Decreased insulin receptors but normal glucose metabolism in Duchenne muscular dystrophy.

Compared to matched controls, 17 patients with Duchenne muscular dystrophy showed decreased insulin binding to monocytes due to decreased receptor concentration. These patients showed no signs of altered glucose metabolism and retrospective analysis of the clinical records of a further 56 such patients revealed no modification in carbohydrate metabolism. These data suggest that reduced insulin receptor number does not produce overt modifications of glucose metabolism in Duchenne muscular dystrophy.

Tissue-specific antibodies against the fibroblast insulin receptor in a patient with lupus nephritis and hypoglycemia.

We recently reported that the serum from a patient with lupus nephritis, insulin resistance, and hypoglycemia contains multiple populations of antibodies directed at the human insulin receptor. In the present study, we found a subpopulation of antibodies (eluted from a protein A-Sepharose affinity column at pH 4.3) directed at the human fibroblast insulin receptor. When tested against human placental membranes, IM-9 lymphocytes, circulating monocytes and erythrocytes, and isolated adipocytes, the antibody subpopulation did not compete with 125I-insulin for binding to its receptor. In contrast, the antibody subpopulation competed with 125I-insulin for binding to the human fibroblast insulin receptor. This antibody subpopulation stimulated [3H]alpha-aminoisobutyric acid [( 3H]AIB) uptake to these cells. Unlike the effect of insulin, however, this regulation of transport was not antagonized by a mouse monoclonal antibody to the human insulin receptor that inhibits 125I-insulin binding. These studies indicate, therefore, that a tissue-specific antibody subpopulation can occur spontaneously in patients with antibodies to the human insulin receptor. Furthermore, they indicate the presence of anti-insulin receptor autoantibodies specifically directed against a tissue that is not primarily involved in glucose metabolism.

Viral and Antibody Prevalence of Hepatitis E in European Wild Boars (Sus scrofa) and Hunters at Zoonotic Risk in the Latium Region.

Hepatitis E virus (HEV) is a member of the genus Hepevirus within the family Hepeviridae. Hepatitis E is recognized as a zoonosis, and swine and wild boars (Sus scrofa) are known reservoirs of HEV infection. The aim of this study was to investigate the presence of HEV in wild boars and hunters exposed to infection in central Italy (Latium region). During the hunting season, blood samples were collected from 228 wild boars and 20 hunters. The seroprevalence of HEV infection was determined using a commercial enzyme-linked immunosorbent assay, previously validated for use in man, pigs and wild boars. The estimated HEV seroprevalence in wild boars and in hunters was 40.7% (93/228; 95% confidence interval [CI] 34.4-47.1%) and 25% (5/20; 95% CI 6.1-43.9%), respectively. Liver samples were collected from the boars and HEV RNA was detected by nested reverse transcriptase polymerase chain reaction. Fifty-five of 164 tested wild boar liver samples (33.5%; 95% CI 26.2-40.7%) and three of 20 (15.0%; 95% CI 1.3-28.7%) tested human serum samples were positive for HEV RNA. Phylogenetic analysis of the nucleotide sequences obtained from PCR products indicated that the HEV strains present in wild boars and the human population all belonged to genotype 3, supporting the zoonotic role of wild boars in the spread of HEV infection.

Insulin receptors on monocytes and erythrocytes from obese patients.

Insulin receptors were studied in monocytes and erythrocytes [red blood cells (RBC)] isolated from 15 normal and 15 nondiabetic obese outpatients on an unrestricted diet. Insulin binding on both monocytes (P < 0.001) and RBC (P < 0.01) was higher in normal than in obese subjects due to different receptor concentrations. In some obese patients, binding to monocytes was decreased, while binding to RBC was normal. These data demonstrate that obese out-patients on an unrestricted diet have a reduced number of insulin receptors. It is suggested that interpretation of insulin binding based upon RBC should be used with caution, since a discrepancy exists in some subjects in the results obtained with these cells and monocytes.

Effect of age and relation to mortality on serial changes of vasoactive intestinal peptide in acute myocardial infarction.

Plasma levels of vasoactive intestinal peptide increase early after acute myocardial infarction (AMI) and are significantly higher during the first 2 weeks of AMI in survivors and younger patients (<60 years) than in those who died and in older (>60 years) patients. Data suggest that vasoactive intestinal peptide is involved in neuroendocrine activation occurring in AMI and could be regarded as a marker of the course of AMI.

Cardiac troponin I in acute coronary ischemic syndromes. Epidemiological and clinical correlates.

UNLABELLED: The present study was aimed to investigate the variability of cardiac troponin I (cTnI) in the first week of acute myocardial infarction (AMI) course with regard to some epidemiological and clinical parameters and in patients with non-AMI acute coronary ischemic disease. Serum cTnI was assayed in 82 patients, 42 affected with AMI and 40 with non-AMI acute coronary ischemic disease, on admission in coronary care unit, within 6 h after the onset of symptoms, and, in AMI group, on 24 and 48 h and 7th day of illness course. cTnI is increased within the first 6 h, remaining above normal until 7th day. However, some distinctive features in the subgroups scheduled for this study are present. (1) The mean values of cTnI in AMI patients who died, >60 years old and with anterolateral necrosis are constantly higher than in survivors, <60 years old and with inferoposterior necrosis, respectively. (2) The cTnI concentration is already returned in normal range at 7th day of illness course in survivors and in patients with inferoposterior AMI. (3) The 24-h peak level of cTnI is significantly higher in fibrinolysed than in patients who didn't undergo fibrinolysis. (4) A direct correlation between the cTnI value and the Killip class is present either in the whole group or in any subset of patients and the progressive decrease of the cTnI concentration along the AMI course doesn't occur in Killip>2 group. (5) cTnI is higher in unstable than in stable anginous patients and normal subjects but not in stable angina with respect to healthy controls. CONCLUSIONS: (1, 2) The less increase and the early return in normal range of cTnI serum levels which occur in AMI subgroups with a better prognosis could be regarded as favourable prognostic signs. (3) The persistent higher values of cTnI in fibrinolysed subjects being associated with the angiographic finding of patent coronary arteries, it can be suggested that the large and persistent relase of cTnI from myocardium represents a reliable biochemical marker following the wash-out associated to a successful reperfusion. (4) The persistent increase of cTnI in AMI patients with advanced Killip class suggests that the high cTnI values are not only a strong index of myocardial necrosis but also of ongoing myocyte injury and hemodynamic impairment predictive of poor outcome. (5) The hypothesis can be reasonably advanced that the higher values of cTnI in unstable angina are due to focal areas of myocardial necrosis undetectable by the conventional serum markers or to a clinically silent AMI occurred in the week or so before in-hospital admission.

Erythrocyte uroporphyrinogen decarboxylase activity: diagnostic value and relationship with clinical features in hereditary porphyria cutanea tarda.

A marked discrepancy between mild and late clinical features and a nearly complete absence of erythrocyte uroporphyrinogen decarboxylase activity (Ery-UROD activity) was observed in a case of inherited porphyria cutanea tarda. The entity and time of appearance of clinical features, the onset of clinical symptoms after exposure to contributing factors, the effectiveness of phlebotomies and heterozygosity of the mother alone for uroporphyrinogen decarboxylase (UROD) deficiency were typical for familial porphyria cutanea tarda (F-PCT), whereas the extremely low UROD activity was peculiar to hepatoerythropoietic porphyria (HEP). These observations indicate that: 1) Ery-UROD activity may not always be useful to discriminate between F-PCT and HEP; 2) Ery-UROD activity does not always correlate with clinical symptoms; 3) in inherited UROD deficiency, the genetic defect may be heterogeneous. Finally, the observed discrepancy may provide additional evidence for the existence of tissue-specific isozymes.

The synergistic effect of simultaneous addition of retinoic acid and vitamin D3 on the in-vitro differentiation of human promyelocytic leukemia cell lines could be efficiently transposed in vivo.

Both human cell lines HL-60 and AML-193 exhibit a myeloblastic and promyelocytic morphology, respectively, but may be regarded as bipotent leukemic precursors. They can be triggered to differentiate to either granulocytes or monocytes upon retinoic acid (RA) or 1,25-dihydroxyvitamin D (D3) addition, respectively. We have investigated the effect of combined addition of these chemical inducers on the in-vitro differentiation of both cell lines. RA and D3 added together exert synergistic effects on the in-vitro maturation of these myeloid cell lines. Interestingly, the additive effects were lost if the cells were incubated with the inducers added at sequential times. The synergistic effect could be transposed in vivo and could be clinically significant in the treatment of the promyelocytic leukemia. This clinical strategy may help to prevent retinoic acid resistance or to overcome it in patients relapsed after RA therapy and usually unresponsive to a reinduction therapy with RA alone.

[Efficacy of L-thyroxine (L-T4) therapy on the volume of the thyroid gland and nodules in patients with euthyroid nodular goiter (ENG)]. / Efficacia della terapia con L-tiroxina (L-T4) sul volume della tiroide e dei noduli in pazienti con gozzo nodulare eutiroideo (GNE).

The efficacy of treatment with TSH suppressive doses of L-thyroxine was evaluated by echography in 35 patients with euthyroid nodular goiter. Patients have been subdivided in two groups comparable for sex age and size of the goiter. Sixteen patients were treated for nine months with suppressive doses of thyroxine and nineteen were followed without therapy as control. Patients in treatment were then followed up for additional 9 months without therapy. The mean decrease of thyroid volume at nine months was 25% (27 +/- 10 ml vs 20 +/- 8 ml; p < 0.01). After discontinuation of treatment thyroid volume increased and had returned to base line values after nine months of follow up. In the control group mean thyroid volume had increased by 17.7% at nine months (28 +/- 17 vs 33 +/- 19 ml; p < 0.001). Thyroid nodules in response to thyroid hormone treatment showed a variable behaviour: 30.7% (4/13) of the nodules responded to the therapy with a reduction > to 25% at the ninth month; the remaining nodules were insensitive to the therapy. In conclusion suppressive thyroxine treatment is effective in reducing the goiter, nodules instead are only in part sensitive to the treatment. Thyroxine therapy of euthyroid nodular goiter must be followed for long term since upon thyroxine discontinuation there is a prompt reappearance of the goiter.

[Hypothyroidism in adults: a magnetic resonance study of cerebral and hypophyseal changes]. / Ipotiroidismo dell'adulto: studio con la risonanza magnetica delle alterazioni cerebrali e ipofisarie.

The case of a 55-year-old woman with postpartum (at age of 22) hypopituitarism is reported. The patient, with signs of myxedema, was admitted to a psychiatric hospital for hallucinations. In addition to routine tests and measurements of thyroid hormones level, magnetic resonance imaging (MRI) of the brain and pituitary region was performed. The results of MRI showed cerebral atrophy and a large "empty sella". On the basis of clinical, laboratory and instrumental data, a diagnosis of panhypopituitarism with prevalent hypothyroidism was achieved. Many hypotheses could be made regarding its pathogenesis. Initially we considered the diagnosis of Sheehan's syndrome in which the sella turcica usually presents normal or reduced dimensions. However the presence of a large "empty sella" with thin walls, excludes this diagnosis. The delay of menarche and the short stature suggest the hypothesis of a preexistent pathological condition. It is possible that the patient had liquefied pituitary adenoma as a consequence of the postpartum shock or that she was hypothyroid, a condition in which the "empty sella" is very common.

[Neuroendocrine activation in acute myocardial infarction: state of the art and preliminary results on intestinal vasoactive peptide]. / Attivazione neuroendocrina nell'infarto acuto del miocardio: stato dell'arte e risultati preliminari sul peptide vasoattivo intestinale.

Acute myocardial infarction (AMI) is known to be associated with a complex neuroendocrine activation, especially concerning sympathetic and renin-angiotensin systems, cortisol, atrial natriuretic peptide and endothelin. Results of our study show that the vasoactive intestinal peptide (VIP), also, is early involved in the neuroendocrine activation occurring in AMI. Plasma concentration of VIP, significantly increased in AMI patients within 6 hours after the onset of chest pain, soon decreased and remained below than normal along the first week. At the 14th day of the AMI, plasma levels of VIP returned into the normal range. A significant increase of VIP plasma concentration is detectable in the first hours of AMI in survived as compared with died patients. The phenomenon seems to be a suitable process to provide an endogenous support to the ischemic heart and to counteract the negative effects of other neuroendocrine activated factors.

[Vasoactive intestinal peptide in heart failure]. / Il peptide vasoattivo intestinale nello scompenso cardiaco.

BACKGROUND: The aim of our study was to investigate the pathophysiological role of the vasoactive intestinal peptide (VIP), a vasodilating neuropeptide with positive inotropic and chronotropic properties, in heart failure. METHODS: The study was carried out in 35 patients with heart failure due to dilated cardiomyopathy, who underwent a peripheral venous blood sample for radioimmunoassay of VIP within the first in-hospital day. RESULTS: The plasma concentration of VIP: 1) is not higher than normal in the whole group of patients with heart failure; 2) is higher in younger than in elderly healthy subjects but does not significantly change in relation to age in heart disease patients; 3) is higher in elderly (> 60 years) but not in younger (< 60 years) patients compared to healthy subjects of the same age; 4) is higher in NYHA functional class 2 than in NYHA functional class > 2 groups and in normal subjects; 5) is not correlated with echocardiographic parameters; 6) does not significantly change with respect to the etiology of dilated cardiomyopathy. CONCLUSIONS: The plasma concentration of VIP in heart failure is conditioned by some epidemiological and clinical variables. Unlike the healthy group, differences are not detectable with respect to the age of patients; thus, in elderly heart disease subjects the neuropeptide productive potentiality is preserved. Taking into account the physiological properties of VIP, its plasma increase in the initial phase of heart failure can be reasonably regarded as a further mechanism to restore the compromised hemodynamic balance. Its decrease, related to worse clinical conditions, could be due to a progressive depletion from the pre-synaptic nerve endings and to a deficiency in the neurogenic productive capacity of the molecule.

[Troponin I in acute ischemic cardiopathy]. / La troponina I nella cardiopatia ischemica acuta.

BACKGROUND: The present study was aimed at investigating cardiac troponin I values in the first week of acute myocardial infarction and in non-infarct acute coronary ischemic syndromes. METHODS: Eighty-two patients, 42 with acute myocardial infarction, 10 with stable angina and 30 with primary unstable angina, were enrolled in the study. Blood was collected within 6 hours of symptom onset and, in the group with acute myocardial infarction, after 24 and 48 hours, and on day 7. RESULTS: Serum troponin I increased within the first 6 hours of myocardial infarction, reached the peak after 24 hours, at 48 hours it decreased, and remained above the normal range until day 7. However, troponin I values 1) were constantly higher in patients who died, in those > 60 years old and in those with antero-lateral necrosis than in survivors, in those < 60 years old and in those with infero-posterior necrosis, respectively; 2) returned to normal range on day 7 in survivors and in patients with infero-posterior acute myocardial infarction; 3) were significantly higher in fibrinolysed patients than in those who did not undergo thrombolysis; 4) were higher in patients classified as Killip class > 2. Serum troponin I values were in the normal range in non-infarct acute coronary ischemic syndromes, but were higher in unstable than in stable angina. CONCLUSIONS: The lesser increase and the early return to the normal range of cardiac troponin I levels in the subgroups of patients with myocardial infarction having a better clinical course could be regarded as a favorable prognostic sign. Since the persistent higher values of cardiac troponin I in fibrinolysed subjects are associated with the angiographic finding of patent coronary arteries, it can be suggested that the large and persistent post-thrombolysis release of cardiac troponin I from the myocardium represents a biochemical marker of a successful reperfusion. The persistent high cardiac troponin I values in patients with advanced Killip class suggest that the neuropeptide is an index of ongoing myocyte injury and hemodynamic impairment as well. The higher values of cardiac troponin I in unstable angina are probably due to focal areas of myocardial necrosis undetectable by conventional enzymatic serum markers.

Instrumentation for diagnostics and control of laser-accelerated proton (ion) beams.

Suitable instrumentation for laser-accelerated proton (ion) beams is critical for development of integrated, laser-driven ion accelerator systems. Instrumentation aimed at beam diagnostics and control must be applied to the driving laser pulse, the laser-plasma that forms at the target and the emergent proton (ion) bunch in a correlated way to develop these novel accelerators. This report is a brief overview of established diagnostic techniques and new developments based on material presented at the first workshop on 'Instrumentation for Diagnostics and Control of Laser-accelerated Proton (Ion) Beams' in Abingdon, UK. It includes radiochromic film (RCF), image plates (IP), micro-channel plates (MCP), Thomson spectrometers, prompt inline scintillators, time and space-resolved interferometry (TASRI) and nuclear activation schemes. Repetition-rated instrumentation requirements for target metrology are also addressed.

[Oestrogens in the stimulation of adrenal steroid production in the rat]. / La corticosteroidogenesi nel surrene di ratto: ruolo degli estrogeni.

Chronic administration of oestradiol has several times been reported as leading to stimulation of in vitro adrenal hydroxylative activity in the rat. It is now shown that acute stimulation is also possible, provided ACTH is present in the system. Synthetic oestrogens with metabolic activity equivalent to that of oestradiol, however, are incapable of stimulating steroid production. It is clear that the mechanism of action of oestrogens is extremely complicated as far as the adrenal glands are concerned.