We conducted a case–control study to analyse the association of psoriasis of recent onset with smoking habits, body mass index (BMI) and stressful life events. Cases (n=560; median age 38) were ...patients with a first diagnosis of psoriasis and a history of skin manifestations of no longer than two years after the reported disease onset. Patients with a new diagnosis of skin diseases other than psoriasis (n=690; median age 36) were selected as controls. The risk of psoriasis was higher in ex- and current smokers than in never-smokers, the relative risk estimates (OR) being 1.9 for ex-smokers and 1.7 for smokers. Smoking was strongly associated with pustular lesions (32 patients, OR=5.3 for smokers). The frequency of psoriasis varied significantly in relation to a family history of psoriasis in first degree relatives, BMI (OR=1.6 and 1.9 for over weighted, BMI 26–29, and obese, BMI ≥ 30, respectively) and stressful life event score (compared to the lower index quartile, the OR being 2.2 for index values ≥115). Risk estimates, when taking into consideration the combined effect of these factors with smoking habits, were consistent with a multiplicative model of risk combination with no significant statistical interaction.
Mutations in nuclear genes involved in the maintenance of mitochondrial DNA (mtDNA) are associated with an extensive spectrum of clinical phenotypes, manifesting as either mtDNA depletion syndromes ...or multiple mtDNA deletion disorders.(1.)
Introduction Adult Separation Anxiety Disorder (ASAD) is related to greater personal dysfunction and to a reduced sensitivity to conventional treatment, such as cognitive-behavioural therapy or ...anti-panic drugs, even considering severity of anxiety symptoms, number of co-morbid disorders, socioeconomical status, disease duration, and severity of agoraphobia. Objectives To evaluate separation anxiety, psychiatric co-morbidity, levels of anxiety, character and temperament personality traits, and global functioning, in subjects with anxiety disorders attending a tertiary-level outpatient clinic. Aims To predict the outcome and customize treatment for anxiety disorders. Methods After symptom stabilization of one month (T0) 40 patients with anxiety disorders were assessed by means of SCI- SAS, SASI, ASA -27, MINI, HAM- A, TCI-R, GAF. Prospective evaluation is planned at T60 and T180. Results According to preliminary cross-sectional data, higher scores of separation anxiety show statistically significant correlations with some domains of the TCI-R; in addition, patients with ASAD show greater psychiatric co-morbidity. No correlations were found between the presence of separation anxiety and levels of anxiety at HAM-A or GAF scores at baseline. Conclusions The prospective study of long-term response to treatment is ongoing and the sample will be expanded. The comprehension of anxiety symptoms appraisal in the framework of psychobiological personality characteristics is expected to influence the choice of both pharmacological and psychological therapeutic tools, particularly in patients showing higher levels of dysfunction.
Selective and effective TK2 inhibitors can be obtained by introduction of bulky lipophilic chains (acyl or alkyl entities) at the 2′ position of araT and BVaraU, nucleoside analogues naturally ...endowed with a low TK2 affinity. These derivatives showed a competitive inhibitory activity against TK2 in micromolar range. BVaraU nucleoside analogues, modified on the 2′-
O-acyl chain with a terminal
N-Boc amino-group, conserved or increased the inhibitory activity against TK2 (
7l and
7m IC
50: 6.4 and 3.8
μM, respectively). The substitution of an ester for a carboxamide moiety at the 2′ position of araT afforded a consistent reduction of the inhibitory activity (
25, IC
50: 480
μM). On the contrary, modifications at 2′-OH position of araC and araG, have provided inactive derivatives against TK2 and dGK, respectively. The biological activity of a representative compound, 2′-
O-decanoyl-BVaraU, was also investigated in normal human fibroblasts and was found to impair mitochondrial function due to TK2 inhibition.
Background/aims: Antioxidants have been proposed, over the last decade, as functional ingredients for anti aging preparations and to prevent and modulate oxidative skin damages. Up to date, beside ...the photo‐induced oxidative skin damages model, none in vivo protocols have shown sufficient reproducibility for the validation of the antioxidant claim for a cosmetic finished product. To this aim, we have recently anticipated a new in vivo protocol based on a microinflammatory model, driven by reactive oxygen species. In the present study our model was validated by comparison with four different instrumental methods.
Methods: The effects of a pre‐treatment of two different formulations based on antioxidant functional ingredients, were investigated on forearm skin of 15 healthy volunteers, and compared to a cosmetic base and control area. The instruments considered in the study were Chromameter (CR‐300 Minolta), Tewameter TM 210 (Courage‐khazaka, Cologne, Germany), Laser Doppler Perfusion Imager (PIM1.0 Lisca Development AB, Sweden), in comparison to DermAnalyzer®, an easy to use software program developed by us, using the CIE L*a*b* color space parameters.
Results: The comparative measurements showed that the antioxidant formulations tested were all able to reduce, in different but statistically significant extent, the intensity of skin redness, and of cutaneous blood flow, when compared to control area (P < 0.0001).
Conclusions: The methyl nicotinate (MN) based microinflammatory model, in conjunction with objective measure‐ ments, resulted an effective tool for in vivo assessment of oxidative skin injuries. In view of the high level of repeatability, short time of answer and simplicity, the procedure by us developed, is proposed as a possible protocol for the evaluation of in vivo efficacy of antioxidant functional ingredients in cosmetic formulations.
During a random screening of representative libraries of nucleoside analogues we discovered that the adenine derivatives FEVB28 and FEG118 were Flaviviridae inhibitors endowed with potency ...comparable, if not superior, to that of ribavirin. Those studies prompted us to design a new class of protected nucleoside analogs, reported herein, which displays interesting anti-bovine viral diarrhea virus (BVDV) activity and low cytotoxicity in cell-based assays (4, 23, 29 EC sub(50): 14, 11, 26 mu M respectively, CC sub(50)>100 mu M) and appreciable activity in enzyme assays against the RNA dependent RNA polymerase (RdRp) of BVDV (4, 23, 29, RdRp inhibition activity 27, 16, 15 mu M respectively). A molecular modeling study was also carried out to highlight the possible interactions between this compounds class and the corresponding hepatitis C virus (HCV) enzyme.
Highly selective arabinofuranosyl nucleosides, which inhibit the mitochondrial thymidine kinase (TK-2) without affecting the closely related herpes simplex virus type 1 thymidine kinase (HSV-1 TK), ...varicella-zoster virus thymidine kinase (VZV-TK), cytosolic thymidine kinase (TK-1) or the multifunctional
Drosophila melanogaster deoxyribonucleoside kinase (
Dm-dNK), have been obtained. SAR studies indicate a close relation between the length of the substituent at the 2′ position of the arabinofuranosyl moiety and the inhibitory activity.
Synthesis, modeling studies and preliminary biological activity of potent and selective inhibitors of the mitochondrial thymidine kinase (TK-2) are described.
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