Protective effect of sivelestat,a neutrophil elastase inhibitor,on ipsilateral and contralateral testes after unilateral testicular ischaemia–reperfusion injury in rats

What’s known on the subject? and What does the study add? Following ischemic damage, reperfusion may cause further injury paradoxically in the ischemic tissue, known as reperfusion injury. Decreased blood flow causes hypoxia, leading to increased levels of lactic acid, hypoxanthine, and lipid peroxides in ischemic tissues and subsequent increase in blood flow after lipid peroxidation produces reactive oxygen species. In addition, several experimental studies and clinical trials demonstrated that unilateral testicular torsion has a detrimental effect also to the contralateral testis. Although the basic pathological mechanism underlying testicular ischemia/reperfusion injury has not been completely understood, it has been shown that reactive oxygen species formed during ischemia/reperfusion play the key role in this process. In the international literature there is no information available regarding the effects of neutrophil elastase inhibitors such as sivelestat sodium aminoacetate tetrahydrate on the ischemia/reperfusion injury of the testis. In this study we investigated the effects of sivelestat in the testes bilaterally, after unilateral testicular ischemia/reperfusion injury using an experimental unilateral testicular ischemia/reperfusion rat model. We found that sivelestat reduces the oxidative stress and partially prevents the testicular damage both in the ischemic and in the contralateral testis.

OBJECTIVE

To investigate the effect of a neutrophil elastase inhibitor, sivelestat sodium hydrate, on testicular ischaemia–reperfusion (IR)‐injury.

MATERIAL AND METHODS

Eight‐week‐old male Sprague–Dawley rats were divided into four groups: sham‐operated control rats; IR rats (group IR); and IR rats that received intra‐abdominal administration of 15 mg/kg or 60 mg/kg sivelestat (group IR15 and group IR60, respectively). Right testicular vessels were clamped for 90 min in groups IR, IR15 and IR60. Sivelestat had been administered 45 min after the induction of the ischaemia in groups IR15 and IR60. In subpopulations of IR, IR15 and IR60 rats, reperfusion was performed after ischaemia for 2 h (groups IR‐A, IR15‐A and IR60‐A, respectively) or 48 h (groups IR‐B, IR15‐B and IR60‐B, respectively). At the end of the reperfusion period, blood samples were aspirated from both spermatic veins of each rat and testosterone was evaluated. Then both testes from all rats were collected and tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO), and heat‐shock protein‐70(HSP‐70) were evaluated. Testicular tissue samples were also processed for histological evaluation and TUNEL staining.

RESULTS

MDA, MPO and HSP‐70 levels in the ischemic testis were significantly higher in the IR group compared with the control group. MDA and HSP‐70 in the contralateral testis were significantly higher in the IR group compared with the control group. Bilateral testosterone levels were lower in all rat groups in comparison with the control group. Bilateral testicular samples in group IR showed extensive histopathologic degenerative alterations and increased percentage of apoptotic cells. Sivelestat treatment lowered the MDA concentration and the percentage of apoptotic cells bilaterally and ameliorated the testicular histological pattern bilaterally.

CONCLUSIONS

Unilateral testicular ischaemia causes significant contralateral testicular damage. Sivelestat may be a novel adjunct tool for reducing oxidative stress and partially preventing bilateral testicular damage.     

Pars plana vitrectomy in patients with intermediate uveitis

Objective: To describe the effect of pars plana vitrectomy in patients with intermediate uveitis. Methods: Retrospective analysis of the clinical course and visual outcome following pars plana vitrectomy in patients with intermediate uveitis. Results: Thirty-two patients (43 eyes) were included in the study. Pars plana vitrectomy was combined with cataract surgery in 22 of 43 eyes. The intermediate uveitis was associated with sarcoidosis in 16 eyes and multiple sclerosis in five eyes, and was idiopathic in 22 eyes. The mean (±SD) follow-up was 45.6 (±38) months (range: 6–146 months). In 19 of 43 eyes (44.1%), there was improvement in the course of uveitis, allowing the discontinuation of immunosuppressive treatment in seven patients. Cystoid macular edema resolved in 12 of 37 eyes (32.4%). Forty of 43 eyes achieved a better or retained their initial visual acuity. The remaining three eyes deteriorated by two or more lines in the Snellen chart due to the progression of cataract, chronic cystoid macular edema, and glaucomatous optic atrophy, respectively. Conclusions: The results of this study suggest that pars plana vitrectomy may have a beneficial effect on the course of uveitis and the associated complications of cystoid macular edema, thereby reducing the need for long-term immunosuppression. Pars plana vitrectomy combined with simultaneous cataract surgery can improve the visual outcome in these patients.     

Reference values for the 6-min walk test in healthy subjects 20-50 years old

In 102 healthy Caucasians, 20-50 years old, we investigated the effect of anthropometrics on the 6-min walk test (6MWT), in order to provide reference values for walk distance (6MWD), oxygen saturation (SpO2), pulse rate (PR), respiratory rate (RR), breathlessness perception (VAS) and for the walking distance and body weight product (DW). The mean 6MWD and DW values were 593 +/- 57 and 638+/-44 m (P < 0.01) and 35,030 +/- 5306 and 48,882 +/- 6555 kg m (P < 0.01), respectively for women and for men. While walking, SpO2 remained unaltered and subjects reached 67 +/- 10% of their maximal predicted heart rate and a RR mean value of 19 +/- 4 bpm. VAS ratings were significantly higher in females as compared to males (24 +/- 15 vs. 18 +/- 5 mm, P < 0.05), however, when corrected for PR change while walking, they were not different. The equation by stepwise multiple regression analysis included height, age and gender for the 6MWD and accounted for 42% of the total variance. This study confirms the relevant effect of anthropometrics on walking capacity and suggests that when rating dyspnea, the change in heart rate during walking should be considered.     

Risk profiles for overweight/obesity among preschoolers

Background

The epidemic of overweight/obesity among U.S. children has led to an alarming increase in health-related consequences, including early-onset diabetes and cardiovascular disease. Recent research has identified the independent contribution of several maternal and child factors to the development of childhood overweight/obesity. Few studies, however, have examined risk profiles of childhood obesity.

Aim

This study used classification and regression tree (CART) analysis to examine the combined effect of maternal and child factors in generating risk profiles for overweight/obesity among preschoolers.

Study design

Data from the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B) study were used. The sample was comprised of preschool children. CART and logistic regression models were built and compared.

Results

Children who were overweight/obese at two years of age had an increased risk of being overweight/obese at four years of age. Children born to overweight/obese mothers were more likely to be overweight/obese by age four, even if their BMI at two years of age was normal. Children with high birth weight (≥ 4000 g.) were also more likely to be overweight/obese at age four years if they were born to mothers with a normal pregravid BMI, but were of a lower socioeconomic status. Among preschoolers whose mothers were black or white and who had a high pregravid BMI, breastfeeding duration and parity played an important role in determining their risk of being overweight/obese.

Conclusions

Classification tree analysis confirms and extends current knowledge of preschool overweight/obesity by providing preliminary risk profiles that are structured within the context of prenatal and postnatal maternal and child characteristics.     

FIP1L1-PDGFRA molecular analysis in the differential diagnosis of eosinophilia

Background  

Primary eosinophlia associated with the FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment. This study was undertaken in order to examine the prevalence and the associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 15 adult patients presenting with profound eosinophilia (> 1.5 × 10⁹/L).     

Combined thirty-day exposure to thioacetamide and choline-deprivation alters serum antioxidant status and crucial brain enzyme activities in adult rats

Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300 mg/L of drinking water) on the serum total antioxidant status (TAS) and the activities of brain acetylcholinesterase (AChE), Na⁺,K⁺-ATPase and Mg²⁺-ATPase of adult rats. Twenty male Wistar rats were divided into four groups: A (control), B (CD), C (TAA), D (CD+TAA). Dietary CD was provoked through the administration of Ch-deficient diet. Rats were sacrificed by decapitation at the end of the 30-day experimental period and whole brain enzymes were determined spectrophotometrically. Serum TAS was found significantly lowered by CD (−11% vs Control, p < 0.01) and CD+TAA administration (−19% vs Control, p < 0.001), but was not significantly altered due to TAA administration. The rat brain AChE activity was found significantly increased by TAA administration (+11% vs Control, p < 0.01), as well as by CD+TAA administration (+14% vs Control, p < 0.01). However, AChE was not found to be significantly altered by the 30-day dietary CD. On the other hand, CD caused a significant increase in brain Na⁺,K⁺-ATPase activity (+16% vs Control, p < 0.05) and had no significant effect on Mg²⁺-ATPase. Exposure to TAA had no significant effect on Na⁺,K⁺-ATPase, but inhibited Mg²⁺-ATPase (−20% vs Control, p < 0.05). When administered to CD rats, TAA caused a significant decrease in Na⁺,K⁺-ATPase activity (−41% vs Control, p < 0.001), but Mg²⁺-ATPase activity was maintained into control levels. Our data revealed that an adult-onset 30-day dietary-induced CD had no effect on AChE activity. Treatment with TAA not only reversed the stimulatory effect of CD on adult rat brain Na⁺,K⁺-ATPase, but caused a dramatic decrease in its activity (−41%). Previous studies have linked this inhibition with metabolic phenomena related to TAA-induced fulminant hepatic failure and encephalopathy. Our data suggest that CD (at least under the examined 30-day period) is an unfavorable background for the effect of TAA-induced hepatic damage on Na⁺,K⁺-ATPase activity (an enzyme involved in neuronal excitability, metabolic energy production and neurotransmission).     

Sleep-disordered breathing in a general heart failure population: relationships to neurohumoral activation and subjective symptoms

The aim of this study was to determine the prevalence of sleep-related breathing disorders (SDB) in a UK general heart failure (HF) population, and assess its impact on neurohumoral markers and symptoms of sleepiness and quality of life. Eighty-four ambulatory patients (72 male, mean (SD) age 68.6 (10) yrs) attending UK HF clinics underwent an overnight recording of respiratory impedance, SaO2 and heart rate using a portable monitor (Nexan). Brain natriuretic peptide (BNP) and urinary catecholamines were measured. Subjective sleepiness and the impairment in quality of life were assessed (Epworth Sleepiness Scale (ESS), SF-36 Health Performance Score). SDB was classified using the Apnoea/Hypopnoea Index (AHI). The prevalence of SDB (AHI > 15 events h(-1)) was 24%, increasing from 15% in mild-to-moderate HF to 39% in severe HF. Patients with SDB had significantly higher levels of BNP and noradrenaline than those without SDB (mean (SD) BNP: 187 (119) versus 73 (98) pg mL(-1), P = 0.02; noradrenaline: 309 (183) versus 225 (148) nmol/24 h, P = 0.05). There was no significant difference in reported sleepiness or in any domain of SF-36, between groups with and without SDB (ESS: 7.8 (4.7) versus 7.5 (3.6), P = 0.87). In summary, in a general HF clinic population, the prevalence of SDB increased with the severity of HF. Patients with SDB had higher activation of a neurohumoral marker and more severe HF. Unlike obstructive sleep apnoea, SDB in HF had little discernible effect on sleepiness or quality of life as measured by standard subjective scales.     

Intermediate postchallenge hyperglycemia in overweight and obese subjects: a new marker of impaired glucose regulation?

The objective of this study was to compare subjects with intermediate postchallenge hyperglycemia (INPH) to those with normal glycemic status, impaired fasting glucose (IFG), and/or impaired glucose tolerance (IGT), as well as type 2 diabetes mellitus. Furthermore, the authors evaluated the impact of INPH on target organ damage. In total, 487 overweight and obese adults (BMI > or =27 kg/m(2)), 252 men and 235 women, mean age 52.9 +/-10.2 years, were studied. All participants underwent a clinical and laboratory evaluation, as well as an oral glucose tolerance test (OGTT). They were also investigated by echocardiography, carotid ultrasonography, and pulse wave analysis. Overall, 302 (62%) subjects had normal glycemic status, 64 (13.1%) had IFG and/or IGT, 95 (19.5%) had type 2 diabetes mellitus, and 26 (5.4%) had INPH. Individuals with INPH had an increased index of insulin resistance (higher homeostasis model assessment-insulinogenic index [HOMA-IR], p<0.0001), impaired insulin secretion (lower insulinogenic index, p<0.0001), and higher glycosylated hemoglobin (HbA(1c)) levels (p<0.0001) in comparison with the normoglycemic subjects, but not to those with IFG and/or IGT or diabetes (p = 0.6). No difference was observed concerning the risk factors studied, left ventricular mass and vascular remodeling, among subjects with INPH, IFG and/or IGT, and diabetes. However, individuals with INPH had a higher proportion of echolucent carotid artery plaques in comparison with the normoglycemic subjects (p = 0.04) and those with IFG and/or IGT (p = 0.01). Intermediate postchallenge hyperglycemia seems to represent a new category of glucose metabolism disturbances with increased atherogenic impact. Therefore, evaluating intermediate glucose levels in an OGTT could contribute to better identify overweight individuals at risk of developing diabetes mellitus and cardiovascular events.