Gastroprotective effects of amifostine in rats treated by T-2 toxin

Cytoprotector amifostine (AMI) was given in a dose of 50, 100 or 150?mg/kg ip in rats treated with several highly toxic doses of T-2 toxin. The best survival rate (24?h and 7?days after treatment) was obtained with AMI50 (50?mg/kg ip). After T-2 intoxication, a peak in the mean number of gastric lesions (petechiae and ulcerations) was reached on the third day (26.40?±?6.24). Administration of AMI50 reduced, almost completely, the total number of gastric lesions in rats acutely poisoned by 0.5 LD₅₀ T-2 (1.5?mg/kg sc), starting with day 1 after intoxication (5.60?±?3.42).     

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.     

Predictors of severe pain in the immediate postoperative period in elderly patients following hip fracture surgery

Introduction

The aim of this study was to identify risk factors for severe postoperative pain immediately after hip-fracture surgery.

Patients and methods

Three hundred forty-four elderly patients with an acute hip fracture were admitted to the hospital during a 12-months period. All patients who entered the study answered a structured questionnaire to assess demographic characteristics, previous diseases, drug use, previous surgery, and level of education. Physical status was assessed through the American Society of Anesthesiologists’ preoperative risk classification, cognitive status using the Short Portable Mental Status Questionnaire, and depression using the Geriatric Depression Scale. The presence of preoperative delirium using the Confusion Assessment Method was assessed during day and night shifts until surgery. Pain was measured using a numeric rating scale (NRS). An NRS ≥7 one hour after surgery indicated severe pain.

Results

Patients with elementary-level education (8 yr in school) presented a higher risk for immediate severe postoperative pain than university-educated patients (>12 yr in school) (P < 0.05). Higher cognitive function was associated with higher postoperative pain (P < 0.01). Patients with symptoms of depression and patients with preoperative delirium presented a higher risk for severe pain (P < 0.05, P < 0.01, respectively). Multivariate analysis showed that depression and a low level of education were independent predictors of severe pain immediately after surgery.

Conclusion

Depression and lower levels of education were independent predictors of immediate severe pain following hip-fracture surgery. These predictors could be clinically used to stratify analgesic risk in elderly patients for more aggressive pain treatment immediately after surgery.     

Peritoneal exudate cells from long-lived rats exhibit increased IL-10/IL-1β expression ratio and preserved NO/urea ratio following LPS-stimulation in vitro

In humans, usual aging, differently from successful aging, is associated with deregulation of proinflammatory/anti-inflammatory cytokine balance. The corresponding data from rat studies are limited. Therefore, we examined (i) cytokine messenger RNA (mRNA) profile of fresh peritoneal cells from 6- (adult), 24- (old), and 31-month-old (long-lived) AO rats and (ii) proinflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine, NO, and urea production in their LPS-stimulated cultures. Comparing with adult rats, cells from old ones expressed lower amount of TNF-α and IL-6 mRNAs, but greater amount of IL-1β mRNA. On the other hand, cells from long-lived rats exhibited a dramatic increase in IL-10 mRNA expression followed by diminished TNF-α and IL-6 mRNA expression, and comparable expression of IL-1β mRNA relative to adult rats. Consequently, IL-10/IL-1β mRNA ratio was greater in cells from long-lived rats than in adult and old rats. In LPS-stimulated peritoneal cell cultures (contained ≥95 % macrophages) from old rats, concentration of common proinflammatory cytokines was higher than in those from adult rats. Comparing with adult and old rats, in LPS-stimulated macrophage cultures from long-lived rats, TNF-α and IL-6 concentrations were lower; IL-1β concentration was comparable or greater (in respect to adult rats), whereas that of IL-10 was strikingly higher. Consistently, in macrophage cultures from long-lived rats, NO (iNOS activity marker)/urea (arginase activity marker) ratio was less and not different from that in old and adult rats, respectively. The study suggests that macrophages from long-lived rats, differently from those of old ones, have substantial ability to limit proinflammatory mediator production, which may contribute to their longevity.     

Clinical and epidemiological features of Guillain‐Barré syndrome in the Western Balkans

The aim of this study was to define features of Guillain‐Barré syndrome in a large cohort of patients from three Western Balkans countries. Data from adult Guillain‐Barré syndrome (GBS) cases from 2009 to 2013 were retrospectively obtained from all tertiary health care centers. During the 5‐year period, 327 new cases of GBS were identified with a male to female ratio of 1.7 : 1. The most common GBS variants were demyelinating (65%) and axonal (12%). At nadir 45% of patients were chair‐bound, confined to bed, or required assisted ventilation, while 5% died. The crude incidence of GBS in Serbia and Montenegro was 0.93 per 100,000 population, and age‐adjusted incidence according to the world standard population was 0.86 per 100,000. Incidence was particularly high in 50‐ to 80‐year‐old men. Statistically significant seasonal variations of GBS were not observed. This study of patients with GBS in the Western Balkans allows us to prepare the health system better and to improve the management of patients. This study also opens opportunities for international collaboration and for taking part in the multinational studies on GBS.     

Serum Leptin and Skeletal Differences between Obese and Non-Obese Patients with Chronic Obstructive Pulmonary Disease

ObjectiveChronic obstructive pulmonary disease (COPD) affects body composition, adipokine secretion, and skeletal integrity. The aim was to determine the association between leptin, body mass (BM) and body composition parameters - fat mass (FM) and fat mass index (FMI), lean tissue mass (LTM), lean tissue mass index (LTMI) and bone mineral density (BMD) in 67 male COPD patients.MethodsBM, body composition and biochemical indicators were measured or calculated using standard methods. Data were analyzed according to groups: non-obese (N = 48, BMI 21.0-29.9 kg/m²) and obese (N = 19, BMI ≥ 30.0 kg/m²).ResultsIn the non-obese group statistically significant correlations were observed: negative ones of age with most BMD T scores, positive ones of BMI with all T scores, FM, FMI, LTMI and leptin, of FMI with leptin and all T scores, and of LTMI with most T scores. In the obese group also statistically significant correlations were found: positive ones of BMI with FMI, LTM, leptin and T scores (trochanter, total hip); of FMI with leptin; and of leptin with total hip T score.ConclusionA positive relationship between FMI and BMD was found only in non-obese but not in obese COPD patients. Leptin concentration was associated positively with the total hip T score only in obese COPD patients, suggesting its protective role on the skeleton of obese COPD patients.Key Words: Body mass, Body mass index, Fat mass, Fat mass index, Lean tissue mass, Lean tissue mass index, 25-OH vitamin D, Leptin, Bone mineral density