Lombardy diagnostic and therapeutic network of thrombotic microangiopathy.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA) requiring urgent treatment. Standardization of its diagnosis and optimal management is challenging. This study aimed to evaluate the role of centralized, rapid testing of ADAMTS13 in patients experiencing acute TMAs requiring plasma-exchange (PEX) and to estimate the incidence of TTP in a large Italian Region. METHODS: We perfomed a cohort study in the frame of the project "Set-up of a Lombardy network for the study and treatment of patients undergoing apheresis", including 11 transfusion centers in the Region. Consecutive patients referred from 2014 to 2016 with acute TMAs requiring PEX were enrolled. Centralized ADAMTS13 activity testing was performed at the Milan Hemophilia and Thrombosis Center within 24 h. RESULTS: Forty-three TMA patients (44 events) were enrolled, of whom 35 (81%) had severe ADAMTS13 deficiency. Patients with severe ADAMTS13 deficiency were younger, mainly women, with a higher prevalence of autoimmune disorders and a lower prevalence of cancer. Clinical and laboratory characteristics of patients with and without severe ADAMTS13 deficiency largely overlapped, with a lower platelet count being the only baseline marker that significantly differed between the two patient groups (ADAMTS13 activity < 10% vs ≥ 10%: median difference of -27 × 109/l, 95% CI - 37 to - 3). PEX treatment was initiated in all patients, but soon discontinued in cases without severe ADAMTS13 deficiency. In this group, the mortality rate was higher and no episode exacerbations or relapses within 6 months occured. The estimated average annual incidence of acute acquired TTP events was 1.17 [0.78-1.55] per million people. CONCLUSIONS: Severe ADAMTS13 deficiency distinguished two groups of patients with largely overlapping clinical features but different treatment and disease course. This study provides a feasible model implemented in a large Italian region for the practical clinical approach to TMAs and underlines the importance of urgent ADAMTS13 activity testing for an accurate differential diagnosis and therapeutic approach.

Effects of aging and physical activity on articular cartilage: a literature review

The overall aim of this literature review is, by making use of major databases, to introduce the conceptsabout the articular cartilage structure and the effects of aging on articular cartilage. The effects of physicalexercises on those cartilages are also discussed. The most important observations found are: cartilage thicknessdecreases gradually with age as well the content of proteoglycans and water, and there is an increase and thecollagen fibrils, which may be associated with the increased rigidity and fragility of the articular cartilage. Whenproperly done, physical activities produce compressive stimuli which enhance the activity of chondrocytesincreasing its nuclear volume density per area, as well as the width of the layers leading to greater resistance tocompression. Another consequence is extracellular matrix hydration resulting in greater mechanical resistanceand elasticity and a consequent increase the number of collagen fibrils which generates greater resistance todeformation and implies less rigidity. These facts reduce the risk of breakdown of cartilage when it is subjectedto high mechanical demand.

[Hand management in recessive dystrophic bullous epydermolysis]. / Il trattamento della mano nel paziente affetto da epidermolisi bollosa distrofica recessiva.

PURPOSE: Recessive distrofic epidermolysis bullosa creates severe hand deformities with disabling functional limitations. Hand surgeon should perform surgery when deformity inibits function, in order to restore the pinch. MATERIALS AND METHOD: We present our experience on 44 patients and 58 operated hands, with the following schema: hand degloving, grafting of the first web and intraoperative dynamic splinting. RESULTS: In 30 patient with an 8 years follow up, 25 had had good or excellent results, and the 5 remaining shows early recurrence. CONCLUSION: Association of a correct surgical approach and adequate intra and post-operative rehabilitation improve hand function and a slow down inevitable recurrence.

ATP-Citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo.

A series of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids have been synthesized and evaluated as inhibitors of the recombinant human form of ATP-citrate lyase. The best of these have Ki's in the 200-1000 nM range. As the corresponding thermodynamically favored gamma-lactone prodrugs, a number of compounds are able to inhibit cholesterol and fatty acid synthesis in HepG2 cells and reduce plasma triglyceride levels in vivo. The best of these, compound 77, is able to induce clear hypocholesterolemic and hypotriglyceridaemic responses when administered orally to rat and dog. These results provide evidence to support the hypothesis that compounds which inhibit ATP-citrate lyase have the potential to be a novel class of hypolipidemic agent, which possess combined hypocholesterolemic and hypotriglyceridemic activities.

Cytomegalovirus in peripheral blood leukocytes of infants with congenital or postnatal infection.

BACKGROUND: Cytomegalovirus (CMV) is the most frequent agent of viral infection in the fetus; it causes varying damage, particularly neurologic, which becomes evident at birth or in infancy in about 20% of infected individuals. Postnatal acquisition is usually asymptomatic and without sequelae. Laboratory diagnosis of congenital and postnatal infection is based on the demonstration of virus in urine. OBJECTIVES: To investigate the systemic spread of CMV in neonates with congenital or postnatal infection and to evaluate its significance in diagnosis and in monitoring anti-CMV treatments. DESIGN: Quantitative determinations of infective CMV (viremia) and viral antigen pp65 (antigenemia) were performed on peripheral blood leukocytes (PBL) from the buffy coat of heparinized blood from children with a diagnosis of congenital (n = 19) or postnatal (n = 19) infection based on viral isolation from urine. RESULTS: Antigen pp65 in PBL was detected particularly in children with symptomatic infection, both congenital (100%) and postnatal (79%; P > 0.05), and significantly less frequently (50%; P < 0.001) in those with asymptomatic infection. Viremia was observed less often but always in association with antigenemia. Both tests became negative within 6 months. Neither viral titer nor persistent positivity was related to clinical manifestations. In the nine infants given anti-CMV therapy (ganciclovir and/or hyperimmune gamma-globulins) an early suspension of treatment resulted in the appearance of antigenemia and/or viremia. CONCLUSIONS: Cytomegalovirus was detected in PBL mainly in the most severely affected children. Monitoring antigenemia and viremia in CMV-infected infants is recommended to demonstrate persistent systemic infection and to evaluate virologic results of treatment.

ATP-citrate lyase as a target for hypolipidemic intervention. Design and synthesis of 2-substituted butanedioic acids as novel, potent inhibitors of the enzyme.

ATP-citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Inhibitors of the enzyme represent a potentially novel class of hypolipidemic agent, which are anticipated to have combined hypocholesterolemic and hypotriglyceridemic properties. A series of 2-substituted butanedioic acids have been designed and synthesized as inhibitors of the enzyme. The best compounds, 58, 68, 71, 74 have reversible Ki's in the 1-3 microM range against the isolated rat enzyme. As representative of this compound class, 58, has been shown to exert its inhibitory action through a mainly competitive mechanism with respect to citrate and a noncompetitive one with respect to CoA. None of the inhibitors were able to inhibit cholesterol and/or fatty acid synthesis in HepG2 cells. This has been attributed to the adverse physicochemical properties of the molecules leading to a lack of cell penetration. Despite this, a lead structural class of compound has been identified with the potential for modification into potent, cell-penetrant, and efficacious inhibitors of ATP-citrate lyase.

[The action on bacterial plaque of the mastication of a sorbitol chewing gum]. / Azione sulla placca batterica della masticazione di chewing-gum al sorbitolo.

The authors made a clinical evaluation of mastication of sorbitol chewing gum and its interference on plaque accumulation on teeth in 14 volunteers, 10 men and 4 women with an age average of 27 y.o., who joined both control and gum groups for 1 or 2 or 3 days. Both groups, after perfectly cleaning their teeth, were requested to avoid any measure of oral hygiene for the whole time of the study and the gum group was advised to chew one sorbitol chewing gum immediately after every assumption of solid food for unless than 30' minutes with a minimum of 4 pieces a day (after breakfast, after lunch, during the afternoon, after dinner). They were supplied with one of two most diffused sorbitol chewing gums in Italy: Vivident in 8 and Happydent in 6 cases. The choice of sorbitol was made because it can be considered a non-cariogenic sweetener and because in our country it is the most used in the so called "senza zucchero" gums and sweets. Plaque extension was evaluated by Quigley-Hein plaque index with the same procedure of the original work and taken as a parametric value in order to apply parametric tests as media, normal distribution, standard deviation, variance, Student's tests, etc. These evaluations were made on Ramfjord's teeth: 1.6, 2.1, 2.4, 3.6, 4.1, 4.4 each one divided in two half. Results, so processed, showed a significant reduction (-0.96%; p < 0.01) of plaque index for 1 day with best effect on vestibular half of frontal teeth (p between < 0.01 and < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Dentin adhesives. An update]. / Gli adesivi dentinali. Aggiornamento.

Even if mechanical bonding to enamel utilizing the acid-etch technique has been very successful, adhesion to dentin is still a challenge to researchers and clinicians. Dentin is a vital tissue and differs in composition from enamel: acid-etching does not enhance the bond strength of composite resins to dentin and may elicit a severe pulpal response. For an effective bond to occur, a dentin bonding system has to be used. The first generation of methacrylate-based dentin adhesives was capable of chemical bonding to the inorganic phase of dentin. The chemical basis for this resin-dentin adhesive was the interaction between a phosphate group attached to the methacrylate and the calcium ions on the dentin surface. This system yielded rather low bond strengths which were clinically unsatisfying. The second generation of dentin adhesives became available to the profession recently. Each of these new bonding systems use similar chemical composition for the same purpose of bonding with physicochemical interaction to the hard tooth tissues. All these systems contain a mild acid dentin conditioner to remove the smear layer and an aqueous resin containing primer to improve monomer penetration into the hydrophilic dentin surface. The second generation dentin bonding systems are extremely sensitive to variations upon the completeness of instructions and how accurately these are followed by dental practitioners.