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.     

The effect of sevoflurane on ciliary motility in rat cultured tracheal epithelial cells: a comparison with isoflurane and halothane

Halothane and isoflurane potently depress airway ciliary motility. We compared the effect of sevoflurane on ciliary beat frequency (CBF) with that of halothane and isoflurane using purified and cultured rat tracheal epithelial cells. Rat tracheal epithelial cells were isolated from adult male Sprague-Dawley rats to establish an air-liquid interface culture. Apical surfaces of the cells were exposed to a fresh gas containing humidified and warmed (25 degrees C) air (vehicle) with or without sevoflurane (0%-4%), halothane (0%-2%), or isoflurane (0%-2%). The images of motile cilia were videotaped and CBF was analyzed using a computer. Baseline CBF (= 100%) and CBF 30 min after the exposure were measured. CBF 30 min after vehicle exposure was 101% +/- 4% (mean +/- sd). Exposures to 0.25%-2% sevoflurane did not change CBF significantly, although exposures to 0.25%-2% halothane or isoflurane decreased CBF dose-dependently. CBFs 30 min after exposures to 2% of sevoflurane, halothane, and isoflurane were 97% +/- 9%, 56% +/- 14%, and 47% +/- 6%, respectively (n = 5 each). Sevoflurane 4% reduced CBF significantly but slightly (84% +/- 2%, n = 5). These results show that sevoflurane has a direct cilioinhibitory action but its action is much weaker than that of halothane and isoflurane in isolated rat tracheal epithelial cells.     

Prognostic Significance of Complications after Curative Surgery for Gastric Cancer

Background

Postoperative complications such as anastomotic leakage were reported to be a major independent prognostic factor for long-term survival in gastrointestinal malignancies. This study sought to clarify the prognostic significance of postoperative inflammatory complications specifically for patients with gastric cancer.

Methods

This study included 1,395 patients who underwent curative resection for gastric cancer from 2005 to 2008. Complications were evaluated according to the Clavien-Dindo classification. Overall survival (OS) and disease-specific mortality (DSM) were compared between complication and no-complication groups. Presence of complications was modeled by the Cox proportional hazard model for OS and the Fine and Gray competing risk regression model for DSM to assess the correlation between complication and prognosis.

Results

The median follow-up time was 3.1 years. Two hundred seven patients (14.8 %) had complications of grade 2 or higher. Of 131 patients who died within this period, 87 died of gastric cancer. The 3-year OS in the complication group was 84.1 % compared to 93.1 % in the no-complication group (P < 0.0001). The cumulative incidence of DSM was also significantly worse in patients with complications (P < 0.0001). Multivariate analysis identified the same significant increasing risk of complication for both OS (hazard ratio 1.88; 95 % confidence interval 1.26–2.80) and DSM (hazard ratio 1.90; 95 % confidence interval 1.19–3.02).

Conclusions

Postoperative complications that can cause prolonged inflammation have an obvious impact not only on the OS but also on the DSM of patients with gastric cancer even if the tumor is resected curatively.     

Vasoactive intestinal peptide decreases inflammation and tight junction disruption in experimental necrotizing enterocolitis

Background and PurposeExcessive inflammatory cell infiltration and accumulation in the intestinal mucosa are pathological features of necrotizing enterocolitis (NEC) leading to intestinal barrier disruption. Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent that regulates intestinal epithelial barrier homeostasis. We previously demonstrated that VIP-ergic neuron expression is decreased in experimental NEC ileum, and this may be associated with inflammation and barrier compromise. We hypothesize that exogenous VIP administration has a beneficial effect in NEC.MethodsNEC was induced in C57BL/6 mice by gavage feeding, hypoxia, and lipopolysaccharide administration between postnatal day (P) 5 and 9. There were four studied groups: Control (n = 6): Breast feeding without stress factors; Control + VIP (n = 5): Breast feeding + intraperitoneal VIP injection once a day from P5 to P9; NEC (n = 9): mice exposed to NEC induction; NEC + VIP (n = 9): NEC induction + intraperitoneal VIP injection. Terminal ileum was harvested on P9. NEC severity, intestinal inflammation, (IL-6 and TNFα), and Tight junctions (Claudin-3) were evaluated.ResultsNEC severity and intestinal inflammation were significantly decreased in NEC + VIP compared to NEC. Tight junction expression was significantly increased in NEC + VIP compared to NEC.ConclusionVIP administration has a beneficial therapeutic effect in NEC by reducing inflammation and tight junction disruption.     

Nystagmus using video-oculography in psychiatric patients

To evaluate whether nystagmus has clinical significance in psychiatric patients who have functional and/or organic brain dysfunction. We performed gaze, positional and positioning nystagmus tests on 227 patients with psychiatric diseases (144 men, 83 women, with an average age ± SD of 62.5 ± 14.0 years) in order to evaluate the frequency and characteristics of nystagmus. Patients were classified according to the underlying disease. Normal control subjects were 107 subjects (26 men, 81 women, with an average age ± SD of 35.6 ± 10.0 years). Nystagmus was observed in 56 (24.7%) of 227 cases. Nystagmus was seen in 16 (59.3%) of 27 cases of alcoholism, 14 (22.2%) of 63 cases of organic psychiatric disorders, 25 (20.2%) of 124 cases of schizophrenia, 1 (20.0%) of 5 cases of excited mental retardation, 0 (0.0%) of 7 cases of mood disorders, 0 (0.0%) of 1 case of anxiety disorders and 1 (0.9%) of 107 subjects of normal control. There was a significant difference between psychiatric diseases and normal control. These results indicate that nystagmus may also be a very important clinical finding not only in patients with neurological and neuro-otological diseases, but also in patients with psychiatric diseases.     

How is "coverage" defined for occupational health services?

The proportion of workers receiving occupational health services (OHS), or OHS coverage, is considered an important indicator in the evaluation of the national OHS levels. Although the term "coverage" is used in some papers, the definition of the term appears to vary from author to author. Despite vague definitions of the term, the issue has not been much studied. It appears that this vagueness has not led to attempts to establish a clear definition of the term. This study, was undertaken to clarify the meaning of "coverage" when used in relation to OHS. Papers using "coverage" as an indicator of the OHS levels or discussing the issue were collected and analyzed. The first aspect examined concerned the definition of "coverage." Next, the denominator (the target population), and methods for estimating the numerator (the number of workers provided with OHS) were described according to this definition. Few papers dealing with OHS coverage provided an explicit definition: none of the papers stated clearly the OHS functions encompassed when considering coverage, using simply the term in the context. Nor was the worker category to be represented in the denominator discussed, e.g. employees only, or the entire working population. The method for estimating the numerator was generally undefined. This study makes it clear that the term "coverage" in relation to OHS is currently used without clear definition. To permit objective assessments of the national OHS levels, "coverage" must be defined in terms of three elements: OHS functions, the numerator and the denominator of the proportion representing the extent of OHS coverage.     

Effect of prophylactic intracerebroventricular injection of methylprednisolone on nitrogen and catecholamine excretion in the urine after laparotomy in rats

BACKGROUND: This study was carried out to determine whether the prophylactic injection of glucocorticoid into the intracerebroventricular (i.c.v.) space reduced TNF-alpha and IL-1beta mRNA synthesis in the brain after laparotomy, resulting in a reduction of nitrogen excretion in the urine. PATIENTS AND METHODS: Male SD rats (body wt., 225-250 g, n = 114) were catheterized into the i.c.v. space on day 0. On day 4, the rats were assigned to four groups: (1) Control, (2) laparotomy (Trauma), (3) intraperitoneal (i.p.) injection of methylprednisolone (MP) plus laparotomy (IPMP), and (4) i.c.v. injection of MP plus laparotomy (ICVMP). Either 3 or 24 h after surgery, the animals were sacrificed. TNF-alpha and IL-1beta mRNA levels in tissues, including the brain cortex and hypothalamus, were measured by RT-PCR. The amounts of nitrogen and catecholamine excretion in the 24-h urine were determined. RESULTS: The i.p. injection of MP reduced TNF-alpha and IL-1beta mRNA levels in all the tissues 3 h after laparotomy compared with those of the Trauma group. The icv injection of MP prevented elevation of the TNF-alpha and IL-1beta mRNA levels in the brain (cortex, TNF-alpha, ICVMP 0.43 +/- 0.06, P < 0.05, vs Trauma; cortex, IL-1beta, ICVMP 0.25 +/- 0.09, P < 0.05, vs. Trauma; hypothalamus, TNF-alpha, ICVMP 0.31 +/- 0.04, P < 0.05, vs. Trauma; hypothalamus, IL-1beta, ICVMP 0.25 +/- 0.14, P < 0.05, vs. Trauma), but did not inhibit an increase in TNF-alpha and IL-1beta mRNA levels in the liver and skeletal muscle. Both nitrogen and catecholamine excretions in the urine were decreased by ip and by i.c.v. injection of MP compared to those of the Trauma group (nitrogen, ICVMP 559.3 +/- 52.0 mg/day, P < 0.05, vs. Trauma; catecholamine, ICVMP 13.8 +/- 1.8 microg/day, P < 0.05, vs. Trauma). CONCLUSION: A reduction in TNF-alpha and IL-1beta mRNA synthesis in the brain due to prophylactic injection of MP into the icv space reduced the catabolic response after laparotomy.     

Clinical manifestations of 25 patients with prostatic-type polyps in the prostatic urethra

To clarify the clinical manifestations of prostatic-type polyps (PP) in the prostatic urethra, a sample of 25 patients with PP who presented themselves to our hospital with hematuria or hematospermia was reviewed with respect to their symptoms and endoscopic findings. Recurrence of the conditions was also investigated. The patients were 26 to 68 years old, with a mean age of 48.5 years. Sixteen patients (64%) had hematuria and 8 (32%) had hematospermia. A bloody urethral discharge was observed in 6 patients (24%). Analysis of the character of the hematuria showed that total hematuria occurred in 44% of the patients. In 38% of the patients with hematospermia there was the additional symptom of post-ejaculatory hematuria. PP developed beside the verumontanum in 18 patients (72%), on the posterior urethral wall lateral to the verumontanum in 4 patients (16%), and on the verumontanum in 7 patients (28%). The prognosis could be investigated only in 22 (88%) of the 25 patients. Two patients (9%) experienced reccurrence during the follow-up period (1 to 5.8 years, mean: 3.7 years). Consequently, special attention should be paid to the possibility of PP in the prostatic urethra, particularly the verumontanum and nearby area, during endoscopic examination, when diagnosing patients with hematuria, hematospermia or with bloody urethral discharge.     

Risk of pancreatic cancer in relation to alcohol drinking,coffee consumption and medical history: findings from the Japan collaborative cohort study for evaluation of cancer risk

We evaluated the associations of such lifestyle factors as alcohol drinking, coffee consumption and medical history with risk of death from pancreatic cancer in a large-scale prospective cohort study [the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC study)] in Japan. Subjects were 110,792 (46,465 men and 64,327 women) inhabitants who were enrolled from 45 areas throughout Japan. At baseline, a self-administered questionnaire was used to obtain information on lifestyle factors and medical history. Cox proportional hazard models were used to calculate relative risks. During the follow-up period (mean +/- SD 8.1 +/- 1.8 years), 225 deaths due to pancreatic cancer were identified. Overall, neither alcohol nor coffee intake was associated with risk of death from pancreatic cancer. Heavy coffee consumption (> or =4 cups/day), however, may increase the risk. Men who reported a history of diabetes mellitus and women who reported a history of gallstone/cholecystitis were at significantly (2-fold) increased risk of death from pancreatic cancer.