Osteoprotegerin and bone mineral density in hemodiafiltration patients.

A newly identified cytokine, osteoprotegerin (OPG) appears to be involved in the regulation of bone remodeling. In vitro studies suggest that OPG, a soluble member of the TNF receptor family of proteins, inhibits osteoclastogenesis by interrupting the intercellular signaling between osteoblastic stromal cells and osteoclast progenitors. As patients with chronic renal failure (CRF) often have renal osteodystrophy (ROD), we investigated the role of osteoprotegerin (OPG) in ROD, and investigated whether there was any relationship between serum OPG, intact parathyroid (PTH) (iPTH), vitamin D, and trabecular bone. Serum OPG combined with iPTH might be a useful tool in the noninvasive diagnosis of ROD, at least in cases in which the range of PTH values compromises reliable diagnosis. Thirty-six patients on maintenance hemodiafiltration (HDF) and a control group of 36 age and sex matched healthy subjects with no known metabolic bone disease were studied. The following assays were made on serum: iPTH, osteocalcin (BGP), bone alkaline phosphatase, 25(OH)-cholecalciferol, calcium, phosphate, OPG, IGF-1, estradiol, and free testosterone. Serum Ca++, P, B-ALP, BGP, IGF-1, iPTH, and OPG levels were significantly higher in HDF patients than in controls, while DXA measurements and quantitative ultrasound (QUS) parameters were significantly lower. On grouping patients according to their mean OPG levels, we observed significantly lower serum IGF-1, vitamin D3 concentrations, and lumbar spine and hip bone mineral density in the high OPG groups. No correlation was found between OPG and bone turnover markers, whereas a negative correlation was found between serum OPG and IGF-1 levels (r=-0.64, p=0.032). Serum iPTH concentrations were positively correlated with bone alkaline phosphatase (B-ALP) (r=0.69, p=0.038) and BGP (r=0.92, p<0.001). The findings made suggest that an increase in OPG levels may be a compensatory response to elevated bone loss. The low bone mineral density (BMD) levels found in the high OPG group might have been due to the significant decrease in serum IGF-1 and vitamin D3 observed. In conclusion, the findings made in the present study demonstrate that increased OPG in hemodiafiltration patients is only partly due to decreased renal clearance. As it may partly reflect a compensatory response to increased bone loss, this parameter might be helpful in the identification of patients with a marked reduction in trabecular BMD.

Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries.

Over a period of almost 10 yr, we carried out a prospective study of the neuropsychological development of the offspring of 16 women from a moderately iodine-deficient area (area A) and of 11 control women from a marginally iodine-sufficient area (area B) whose thyroid function had been monitored during early gestation. Attention deficit and hyperactivity disorder (ADHD) was diagnosed in 11 of 16 area A children (68.7%) but in none from area B. Total intelligence quotient score was lower in area A than in area B children (92.1 +/- 7.8 vs. 110 +/- 10) and in ADHD children when compared with both non-ADHD children from the same area and control children (88.0 +/- 6.9 vs. 99.0 +/- 2.0 and 110 +/- 10, respectively). Seven of 11 ADHD children (63.6%) were born to the seven of eight area A mothers who became hypothyroxinemic at early gestation, whereas only one of five non-ADHD children was born to a woman who was hypothyroxinemic at 20 wk of gestation. So far, a similar prevalence of ADHD has been reported only in children with generalized resistance to thyroid hormones. This might suggest a common ADHD pathogenetic mechanism consisting either of reduced sensitivity of the nuclear receptors to thyroid hormone (generalized resistance to thyroid hormones) or reduced availability of intracellular T3 for nuclear receptor binding. The latter would be the ultimate consequence of maternal hypothyroxinemia (due to iodine deficiency), resulting in a critical reduction of the source of the intracellular T3 available to the developing fetal brain.

Leptin and norepinephrine plasma concentrations during glucose loading in normotensive and hypertensive obese women.

We performed this study to investigate whether changes in plasma glucose, insulin, and norepinephrine concentrations during an oral glucose tolerance test (OGTT) are associated with changes in plasma leptin levels in normotensive and hypertensive obese women. Plasma insulin, glucose, norepinephrine, and leptin concentrations were evaluated at the baseline and during OGTT in normotensive women (NT-Ob, N = 24, mean age 38.3+/-1.8 years, body mass index [BMI] 37.9+/-1.1 kg/m2) and hypertensive (HT-Ob, N = 25, mean age 37.7+/-1.9 years, BMI 39.4+/-1.3 kg/m2) obese women, and in a group of normal-weight women (controls, N = 20, mean age 38.3+/-1.3 years, BMI 23.1+/-0.4 kg/m2). The OGTT caused a significant increase in plasma leptin concentrations in both NT-Ob and HT-Ob groups, whereas no such change was detectable in control subjects. Area under curve (AUC) for plasma leptin showed a direct correlation with norepinephrine AUC in both NT-Ob (r = 0.73, P = .001) and HT-Ob (r = 0.74, P = .001) group, which was still detectable in multivariate analysis (P = .014 and P = .017, respectively). Our study confirms that glucose loading increases circulating leptin concentrations in obese women, and demonstrates the existance of an association between leptin and norepinephrine changes during OGTT in both normotensive and hypertensive obese women. We hypothesize that this association may reflect the lack of leptin suppression by catecholamines or a direct leptin-induced sympathoactivation. These findings suggest that leptin could be relevant in the regulation of blood pressure in obese women.

Plasma leptin concentrations in relation to sick euthyroid syndrome in elderly patients with nonthyroidal illnesses.

BACKGROUND: Leptin, the ob gene product, seems to be involved in regulating energy expenditure in humans, but its role in the pathophysiology of the energy imbalance in chronically ill patients is largely unknown. OBJECTIVE: To evaluate plasma leptin concentrations and thyroid function in elderly patients with nonthyroidal illnesses (NTI). METHODS: Sixty-four NTI elderly patients (75.0 +/- 6.3 years, 27 males and 37 females) and 21 age- and sex-matched healthy controls (73.0 +/- 5.5 years, 9 males and 12 females) were enrolled in the study. In all subjects tri-iodothyronine (T(3)), thyroxine (T(4)), reverse T(3) (rT(3)), free T(3) (fT(3)), free T(4) (fT(4)), TSH, and plasma leptin concentrations were measured. Nutritional status was also evaluated in all subjects studied by the measurement of body mass index (BMI), lymphocytes, serum iron, hemoglobin, plasma albumin, transferrin and total cholesterol. RESULTS: The data on thyroid hormones enabled us to identify three groups: group A, subjects (15 patients) with T(3) and fT(3) levels comparable to those of controls; group B, subjects (25 patients) with T(3) and fT(3) levels lower than controls and rT(3) levels comparable to those of controls; group C, subjects (24 patients) with T(3) and fT(3) levels lower than those of controls and high rT(3) levels. The patients of group C showed lower plasma leptin levels than the controls, 6.6 (5.5-14.2) and 16.3 (7.2-23.7) ng/ml (median with interquartile range in parentheses, p < 0.05), respectively. Females also showed higher plasma leptin levels than males in the controls, group A and group B, but not in group C. Moreover, plasma leptin concentrations were directly correlated to BMI in all the groups studied, while a negative correlation between leptin and rT(3) was detectable in group C (r = -0.44, p < 0.05), also after adjusting for BMI and sex. CONCLUSIONS: The concurrence of modifications in plasma leptin and thyroid hormones concentrations found in elderly NTI patients with a sick euthyroid syndrome could reflect a particular neuroendocrine status, leading to a reduction in the catabolic processes in the course of chronic diseases.

Post-Chernobyl increased prevalence of humoral thyroid autoimmunity in children and adolescents from a moderately iodine-deficient area in Russia.

Circulating thyroglobulin antibodies (TgAb) and thyroperoxidase antibodies (TPOAb) were measured in 143 iodine-deficient children, 5 to 15 years of age, from the Region of Tula, Russia, who had been moderately contaminated after the Chernobyl disaster (37-185 GBq/km2 of caesium-137, [group A]) and in 40 sex- and age-matched subjects from an uncontaminated neighboring area (<3.7 GBq/km2 of caesium-137, [group B]). Increased thyroid size at sonography was found in 41% and in 45% subjects from group A and group B, respectively, associated with supranormal thyrotropin (TSH) values in 7.7% of group A and 7.5% of group B, without differences in average serum free thyroxine (FT4), free triiodothyronine (FT3) and TSH. Serum thyroperoxidase antibody (TPOAb)-associated or not with thyroglobulin-antibody (TgAb) as detected in 18.9% of children and adolescents from group A, about four-fold higher than in group B (5%, Fischer's exact test p<0.05). A 24% frequency was found in subjects whose age, at the moment of the disaster was 0-72 months or were in utero, but the frequency was about 7%, similar to that in group B, in those who had not yet been conceived at that time. Less than half of antibody-positive group A children were hyperthyrotropinemic, whereas no group B subclinical hypothyroid subject was antibody-positive, thus excluding the autoimmune etiology of the subclinical thyroid failure; more likely it is attributable to iodine malnutrition. The high prevalence of humoral thyroid autoimmunity phenomena in the investigated area suggests a combined role of iodine malnutrition in enhancing the effects of short lived iodine isotopes, particularly evident in pubertal individuals conceived or born immediately before the Chernobyl disaster.

Increased risk of maternal thyroid failure with pregnancy progression in an iodine deficient area with major iodine deficiency disorders.

In an effort to assess the impact of moderate iodine deficiency on maternal thyroid function during pregnancy, we measured serum thyrotropin, total and free thyroid hormones, thyroid-binding globulin (TGB) at 8, 14, 20, 29, and 36 weeks of gestation, along with urinary iodide excretion, in 10 healthy women from a moderately iodine deficient region (group A), and compared them with 6 women from an iodine sufficient region (group B). Serum total thyroxine (T4) fell significantly in group A, and was significantly lower than in group B at 29 and 36 weeks (p<0.05). TBG saturation was significantly lower in group A throughout pregnancy, and declined in both groups as pregnancy progressed. Free thyroxine (T4) and triiodothyronine (T3) concentrations fell in both groups, and FT4 values were significantly lower in group A than group B in the third trimester (p<0.05). Urinary iodine excretion was lower in group A women with respect to group B and did not vary significantly in either group as gestation progressed. The serum T3/T4 molar ratio increased through pregnancy only in group B. Thyrotropin concentrations rose in both groups through pregnancy, and were higher in group A at term (p< 0.01). The incidence of isolated hypothyroxinemia or biochemical hypothyroidism doubled (30% to 70%) between midgestation and term in group A, suggesting that moderate iodine deficiency may result in maternal thyroid failure during the later stages of pregnancy.

Uso de captopril durante a gestaçäo e suas repercussöes sobre o feto e o recém-nascido: relato de caso / Neonatal and fetal effects of captopril use in pregnancy: case report

Os inibidores da enzima conversora da angiotensina tem sido largamente utilizados para o controle da hipertensao, mas o uso destes durante a gestacao pode provocar obito fetal, retardo de crescimento intra-uterino, sequencia de oligamnio, hipotensao e insuficiencia renal aguda no periodo neonatal e persistencia de canal arterial. O objetivo e chamar a atencao para os possiveis efeitos neonatais do uso desta droga durante a gestacao. Os autores descrevem um caso de uso de captopril durante a gestacao, cujo RN apresentou insuficiencia renal aguda logo apos o nascimento e persistencia de canal arterial necessitando de tratamento clinico...

Vitamins A and E in neoplastic disease.

Vitamins A and E play an important role against 'free radicals' (FRs). Their antioxidant action is evident in neoplastic disease (ND) that is known to have a FRs pathology. This finding has been supported by previous research showing increased lipid peroxidation of the erythrocyte membrane with increased permeability and higher hemoglobin susceptibility to oxidative stress. Connections exist between the two vitamins and FRs lipid peroxidation of the membranes. In order to study A and E vitamin behaviour in ND, they were assayed in the sera of 88 cancer patients versus 94 healthy subjects. In the 88 cancer cases, without considering variables such as age, sex and smoking habits, the average amount of vitamin A was 47.44+/-19.60 mu g/dl versus 71.77+/-18.30 in controls (P<0.0001). The average amount of vitamin E was 1144.42+/-507.45 in ND versus 1497.45+/-397.74 in controls (P<0.0001). The two vitamins were simultaneously assayed in the same serum by high pressure liquid chromatography. The method is rapid and gave exact and repeatable results. Reasons for vitamin decrease are discussed.

Anti free radical action of calcium antagonists and H1 and H2 receptors antagonists in neoplastic disease.

The blood of the subjects suffering from Neoplastic Disease (ND) shows phenomena of membrane peroxidation due to the presence of Free Radicals (FRs), in a quantity much greater than the one observed in the blood of healthy subjects. This can be detected either by calculating the time necessary for the formation of "Heinz bodies" (Hbs), (p < 0.00001) after oxidative stress of the blood in vitro with acetylphenylidrazine (APH), or by calculating the methemoglobin (metHb) quantity that forms after the same treatment (P < 0.00001). The statistical analyses we carried out showed that metHb formation was not affected by age, sex, smoking habits, red blood cell number, Hb, Ht or tumor staging. In this study, by using equal parameters of investigation, we noted that the blood of the subjects with ND who were previously treated with calcium-antagonists drugs and with antagonists of H1 and H2 receptors, gave results completely superimposable on the results obtained from healthy subjects, implying that the treatment had avoided the increase of FRs. Therefore we concluded that calcium-antagonists and the antagonists of the H1 and H2 receptors behave as antioxidant substances, having decreased the FRs damaging activity on the cellular membranes, thus controlling, although to a limited degree, the pejorative evolution of the disease. It is also important to remember that investigations into the ND, even possible screenings, must take into account the above said data, submitting the subjects under investigation to a pharmacological wash out, particularly with those substances which, are considered to be scavengers of FRs. Some of these substances are investigated in this work.

Iron status in schizophrenic patients with acute neuroleptic-induced dystonic reactions.

1. Serum iron parameters were measured in a group of schizophrenic patients who had developed acute neuroleptic-induced dystonia (N = 17) and in control patients with no history of extrapyramidal disorders (N = 16). No differences were found between the two groups for iron, ferritin or transferrin levels. 2. Iron status was estimated in 44 schizophrenic patients starting treatment with high-potency neuroleptics before and after 3 weeks of medication. In the 6 patients developing dystonia serum iron levels as well as other iron parameters did not differ from the values observed in the remaining 38 patients either on admission or after neuroleptic treatment. In each group the haematological profile was not modified by neuroleptic medication. 3. These results do not support an association between low serum iron and the occurrence of neuroleptic-induced dystonic reactions.

Gastrin 17 and gastrin 34, before and after a meal, in newborn infants.

In 89 healthy full-term newborn infants, we studied the different contribution of gastrin 17 (G17) and gastrin 34 (G34) to neonatal hypergastrinemia and the G17 and G34 response to a meal in the first days of life. Serum concentrations of G17 and G34 were measured by radioimmunoassay specific for the NH2-terminus of G17 and G34 in 23 newborn infants in the cord blood and in 66 newborn infants before or 20 min after bottle-feeding. Basal serum G17 and G34 values were also obtained in 38 healthy fasting adults. Mean (+/- SEM) G17 levels in the cord blood were not different from those of the adult controls (29.28 +/- 4.16 versus 31.00 +/- 2.62 pg/ml) and increased significantly either at 12 h (48.06 +/- 7.32 pg/ml, p less than 0.025) or on the 4th day of life (80.56 +/- 9.99 pg/ml, p less than 0.01). Serum G34 levels in the cord blood were significantly higher than in adult controls (163.22 +/- 11.19 versus 126.68 +/- 5.57 pg/ml, p less than 0.005) and increased at 12 h of life (225.22 +/- 25.95 pg/ml, p less than 0.02), but no increase was found on the 4th day of life (204.87 +/- 18.08 pg/ml). Neither postprandial G17 nor G34 increases were found on the 1st or on the 4th day of postnatal life. The study supports the following conclusions: (a) neonatal hypergastrinemia is mainly due to G34 fraction; (b) the increased levels of gastrin on the 4th day of life are due to G17 fraction; (c) bottle-feeding does not stimulate either G17 or G34 release in the first 4 days of life.

Usefulness of carcinoembryonic antigen measurement in gastric juice of patients with gastric disorders.

Due to conflicting reports on the role of CEA measurement in the gastric juice of patients with gastric malignancy, we have assessed gastric CEA levels in a variety of both nonmalignant and malignant lesions of the stomach. The average gastric CEA levels were higher in patients with gastric ulcer and gastric cancer than in healthy subjects and those with duodenal ulcer. In addition, the frequencies of abnormally high values were significantly (P less than 0.001) higher in gastric ulcer or gastric cancer than in healthy or duodenal ulcer groups, whereas there was no difference between gastric ulcer and gastric cancer groups. The evaluation of gastric CEA levels in relation to gastric inflammatory changes leads us to suggest a close relationship between gastric CEA values and the degree of gastric inflammation. Gastric lavage cytology did not provide a sensitive tool for detection of gastric disorders. This study suggests little value for gastric CEA determination in gastric cancer detection. However, we believe the association of rising gastric CEA levels with various types of gastritis justifies measuring gastric CEA to recognize "precancerous" mucosal changes of the stomach.

[Inhibitory effect of somatostatin on the secretion of duodenal gastrin]. / Effetto inibitorio della somatostatina sulla secrezione di gastrina duodenale.

This study covers 14 patients subjected to truncal Vagotomy + Antrectomy acc. BI, in order to ascertain whether somatostatin is capable of inhibiting duodenal gastrin release. Somatostatin infusion significantly inhibits the gastrinic response to a protein meal, but does not affect basal levels of the hormone. This suggests that facilitation of duodenal gastrin release after vagal section may be mediated by the reduced somatostatin release.

[Autograft of pancreatic tissue in the spleen of pancreatectomized dogs]. / Autotrapianto di tessuto pancreatico nella milza di cani pancreatectomizzati.

The intrasplenic autotransplant of pancreatic fragments in dogs subjected to total pancreatectomy can prevent diabetes as it maintains normoglycaemic condition and a normal insulinaemic response to i.v. infusion of glucose. By adopting a pancreatic tissue preparation technique which provides for a very short collagenasis digestion time (4 minutes), B cells took and normal glucidic metabolism was maintained.