Functional mechanism underlying cyclooxygenase-2 expression in rat small intestine following administration of indomethacin: Relation to intestinal hypermotility

Background and Aim:  We recently reported that cyclooxygenase (COX)-2 is upregulated in the rat small intestine after administration of indomethacin, and this may be the key to non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage. The present study investigated the mechanism for COX-2 expression induced in the rat small intestine by indomethacin, in relation with ulcerogenic processes.
Methods:  Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results:  Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE₂ content was decreased by SC-560 at 3 h but recovered 12 h later, and this recovery of PGE₂ was attenuated by both atropine and ampicillin, in addition to rofecoxib. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE₂ and atropine, but not ampicillin. Yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 and iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in the prevention of intestinal lesions.
Conclusion:  These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties.     

Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer

BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the patients with non-seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs. RESULTS: Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non-seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.     

Prevalence of and risk factors for nocturia: Analysis of a health screening program

BACKGROUND: We examined the prevalence of and risk factors for nocturia in Kurashiki city and the surrounding area, a rural area in Japan. MATERIALS AND METHODS: We collected data on 6517 individuals (4568 men and 1949 women) who participated in a multiphasic health screening. We analyzed the relationships between nocturia assessed by a questionnaire (voiding twice or more during night) and other variables including age, hypertension, cardiovascular disease, cerebrovascular disease, chronic obstructive pulmonary disease, diabetes mellitus (DM), chronic renal failure, benign prostatic hyperplasia (BPH), smoking habit and alcohol intake. RESULTS: Overall, 1856 individuals (28.5%) answered that they arose to urinate at least twice during the night. This rate increased with age from 16.5% in individuals younger than 50 to 60.0% in those older than 69. Logistic regression analysis revealed that cohorts of subjects 50-59, 60-69, and 70 years old or over had, respectively, 1.75, 3.35, and 6.21 times the prevalence of nocturia of the 49 years or younger cohort. Hypertension (odds ratio [OR] 1.64) and DM (OR 1.70) were other independent positive risk factors for nocturia. On the other hand, current smokers who smoked 20 or more cigarettes per day were less likely to have nocturia than non-smokers (OR 0.72). In male individuals, BPH was another independent positive risk factor (OR 1.35). Gender was not associated with nocturia. CONCLUSIONS: Although population bias is an important limitation to this study, nocturia is associated with various factors suggesting that multiple approaches are needed to the treatment of patients with nocturia.     

The Synergistic Purgative Action of Aloe-emodin Anthrone and Rhein Anthrone in Mice: Synergism in Large Intestinal Propulsion and Water Secretion

This study aimed to explore the mechanism involved in the synergistic purgative action of aloe-emodin anthrone and rhein anthrone, the active metabolites of sennoside C. Aloe-emodin anthrone and rhein anthrone, and their equimolar mixture, induced excretion of an approximately equal number of faeces by intracaecal administration at a dose of 23.2 μmol kg^?1 in mice (= 10 standard dose). The number of wet faeces induced by aloe-emodin anthrone was less than those of rhein anthrone and the mixture. At the same dose, rhein anthrone and the mixture significantly stimulated large intestinal propulsion, though aloe-emodin anthrone had little stimulatory effect. Aloe-emodin anthrone and rhein anthrone decreased net water absorption but could not reverse it to the net secretion at 1/2 dose. The mixture significantly decreased net water absorption and reversed it to the net secretion at this dose. These anthrones did not stimulate mucus secretion in the colon at 1/2 dose. We concluded that the synergistic purgative effect of aloe-emodin anthrone and rhein anthrone in mice results from synergistic stimulation of large intestinal transit and large intestinal water secretion.     

Experimental Assessment of Right Ventricular Function in Normal Pigs with a Left Ventricular Assist Device

Abstract: Right ventricular (RV) failure during the use of a left ventricular assist device (LVAD) is the leading cause of death in circulatory support patients. Previous work, both experimentally and clinically, has shown the difficulties in predicting the behavior of the right ventricle at the start of LVAD. An experimental study has been designed to evaluate RV functional changes during LVAD and its relation to preload changes. The model used adult mongrel pigs (n = 10). Right ventricular functional parameters were measured with a thermodilution RV ejection fraction catheter. The left ventricle was supported by a Nippon Zeon blood pump. Two groups were studied, the first one was the LVAD–off group (n = 5) and the other was the LVAD–on group (n = 5) which was supported by LVAD at maximum flow. Change of cardiac output, mean pulmonary artery pressure (PAP), RV stroke work, and RV ejection fraction in both groups were not significantly different. However, the relationship between right ventricular end–diastolic pressure (RV–EDP) and right ventricular stroke volume (RVSV) was significantly changed at a high level of RV–EDP. When RV–EDP was over 6. 5 mm Hg in the LVAD–off group, RVSV decreased to 52. 3 ± 11. 5 ml while in the LVAD–on group, RVSV increased to 97. 2 ± 22. 0 ml. The change in PAP in the LVAD–on group was lower than in the LVAD–off group. We conclude that, at the volume overload state, LVAD can reduce the afterload of the right ventricle and maintain Frank–Starling's effect, thus having a beneficial effect on right ventricular performance.     

Comparison of Single and Dual Monitoring during Carotid Endarterectomy

We compared the rate of selective shunt and pattern of monitoring change between single and dual monitoring in patients undergoing carotid endarterectomy (CEA). A total of 121 patients underwent 128 consecutive CEA procedures. Excluding five procedures using internal shunts in a premeditated manner, we classified patients according to the monitoring: Group A (n = 72), patients with single somatosensory evoked potential (SSEP) monitoring; and Group B (n = 51), patients with dual SSEP and motor evoked potential (MEP). Among the 123 CEAs, an internal shunt was inserted in 12 procedures (9.8%) due to significant changes in monitoring (Group A 5.6%, Group B 15.7%, p = 0.07). The rate of shunt use was significantly higher in patients with the absence of contralateral proximal anterior cerebral artery (A1) on magnetic resonance angiography (MRA) than in patients with other types of MRA (p <0.001). Significant monitor changes were seen in 16 (12.5%) in both groups. In four of nine patients in Group B, SSEP and MEP changes were synchronized, and in the remaining five patients, a time lag was evident between SSEP and MEP changes. In conclusion, the rate of internal shunt use tended to be more frequent in patients with dual monitoring than in patients with single SSEP monitoring, but the difference was not significant. Contralateral A1 absence may predict the need for a shunt and care should be taken to monitor changes throughout the entire CEA procedure. Use of dual monitoring can capture ischemic changes due to the complementary relationship, and may reduce the rate of false-negative monitor changes during CEA.     

Feedback mechanism in sulpiride-induced hyperprolactinaemia

Summary. Feedback of oestrogen on gonadotrophin release was studied in five normally cycling normoprolactinaemic women who were rendered moderately hyperprolactinaemic by oral administration of sulpiride (150mg daily) for 11 consecutive days. Five patients with peptic ulcer, who had been given 150 mg of sulpiride for 3–18 months and had chronic marked hyperprolactinaemia were also studied. Ethinyl oestradiol (200μg) was administered by mouth daily for 4 consecutive days and serum concentration of prolactin, luteinizing hormone (LH), follicle- stimulating hormone (FSH) and oestradiol were measured by a doubleantibody radioimmunoassay for 11 days. Oral administration of ethinyl oestradiol caused an initial decrease followed by a rebound of LH with a peak in all the women tested. The serum FSH levels showed only the initial decrease, followed by a slight rebound. Serum oestradiol levels decreased during oral administration of ethinyl oestradiol in all the women. The results of the present investigation suggest that oestrogen feedback effect on LH release is maintained in sulpiride-induced hyperprolactinaemic women as well as in women with normal cycles.     

The effect of nifedipine on monocrotaline-induced pulmonary hypertension in rats

Effective drug therapy for pulmonary hypertension has not yet been developed. This study was designed to estimate the long-term hemodynamic and histopathological effects of nifedipine on severe pulmonary hypertension using animal models. Injection of one dose of monocrotaline produced subacute pulmonary hypertension in 7 week old Sprague-Dawley rats. Nifedipine (10 mg/kg) was administered intraperitoneally every day. For 5 weeks, bodyweight and hemodynamic parameters were measured, and right ventricle (RV) and left ventricle with septum (LV + S) were weighed separately. Medial thickness of the small pulmonary arterial wall was calculated by Suwa's method. Compared with the control group, the increase in right ventricular systolic pressure, total pulmonary resistance index, weight ratio of RV/(LV + S) and medial hypertrophy in the nifedipine-treated rats were significantly limited without causing systemic hypotension. These results suggest that treatment with nifedipine may also be effective in attenuation of pulmonary hypertension when applied to humans.