoospermia. SDF values were normal in cases and controls. AMH, AFC and FSH did not differ between cases and controls. LH was significantly lower in cases (3.36 ± 1.65 mIU/ml) than controls (6.25 ± 1.03 mIU/ml, P < 0.0001). A non-responder woman who developed neurological signs had a 7-year history of infertility. CONCLUSIONS: WD patients with hepatic onset, diagnosed early and treated, have no impairment in fertility potential even if males show reduced sperm motility and females lower LH values. Only patients with poor disease control have some evidence of impaired fertility.


Subject(s)
Fertility , Hepatolenticular Degeneration/physiopathology , Ovarian Reserve , Sperm Motility , Adult , Female , Hepatolenticular Degeneration/blood , Hepatolenticular Degeneration/therapy , Hormones/blood , Humans , Male , Prospective Studies , Reproductive Health , Young Adult
4.
Monaldi Arch Chest Dis ; 87(3): 838, 2017 09 28.
Article in English | MEDLINE | ID: mdl-29424197

ABSTRACT

Pregabalin, widely used in the treatment of several pain disorders, is usually well tolerated. Uncommonly, the drug may induce cardiac side effects, rarely prolongation of the PR interval. The latter has never been described in patients with healthy heart or normal renal function. We characterize a unique case of a young man with extrapulmonary tuberculosis and no detectable or known cardiac or kidney diseases, treated with pregabalin to control the severe pain due to the involvement of the spinal cord by the tuberculosis, showing an atrioventricular (AV) block due to pregabalin administration. The reported case emphasizes the need of monitoring PR interval during treatment with pregabalin, even in patients without background of cardiac or renal diseases.


Subject(s)
Atrioventricular Block/chemically induced , Pain/drug therapy , Pregabalin/adverse effects , Tuberculosis, Central Nervous System/complications , Atrioventricular Block/physiopathology , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/therapeutic use , Electrocardiography/instrumentation , Humans , Male , Pregabalin/administration & dosage , Pregabalin/therapeutic use , Treatment Outcome , Tuberculosis, Central Nervous System/diagnostic imaging , Tuberculosis, Central Nervous System/drug therapy , Tuberculosis, Central Nervous System/pathology , Young Adult
7.
Parkinsonism Relat Disord ; 24: 15-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26851839

ABSTRACT

BACKGROUND & AIMS: Wilson's disease (WD) is a genetic disorder of copper metabolism causing dysfunctions of various organs, mostly the liver and brain. If untreated, WD is fatal, but early treatment results in a good prognosis, although the long-term neurological outcome has not yet been clarified. To address this issue, we evaluated the neurological status of early-treated WD patients without overt nervous system impairment using neurophysiological, neuropsychological and neuroimaging procedures at least 10 years after treatment onset. METHODS: Thirty-eight WD patients (18 females, aged 24.47 ± 7.50 years), who received an early diagnosis (in presymptomatic or mild/moderate liver disease stages without neurological involvement) and prompt treatment, were clinically evaluated with the Global Assessment Scale. Presentation was hepatic in 36 subjects (95%), while 2 patients (5%) were presymptomatic. A neurophysiological study was performed to explore the central motor conduction time of the upper and lower limbs, and motor cortex excitability using single pulses and paired-pulse transcranial magnetic stimulation. Neuroimages were obtained with brain magnetic resonance scans. Cognitive abilities, and psychiatric and behavioral disturbances were evaluated with neuropsychological tests. RESULTS: Patients were undergoing treatment with penicillamine (7 patients) or zinc salts (31 patients) with good adherence. They did not present any neurological signs at clinical evaluation or at specific scale of impairment, the mean Global Assessment Scale score was 0.3 ± 0.7. Magnetic resonance imaging, transcranial magnetic stimulation studies and neuropsychological/neuropsychiatric assessment ruled out subclinical involvement. CONCLUSIONS: This study suggests that early diagnosis and treatment of WD may prevent the onset of neurologic damage, even at subclinical level.


Subject(s)
Hepatolenticular Degeneration/therapy , Nervous System Diseases/etiology , Adenosine Triphosphatases/genetics , Adolescent , Adult , Analysis of Variance , Brain/diagnostic imaging , Brain/pathology , Cation Transport Proteins/genetics , Copper-Transporting ATPases , Disease Progression , Female , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/diagnosis , Hepatolenticular Degeneration/genetics , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Nervous System Diseases/diagnosis , Nervous System Diseases/prevention & control , Neurologic Examination , Neuropsychological Tests , Penicillamine/therapeutic use , Psychiatric Status Rating Scales , Retrospective Studies , Young Adult , Zinc/therapeutic use
10.
Clin Endocrinol (Oxf) ; 72(1): 107-11, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19508590

ABSTRACT

OBJECTIVE: Vascular dysfunction and accelerated atherosclerosis are prominent features of hypothyroidism. The relative roles of thyroid hormone (TH) deficiency and the associated vascular risk conditions are still unclear. We studied the impact of acute and chronic hypothyroidism on vascular reactivity. PATIENTS: We studied 12 patients with chronic primary hypothyroidism (cHY; TSH: 52 +/- 14 mU/l), seven patients with acute hypothyroidism secondary to total thyroidectomy (aHY; TSH: 97 +/- 24) and 13 healthy subjects (TSH: 1.2 +/- 0.5). MEASUREMENTS: We measured forearm blood flow (FBF) using plethysmography during intra-brachial infusion of: acetylcholine (ACh), sodium nitroprusside (NP) and norepinephrine (NE). We also measured serum C-reactive protein (CRP), TNF-alpha, asymmetric dimethylarginine (ADMA) and the forearm balance of nitric oxide (NO) during ACh infusion. RESULTS: As compared with the controls, the vasodilatory response to ACh was reduced in cHY (P = 0.001) and aHY (P = 0.04), as was the forearm release of NO (P < 0.05). During NP infusion, FBF rose to 24 +/- 2 ml/dl/min in the controls and to significantly lower values in cHY (12 +/- 1; P = 0.001) and aHY (15 +/- 2; P = 0.004). NE-induced vasoconstriction was similar in the controls and aHY, but blunted in cHY. Serum CRP, TNF-alpha and ADMA were not different in the three groups. CONCLUSIONS: (i) Hypothyroidism associates with endothelial and nonendothelial mediated vascular dysfunction; (ii) these defects are evident even after short-term hypothyroidism, indicating that TH deficiency per se is sufficient to alter vascular homeostasis; and (iii) chronic, but not acute, hypothyroidism impairs the vasoconstrictory effect of NE in the resistance vessels.


Subject(s)
Brachial Artery/physiology , Endothelium, Vascular/physiology , Hypothyroidism/physiopathology , Vasodilation/physiology , Acetylcholine/administration & dosage , Acetylcholine/pharmacology , Acute Disease , Adult , Brachial Artery/drug effects , Chronic Disease , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Female , Forearm/blood supply , Humans , Male , Middle Aged , Nitroprusside/administration & dosage , Nitroprusside/pharmacology , Regional Blood Flow/drug effects , Vasodilation/drug effects
11.
J Clin Endocrinol Metab ; 94(3): 1012-6, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19106266

ABSTRACT

CONTEXT: Endothelial cells possess receptors to TSH. Their role is largely unknown. OBJECTIVES: The objective of the study was to determine whether elevated serum TSH levels, as occur in hypothyroidism, affect endothelial function of large arteries and vascular risk biomarkers. SUBJECTS AND METHODS: Thirty-four consecutively recruited patients, who had undergone thyroidectomy for thyroid carcinoma, were studied in connection with one of the monitoring procedures based on recombinant human (rh) TSH administration. Flow-mediated dilation (FMD) of the brachial artery and serum vascular risk markers were measured at baseline and for 5 d after the administration of rhTSH (0.9 mg im on d 1 and 2). Holter electrocardiogram and echocardiography were performed on d 2. RESULTS: rhTSH caused a rapid increase in flow-mediated dilation from the basal value of 10.2 to 15.6% at 6 h (P < 0.0000001), to 16.1% on d 2 (P < 0.0000001), and to 14.9% on d 6 (P = 0.0015). The results were identical when the analysis was made in a subgroup of 19 patients free of vascular risk conditions. Vascular cell adhesion molecule-1, TNFalpha, IL-6, and high sensitive C-reactive protein were unaffected by rhTSH, whereas homocysteine was decreased. Arterial blood pressure, mean 24-h heart rate, and left ventricular function were unaffected by rhTSH. CONCLUSIONS: rhTSH causes marked and persistent activation of the endothelial mediated vasodilation, independent of systemic hemodynamic changes.


Subject(s)
Endothelium, Vascular/physiology , Thyrotropin/pharmacology , Vasodilation/drug effects , Brachial Artery/drug effects , Brachial Artery/physiology , Electrocardiography/drug effects , Female , Hemodynamics/drug effects , Humans , Male , Middle Aged , Recombinant Proteins/pharmacology , Thyrotropin/blood
12.
J Clin Endocrinol Metab ; 93(5): 1959-63, 2008 May.
Article in English | MEDLINE | ID: mdl-18334596

ABSTRACT

CONTEXT: The cardiovascular consequences of thyroid diseases are attributed to the altered secretion of thyroid hormones. The possibility that TSH also affects the cardiovascular system has been poorly explored. Endothelial cells and vascular smooth muscle cells possess TSH receptors. OBJECTIVE: The study was designed to determine whether TSH exerts any effect on vascular homeostasis. SUBJECTS AND METHODS: Two different double-blind, controlled studies were performed, one in eight healthy volunteers and the other in six thyroidectomized patients. Recombinant human (rh) TSH (or saline) was infused intrabrachially (1 mU/min) to raise TSH to severe hypothyroidism levels (approximately 100 microU/ml). Endothelium-dependent and -independent vasodilation was tested by intraarterial infusion of acetylcholine and sodium nitroprusside, respectively, and forearm blood flow was measured by plethysmography. RESULTS: Endothelium-dependent vasodilation was potentiated by rhTSH (P < 0.05 for the treatment effect; general linear model). The dynamics of the response was also profoundly affected by rhTSH because the dose-response curve was much steeper than in controls (P < 0.02 for the interaction between TSH and acetylcholine). rhTSH had no effect on endothelium-independent vasodilation (P = NS for both treatment and interaction). During rhTSH infusion, free T(3) levels increased slowly from 2.3 +/- 0.2 to 3.6 +/- 0.2 pg/ml. In thyroidectomized patients, rhTSH potentiated endothelium-mediated vasodilation to an extent similar to that of healthy subjects (P = 0.05 for the treatment effect and P = 0.01 for the interaction), without affecting the response to nitroprusside. In these patients, thyroid hormones remained unchanged during rhTSH infusion. CONCLUSIONS: rhTSH exerts marked effects on the resistance vessels by enhancing endothelial-mediated vasodilation, independent of changes in thyroid hormone concentration.


Subject(s)
Endothelium, Vascular/drug effects , Thyrotropin/pharmacology , Adult , Dose-Response Relationship, Drug , Endothelium, Vascular/physiology , Female , Forearm/blood supply , Hemodynamics/drug effects , Humans , Male , Middle Aged , Recombinant Proteins/pharmacology , Thyrotropin/blood
13.
J Clin Endocrinol Metab ; 92(1): 250-4, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17047021

ABSTRACT

CONTEXT: Thyroid hormone regulates several cardiovascular functions, and low T(3) levels are frequently associated with cardiovascular diseases. Whether T(3) exerts any acute and direct effect on endothelial function in humans is unknown. OBJECTIVE: Our objective was to clarify whether acute changes in serum T3 concentration affect endothelial function. DESIGN, SETTING, AND SUBJECTS: Ten healthy subjects (age, 24 +/- 1 yr) participated in a double-blind, placebo-controlled trial at a university hospital. INTERVENTIONS: T3 (or placebo) was infused for 7 h into the brachial artery to raise local T3 to levels observed in moderate hyperthyroidism. Vascular reactivity was tested by intraarterial infusion of vasoactive agents. MAIN OUTCOME MEASURES: We assessed changes in forearm blood flow (FBF) measured by plethysmography. RESULTS: FBF response to the endothelium-dependent vasodilator acetylcholine was enhanced by T3 (P = 0.002 for the interaction between T3 and acetylcholine). The slopes of the dose-response curves were 0.41 +/- 0.06 and 0.23 +/- 0.04 ml/dl x min/microg in the T3 and placebo study, respectively (P = 0.03). T3 infusion had no effect on the FBF response to sodium nitroprusside. T3 potentiated the vasoconstrictor response to norepinephrine (P = 0.006 for the interaction). Also, the slopes of the dose-response curves were affected by T3 (1.95 +/- 0.77 and 3.83 +/- 0.35 ml/dl x min/mg in the placebo and T3 study, respectively; P < 0.05). The increase in basal FBF induced by T3 was inhibited by NG-monomethyl-L-arginine. CONCLUSIONS: T3 exerts direct and acute effects on the resistance vessels by enhancing endothelial function and norepinephrine-induced vasoconstriction. The data may help clarify the vascular impact of the low T3 syndrome and point to potential therapeutic strategies.


Subject(s)
Endothelium, Vascular/drug effects , Triiodothyronine/pharmacology , Adult , Dose-Response Relationship, Drug , Double-Blind Method , Endothelium, Vascular/physiology , Female , Forearm/blood supply , Humans , Male , Norepinephrine/pharmacology , Regional Blood Flow/drug effects , Vasoconstriction/drug effects
14.
Metabolism ; 54(3): 306-13, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15736107

ABSTRACT

Epidemiological studies have shown that red wine consumption is associated with less cardiovascular mortality in the general population and in the diabetic patients. To determine whether red wine improves insulin resistance in diabetic patients and to explore the relation between insulin sensitivity and endothelial function, we studied vascular reactivity and insulin-mediated glucose uptake in 9 type 2 diabetic patients before and after 2 weeks of red wine consumption (360 mL/d, wine-treated diabetics) and 8 type 2 diabetic patients who did not consume wine (control diabetics). Vascular reactivity was evaluated by plethysmography during intraarterial infusion of acetylcholine (Ach), sodium nitroprusside, and L-N-monomethylarginine. Forearm nitrite balance was measured during Ach infusion. Insulin sensitivity was measured by euglycemic hyperinsulinemic clamp at 1 mU/kg per minute. The basal forearm blood flow and the response to Ach, to sodium nitroprusside, and to L-N -monomethylarginine were unchanged both in the wine-treated and in the control diabetics. In contrast, insulin-mediated whole body glucose disposal improved by 43% after red wine consumption (from 2.79 +/- 0.4 to 4.02 +/- 0.5 mg/kg of lean body mass per minute, P = .02), but did not change in the control group. In conclusion, red wine consumption for 2 weeks markedly attenuates insulin-resistance in type 2 diabetic patients, without affecting vascular reactivity and nitric oxide production.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Endothelium, Vascular/physiopathology , Insulin Resistance , Wine , Acetylcholine/administration & dosage , Aged , Blood Flow Velocity , Brachial Artery , Diabetes Mellitus, Type 2/therapy , Female , Glucose Clamp Technique , Humans , Infusions, Intra-Arterial , Insulin/blood , Male , Middle Aged , Nitric Oxide/antagonists & inhibitors , Nitroprusside/administration & dosage , Plethysmography , Vasodilation , omega-N-Methylarginine/administration & dosage
15.
Metabolism ; 53(8): 1081-6, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15281023

ABSTRACT

Experimental hyperglycemia and hyperinsulinemia have been shown to affect vascular reactivity. Chronic red wine consumption is associated with less cardiovascular mortality. Whether ingestion of a natural meal and red wine causes acute changes in vascular homeostasis is poorly understood. The aim of the current study was to clarify whether meal ingestion, with and without red wine, exert acute effects on vascular reactivity in healthy humans. We studied vascular reactivity and forearm nitrite balance in 10 healthy subjects under 3 different circumstances: (1) fasting; (2) after ingestion of a standard natural meal (1,050 kcal); and (3) after the same meal enriched with a glass of red wine. We measured forearm blood flow (FBF) by strain-gauge plethismography during intrabrachial, graded infusion of acetylcholine (ACh), sodium nitroprusside (NP), and norepinephrine (NE). We also measured the forearm balance of nitrite before and during ACh infusion. Despite significant increases in plasma glucose and insulin concentrations, the vasodilatory response to Ach and NP after meal ingestion was not different from the fasting response. Similarly, the vasoconstrictory response to NE was similar postprandially and during fasting. Addition of red wine did not modify the response to any of the vasoactive agents. Finally, the forearm nitrite production during Ach infusion was not different in the 3 experimental settings. Food intake, whether associated or not with red wine, does not affect vascular reactivity in normal human subjects.


Subject(s)
Blood Vessels/physiology , Food , Wine , Acetylcholine/pharmacology , Adult , Blood Glucose/metabolism , Blood Vessels/drug effects , Body Mass Index , Female , Forearm/blood supply , Humans , Insulin/blood , Male , Nitrates/metabolism , Nitroprusside/pharmacology , Regional Blood Flow/drug effects , Vasodilator Agents/pharmacology
16.
Clin Chem Lab Med ; 42(1): 17-24, 2004 Jan.
Article in English | MEDLINE | ID: mdl-15061375

ABSTRACT

Hereditary haemochromatosis is an autosomal recessive disorder of iron regulation that results in abnormal intestinal iron absorption with progressive iron overloading of parenchymal cells. Two specific, single point mutations of the HFE gene (C282Y and H63D) have been described in haemochromatosis patients. Epidemiological studies have revealed a strict association between hereditary haemochromatosis and C282Y homozygosis or C282Y/H63D compound heterozygosis, suggesting that these mutations may provide a useful tool for diagnosis. However, recent investigations from southern Europe have reported lower allelic frequencies of the C282Y mutation among haemochromatosis patients, apparently depending on the geographical area of the population analysed. To assess the predictive value of the detection of the C282Y and H63D HFE mutations in our geographical area, we have evaluated their occurrence in 46 haemochromatosis patients from southern Italy. We found that only 19.6% of our patients were homozygous for the C282Y mutation and 21.7% were compound C282Y/H63D heterozygotes. Among the remaining 59%, approximately 40% did not display any of the known HFE mutations. We conclude that, in southern Italy, another genetic determinant/s must be responsible for many haemochromatosis cases and that a genetic screening for the C282Y and H63D HFE mutations is not sufficient for hereditary haemochromatosis diagnosis.


Subject(s)
Hemochromatosis/epidemiology , Hemochromatosis/genetics , Adult , Aged , Case-Control Studies , Cysteine/genetics , Female , Gene Frequency , Hemochromatosis/pathology , Hemochromatosis Protein , Heterozygote , Histidine/genetics , Histocompatibility Antigens Class I/genetics , Homozygote , Humans , Italy/epidemiology , Male , Membrane Proteins/genetics , Middle Aged , Mutation/genetics , Prevalence
17.
J Clin Endocrinol Metab ; 88(6): 2817-20, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12788893

ABSTRACT

GH is involved in the long-term regulation of peripheral vascular resistance and vascular reactivity. We determined whether GH plays a role in the acute regulation of vascular function in humans. The acute vascular effects of GH were studied in eight healthy subjects according to a double-blind, placebo-controlled design. Forearm blood flow (FBF), vascular resistance, and nitric oxide (NO) production were monitored during a 4-h infusion of GH into the brachial artery at a rate chosen to raise local GH to stress levels (approximately 40 ng/ml). During GH infusion, FBF rose 75% (P < 0.05), whereas forearm vascular resistance decreased comparably (P < 0.05). These changes were paralleled by augmented forearm release of NO (P < 0.02). GH heightened the response of FBF to the endothelium-dependent vasodilator acetylcholine (Ach; P < 0.02). With the highest Ach dose, FBF reached 30.4 +/- 4.2 and 16.9 +/- 3.1 ml/dl x min in the GH and placebo studies, respectively (P < 0.005). The slopes of the dose-response curves also differed markedly (0.45 +/- 0.07 and 0.25 +/- 0.05 ml/dl x min/ microg in the GH and placebo studies, respectively; P < 0.01). GH caused an upward shift of the FBF response to the endothelium-independent vasodilator sodium nitroprusside (P < 0.01), but did not affect the slope of the dose-response curve. GH infusion did not cause any appreciable increment in the venous IGF-I concentration in the test arm. In conclusion, GH acutely lowers peripheral vascular resistance and stimulates endothelial function. These effects are mediated by activation of the NO pathway and appear to be independent of IGF-I.


Subject(s)
Blood Vessels/drug effects , Growth Hormone/physiology , Acetylcholine/administration & dosage , Adult , Blood Vessels/physiology , Brachial Artery/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Forearm/blood supply , Growth Hormone/administration & dosage , Humans , Injections, Intra-Arterial , Male , Nitric Oxide/biosynthesis , Plethysmography , Reference Values , Regional Blood Flow/drug effects , Vascular Resistance/drug effects , Vasodilator Agents/administration & dosage
18.
Cell Transplant ; 11(2): 103-12, 2002.
Article in English | MEDLINE | ID: mdl-12099634

ABSTRACT

Insulin-deficient rats are characterized by multiple defects in the pathway of glycogen synthesis and breakdown in both liver and skeletal muscle. The aim of this study was to clarify whether islet transplantation under the kidney capsule, which is associated with delivery of insulin into the peripheral circulation, is able to normalize glycogen metabolism in liver and muscle of streptozotocin-diabetic rats. Three groups of male Lewis rats were studied under fasting condition: controls, untreated diabetics, and islet transplanted diabetics. Glycogen content, glucose-6-phosphate concentration, and glycogen synthase activity were measured in both liver and skeletal muscle. Untreated diabetic rats were characterized by an increase in glycogen content of 178% and a reduction of glucose-6-phosphate level of 50%. Both glycogen and glucose-6-phosphate contents were restored to normal in transplanted diabetic rats. Active glycogen synthase (0.35 +/- 0.1 nmol/min/mg) and activity ratio (0.22 +/- 0.04) were significantly impaired compared with controls (0.99 +/- 0.2 nmol/min/mg and 0.43 +/- 0.06, respectively) and were normalized by islet transplantation. In the skeletal muscle, glycogen content was similar in the three groups of animals, whereas muscle glucose-6-phosphate level was reduced by 28% and glycogen synthase was in a less active state in the untreated diabetic rats. Both the glucose-6-phosphate concentration and the kinetic profile of glycogen synthase were normalized by islet transplantation. In conclusion, islet transplantation under the kidney capsule corrects the diabetes-induced abnormalities in glycogen and glucose-6-phosphate content and glycogen synthase activity in both liver and skeletal muscle.


Subject(s)
Diabetes Mellitus, Experimental/surgery , Glycogen/metabolism , Islets of Langerhans Transplantation/methods , Islets of Langerhans Transplantation/trends , Islets of Langerhans/metabolism , Kidney/surgery , Liver/metabolism , Muscle, Skeletal/metabolism , Animals , Blood Glucose/metabolism , Glucose-6-Phosphate/metabolism , Glycogen Synthase/metabolism , Insulin/metabolism , Insulin Secretion , Islets of Langerhans Transplantation/standards , Kidney/physiology , Liver/physiopathology , Male , Muscle, Skeletal/physiopathology , Rats , Rats, Inbred Lew
19.
J Am Coll Cardiol ; 39(1): 90-5, 2002 Jan 02.
Article in English | MEDLINE | ID: mdl-11755292

ABSTRACT

OBJECTIVES: The goal of this study was to test the hypothesis that growth hormone (GH) administration to patients with chronic heart failure (CHF) corrects their vascular dysfunction. BACKGROUND: Endothelial dysfunction is a prominent feature of CHF. Recent evidence indicates that GH plays a role in vascular reactivity. METHODS: We studied vascular reactivity in 16 patients with CHF (New York Heart Association class II to III) before and after three months of GH (4 IU subcutaneously every other day) or placebo administration in a randomized, double-blind trial. We measured forearm blood flow (FBF) by strain-gauge plethysmography during intrabrachial, graded infusion of acetylcholine (ACh) and sodium nitroprusside (NP). We also measured the forearm balance of nitrite and cyclic guanosine monophosphate (cGMP) before and during ACh infusion. Maximal oxygen uptake (VO2max) was measured by breath-to-breath respiratory gas analysis. RESULTS: Before treatment, the response of FBF to ACh was flat (p = NS). Growth hormone, but not placebo, greatly improved this response (p = 0.03) and, concomitantly, increased the forearm release of nitrite and cGMP (p < 0.05). Growth hormone also potentiated the FBF response to NP (p = 0.013). Growth hormone interacted with ACh response (p = 0.01) but not with the response to NP (p = NS). Accordingly, GH enhanced the slope of the dose-response curve to ACh (p < 0.05) but not to NP. The VO2max increased significantly after GH treatment (20 +/- 2 and 26 +/- 2 ml x Kg(-1) x min(-1) before and after GH treatment, respectively, p < 0.05) but not after placebo. CONCLUSIONS: A three-month treatment with GH corrected endothelial dysfunction and improved non-endothelium-dependent vasodilation in patients with CHF. The data highlight the potential role of GH in the progression of congestive heart failure.


Subject(s)
Endothelium, Vascular/drug effects , Heart Failure/physiopathology , Human Growth Hormone/therapeutic use , Vasodilation/drug effects , Acetylcholine/pharmacology , Dose-Response Relationship, Drug , Double-Blind Method , Endothelium, Vascular/physiopathology , Female , Forearm/blood supply , Humans , Insulin-Like Growth Factor I/analysis , Male , Middle Aged , Regional Blood Flow/drug effects
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