Effects of micronutrient antioxidants (alpha-tocopherol and ascorbic acid) on skin thickening and lung function in patients with early diffuse systemic sclerosis

To assess the effects of alpha-tocopherol and ascorbic acid on skin thickening and lung function in patients with early diffuse systemic sclerosis (SSc), thirteen patients with early diffuse SSc, with positive anti-topoisomerase-I antibody, high skin thickening progression rate (STPR ≥ 12/year) and decreased lung diffusing capacity (DLCO ≤ 75%) were included in this study. Patients were randomized into two subgroups: Subgroup A—six patients, treated with intravenous cyclophosphamide (CyP) (500 mg/m² of body surface monthly) and antioxidants (alpha-tocopherol 400 IU/day and ascorbic acid 1,000 mg/day), and Subgroup B—seven patients, who received CyP without antioxidants. In both subgroups, effects of treatment on skin thickening and lung function were evaluated by comparison of the modified Rodnan skin score (MRSS), STPR, forced vital capacity (FVC), transfer-factor (DLCO) and diffusing coefficient for carbon monoxide (DLCO/VA) at baseline and 1 month after the sixth pulse of CyP. The mean MRSS did not change from baseline to the end of the follow-up in subgroup A (15.7 vs. 16.4, P = 0.50), but it increased significantly in subgroup B (17.9 vs. 23.6, P = 0.03). Although the mean STPR decreased notably in both subgroups of patients (in subgroup A–from 18.9/year to 2.2/year, P = 0.03, and in subgroup B–from 17.5/year to 8.6/year, P = 0.03), the mean STPR at the end of the treatment period was significantly lower in subgroup A (2.2/year vs. 8.6/year, P = 0.04). The mean value of FVC did not change either in subgroup A (91.0–87%, P = 0.2) or in subgroup B (from 101.2 to 99.7%, P = 0.7). Parameters of lung diffusing capacity improved somewhat in subgroup A (DLCO from 55.7 to 62.0% and DLCO/VA from 68.7 to 74.2%) and decreased in subgroup B (DLCO from 66.2 to 60.6% and DLCO/VA from 76.9 to 71.6%), but differences were not statistically significant. After 6 months of therapy, patients treated with CyP and antioxidants had a significantly lower STPR, compared to patients treated with CyP only. Lung function parameters remained stable in both subgroups. However, lung diffusing capacity improved slightly, without statistical significance, in patients treated with CyP and antioxidants, and it deteriorated in patients without antioxidants.     

The assessment of airbag deployment and seatbelt use in preventing facial injuries

This study aimed to determine the effectiveness of airbags and seatbelts in the prevention of facial fractures and slight facial injuries in relation to the speed and kinetic energy experienced in frontal collisions. All cases of vehicle occupants who had been in frontal collisions and had subsequently been examined in the Institute for Emergency Medical Assistance and the Clinical Center of Montenegro in 2017 were analyzed. There were 29 cases of facial fractures (Group 1), 35 cases of slight facial injuries (including nondisplaced nasal fractures) (Group 2), and 26 cases of occupants who had suffered no facial injuries (control Group 3). In all assessed cases all of the subjects had been wearing a seatbelt and the airbag had deployed at the time of impact. A frontal collision is defined as a collision in which the principal force acts within a range of 90° from the longitudinal axis of the vehicle. Using the mass and the speed of the vehicles, the total kinetic energy (KE) of all frontal collisions being analyzed was calculated. The cut-off value of total KE in frontal collisions that were associated with either facial fractures or slight facial injury was estimated using a receiver operating characteristic (ROC) curve. The cut-off amounts of KE were then used to calculate the barrier equivalent velocity (BEV). The BEV for a vehicle of average mass was estimated to be 55.7 km/h (34.6 mph) in Group 1, and 49.2 km/h (30.6 mph) in Group 2. Airbags and seatbelts are effective in preventing facial injuries in vehicles of average mass that are traveling at speeds under 49.2 km/h (30.6 mph) at the point of impact, but they do not protect from facial fractures when the vehicle speed exceeds 55.7 km/h (34.6 mph).     

Bioequivalence study of two formulations of itraconazole 100 mg capsules in healthy volunteers under fed conditions: a randomized,three-period,reference-replicated,crossover study

Background: The aim of the study was to evaluate the bioequivalence of two itraconazole 100 mg capsule formulations.

Research design and methods: The single-center, open-label, randomized, three-period, three-sequence, reference-replicated, cross-over study included 38 healthy subjects under fed conditions. In each study period (separated by a 14-day washout), a single oral dose of the test (T) or reference (R) product was administered. Blood samples were collected at pre-dose and up to 72.0 h after administration. The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxy itraconazole, were AUC_0-72h, AUC_0-∝, C_max, T_max, T_1/2 and K_el.

Results: The 90% CI for the test/reference geometric means ratio for the parent compound, itraconazole, was in the range from 85.29% to 116.07% for AUC_0-72h. Since the coefficient of variation (CV) for the reference product was 44.95% for C_max, the 90% CI for this parameter for itraconazole was 93.49–133.78%, which was within the proposed limits of the EMA for bioequivalence of 72.15–138.59%. During the study, 4 subjects encountered a total of 14 mild adverse events.

Conclusions: The use of the reference-scaling approach with 3-period design (TRR, RTR, and RRT) was an efficient way to demonstrate that two commercially available oral itraconazole formulations met the predetermined bioequivalence criteria.     

The impact of depression,microvasculopathy, and fibrosis on development of erectile dysfunction in men with systemic sclerosis

This article is a small case series that aims to discuss the impact of depression, vascular, and fibrotic changes on development of erectile dysfunction (ED) in patients with systemic sclerosis (SSc). In this paper, we present five male patients with SSc, aged 30–48 years. All patients are nonsmokers, and their past medical history does not reveal any other diseases or treatment procedures (drugs) that may have influence on erectile function. We used a five-item questionnaire, the International Index of Erectile Function (IIEF-5), to assess ED in our patients. Microvascular abnormalities (estimated by nailfold capillaroscopy), fibrotic changes (assessed by skin score, chest X-ray and reduction in forced vital capacity), and presence of depression (estimated using the Beck’s Depression Inventory) were evaluated. To assess efficacy of sildenafil citrate (25–50 mg 1 h before each sexual activity), patients with ED filled up the IIEF-5 before and after 1-month therapy. We concluded that ED is a frequent and early clinical feature in men with SSc. Microvascular abnormalities are similar in patients with and without ED. Although patients with ED had higher depression indices, an unsatisfactory response to sildenafil citrate indicates that psychoneurogenic factors are not crucial in development of ED in SSc. Patients with ED had more extended fibrotic changes, which indirectly suggests that fibrosis of the corporal body may play the main role in the pathogenesis of ED in SSc.