Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine the prevalence of low serum insulin-like growth factor-I (IGF-I) and testosterone in men with poststroke hemiplegia. Serum concentrations of IGF-I, total testosterone, and free testosterone were compared in healthy young men, healthy old men, and old men with poststroke hemiplegia. A low IGF-I level, below the lower 2.5 percentile of the healthy young men, occurred in 85% of the healthy old men, and in 88% of the poststroke hemiplegic patients. When a low IGF-I was defined as a value below the lower 2.5 percentile of the healthy old men, the prevalence in the hemiplegic men was 5%. For total testosterone, a value below the lower 2.5 percentile in the healthy young men occurred in 78% of the healthy old men and in 79% of the stroke survivors. Low total testosterone, defined as a value below the lower 2.5 percentile of the healthy old men, occurred in 17% of the hemiplegic men. The results with free testosterone were similar. Compared with healthy young men, most healthy old men have low serum IGF-I and testosterone levels. Old hemiplegic men resemble healthy old men in their IGF-I levels, but they have more cases of severe hypogonadism (total tostosterone < 193ng/dL). Because correction of IGF-I and testosterone deficiencies in younger adults improves muscle strength, work capacity, and quality of life, treatment with human growth hormone and testosterone may be a useful adjunct to physical measures in the rehabilitation of selected hemiplegic stroke survivors.
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PMID:Hyposomatomedinemia and hypogonadism in hemiplegic men who live in nursing homes. 818 56

We evaluated the protective effects of manidipine, which is a long-lasting calcium-channel blocker, against damage to spermatogenesis arising from hypertensive vascular changes in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP showed severe hypertension at 11 weeks of age, followed by hypertensive changes in intratesticular arterioles from 15 weeks of age. Manidipine lowered the blood pressure and the hypertensive vascular changes of intratesticular arterioles in SHRSP. The percentages of atrophic seminiferous tubules and tubules with less-differentiated germ cells were increased in SHRSP at 23 weeks of age, although the administration of manidipine preserved spermatogenesis at a normal level. The transferrin concentration in testicular cytosol was comparable, whereas insulin-like growth factor-I (IGF-I) was reduced from 19 weeks of age in SHRSP. Manidipine preserved the normal IGF-I concentration. Therefore, manidipine prevented the development of hypertensive vascular changes in the testis and maintained normal Sertoli cell function. As a result, manidipine protected spermatogenesis in SHRSP. These findings also suggested that hypertensive vascular changes in the testes play the most important role in spermatogenic damage in SHRSP.
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PMID:Manidipine improves spermatogenesis in the stroke-prone spontaneously hypertensive rat. 915 16

The aim of this study was to evaluate the impact of age and disease duration on cardiac performance in acromegaly. To address these issues, the left ventricular function at rest and during physical exercise was assessed by equilibrium radionuclide angiography in 40 rigorously selected patients with active acromegaly but without evidence of other complications able to affect heart function and in 32 healthy controls. Patients and controls were divided in two groups, on the basis of age below and above 40 yr. Circulating GH and insulin-like growth factor-I levels were significantly increased in patients, compared with controls, but were similar in the two groups of patients. At peak exercise, the systolic blood pressure was significantly higher in elderly patients (P < 0.001), whereas diastolic blood pressure was significantly higher in young patients than in age-matched controls (P < 0.01). Heart rate at peak exercise was significantly higher in young than in elderly patients and controls (P < 0.01), without any evidence of arrhythmia in both groups. The left ventricular ejection fraction at rest was normal (>50%) in all but 2 patients and in all controls. The left ventricular ejection fraction at peak exercise was significantly decreased in elderly, compared with young, patients (P < 0.01) and in age-matched controls (P < 0.001). A normal response of the left ventricular ejection fraction to exercise was found in 12 of 40 patients (30%) and in 28 of 32 controls (87.5%) (chi2, 5.764; P < 0.01). Exercise-induced changes in left ventricular ejection fraction were significantly decreased in young (+5.2 +/- 4.4% vs. +21.3 +/- 3.4%, P < 0.005) and elderly patients (-10.2 +/- 2.8% vs. +13.7 +/- 2.7%, P < 0.0001), as compared with age-matched controls. The peak rate of left ventricular filling was significantly higher in young, than in elderly, patients whether peak filling rate was normalized to end-diastolic volume (P < 0.001), or stroke volume (P < 0.0001), or expressed as the ratio of peak filling rate to peak ejection rate (P < 0.001). The peak rate of left ventricular filling was significantly decreased in elderly patients, compared with young patients and age-matched controls, whether peak filling rate was normalized to end-diastolic volume (P < 0.01), or stroke volume (P < 0.005), or expressed as the ratio of peak filling rate to peak ejection rate (P < 0.001). In the patient group, the left ventricular ejection fraction at peak exercise was significantly correlated with age (r = -0.33, P < 0.05), estimated disease duration (r = -0.34, P < 0.05), exercise-induced changes of the left ventricular ejection fraction (r = 0.34, P < 0.05), and the peak rate of left ventricular filling, whether peak filling rate was normalized to end-diastolic volume (r = 0.33, P < 0.05). Age and estimated disease duration were both significantly correlated with the peak rate of left ventricular filling, whether peak filling rate was normalized to end-diastolic volume (r = 0.55, P < 0.001 and r = -0.49, P < 0.001, respectively), or stroke volume (r = 0.5, P < 0.001 and r = -0.57, P < 0.001, respectively), or expressed as the ratio of peak filling rate to peak ejection rate (r = 0.56, P < 0.0001 and r = -0.52, P < 0.001, respectively). In the control group, the left ventricular ejection fraction at peak exercise was significantly correlated with the left ventricular ejection fraction at rest (r = 0.54, P < 0.01), exercise-induced changes of the left ventricular ejection fraction (r = 0.57, P < 0.001), but neither with age nor peak rate of left ventricular filling at all measurements. In conclusion, left ventricular performance is more frequently preserved in young patients with a short disease duration, although the left ventricular response to exercise was already reduced, as compared with controls. (ABSTRACT TRUNCATED)
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PMID:Impact of patient's age and disease duration on cardiac performance in acromegaly: a radionuclide angiography study. 1032 72

Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.
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PMID:Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron syndrome). 1095 79

To determine the effect of ventricular function, size of ventricular septal defect (VSD), and endocrine function on linear growth in children with VSD, we studied 88 children with VSD over a period of 1 year. Growth was assessed by determining the height standard deviation scores (HtSDS) and growth velocity (GV) every 4 months. Two hundred age-matched normal children served as controls for the growth data. Endocrine evaluation was performed in 30 randomly selected children with VSD, and 20 age-matched children with constitutional delay of growth (CSS). Growth hormone (GH) response to clonidine provocation was evaluated and circulating free thyroxine (FT4) and insulin-like growth factor-I (IGF-I) concentrations measured. Echocardiographic evaluation of the different cardiac parameters including shunt size and shunt fraction (Qp/Qs) was performed using a colour-coded echodoppler. The HtSDS, body mass index (BMI), and mid-arm circumference (MAC) of children with VSD were significantly decreased compared to those for the normal control group. The dietary intake evaluated by the recall method, appeared to be adequate in the majority of these children (83/88). IGF-I concentrations were reduced in children with VSD (87.5 +/- 29 ng/ml) versus normal age-matched children (169 +/- 42 ng/ml). Basal and clonidine-stimulated GH concentrations were significantly higher in children with VSD (4.6 +/- 2.1 microg/l and 28.8 +/- 7.9 microg/l respectively) versus controls (17.8 +/- 4.2 microg/l). In these patients (n = 88) the HtSDS was correlated negatively with the size of the shunt (r = -0.793, p < 0.001), shunt fraction (Qp/Qs) (r = -0.76, p < 0.001), pulmonary mean gradient (r = -0.4, p = 0.006), and pulmonary maximum velocity (r = -0.32, p = 0.02). Growth velocity (GV) was correlated negatively with pulmonary maximum gradient (r = -0.3, p = 0.02), pulmonary maximum velocity (r = -0.37, p = 0.007), and pulmonary stroke volume (Qp) (r = -0.345, p = 0.01). The BMI and IGF-I concentrations were correlated significantly with the size of the shunt (r = -0.453, p < 0.01), Qp/Qs (r = -0.432, p < 0.01), HtSDS (r = 0.565, p < 0.01), and BMI (r = 0.435, p < 0.01). It appears that in patients with VSD, the size of the left-to-right shunt and the abnormal hemodynamics in the pulmonary circulation are important factors in the etiology of impaired growth. It is suggested that the hypermetabolic status of these patients compromise nutrition and this decreases IGF-I synthesis with subsequent slowing of linear growth and weight gain.
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PMID:Growth parameters and endocrine function in relation to echocardiographic parameters in children with ventricular septal defect without heart failure. 1141 77

Insulin-like growth factor-I (IGF-I) has been proposed as a treatment for stroke. However, it does not efficiently cross the blood-brain barrier (BBB). Intracerebroventricular injection of IGF-I has been shown to offer protection against cerebral ischemic damage in rats although this invasive method of administration may not be practical in humans. Non-invasive intranasal (IN) delivery of IGF-I to the brain is a promising alternative. We have assessed the therapeutic effect of IN IGF-I in rats following middle cerebral artery occlusion (MCAO). Treatment was initiated 10 min after the onset of MCAO and then again 24 and 48 h later. Intranasal dosing of 75 microg IGF-1 (225 microg total IGF-I over 48 h) significantly reduced corrected infarct volumes by 60% vs. control (P<0.01) and hemispheric swelling by 45.6% vs. control (P<0.05). Neurologic function, assessed by the postural reflex, flexor response and adhesive tape tests, was also improved by IN IGF-I as compared to control. Our study indicates IN delivery of IGF-1 holds significant promise as a non-invasive and efficacious method of bypassing the BBB for the treatment of stroke.
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PMID:Non-invasive intranasal insulin-like growth factor-I reduces infarct volume and improves neurologic function in rats following middle cerebral artery occlusion. 1145 67

Accumulating data show that growth hormone (GH) and insulin-like growth factor-I (IGF-I) have major effects on the cardiovascular system. In the present study we have directly compared GH and IGF-I in an in vivo rat model of experimental myocardial infarction. Four weeks after ligation of the left coronary artery, male rats were treated with recombinant human (rh) GH 1.1 mg/kg per day, rhIGF-I 3.0 mg/kg per day or saline s.c. for 2 weeks. Transthoracic echocardiography was performed before and after the treatment period. Both GH and IGF-I reduced total peripheral resistance (P< 0.01), end-systolic wall stress (P< 0.01) and end-systolic short-axis area (P< 0.001 and P< 0.05). GH also increased area fractional shortening (P< 0.05). Stroke volume (SV) and SV index were improved by IGF-I (P< 0.0001), and SV tended to be increased by GH (P= 0.12). In conclusion, GH and IGF-I had similar beneficial effects on systolic function and peripheral resistance after experimental myocardial infarction.
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PMID:Similar cardiovascular effects of growth hormone and insulin-like growth factor-I in rats after experimental myocardial infarction. 1173 33

Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that has been investigated as a potential neuroprotective drug for the treatment of stroke and other forms of neural damage. Preclinical studies over the last decade have demonstrated that IGF-I and some of its fragments can protect against neuronal and glial cell degeneration in animal models of stroke such as hypoxia-ischemia. Although the results to date are encouraging, the size of the IGF-I molecule has proved problematic and has led researchers to investigate routes of administration that bypass the blood-brain barrier, such as intranasal application, or to focus on fragments of IGF-I, such as the N-terminal peptide Gly-Pro-Glut (GPE). While the results of these studies have also been positive, systematic dose-response comparisons with recognized neuroprotectants have not yet been published, the time window for therapeutic effects is not yet clear and long-term functional studies have not been conducted.
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PMID:Neuroprotection against hypoxia-ischemia by insulin-like growth factor-I (IGF-I). 1466 28

Modern societies face new public health challenges associated with an increasingly aging population. Among these, pathological conditions linked to brain aging are paramount. Old age is a risk factor for important neurological impairments such as Alzheimer's disease or stroke. Even healthy elderly people usually present with milder forms of cognitive decline. This is possibly related to less-pronounced brain deficits seen in normal aging, including the shrinkage of neurons and the dense network of neurons and glia in the central nervous system known as the neuropil, a lower neurogenetic rate, impaired angiogenesis or brain accumulation of deleterious compounds. At least in mammals, age is also associated with a decline in insulin-like growth factor-I (IGF-I) levels, a well-known neuroprotective agent. Recently, a relationship between serum IGF-I and "house-keeping" mechanisms in the brain has been evidenced in laboratory rodents. Serum IGF-I increases adult neurogenesis, sustains neuronal health through a variety of fundamental homeostatic mechanisms, participates in brain angiogenesis, contributes to brain beta-amyloid clearance and affects learning and memory. Overall, diminished trophic input resulting from decreasing serum IGF-I levels during aging likely contributes to brain senescence in mammals.
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PMID:Role of serum insulin-like growth factor I in mammalian brain aging. 1513 75

Insulin-like growth factor-I (IGF-I) signalling is reported to contribute to the modulation of blood pressure and set survival and hypertrophic responses in cardiac tissue. However, whether IGF-I signalling normally acts in cardiac tissues of hypertensive rats is unknown. In this study, using spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SPSHR), both with early blood pressure increases, and Wistar-Kyoto (WKY) rats as controls, we measured the hypertrophic and IGF-I signalling activity changes in rat hearts at 4, 6 and 12 weeks of age. Both SHR and SPSHR were found to have significantly increased blood pressures and ratios of heart- and left ventricle- to body weight at 12 weeks of age. However, IGF-IR and its downstream signalling, including the protein levels of PI3K and phosphorylated Akt, known to maintain physiological cardiac hypertrophy and cardiomyocyte survival, were downregulated. The results of dot blotting showed that cardiac mRNA levels of IGF-I in hypertensive rats were higher than those in controls starting from the age of 4 weeks. This difference suggests the increased ligand IGF-I mRNA levels may be a compensatory response caused by the impaired IGF-I signalling. Moreover, enhanced cardiac cytosolic cytochrome-c, a mitochondria-dependent apoptotic pathway component, tended to occur in both hypertensive rats, although it did not reach a significant level. These findings indicate that impaired IGF-IR signalling occurs at early stages, and it may contribute, at least partially, to the development of hypertension and pathological cardiac hypertrophy and to cardiomyocyte apoptosis at later stages in SHR and SPSHR.
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PMID:Impaired IGF-I signalling of hypertrophic hearts in the developmental phase of hypertension in genetically hypertensive rats. 1599 2


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