Urinary Excretion of Pyridinium Cross-Links and Serum Osteocalcin Levels in Patients with Primary High-Grade Osteosarcoma

Osteosarcoma is the most frequent primary high grade bone tumor, usually occurring in adolescents and children. The aim of the present study was to investigate parameters of bone turnover as urinary excretion of pyridinoline (Pyr), and deoxypyridinoline (D-Pyr), serum osteocalcin (OC), and total alkaline phosphatase (AP) in patients with osteosarcoma. Thirty-five patients aged 7–22 (median age 14) with primary high-grade osteosarcoma of the extremity entered the study. A control population of age- and sex-matched healthy individuals was studied. Urinary excretion of Pyr, D-Pyr was measured on fasting urine specimens, corrected for creatine excretion (Ucr), and expressed as pM/µM UCr. At the same time as urine collection, blood samples were taken for measurement of AP and OC. In patients with osteosarcoma the urinary excretion of D-Pyr (74.5 ± 41) was significantly higher (P = 0.005) than in controls (38.2 ± 22.5). The serum level of OC was significantly lower (P < 0.001) in patients with osteosarcoma than in controls. Moreover, significantly (P = 0.03) higher excretion of D-Pyr (85.3 ± 43) was found in patients who relapsed after surgical removal of the tumor and chemotherapeutic treatment compared with those (58.1 ± 22) who remained continuously free of disease. The present study showed significant abnormalities of urinary excretion of pyridinium crosslinks and serum OC level in patients with osteosarcoma. The relation between urinary excretion of D-Pyr and biological tumor aggressiveness observed in the present study requires further investigation.     

Progressive worsening of idiopathic pulmonary fibrosis. High resolution computed tomography (HRCT) study with functional correlations

PURPOSE: To evaluate the usefulness of the high-resolution computed tomography (HRCT) visual score in idiopathic pulmonary fibrosis (IPF) and its correlation with respiratory function tests. MATERIAL AND METHODS: We studied the pulmonary function tests and HRCT scans of 42 IPF patients, at presentation (T0) and follow-up (T1: mean 13.7 months post-diagnosis). Of the 42 patients, 21 had been treated with steroid and immunosuppresion therapy. The pulmonary function tests considered were vital capacity (VC), diffusion lung capacity for carbon monoxide (D(L)CO) and arterial blood oxygen partial pressure (PaO(2)). The main HRCT parameters were type of lesion, and site and extent, the latter calculated by means of the visual score. RESULTS: Between T0 and T1, both mean HRCT score (from 43.57% to 50.64%) and lung function tests worsened (VC from 68.43% to 64.18%; D(L)CO from 36.31% to 28.97%; PaO(2) from 76.31 to 68.89 mmHg), without considerable differences between treated and untreated patients. At presentation (T0), the HRCT visual score had a significant correlation with lung function tests and these correlated with one another. Similar correlations were found at T1, but not for HRCT score and D(L)CO. In the interval between T0 and T1 the variations correlated significantly with each other, with two exceptions: HRCT score and D(L)CO, and D(L)CO and PaO(2). DISCUSSION AND CONCLUSIONS: IPF exhibited a progressive deterioration both in HRCT extent of disease and lung function impairment. There is a significant correlation between HRCT visual score and lung function tests both at diagnosis and at follow-up. The HRCT study is able to identify and quantify anatomic IPF and also to evaluate the progression of the disease. In clinical practice, the HRCT visual score of disease extent can be used in association with function tests to monitor IPF evolution, and to evaluate prognosis and therapy. In the future, helical CT with 3D model construction will provide a more precise IPF quantification with automatic score.     

Zonula occludens toxin: an innovative method of oral drugs delivery

Conventional forms of administration of nonabsorbable drugs and peptides often rely on parenteral injection, because the intestinal epithelium represents a major barrier to the oral absorption of these therapeutical agents into the systemic circulation. Recently, a number of innovative drug-delivery approaches have been developed, including drug entrapment within small vesicles or the passage of the therapeutic molecules through the space between adjacent intestinal cells. This article reviews some of the most promising techniques currently available for oral delivery and their possible practical applications for the delivery of vaccines and drugs for the treatment of clinical conditions that require frequent, chronic parenteral administration.     

Diverse manifestations of acute sickle cell hepatopathy in pediatric patients with sickle cell disease: A case series

The hepatic complications of sickle cell disease (SCD) are associated with increased morbidity and mortality in adults; children usually survive but may suffer significant sequelae. Few diagnostic tools differentiate the various hepatic manifestations of SCD. Why patients exhibit one hepatic pathology versus another is unclear. We report four pediatric patients with hemoglobin SS disease with diverse manifestations of acute hepatic involvement including acute sickle hepatic crisis, hepatic sequestration, sickle cell intrahepatic cholestasis, and a non‐SCD cause of hepatopathy in a patient with viral hepatitis. These complications require a systematic approach to extensive evaluation and coordinated multidisciplinary care.     

Pisa syndrome in Parkinson’s disease: an electrophysiological and imaging study

The pathophysiology of postural abnormalities in patients with Parkinson’s disease is poorly understood. In the present study, 13 patients with Pisa syndrome (PS) underwent EMG study of paraspinal lumbar (L2–L4) and thoracic (T8–T10) muscles, and of non-paraspinal muscles. Patients also underwent a whole spine X-ray and an MRI assessment of paraspinal muscles (L1–S1). The EMG evaluation disclosed two main patterns: patients with pattern I (n = 6, hyperactivity of lumbar paraspinals ipsilateral to the trunk leaning side) or pattern II (n = 7: hyperactivity of lumbar paraspinals contralateral to the trunk leaning side. In pattern I, half the patients also had ipsilateral hyperactivity of the thoracic paraspinals, the other half had contralateral thoracic hyperactivity; in pattern II, thoracic paraspinal hyperactivity was contralateral in all patients (like the lumbar paraspinal hyperactivity). Non-paraspinal muscles were hyperactive ipsilaterally in four of six patients with pattern I and in all patients with pattern II. The MRI showed mild muscular atrophy with fatty degeneration in patients with pattern I, whereas in pattern II patients this was greater and prevalent on paraspinal lumbar muscles ipsilateral to the leaning side. The present data support the hypothesis that two main patterns of muscular activation are associated with PS. In both patterns, hyperactivity of contralateral paraspinal muscles is probably compensatory for the trunk leaning.     

Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer

The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a "leaky gut" in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.     

Regulation of androgen production by frog (Rana esculenta) testis: an in vitro study on the effects exerted by estradiol, 5 alpha-dihydrotestosterone, testosterone, melatonin, and serotonin

The possible role of estradiol-17 beta (E2), testosterone (T), 5 alpha-dihydrotestosterone (DHT), melatonin, and serotonin on the regulation of androgen (A) production by the frog, Rana esculenta, testes was studied in vitro. E2 (10(-6) M) inhibited A production whether alone or in combination with oLH (20 micrograms) after 6 hr incubation. After 24 hr incubation. A production was reduced by E2 concentration of around 10(-6) and 10(-9) M. Melatonin and serotonin did not induce any change whichever experimental condition was used. Preincubation for 6 hr with 10(-6) M T or DHT enhanced the oLH-stimulated A production after 18 hr incubation. These data suggest that steroids may regulate their intratesticular levels without passing into the blood stream.     

Interference by sulphinpyrazone with the antihypertensive effects of oxprenolol

Summary The interfering effect of sulphinpyrazone, a uricosuric agent which reduces the activity of cyclo-oxygenase, with the antihypertensive activity of oxprenolol, a non-cardioselective beta-blocker with sympathomimetic activity, has been evaluated. Ten patients with primary arterial hypertension of mild to moderate degree entered a randomized doubleblind cross-over study versus placebo. They were given oxprenolol + placebo or oxprenolol + sulphinpyrazone for 15 days, and then the treatments were crossed-over for a further 15 days. Oxprenolol significantly reduced blood pressure (161±3/101±1 vs 149±4/96±2 mmHg) and heart rate (72±3 vs 66±3 beats/min). During administration of the combination with sulphinpyrazone the blood pressure increased to its pretreatment level (156±5/101±2 mmHg). The effect of oxprenolol on heart rate was not influenced by the combined treatment (67±6 beats/min). The results may be explained by 1) sulphinpyrazone-induced inhibition of prostaglandin synthesis, which could interfere with the antihypertensive activity of oxprenolol, or 2) sulphinpyrazone-induced acceleration of the metabolism of oxprenolol.