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N Frisina

Publications and source records attributed to N Frisina.

At least 19 recordsLinked to original sources
PubMed2006

From the oxygen to the organ protection: erythropoietin as protagonist in internal medicine.

Erythropoietin (EPO), already known as the stimulating hormone for erythropoiesis, has shown different and interesting pleiotropic actions. It does not only affect erythroid cells, but also myeloid cells, lymphocytes and megakaryocytes. This hormone can also enhance phagocytic function of the polymorphonuclear cells and reduce the activation of macrophages, thus modulating the inflammatory process.Moreover, hematopoietic and endothelial cells probably have the same cellular origin, and the discovery of erythropoietin receptors (EPO-R) also on mesangial and myocardial cells, smooth muscle fibrocells and neurons has prompted the study of the non-erythropoietic functions of this hormone.The interaction between EPO and VEGF may be of particular importance in neovascularization and wound healing. Different studies have demonstrated that EPO has an important direct hemodynamic and vasoactive action, which does not depend exclusively on any increase in hematocrit and viscosity. Moreover EPO showed protective effects on myocardial cells against apoptosis induced by ischemia/repefusion injury, but it could negatively affect pulmonary hypertension in patient with chronic cor pulmonale.This review aims to stress the importance of the increasing interest in EPO applications and the necessity of further studies to gain a deeper knowledge of this hormone and its pleiotropic and complex actions.

Anemia↗
PubMed2005

Hepatic osteodystrophy: does the osteoprotegerin/receptor activator of nuclear factor-kB ligand system play a role?

Multiple factors can contribute to the development of osteodystrophy in patients with chronic liver disease (CLD). Recently, two new cytokines, osteoprotegerin (OPG) and the receptor activator of nuclear factor-kB ligand (RANKL), have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Therefore, the aim of our study was to evaluate bone metabolism, bone mineral density (BMD) and OPG/RANKL system in 65 male patients with CLD and in 65 healthy controls. Our patients showed lower BMD values than controls both at lumbar and femoral levels. Moreover, they had an unbalanced bone turnover with an increased resorption phase, as shown by high levels of urinary deoxypyridinoline and a decreased formation phase, as shown by the slightly, but significant, low levels of bone-alkaline phosphatase. Patients showed lower plasma levels of free-testosterone than controls and higher - although not significantly so - plasma levels of 17 beta-estradiol. Furthermore, patients with CLD had higher levels of sex hormone-binding globulin and OPG, and lower levels of 25-hydroxyvitamin D (25-HOD) and IGF-I than the control group, while RANKL levels were similar in the two groups. In conclusion, our data do not confirm the hypothesis that the OPG/RANKL system could exert a key role in the pathogenesis of hepatic osteodystrophy, but rather that the observed increase in OPG levels may represent either the result of the inflammatory process per se or a compensation for the observed enhanced bone resorption.

Absorptiometry, Photon↗
PubMed2005

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.

Absorptiometry, Photon↗
PubMed2004

Effects of a long-term treatment with raloxifene on insulin sensitivity in postmenopausal women.

AIMS/HYPOTHESIS: Our aim was to investigate the effect of long-term administration of raloxifene, a selective estrogen receptor modulator, on insulin sensitivity, glucose tolerance and plasma lipid concentrations in a group of postmenopausal women. METHODS: A total of 24 women with postmenopausal osteoporosis were consecutively enrolled and randomly assigned to take raloxifene, 60 mg/day for 12 months or placebo. At baseline and after 6 and 12 months, in each subject insulin sensitivity (M-index) was assessed by means of an euglycaemic hyperinsulinaemic clamp. Plasma concentrations of total cholesterol, triglycerides and HDL-cholesterol were also measured and glucose tolerance was evaluated. RESULTS: In the raloxifene-treated group, the M index decreased after 6 and 12 months with respect to the placebo group (-21%, p=0.042 and -23%, p=0.018, respectively). Neither fasting plasma glucose nor glucose tolerance changed in the raloxifene-treated group, compared to the placebo group. Low density lipoprotein cholesterol concentrations decreased at 12 months (-13%, p=0.047). CONCLUSION/INTERPRETATION: A long-term treatment with raloxifene in osteoporotic, otherwise healthy post-menopausal women can reduce insulin sensitivity without affecting glucose tolerance.

Blood Glucose↗
PubMed2004

Effect of interleukin 8 and ICAM-1 on calcium-dependent outflow of K+ in erythrocytes from subjects with essential hypertension.

INTRODUCTION: The pathogenic mechanisms underlying the increase in peripheral resistance and the contraction of smooth muscular fibre cells in essential hypertension are not yet clearly understood. However, it is now known that immune system activation plays a role in the pathogenesis of some forms of arterial hypertension, and recent data show that the Ca2+ influx in some cells (i.e. red blood cells, leukocytes, platelets, smooth muscular fibre cells) is increased in subjects with essential hypertension, thus revealing a possible alteration in cellular membrane. The end-points of this study were therefore to ascertain whether red blood cells used as a cellular membrane model have a greater Ca2+ dependent K+ flow (Gardos effect) in hypertensive patients than in normotensive controls, to point out a different regulation of ionic channels, and whether IL-8 and the adhesion molecule ICAM-1 influence the membranous outflow. MATERIAL AND METHODS: The study was conducted on 87 Caucasian subjects. Of these, 50 (25 men, 25 women; mean age 43 +/- 3 years, mean body mass index (BMI) 27 +/- 0.5 and 22.3 +/- 0.3 kg/m(2), respectively) had mild-to-moderate hypertension (mean arterial blood pressure 120 +/- 8 mmHg ). The other 37 (18 men, 19 women; mean age 39 +/- 3 years; BMI 23.8 +/- 0.5 kg/m(2) and 22.8 +/- 0.5 kg/m(2), respectively were normotensive healthy volunteers (mean arterial blood pressure 89 +/- 2 mmHg). All the patients and subjects were untreated for at least 4 weeks before blood sampling. RESULTS: Ca2+-dependent K+ outflow was found to be greater in samples from patients with essential hypertension than in those from normotensive controls. lL-8 and ICAM-1 significantly enhanced the Ca2+-dependent K+ outflow in red blood cells from hypertensive subjects but had an inhibitory effect on cells from controls. In the experimental model, the presence of TMB-8, a membrane calcium antagonist, significantly reduced the Ca2+-dependent K+ efflux. CONCLUSION: Vasoconstriction in subjects with essential hypertension may therefore depend on a different regulation of ionic flow that probably supports an increased Ca2+ inflow in smooth muscle fibre cells. Under certain pathological conditions, some immune system components (i.e. interleukins, adhesion molecules) may directly enhance membrane permeability to Ca2+, thus inducing vasoconstriction in the smooth muscle cells.

Adult↗
PubMed2003

Three-year effectiveness of intravenous pamidronate versus pamidronate plus slow-release sodium fluoride for postmenopausal osteoporosis.

All currently available and approved therapies for osteoporosis inhibit bone resorption. But, despite their great value, antiresorptive agents are generally not associated with dramatic increases in bone mass. In light of these data, the aim of our prospective, placebo-controlled, randomized clinical trial, with a 3-year follow up, was to examine the effects of cyclic intravenous pamidronate and fluoride in combination, versus pamidronate alone, on bone mineral density (BMD) at vertebral and femoral levels, biochemical markers of bone turnover, IGF-1 serum levels, and safety and tolerability in 40 postmenopausal women with osteoporosis. During the treatment period, pamidronate alone reduced both markers of bone formation and bone resorption, resulting in an increase of BMD, after 3 years, of 7.07% at the lumbar level and of 6.76% at the femoral level. In the group treated with pamidronate and fluoride, markers of bone turnover had a different trend: after 3 years, there was a lower reduction of bone resorption and an increase of bone formation markers, with a concomitant increase in IGF-1 levels. This resulted, after 3 years of treatment, in a marked variation of BMD at the lumbar level (+12.74%) and a reduced, but still significant, increase at the femoral level (3.89%). Spine radiography and clinical evaluation did not reveal any vertebral fractures in either treatment group. In conclusion, the combined use of pamidronate and fluoride produced somewhat larger, continuous increases in BMD, at the lumbar level, than pamidronate alone.

Alkaline Phosphatase↗
PubMed2003

The pleiotropic effects of erythropoietin in the central nervous system.

Erythropoietin (Epo) is a hydrophobic sialoglycoproteic hormone produced by the kidney and responsible for the proliferation, maturation, and differentiation of the precursors of the erythroid cell line. Human recombinant erythropoietin (rHuEpo) is used to treat different types of anemia, not only in uremic patients but also in newborns with anemia of prematurity, in patients with cancer-related anemia or myeloproliferative disease, thalassemias, bone marrow transplants, or those with chronic infectious diseases. The pleiotropic functions of Epo are well known. It has been shown that this hormone can modulate the inflammatory and immune response, has direct hemodynamic and vasoactive effects, could be considered a proangiogenic factor because of its interaction with vascular endothelial growth factor, and its ability to stimulate mitosis and motility of endothelial cells. The multifunctional role of Epo has further been confirmed by the discovery in the central nervous system of a specific Epo/Epo receptor (EpoR) system. Both Epo and EpoR are expressed by astrocytes and neurons and Epo is present in the cerebrospinal fluid (CSF). Therefore, novel functions of Epo, tissue-specific regulation, and the mechanisms of action have been investigated. In this review we have tried to summarize the current data on the role of Epo on brain function. We discuss the different sites of cerebral expression and mechanisms of regulation of Epo and its receptor and its role in the development and maturation of the brain. Second, we discuss the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischemia, and subarachnoid hemorrhage, and the consequent possibility that rHuEpo therapy could soon be used in clinical practice to limit neuronal damage induced by these diseases.

Animals↗
PubMed2002

Osteoporosis and beta-thalassemia major: role of the IGF-I/IGFBP-III axis.

Patients with beta-thalassaemia major are susceptible to osteopenia due to several factors which interfere with bone remodeling. It is known that bone metabolism and skeletal consolidation result from a complex sequence of hormonal changes, where the concerted actions of GH, IGF-I and sex hormones and their receptors, are responsible for the timing and attainment of skeletal consolidation. IGF-I and the corresponding binding protein (IGFBP-III), markers of bone metabolism and lumbar and femoral neck BMD were measured in 28 adult patients, undergoing hormonal replacement and chelation therapy and a hypertransfusion program, with beta-thalassaemia major (12 males with mean age 22.5+/-3.1 and 16 females with mean age 27.5+/-8.2), and in 28 healthy volunteers matched for age, anthropometric features and sex to the patients. BMD values, both at lumbar and femoral neck level were significantly lower (p<0.001 and p<0.05) by 18.7 and 4.2% respectively, in patients than in the controls. Markers of bone resorption [pyridinoline (Pyr) 78.1+/-15.7 vs 47.5+/-11.2 pmol/pmol urinary creatinine, p<0.001 and deoxypyridinoline (D-Pyr) 21.9+/-3.5 vs 14.5+/-5.4 pmol/ micromol urinary creatinine, p<0.001] were higher in patients than in controls, whereas the marker of bone formation was slightly lower [osteocalcin (BGP) 3.8+/-0.6 vs 4.6+/-1.7 pmol/ml, p<0.05]. Plasma levels of IGF-I (21.07+/-5.12 vs 35.25+/-8.33 nmol/ml, p<0.001) and IGF binding protein III (IGFBP-III) (1.9+/-0.4 vs 2.5+/-0.1 mg/ml, p<0.001) were lower in patients than in controls and positively correlated with BMD L2-L4 (r=0.57, p<0.05 and r=0.47, p<0.05 respectively), BMD neck (r=0.40, p<0.05 and r=0.34, p<0.05 respectively) and BGP (r=0.52, p<0.05 and r=0.34, p<0.05 respectively). Our beta-thalassaemic patients, in spite of normalizing hemoglobin levels, adequate hormone replacement and chelation therapies, showed osteopenia and an unbalanced bone turnover with an increased resorptive phase and a decreased formation phase probably correlated to low levels of IGF-I and IGFBP-III observed in our study.

Adult↗
PubMed2002

Bisphosphonates in the treatment of thalassemia-induced osteoporosis.

The aim of our randomized, placebo-controlled study was to investigate the effects of 2 years' daily oral administration of alendronate or intramuscular administration of clodronate every 10 days, on bone remodeling parameters and bone mineral density (BMD), safety and tolerability in a group of osteoporotic thalassemic patients. Twenty-five young patients (mean age 26.6 +/- 7.1 years) with beta-thalassemia major were randomly divided to receive placebo or 100 mg of clodronate intramuscularly every 10 days or 10 mg of alendronate per os daily. All patients took 500 mg of elemental calcium and 400 IU cholecalciferol in the evening at meal time. After 2 years, pyridinium crosslinks, which are bone resorption markers, did not differ significantly from baseline values in the placebo group, whereas they had decreased significantly in the clodronate and alendronate groups. Osteocalcin, a bone formation marker, did not change significantly in the placebo group, whereas it decreased slightly, but not significantly, in the clodronate and alendronate groups after 12 and 24 months. At the end of the study, the lumbar spine BMD had decreased significantly in the placebo group; it did not change significantly in the clodronate group; in the alendronate group it had increased but not significantly, whereas the increase was significant with respect to the placebo group. Femoral neck BMD decreased significantly in the placebo group; it did not change significantly in the clodronate group, but increased significantly in the alendronate group. No relevant side effects were recorded during our study. In conclusion, in patients with thalassemia-induced osteoporosis, the daily administration of alendronate significantly increases BMD, the most important predictor of the risk of fracture at several sites. Clodronate treatment at our dosage is ineffective in this pathology in spite of the good compliance of patients.

Absorptiometry, Photon↗
PubMed2002

Erythropoietin and the brain: from neurodevelopment to neuroprotection.

It is now widely known that erythropoietin (Epo) does not only affect the haematopoietic system, but it can be considered a multifunctional trophic factor with an effect on the general homoeostasis of the entire organism. The recent discovery of a specific Epo/Epo-receptor system in the central nervous system (CNS) and cerebrospinal fluid, independently of the haematopoietic system, has further paved the way for new studies aimed at investigating the different sites of cerebral expression of Epo and its receptor, the regulation of their expression and, finally, the effects that this hormone has on the development and maturation of the brain. A further aim has been to investigate how it influences CNS homoeostasis and neurotransmission in adult brain. Attention has also been focused on the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischaemia and subarachnoid haemorrhage, and therefore on the possibility that human recombinant Epo therapy could soon be used in clinical practice, also to limit neuronal damage induced by these diseases.

Animals↗
PubMed2002

Effect of stress on the paracellular barrier in the rat ileum.

BACKGROUND: Restraint stress induces permeability changes in the rat small intestine but little is known of the ultrastructural events leading to defects of the paracellular sealing or of the short term evolution of these alterations. METHODS: In the present study, we performed transmission electron microscopy in the terminal ileum perfused with lanthanum after two hours of immobilisation stress and in non-stressed control rats. Moreover, immunohistochemistry of the tight junction (TJ) associated proteins, occludin and zonula occludens 1 (ZO-1), was carried out together with western blot analysis of the transmembrane protein occludin. TJ morphology was also assessed after a 22 hour recovery period. RESULTS: Immobilisation stress induced a significant increase in epithelial permeability to the lanthanum tracer (p<0.005) which recovered completely after 22 hours. Compared with unstressed controls, in stressed rats no differences were found on freeze fracture analysis. The TJ related immunofluorescence signals of occludin and of ZO-1 were irregularly distributed in stressed rats after two hours but returned to a normal pattern at 24 hours although with minor intensity. No quantitative alterations in occludin were detectable in stressed rats by immunoblot whereas a perinuclear concentration of occludin was observed by immunolocalisation. CONCLUSIONS: Immobilisation stress induced an increase in TJ permeability in the rat terminal ileum. These changes were mainly due to modifications and redistribution of the TJ transmembrane protein occludin and of the plaque protein ZO-1 whereas protein synthesis, at least that of occludin, was not affected by stress.

Animals↗
PubMed2002

AQP1 in red blood cells of uremic patients during hemodialytic treatment.

Hemodialysis influences the transport of water through the erythrocytic membrane, and induces morphologic and functional modifications. Recently water channels, called aquaporins (AQP), have been identified on the membrane of red blood cells. The aim of the present study was, therefore, to evaluate any relationships between volumetric changes in erythrocytes (MCV), plasma osmolarity and membrane expression of AQP1 in 22 uremic patients during a hemodialysis session, and compare value with those in a control group of 22 healthy volunteers. Membranal AQP1 expression was evaluated using three methods: indirect immunofluorescence under confocal microscopy, immunoenzymatic method after membrane extraction, and immunoblotting. In uremic subjects, at baseline membrane AQP1 expression was significantly lower, whereas plasma osmolality was higher than in controls. At 1 and 2 h of replacement therapy, a progressive increase was observed in erythrocytic AQP1, values similar to those in controls being attained after 3.5 h. During the session osmolality values reduced progressively, becoming significantly lower than basal values. The mean erythrocytic corpuscular volume in patients with ESRD was significantly lower than in cntrols at baseline. This value increased during hemodialysis, attaining statistical significance with respect to the basal value at 3.5 h of dialysis. Close correlations were found between plasma osmolality and AQP1 values (r = -0.930; p < 0.05), and also between MCV and plasma osmolality trend (r = -0.909; p < 0.05). There was a linear correlation (r = 0.63, p < 0.05) between plasma AVP concentrations and plasma osmolality. The variations found in plasma osmolarity during hemodialysis, may induce AQP1 expression on the membrane of intact red blood cells.

Adult↗
PubMed2002

Effects of long-lasting raloxifene treatment on serum prolactin and gonadotropin levels in postmenopausal women.

OBJECTIVE: To evaluate the effects of a 6 month administration of raloxifene hydrochloride, a selective estrogen receptor modulator which was recently approved for the prevention of osteoporosis, on serum gonadotropin and prolactin (PRL) levels and on TRH-stimulated PRL responsiveness in postmenopausal women who have not undergone estrogen replacement therapy. DESIGN AND METHODS: Sixteen healthy postmenopausal women were divided into two groups on the basis of their bone status, evaluated by dual energy X-ray absorptiometry at the lumbar level. Eight women (chronological age 52.4+/-4.1 (s.d.) years, menopausal age 42.4+/-3.9 years), in whom T-score L2-L4 was less than -2.5 s.d., were treated with raloxifene (60 mg p.o.) administered daily for 6 months (group 1), while the other eight women (chronological age 52.6+/-2.5 years, menopausal age 42.1+/-3.6 years), in whom the T-score L2-L4 ranged between -1 and -2.5 s.d., were used as a control group (group 2). Serum PRL, FSH, LH and 17beta-estradiol (E2) levels were evaluated at baseline and after 3 and 6 months of treatment. In all subjects, PRL responsiveness to TRH (200 microg i.v.) administration was evaluated at baseline and at the end of the study. RESULTS: At baseline, mean PRL, LH and FSH levels were not significantly different in the two groups (PRL 133.6+/-21.7 vs 136.7+/-28.1 mIU/l (NS), LH 25.1+/-6.8 vs 24.4+/-6.7 mIU/ml (NS), FSH 74.4+/-25.0 vs 71.1+/-24.1 mIU/ml (NS), in group 1 and group 2 respectively). No significant variations in serum FSH and LH values, in either group, or in serum PRL levels in group 2, were observed at the 3 and 6 month examinations. On the contrary, serum PRL values decreased significantly in group 1 after 3 months (100.1+/-47.7 mIU/l, P<0.05) and 6 months (81.5+/-30.2 mIU/l, P<0.001). At baseline, no significant differences were observed in the TRH-stimulated serum PRL peak between the groups (1015.4+/-30.5 vs 1030.2+/-25.7 mIU/l in group 1 and in group 2 respectively), while it decreased significantly at the 6 month examination in group 1 (770.5+/-47.4 mIU/l, P<0.001) and it was significantly lower than in group 2 (1068.1+/-301.8 mIU/l, P=0.02). Serum E2 was not detected at baseline and at each examination, in all patients. CONCLUSIONS: The decrease of PRL values induced by long-term raloxifene administration in postmenopausal women could be explained by a direct antiestrogenic effect of raloxifene on lactotrope cells or by the recently suggested increase of opiatergic tone on the hypothalamic-pituitary region.

Adult↗
PubMed2001

Effects of homocysteine on proliferation, necrosis, and apoptosis of vascular smooth muscle cells in culture and influence of folic acid.

BACKGROUND: It is known that hyperhomocysteinemia is associated with an increased risk of vascular disease, yet little is known about the pathogenic mechanisms underlying the action of homocysteine (Hcy) itself. METHODS: We evaluated the effects of Hcy on cell proliferation, apoptosis, and necrosis in smooth muscle cells (SMCs) cultured for 24 h with different amounts of Hcy. The percentage of apoptotic and necrotic cells from the culture was evaluated using two different techniques: annexin V-FITC and propidium iodide (PI) fluorescence and apoptosis TUNEL assay. RESULTS: The addition of 10 microM/l of Hcy to the medium was followed by a significant increase in cell proliferation and death, through apoptosis and necrosis, respectively. Notwithstanding this apparent balance, a significant increase was found in the total number of cells present in Hcy-treated culture, thus demonstrating a positive dose-dependent correlation with Hcy concentrations in the culture medium. The addition of folic acid to the culture medium significantly reduced both Hcy concentrations in media and the effects of Hcy on the proliferation/apoptosis/necrosis balance of cells in culture. The percentages for apoptotic cells and for cells with a necrotic morphology continued to increase as Hcy concentrations increased, although the absolute values were lower in the culture treated than in that not treated with folic acid. CONCLUSIONS: In the presence of folic acid, at increasing concentrations of Hcy, the total number of cells in culture showed increases far less relevant with respect to the control. Also the percentage of apoptotic cells to that of cells with a necrotic morphology, although conserving the tendency to increase to growth of the concentrations of Hcy, have shown absolute values that were lower in the folic acid-treated cultures.

Apoptosis↗
PubMed2001

Effects of hormonal replacement therapy on bone metabolism in young adults with beta-thalassemia major.

The aim of our cross-sectional study was to evaluate the effects of hormonal replacement therapy (HRT) on a population of young thalassemics in order to understand better the role of hypogonadism in the balance of bone metabolism. Markers of bone turnover and bone mineral density (BMD) were measured in 40 young patients (mean age 19.8 +/- 4.5 years) with beta-thalassemia major: 20 subjects were biochemically eugonadal. since they were undergoing HRT (group A, treated patients), and 20 were hypogonadic, having suspended HRT (group B, untreated patients). We also examined 20 healthy control subjects (group C) matched for age, anthropometric features and sex to the study groups. Our study shows that young thalassemic patients exhibit a significant loss of cortical and trabecular bone [aBMD L2-L4: 0.886 +/- 0.052 g/cm2 (group A), 0.726 +/- 0.040 g/cm2 (group B), 1.083 +/- 0.090 g/cm (group C); aBMD femoral neck: 0.890 +/- 0.071 g/cm2 (group A), 0.700 +/- 0.065 g/cm2 (group B), 0.934 +/- 0.076 g/ cm2 (group C)]. Osteoporosis is only observed at the lumbar level in treated thalassemic patients, while in untreated patients it involves the femoral neck also. Bone turnover in thalassemic patients is higher in the resorptive phase, than in the neoformation phase and this is more marked in hypogonadic untreated patients. In conclusion, our data demonstrate the important role played by hypogonadism in the development and deterioration of osteopenia/osteoporosis in thalassemia major. Consequently, sex hormone replacement therapy represents an appropriate tool in the prevention and treatment of osteoporosis in thalassemics, probably together with bisphosphonates in cases with severely increased bone resorption.

Adolescent↗
PubMed2001

Gastro-intestinal permeability is increased in patients with limited systemic sclerosis.

OBJECTIVE: to evaluate gastro-intestinal (GI) permeability in patients with limited systemic sclerosis (LSS) at baseline and after oral acetylsalicylic acid (ASA). METHODS: 13 patients with LSS and 10 controls were studied. Baseline GI permeability was assessed with orally administered sucrose, mannitol, and lactulose. Gastric lesions and Helicobacter status were investigated by endoscopy. In 5 patients and 6 controls (with normal baseline permeability) the GI permeability response was assessed after oral ASA. RESULTS: compared with controls, gastric (p<0.05) and intestinal (p<0.02) permeability was higher in LSS patients, at baseline. After oral ASA gastric permeability (sucrose) increased in both groups (controls: 186%, LSS: 265%), whereas the lactulose/mannitol ratio raised significantly only in LSS (+31% and +148%; p<0.05 vs controls). CONCLUSIONS: baseline permeability is altered in LSS; the exaggerated response of the small intestine to ASA may represent a genetically determined or a disease-related dysfunction of the mucosal barrier.

Adult↗