Resistin levels and inflammatory and endothelial dysfunction markers in obese postmenopausal women with type 2 diabetes mellitus.

BACKGROUND: Obesity-associated coronary heart disease (CHD) risk is higher in women than in men with type 2 diabetes (T2DM). Resistin, an adipokine secreted by adispose tissue, may contribute to this higher risk. AIMS: To explore the relationships among resistin levels and common inflammatory and endothelial dysfunction markers and CHD risk in obese post-menopausal T2DM women. METHODS: Serum levels of resistin, hsCRP, IL-6, Soluble vascular cell adhesion molecule (sVCAM), homocysteine (tHcy), HOMA-IR and metabolic parameters were determined in a group of 132 T2DM women with and without documented CHD and in 55 non-diabetic women. RESULTS: Resistin, sVCAM, IL-6 and tHcy levels were comparable in T2DM and controls. CHD women showed higher resistin, sVCAM and tHcy levels than those without CHD, and for resistin this difference remained significant after age-adjustment (P = 0.013); conversely hsCRP were ~ 2X higher in T2DM women than in controls (P = 0.0132) without any difference according to CHD history. At univariate analysis resistin levels were significantly associated with age, waist circumference, hypertension, tHcy, hsPCR, sVCAM, IL-6, HDL-cholesterol, triglycerides and creatinine levels, but only creatinine, triglycerides, hsCRP, IL-6 and sVCAM were independently associated to resistin levels at stepwise regression analysis. Resistin levels were independently associated to CHD, increasing the risk by 1.15 times (0.986-1.344 95% CI), together with age, tHcy, LDL-C and hypertension. CONCLUSIONS: Circulating resistin levels were comparable in obese/overweight T2DM and control women. In T2DM women, resistin levels correlated with markers of renal function, systemic inflammation and endothelial dysfunction and were independently associated with a higher CHD risk.

A dynamic distention protocol for whole-organ bladder decellularization: histological and biomechanical characterization of the acellular matrix.

A combined physical-chemical protocol for whole full-thickness bladder decellularization is proposed, based on organ cyclic distention through repeated infusion/withdrawal of the decellularization agents through the urethra. The dynamic decellularization was intended to enhance cell removal efficiency, facilitating the delivery of detergents within the inner layers of the tissue and the removal of cell debris. The use of mild chemical detergents (hypotonic solution and non-ionic detergent) was employed to limit adverse effects upon matrix 3D ultrastructure. Inspection of the presence of residual DNA and RNA was carried out on decellularized matrices to verify effective cell removal. Histological investigation was focused on assessing the retention of adequate structural and functional components that regulate the biomechanical behaviour of the acellular tissue. Biomechanical properties were evaluated through uniaxial tensile loading tests of tissue strips and through ex vivo filling cystometry to evaluate the whole-organ mechanical response to a physiological-like loading state. According to our results, a dynamic decellularization protocol of 17 h duration with a 5 ml/min detergent infusion flow rate revealed higher DNA removal efficiency than standard static decellularization, resulting in residual DNA content < 50 ng/mg dry tissue weight. Furthermore, the collagen network and elastic fibres distribution were preserved in the acellular ECM, which exhibited suitable biomechanical properties in the perspective of its future use as an implant for bladder augmentation.

Migraine and cranial autonomic symptoms in children and adolescents: a clinical study.

The frequency of cranial autonomic symptoms in children affected by primary headaches is uncertain. The aim of our study was to estimate the frequency of symptoms in pediatric headaches and correlate it with main migraine characteristics. A questionnaire investigating the presence of cranial autonomic symptoms was administered to all children with primary headache for 2 years. A total of 230 children with primary headache (105 males, 125 females) were included. Two hundred two children were affected by migraine and 28 (12.2%) by other primary headaches. Cranial autonomic symptoms were significantly complained by migraineurs (55% vs. 17.8%) (P < .001) and by children with higher frequency of migraine attacks (odds ratio = 2.6, confidence interval = 1.4-4.7, P = .001). Our findings show that cranial autonomic symptoms are rather common during pediatric migraine attacks. The association between cranial autonomic symptoms and higher frequency of attacks might suggest the role of the trigeminal-autonomic reflex in migraine pathophysiology.

Immunoglobulin binding of thyroid hormones in a case of Waldenstrom's macroglobulinemia.

This paper describes a case of hypothyroidism in a patient with Waldenström's disease in which the evidence of thyroid failure was accompanied by an abnormal binding of thyroid hormones in the gamma-globulin fraction. A 68-yr-old patient with Waldenström's disease appeared to be hypothyroid by clinical and laboratory criteria. Serum TSH was elevated; serum T3 (measured by RIA) was low, while T4 levels were undetectable or very high according to the method used. Serum free thyroid hormones were in the hypothyroid range, and both antithyroglobulin and antimicrosomal thyroid antibodies were undetectable. The thyroid gland was normal at autopsy. Elevated binding of radiolabeled thyroid hormones by the patient's serum gamma-globulins was demonstrated by reverse flow electrophoresis and cellulose acetate electrophoresis. This binding could be inhibited by preincubation of serum samples with unlabeled T4 and T3, but not with human thyroglobulin, rT3, DIT, or MIT. Immunoprecipitation of the patient's serum incubated with [125I]T4 or [125I]T3 showed that 56% of T4 and 30% of T3, respectively, were precipitated using an antihuman immunoglobulin M(IGM) serum; only [125I]T4 was precipitable (22%) by the addition of an antihuman immunoglobulin G(IgG) serum. The binding of the thyroid hormones by IgM and IgG, which reduced T4 and T3 availability for their metabolic action at the tissue level, could have contributed to the clinical picture.

Correlation between increased serum and tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients.

A group of 14 uremic patients on intermittent hemodialysis was admitted to a cross-over double-blind trial in order to evaluate serum and muscle carnitine levels before and after 60 days of L-carnitine oral (2 g/day) treatment. The morphology of muscle fragments was studied by light and electron microscopy. Symptoms (asthenia, cramps) occurring during hemodialysis were also recorded. After L-carnitine treatment the blood and muscle levels of the metabolite increased simultaneously to reduced asthenia and cramps. Morphological examination of the muscle of 13 of 14 patients did not reveal any pre- or posttreatment pathological alterations. The presence of nemaline rods was morphologically diagnosed in only one case and was no longer observed at the second biopsy at 2 months of L-carnitine treatment.

Supernormal modulation of ventricular parasystole: the triphasic phase-response curve.

Modulation of ventricular parasystole by sinus beats has been shown both in vitro and in vivo to result in a classic biphasic phase-response curve. The first clinical presentation of 3 cases of supernormal modulation of ventricular parasystole resulting in a triphasic phase response curve is reported. Supernormal modulation reflects an unexpected early enhancement expedition of the ectopic ventricular impulses. An alternative explantation for the triphasic phase-response curve is the discharge and resetting of the parasystolic focus by critically timed sinus impulses.

Lymphocyte populations in peripheral blood and in liver biopsy specimens from patients with acute and chronic hepatitis.

Lymphocyte subpopulations, both in peripheral blood and in liver specimens obtained with the Menghini needle, were evaluated by E and EA rosette technique in 30 patients with chronic active hepatitis (CAH), 8 patients with chronic persistent hepatitis (CPH), 11 patients with acute viral hepatitis (AVH) and 11 patients with normal histology or minimal non-specific changes. Circulating E-RCF concentration and percentage were significantly decreased in CAH and CPH patients. Only one patient with acute hepatitis had a decreased number of circulating E-RFC. The ratio of peripheral blood E-RFC to liver tissue E-RFC was decreased in the patient with chronic disease. In all the groups studied, the percentage of liver tissue and peripheral EA-RFC was similar to that found in the blood from controls. Significant differences were not found between patients with and without evidence for HB viral infection.

[Study on the rapid effects of SAMe in primary and secondary triglyceridemias]. / Studio degli effetti rapidi della SAMe nelle ipertrigliceridemie primitive e secondarie

A single dose of 30 mg of S-adenosylmethionine was administered to 15 fasting subjects, scrupolously typified, eight of which were affected with primary hypertriglyceridemia, either of type II B or IV according to Fredrickson's classification, and seven with secondary hypertriglyceridemia. Triglyceride and phosphatide concentrations determined 1, 2, 3 and 4 hours after SAMe administration have shown a decrease in blood triglycerides and an increase in phosphatide levels, with significant values for the subjects with the primary form.

[Chronic idiopathic intestinal pseudo-obstruction associated with volvulus of the transverse colon. The identical mode of clinical presentation and of the intestinal manometric pattern in monozygotic twins]. / Pseudo-ostruzione intestinale cronica idiopatica, associata a volvolo del colon trasverso. Identica modalità di presentazione clinica e del pattern manometrico intestinale in gemelle monozigoti.

Two monozygotic female twins with chronic idiopathic intestinal pseudo-obstruction associated with transverse colon volvulus are described. Quite similar clinical events and temporal coincidences characterized the symptoms which has preceded and followed right colectomy undergone by both of them due to intestinal volvulus. The esophageal, gastroduodenal, colonic and anorectal manometric investigation revealed very similar alterations in both girls. Increased amplitude of distal contractions of the esophagus, a depressed fasting antro-duodenal motility, with absence into antrum and oro-aboral non-propagation in the duodenum of the phase III activity of the interdigestive motor complex were the main findings along with a state of pronounced colonic hypomotility and an hypoesthesia of the rectal ampulla to the volumetric stimulus. This report indicates the association between chronic intestinal pseudo-obstruction and transverse colon volvulus in monozygotic female twins, and it points out the rarity both of the specific symptomatic coincidences and the similar clinical events and of the almost absolute identity of the intestinal motor patterns.

[Compression therapy in deep venous thrombosis]. / La terapia compressiva della trombosi venosa profonda.

External compression, both intermittent by pneumatic pumps and continuous by anelastic or elastic bandages and by graduate compression stockings, play a pivotal role in prophylaxis of Deep Venous Thrombosis (DVT). The use of external compression in DVT therapy and in prophylaxis of pulmonary embolism (PE) and of post-thrombotic syndrome has not been validated as well as in DVT prophylaxis. The pathophysiologic properties of the external compression and the most recent evidences about the early mobilization of the patients with DVT and about Low Molecular Weight Heparin (LMWH) therapy suggest the advantages of the external compression. The authors review the most important clinical investigations about early use of external compression in DVT joined with pharmacological therapy: the results have been the reduction of the growth of the thrombus, the reduction of PE ratio, the prevention of the post-thrombotic syndrome, the indirect improvement of the quality of life. Finally the authors confirm the recommendations about the use of physical therapy with early mobilization and external compression joined with LMWH anticoagulation in DVT.

[Evolution in the pharmacological treatment of venous thrombosis according to evidence-based medicine]. / Evoluzione del trattamento medico farmacologico della trombosi venosa secondo la medicina basata sulle evidenze.

Today therapeutic protocols must be in accordance with Recommendations derived by Randomized Controlled Trials (RCT) Evidences. Deep Venous Thrombosis (DVT), post-thrombotic syndrome and pulmonary embolism (PE) are different forms of the thromboembolic venous disease. The Authors, according with Evidence-Based Medicine, review the most significant RCT about Low-Molecular-Weight Heparin (LMWH). It has been proved that LMWH is more efficacious, easier to administrate and with less significant side effects than Unfractioned Heparin (UH) in DVT treatment. Its higher anti-Xa than anti-IIa activity provides higher anti-thrombotic properties and lower haemorrhagic risk. LMWH does not require anticoagulant monitoring and allows outpatient--ambulatory care. RCT also showed lower PE ratio and lower haemorrhagic risk with LMWH outpatient care than with UH in-hospital care for DVT. RCT showed also a long-term lower DVT relapse and PE incidence with LMWH than with oral anticoagulants. The Authors report their own experience with LMWH and early ambulation for the treatment of DVT versus standard UH therapy. Their retrospective analysis confirms lower incidence of complications: growth of the thrombus, severe haemorrhages, PE.

[Physical treatment of deep venous thrombosis: bed rest or mobilization?]. / Trattamento fisico della trombosi venosa profonda: riposo a letto o mobilizzazione?

The need of prolonged bed-rest for the treatment of Deep Venous Thrombosis (DVT), which was considered essential to control the thrombotic phenomenon and to prevent Pulmonary Embolism (PE) until ten years ago, has now been critically reviewed in the light of the great success of the Low Molecular Weight Heparin (LMWH) in medical therapy of DVT. There is a great evidence for bed-rest and immobility to play a pivotal role in the growth and in the progression of a venous thrombosis. The Authors emphasize, both on the international reports and their own experience, that, in most cases, medical treatment of DVT consists of an outpatient--ambulatory care based on immediate mobilization and ambulation, on external compression therapy, on early LMWH administration and late oral anticoagulation. This regimen provides great benefits in order to prevent PE, to improve the quality of life, to reduce the hospital and the anticoagulant monitoring charges.

[Cardiologic diagnosis of pulmonary embolism: echocardiography]. / Diagnostica cardiologica dell'embolismo polmonare: l'ecocardiografia.

Pulmonary embolism (PE) represents the third more frequent cardiovascular disease following the acute coronary artery disease and stroke. The most important predisposing clinical condition for PE is represented by the deep-vein thrombosis. The clinical diagnosis of PE has a very low accuracy; so the clinical suspect has to be necessarily directed towards the performance of diagnostic procedures. Among the most used procedures, the echocardiography has a diagnostic role but also a prognostic one. Moreover, it offers precious informations useful to perform the most suitable treatment. The echocardiography features which suggest the presence of pulmonary embolism are: right ventricle and atrium dilatation, right ventricular hypokinesia, systolic flattening of the interventricular septum, tricuspid regurgitation, pulmonary artery dilatation, disappearance or reduction of the inspiratory collapse of the inferior vena cava and presence of eventual embolic sources. According to the involvement degree of right ventricular function, it is generally possible to identify a different survival. The subgroup of patients with moderate or severe right ventricular dysfunction shows a high in hospital and within 1 year death rate. For this reason the right ventricular dysfunction degree together with the hemodynamic stability, are the most important parameters in the therapeutic choice. If there is no right ventricular dysfunction a treatment with heparin is indicated. In presence of right ventricular dysfunction and hemodynamic instability, the thrombolytic treatment is necessary. If the patient is hemodynamically stable, a transesophageal echocardiography is recommended; in case of central thrombosis the thrombolytic therapy or surgery are needed, while if no embolic material is shown the heparin treatment is advisable.

[Report on long-term hemofiltration in the treatment of end-stage renal failure]. / Bilancio di una esperienza a lungo termine con emofiltrazione nel trattamento della insufficienza renale cronica terminale.

Thirteen uraemic patients in chronic hemofiltration was studied over a 37.3 +/- 25.4 months period. Hemofiltration value in long-term treatment of uraemia was verified by: dialytic adequacy, clinical data, complications, drop-out morbidity and survival. Our experience indicates that hemofiltration and especially high efficiency hemofiltration is an effective and soft therapy for substitutive long-term treatment in high risk patients.

[Treatment of refractory heart failure with different dialysis technics]. / Il trattamento dello scompenso cardiaco refrattario con differenti tecniche dialitiche.

The efficacy of the dialysis in the heart failure non responsive to the traditional methods is well known. In our study we have evaluated the effects of three different dialytic methods (UFI: ultrafiltration isolate; HF: hemofiltration; CAVH: continuous arteriovenous hemofiltration). These methods are used to cause a good depletion in the patients with intractable heart failure following from ischaemic valvular or primitive cardiomiopathy. We have treated 18 patients (6 for each method) and the patients with organic or functional renal disease were treated with the methods (HF and CAVH) that have depletive and depurative effects. Each of these methods is capable, without important differences, of achieving the following aim: the hydro-sodium depletion, the correction of the haemodynamic alteration and the re-establishment of the response to the traditional medical treatment. Using the hemofiltration and continuous arteriovenous hemofiltration, both soft methods, we have obtained values of dehydratation, absolute and for each session, higher than isolated ultrafiltration. The follow-up has not pointed out differences, of both prognosis and survival among patients treated with the three methods studied, whose effects are always only temporary; only the heart transplantation or the valvular correction, by operating in a very important way on the basal cardiopathy, is the resolutive event.

[Cardiorenal physiopathology and heart failure: current aspects and therapeutic prospects]. / Fisiopatologia cardio-renale e scompenso cardiaco: attualità e prospettive terapeutiche.

The heart and the kidney exert a reciprocal control of their function in order to maintain a steady state of haemodynamics, both in physiological and pathological conditions. The functional relationship between the two organs becomes particularly evident during heart failure. The knowledge of such relationship may play an important role in the management of heart failure. We also report here our experience in the treatment of congestive heart failure with depletive techniques vicarious of kidney function.

[The esophageal motor pattern and the acid exposure of the distal esophagus in patients with gastroesophageal reflux]. / Pattern motorio esofageo ed esposizione acida dell'esofago distale in pazienti con malattia da reflusso gastro-esofageo.

Low-compliance standard manometry and 24-hour ambulatory pH monitoring were performed in 42 patients with typical gastro-esophageal reflux (GER) symptoms in order to assess correlations between esophageal motility pattern and pH profile. Our results show: 1) 36% of GER patients had a normal esophageal acid exposure; 2) pH profile and manometric pattern did not differ in patients with mild esophagitis from those without esophagitis; 3) low esophageal sphincter pressure in GER patients was significantly lower than in control subjects, irrespective of acid exposure; 4) the main motility disorders in the distal esophagus of reflux patients was the increased simultaneous wave rate which seemed to affect both recumbent esophageal clearance and reflux time.

Zinc supplementation in children and adolescents with acute leukemia.

BACKGROUND/OBJECTIVES: Zinc is known as an essential micronutrient for human health because of its structural and biochemical functions, influencing growth and affecting multiple aspects of the immune system. Zinc has been extensively studied in neoplastic processes but its role in children with leukemia still remains to be elucidated in several aspects. The aim of this study was to evaluate the effects of oral zinc supplementation on weight gain and infectious episodes in children and adolescents with acute leukemia. SUBJECTS/METHODS: This study included 38 patients, and was carried out as a randomized, double-blind, placebo-controlled investigation. The dosage of plasma zinc levels and the evaluation of nutritional status were performed during a period of 60 days. Zinc was supplemented orally, 2 mg/kg/day, in the form of amino acid salt. RESULTS: The results showed that plasma zinc concentrations did not increase significantly with the addition of the micronutrient. However, from a clinical point of view, it has become evident that supplementary zinc exerts a positive effect on nutritional status as positive weight gain. Moreover, the number of infection episodes was significantly reduced, possibly because of the immune stimuli. CONCLUSIONS: In conclusion, zinc supplementation can prevent some of the chemotherapy adverse effects in children with leukemia, improving their quality of life.

Computational modeling for the optimization of a cardiogenic 3D bioprocess of encapsulated embryonic stem cells.

We present a computational fluid dynamics (CFD)-based model aimed at the identification of optimized culture conditions promoting efficient cardiogenesis of hydrogel-bead-encapsulated embryonic stem cells (ESCs) within a rotating bioreactor. The numerical approach, integrating diffusion, convection, and multiphase fluid dynamics calculations, allowed to evaluate (i) the microgravity motion of the floating beads, (ii) the O(2) delivery to the cells, also (iii) taking into account the cellular O(2) consumption, as a function of different rotation speeds of the breeding chamber. According to our results, a 25 rpm rotation (i) enhances an adequate mixing of the cell carriers, avoiding sedimentation and excessive packing, also maintaining a quite homogeneous distribution of the suspended beads and (ii) imparts a proper cellular O(2) supply, providing cells close to a normoxia condition. The bioreactor working conditions derived from the numerical analysis allowed the attainment of in vitro long-term cell viability maintenance, supporting efficient large-scale generation of ESC-derived cardiomyocytes (ESC-DCs) through a chemical-based conditioning bioprocess. In conclusion, we demonstrated the feasibility of using CFD-based tools, as a reliable and cost-effective strategy to assist the design of a 3D cardiogenic bioprocess.