Detection of Autoantibodies against Recombinant Desmoglein 1 and 3 Molecules in Patients with Pemphigus vulgaris: Correlation with Disease Extent at the Time of Diagnosis and during Follow-Up

The recent availability of cDNA clones for pemphigus antigens has allowed the production of recombinant desmoglein 1 and desmoglein 3 molecules and the development of an ELISA approach in order to determine levels of antibodies to them. The aim of the study was to determine the relationship between autoantibodies levels and the extent of both mucosal and skin lesions in 20 patients with pemphigus vulgaris at the time of diagnosis and during follow-up. For the detection of autoantibodies by ELISA we used the recombinant proteins expressing overlapping sequences with the entire extracellular desmoglein 1 and desmoglein 3 domains. We showed that in presence of mucosal lesions there was a correlation between extension of mucosal involvement and autoantiboidies titres against both desmoglein 1 and desmoglein 3, whereas in presence of skin lesions there was a statistically significant correlation between extension of skin lesions and autoantibodies titres against desmoglein 3, but not against desmoglein 1. A not negligible number of patients showed variations of the desmoglein 3 autoantibodies titre which did not correlate with the severity of both cutaneous and mucosal involvement. Similar results were obtained analyzing autoantibodies titres against desmoglein 1. In conclusion, we believe that the utilization of recombinant desmoglein 1 and desmoglein 3 proteins by ELISA should be used with caution to monitor disease severity and response to therapy, although it remains a high specific test for the initial diagnosis of pemphigus and the identification of a change in the clinical phenotype of this condition

Addicts with chronic hepatitis C: Difficult to reach, manage or treat?

AIM: To assess the acceptance, safety and efficacy of care and treatment for chronic hepatitis C (CHC) in drug addicts. METHODS: We designed a multidisciplinary, phase IV prospective cohort study. All illicit drug users (IDUs) visited a Territorial Addiction Service (SerT) in the District of Brescia, and hepatitis C antibody (HCVAb) testing positive were offered as part of a standardised hepatologic visit in our Gastroenterology Unit. Patients with confirmed CHC and without medical contraindications were administered peginterferon alfa-2b 1.5 μg/kg per week plus ribavirin (800-1400 mg/d) for 16-48 wk. All IDUs were unselected because of ongoing addiction and read and signed an informed consent form. Virologic responses at weeks 4 and 12 of therapy, at the end of treatment and 24 wk after the end of treatment were the main measures of efficacy. Adherence was estimated according to the 80/80/80 criteria. RESULTS: From November 2007 to December 2009, 162 HCVAb+ IDUs were identified. Sixty-seven patients (41% of the initial cohort) completed the diagnostic procedure, and CHC was diagnosed in 54 (33% of the total). Forty-nine patients were offered therapy, and 39 agreed (80% of acceptance rate). The prevalent HCV genotype was type 1, and the HCV RNA baseline level was over 5.6 log/mL in 61% of cases. Five patients dropped out, two because of severe adverse events (SAEs) and three without medical need. Twenty-three and 14 patients achieved end of treatment responses (ETRs; 59%) and sustained virologic responses (SVRs; 36%), respectively. Thirty-one patients were fully compliant with the study protocol (80% adherence). The prevalence of host and viral characteristics negatively affecting the treatment response was high: age over 40 years (54%), male gender (85%), overweight body type (36%), previous unsuccessful antiviral therapy (21%), HCV genotype and viral load (60% and 62%, respectively), earlier contact with HBV (40%) and steatosis and fibrosis (44% and 17%, respectively). In a univariate analysis, alcohol intake was associated with a non-response (P = 0.0018, 95%CI: 0.0058-0.4565). CONCLUSION: Drug addicts with CHC can be successfully treated in a multidisciplinary setting using standard antiviral combination therapy, despite several "difficult to reach, manage and treat" characteristics

Mediterranean-Oriented Dietary Intervention Is Effective to Reduce Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: Results from an Italian Clinical Trial

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in western countries. Lifestyle interventions are recommended as the primary therapy for NAFLD. Methodology. In this clinical trial, NAFLD patients were enrolled in a 12-month dietary intervention aimed to improve their eating habits according to the Mediterranean pattern, with scheduled appointments every three months. After the exclusion of steatosis, healthy subjects were recruited and received general advice based on current Italian food-based dietary guidelines. Results. One hundred and 8fty 8ve subjects aged 20–59 years underwent (i) liver ultrasound (US), (ii) clinical and anthropometric evaluations, (iii) blood tests, and (iv) assessment of dietary habits. According to US evaluation, 73 of them had severe, moderate, or mild liver steatosis (NAFLD patients) and 82 had no liver steatosis (healthy controls). Fifty-eight NAFLD patients and 73 controls completed the study. Among NAFLD patients, 26 (45%) downgraded steatosis severity, 12 of which achieved complete steatosis regression (21%). *ree of the healthy controls developed NAFLD. *e NAFLD patients improved their dietary habits and reduced BMI and waist circumference, during the study period, more than healthy controls. Liver steatosis remission/regression was independent of changes in BMI or liver enzymes and was more frequent among patients with mild steatosis at baseline. Conclusions. Mediterranean dietary advices, without a personalised meal planning, were eCcient in reducing/remitting NAFLD, especially among patients with mild disease, which argues in favour of early identi8cation and lifestyle intervention. *is trial is registered with NCT03300661

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Eziopatogenesi e terapia dell'acne: studio epidemiologico delle caratteristiche cliniche di una popolazione di pazienti affetti da acne e analisi dei polimorfismi del gene codificante per il recettore degli androgeni e del gene codificante per il citocromo P-450 1A1

Background: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous follicles, which are located on the face, neck, chest, upper back, and upper arms. It is a pleomorphic disorders with multifactorial pathogenesis. Typically, lesions range from open and closed comedones to inflammatory papules, pustules, cysts, nodules and scarring may result. Acne vulgaris is the most common skin disorders. The pathogenesis of acne centers on the interaction of sebaceous hyperplasia, follicular hyperkeratinization, proliferation of Propionibacterium acnes, inflammation and immune reaction. But the aetiology is already understand and the evolution, severity and response to treatment are subject to variations. Some studies have shown the importance of genetic factors in the pathogenesis of acne, but the role of heredity on acne severity and response to treatment remains unclear. The role of androgens is well established and their action is mediated by the androgen receptor. The amino-terminal domain of this receptor, is required for transcriptional activation and contains a region of polyglutamine encoded by CAG trinucleotide repeats. In humans, the number of CAG repeats is polymorphic. Recently some studies have shown an association between this polymorphism and acne and other androgens influence diseases, such as androgenetic alopecia, prostate cancer. Other genetic studies have shown a relationship between polymorphisms in the Human cytochrome P-450 1A1 gene (CYP1A1) and acne. The cytochrome P-450 1A1 is one of the most active enzymes involved in retinoids metabolism. Retinoids are morphogenic for the sebaceous gland. In a recent study it has been signalled in acne patients a high frequency of the thymine-to-cytosine (T-to-C) transition situated at position 6235 creating an additional cleavage site for MspI. In order to improve the treatment of patients, prognostic factors of acne severity and evolution must be studied. Systematic assessment of the severity of acne continues to challenge the clinician. Acne is a pleomorphic disorder of variable course and anatomical distribution. For these reasons, no system has been accepted universally. Aim: The aim of our study was to analyze some clinic and epidemiologic features of patients affected by acne vulgaris to try to understand what role they can play in the pathogenesis of acne and if they can be prognostic factors of acne severity. Second goal is validation of a grading system of severity, which features are accuracy and reproducibility and that can be used also by practicing clinicians. Third purpose of this study is to test for an association between acne and acne severity, and CAG repeat length in the androgen receptor gene, and CYP1A1 polymorphism. Patients and Methods: A descriptive, prospective epidemiological study was conducted from January 2005 to October 2007 . It concerned patients with acne referred to Pediatrics Department and Dermatology Department for treatment of acne. We included patients with mild, moderate or severe acne. Epidemiological and clinical data, such as sex, age, age at onset, prepubertal or not, menarche age, family history of acne (father, mother, both parents, brother or others), body mass index, concomitant diseases (focusing on endocrine conditions), extension of lesion at onset, type and extension of lesions, grading of severity, therapy were collected in a data base. The severity of acne was recorded using Global Acne Grading System (GAGS), (Doshi et al.), Leeds technique (Cunliffe score), Global Evaluation Scale (GES) at first visit and, for some patients, at 3, 6, 12 months. We developed another grading system ("differentiated GAGS"), modifying GAGS in order to obtain a score for the face and a score for the trunk. Epidemiologic analysis was made using t-student, Pearson e Rho di Spearman tests by software SPSS. The polymorphisms were studied with the use of polymerase chain reaction and sequencing for the androgen receptor gene, and restriction fragment length polymorphism for CYP1A1. Comparisons of allele and haplotype frequencies between cases and controls were analyzed by c2-tests. Results and conclusion: 210 patients, 122 females and 88 males, aged 10-39 years, affected by mild to severe acne, were included in this study. Female showed a earlier onset compared to males. We found a role of hereditary factors. Presenting both parents affected by acne did not correlated with severity of the disease but seems with its duration. Late onset acne appears to be different and to be caused by dissimilar pathogenetic mechanisms. It's almost exclusive of female subjects and it's not correlated with hereditary factors. Male hormones are responsible of acne manifestation especially in particular body areas. Female subjects usually develop acne after menarche. Patients developing acne before menarche are prone to more severe truncal involvement. For many reasons it's important to have a separate severity index for face and trunk. We developed the "Differentiated GAGS" scoring index, that significantly correlated with the Cunliffe score index obtained with the Leeds technique. Concerning the analysis of the two genetic factors in our study population, we found a promising role of CYP450 1A1 polymorphisms. Further studies are required to clarify the role of these genetic factors in the pathogenesis of acne

Optimal reproductive policies for Italian Heavy Draught Horse

none3noneMANTOVANI R.; CONTIERO B; PIGOZZI GMantovani, Roberto; Contiero, Barbara; Pigozzi, G