Effectiveness of an anti-inflammatory drug, loxoprofen, for patients with nocturia

AIM: There is increasing evidence that non-steroidal anti-inflammatory drugs are effective for the treatment of nocturia. In this study, we attempted to investigate the role of loxoprofen sodium (loxoprofen) in the therapeutic management of patients with nocturia. METHODS: Fifteen benign protastatic hyperplasia and/or overactive bladder patients (13 males and 2 females, 71.1 +/- 1.5 years old) with three or more voids per night were involved. These patients had received standard drug therapy. Although these patients had received standard drug therapy for more than half a year, they had still three or more episodes of nocturia. The patients took a single dose of 60 mg of loxoprofen at night prior to sleep. Before and 1 week after the initiation of this therapy, the effects of this treatment were assessed by frequency volume chart and a questionnaire. RESULTS: In the questionnaire, seven patients answered as excellent, six patients demonstrated improvement of their symptoms, two patients did not show a significant change in their symptoms and no patients demonstrated a deterioration in the symptoms. In frequency volume chart, total void per day, total void per night, total urine volume per day, total night urine volume per day and single voided volume in the night before and after this treatment were 9.97 +/- 0.81 and 8.99 +/- 0.74 per day, 3.82 +/- 0.25 and 1.82 +/- 0.27 per night, 1349 +/- 81 and 1258 +/- 91 mL per day, 567 +/- 46 and 325 +/- 51 mL per night, and 143 +/- 13 and 149 +/- 10 mL, respectively. CONCLUSION: Loxoprofen can be effective and useful for patients with nocturia. Our data suggest that the main mechanism of this effect is to decrease urine production during a night's sleep.     

Laparoscopic adrenalectomy in patients with large adrenal tumors

OBJECTIVES: The maximum size of adrenal tumors that should be removed by laparoscopic adrenalectomy is controversial. We conducted a retrospective comparison of the results of laparoscopic adrenalectomy between patients with adrenal tumors > or =6 cm ('large tumors') and patients with adrenal tumors <6 cm ('small tumors'). METHODS: The participants in the study were 16 patients with large tumors and 111 patients with small tumors. The patients comprised 59 men and 68 women (mean age, 49.0 years; age range, 23-79) with varying diagnoses. Of the 16 patients with large tumors, five had Cushing's syndrome, four had pheochromocytomas, six had a non-functional tumor and one had malignant lymphoma. Adrenal tumors were confirmed by hormonal assays, biochemical tests and computed tomography. Of the 16 large tumors, five tumors were on the right and 11 were on the left. RESULTS: We found no significant differences in general demographic parameters between patients with large and small tumors. The mean duration of surgery was not significantly different between two groups. (large tumors, 210 min; small tumors,175 min). The mean volume of blood loss was 212 mL for large tumors and 30 mL for small tumors (P < 0.001, significant difference). There was no significant difference in time until walking, duration of hospitalization or number of using analgesics used. The time to first oral intake of group 1 (<6 cm) was significantly shorter than group 2 (> or =6 cm). Tumor size (> or =7.5 cm) was an independent predictor of a longer operation and greater blood loss in large tumors. CONCLUSIONS: Laparoscopic adrenalectomy for large tumors was safe and minimally invasive.     

Inhibition of Rat Acute Inflammatory Paw Oedema by Dihemiphthalate of Glycyrrhetinic Acid Derivatives: Comparison with Glycyrrhetinic Acid

Abstract— The anti-inflammatory profile of dihemiphthalate compounds of glycyrrhetinic acid derivatives in acute rat paw oedema induced by various vasoactive agents was compared with the parent compound. Three dihemiphthalate compounds (the di-sodium salt of 18 β-olean-12-ene-3β,30-diol di-O-hemiphthalate, 18β-olean-9(11),12-dione-3β,30-diol di-O-hemiphthalate and olean-11,13(18)-diene-3β,30-diol di-O-hemiphthalate), significantly inhibited development of carrageenan-induced rat paw oedema during the first 3 h (ED50 70, 90, and 108 mg kg^?1 respectively, p.o.), while glycyrrhetinic acid (ED50, 200 mg kg^?1) showed a significant inhibition of paw oedema 3 h after carrageenan treatment. The dihemiphthalate compounds also suppressed mouse paw oedema induced by histamine, bradykinin, and PAF acether at doses of less than 100 mg kg^?1. However, these compounds failed to inhibit 5-HT-induced mouse paw oedema. Glycyrrhetinic acid had little effect on mouse paw inflammation induced by the above irritants. The three compounds at 10^?7-10^?4 m , inhibited histamine-induced contraction of guinea-pig isolated ileum. However, concentration-response curves to 5-HT and bradykinin were not affected by the same compounds. These results suggest that the dihemiphthalate compounds modulate vascular permeability caused by endogenous vasoactive agents as one of the anti-inflammatory mechanisms. This action is quite different from that of glycyrrhetinic acid.     

A comparison of the dissolution rates of caffeine tablets in a rotating-basket with those in a Sartorius dissolution tester

Uncoated caffeine tablets of four different hardnesses were tested for dissolution rate by the Sartorius (S.S. method) and by the rotating basket method of the U.S.P. XVIII. In both methods the dissolution rate decreased with increasing hardness, and the rate obtained with the S.S. method was always less than that by the U.S.P. method. This result cannot be explained as being due only to the difference in the volume of dissolution medium. Also it was difficult to ensure that the characteristic changes in the process of dissolution paralleled the curves obtained from a plot of % caffeine dissolved vs time. Accordingly, the dissolution rate constants were calculated from the slope of each straight line in a plot of In W^∞/(W^∞ - W) vs time.     

Thromboxane inhibition and monocrotaline-induced pulmonary hypertension in rats

Abstract Monocrotaline (MCT)-induced pulmonary hypertension (PH) is a useful model for the investigation of this disorder in humans. The role of thrombocytes in the genesis of PH has already been addressed; however, the exact mechanism by which they induce PH remains to be elucidated. We investigated the effects of a thromboxane A₂ (TXA₂) synthase inhibitor (OKY-046) and a TXA₂/ prostaglandin H₂ (PGH₂) receptor antagonist (ONO-8809) on the development of MCT-induced PH. A single dose of MCT (60 mg/kg bodyweight; BW) was injected subcutaneously in Wistar rats 24 h after the administration of OKY-046 or ONO-8809. The TXA₂ inhibitors were administered by gavage daily for 3 weeks. Urinary excretion of eicosanoids was determined by radioimmunoassay. At the end of the treatment period, the lungs, heart and kidneys were morphologically examined. The per cent medial thickness of the muscular pulmonary arteries (%MT) and the ratio of the right to the left ventricular mass including the septum (RV/LV+S) increased significantly in MCT-treated rats compared with the control rats. The %MT was attenuated by the administration of ONO-8809. Either OKY-046 or ONO-8809 attenuated the increase in RV/LV+S. In addition, both TXA₂ inhibitors reduced urinary excretion of 11-dehydro-TXB₂, particularly during the early phase of PH, suggesting that platelet aggregation was reduced. These findings suggest that the inhibition of TXA₂ by synthase inhibition or receptor antagonism reduces or delays the development of MCT-induced PH in rats, probably by inhibiting platelet aggregation.     

Endothelial cells upregulate eosinophil superoxide generation via VCAM-1 expression

BACKGROUND: In vitro eosinophil (EOS) adhesion to recombinant human (rh)-vascular cell adhesion molecule (VCAM)-1 stimulates superoxide anion (O2-) generation and enhances formyl-methionyl-leucyl phenylalanine (FMLP)-activated O2- generation. Therefore, EOS adhesion via VLA-4 to VCAM-1 expressed on endothelium may be instrumental in the selective recruitment and function of EOS in airway inflammation. OBJECTIVE: We hypothesized that EOS interaction with endothelial cells expressing VCAM-1 will undergo an enhancement in inflammatory function. METHODS: To determine this possibility, human umbilical vein endothelial cells (HUVEC) were stimulated with either a combination of interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha (100 pM) or medium alone for 24 h; the expression of adhesion proteins on HUVEC and their effect on EOS O2- generation was subsequently determined. RESULTS: As determined by both enzyme-linked immunosorbent assay and flow cytometry, IL-4 and TNFalpha acted synergistically to induce VCAM-1 expression on HUVEC. Treating HUVEC with IL-4/TNFalpha also increased EOS adhesion and primed subsequent FMLP (0.1 microM) activated EOS O2- generation. Although EOS adhesion was partially inhibited by both antialpha4 and antibeta2 monoclonal antibodies (MoAbs), O2- generation was completely inhibited by either antialpha4 integrin MoAb (HP1/2) or anti-VCAM MoAb (BBIG-V1). Furthermore, enhanced O2- generation, but not adhesion, associated with IL-4 + TNFalpha-treatment of HUVEC was inhibited when EOS were treated with the platelet activating factor (PAF)-antagonist WEB 2086 (20 microM), thus suggesting an involvement of PAF in priming EOS. However, paraformaldehyde fixation of IL-4/TFN-alpha treated HUVEC did not significantly alter EOS function. CONCLUSIONS: These results suggest EOS adhesion to endothelial cells via an VLA-4/VCAM-1 interaction may be important in the development of the function of this cell. Furthermore, our results suggest that modulation of EOS function involves two priming factors: EOS adhesion to HUVEC expressing VCAM-1 and PAF.     

Comprehensive treatment of advanced neuroblastoma involving autologous bone marrow transplant

Encouraging results are reported with high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation in the treatment of advanced neuroblastoma. However, relapse remains a significant problem. We used high-dose chemotherapy, surgery, intraoperative radiation and an autologous bone marrow transplant treated in vitro to remove tumor cells followed by 13-cis-retinoic acid to treat 36 children with advanced neuroblastoma. This comprehensive treatment appears to improve the survival rate of patients with advanced neuroblastoma, including those with N-myc amplification and bony involvement. The disease-free survival rate was 66% (95% confidence interval, 49–84%) at 3 years. All patients who received 13-cis-retinoic acid developed cheilitis, but no bone marrow depression occurred in these patients. Five patients developed hemolytic uremic syndrome (HUS) post-transplant. This may have been related to the procedure used for total body irradiation. Patients who had their kidneys shielded during this procedure did not develop this syndrome. Patients who received local irradiation at the primary site showed no evidence of relapse in this region, indicating that such therapy may help to prevent a relapse. These data suggest a high rate of 3 year disease-free survival with this treatment strategy. The nonrandomized nature of the study and use of multiple modalities precludes analysis of the specific contribution of each.     

Helicobacter pylori colonization in children with peptic ulcer disease III. Diagnostic value of the 13C-urea breath test to detect gastric H. pylori colonization

The efficiency of the ¹³C-Urea Breath Test (¹³C-UBT) for the detection of Helicobacter pylori colonization in gastric mucosa was evaluated. The ¹³C-UBT was performed in five pediatric and six adult subjects who had had upper gastrointestinal endoscopy within 2 weeks. H. pylori colonization was confirmed in two pediatric and three adult subjects with peptic ulcer combined with antral gastritis, by histological examination of antral biopsy specimens. When an individual with H. pylori colonization ingested a solution containing ¹³C-urea, a significant amount of ¹³CO₂ appeared in the respiratory CO₂ within 10 min. The mean cumulative percentage dose of ¹³C recovered in the breath over 30 min in the cases with H. pylori colonization was significantly higher than that in those who were not colonized (4.91 vs 0.41, P <0.001). In addition, the effect of antibiotic on the eradication of H. pylori from gastric mucosa was monitored by ¹³C-UBT in two cases. The values of cumulative percentage dose of ¹³C over 30 min fell to the same levels as those observed in H. pylori negative subjects after just 2 weeks treatment with amoxicillin; however, positive results were obtained again 1 month after the withdrawal of amoxicillin. In summary, ¹³C-UBT is a simple, reliable, non-invasive method in the diagnosis of gastric H. pylori colonization especially for pediatric patients.     

Characterization and expression of a stage specific antigen by monoclonal antibody TRA 54 in testicular germ cells

To study the mechanism of spermatogenesis, we have isolated many monoclonal antibodies (mAb) which recognize specific steps of mouse germ cell differentiation and then have evaluated the specific expression and characterization of antigenic molecules using immunohistochemistry and Western blotting. Monoclonal antibody TRA 54 recognized specific organelles in germ cell cytoplasm from spermatocytes to spermatids; that is, a large granule was stained in mid–late pachytene, diplotene and secondary spermatocytes and in round spermatids at stage I while the acrosome of spermatids at steps 2–3 to step 12 were also positive. Thereafter, the antigens disappeared from spermatids at more advanced stages of differentiation. Western blots using TRA 54 revealed broad bands with approximate molecular weights of >200, 190 and 85 kDa in the testis. The expression of these antigens during testicular germ cell development should be of interest in relation to the biogenesis of organelles such as the chromatoid body and acrosome and will be a useful stage-specific molecular marker for the study of spermatogenesis.     

Attenuation of Non‐neuronal Adenosin Triphosphate Release from Human Bladder Mucosa by Antimuscarinic Agents

Objectives: To clarify the contribution of mucosal muscarinic receptors to bladder function, we investigated the effects of various antimuscarinic drugs on stretch‐induced non‐neuronal adenosin triphosphate (ATP) release in human bladder. Methods: Human bladders were obtained from 17 patients. Bladder strips with and without mucosa were suspended in organ baths. A microdialysis probe was inserted into the strip, Ringer's solution was perfused into the probe, and dialysate was collected under tetrodotoxin pretreatment. The amount of ATP released in dialysate was measured by luciferin‐luciferase assay. The effects of various antimuscarinic drugs on non‐neuronal ATP release were evaluated. Results: Non‐neuronal ATP release from bladder strips without mucosa was approximately 10% of that from strips with mucosa. Non‐neuronal ATP release was significantly inhibited by pretreatment with nifedipine or in Ca²⁺‐free medium. Both methoctramine (M₂ receptor selective antagonist) and 4‐diphenyl‐acetoxy‐N‐methylpiperidine methiodide (4‐DAMP [M₃ receptor selective antagonist]) significantly inhibited release. However, M₁ receptor selective antagonist (pirenzepine) did not have a significant effect on release. Oxybutynin, propiverine, tolterodine and solifenacin caused concentration‐dependent inhibition in non‐neuronal ATP release. The rank order of the maximum inhibition rate was propiverine ≥ solifenacin ≥ tolterodine ≥ oxybutynin. Solifenacin showed an inhibitory effect at a lower concentration compared to other drugs. Conclusion: The data suggest that human bladder mucosa is a main source of stretch‐induced non‐neuronal ATP release, and that stimulation of M₂ and M₃ receptor subtypes of mucosa partly contributes to non‐neuronal ATP release. Various antimuscarinic drugs used for the treatment of overactive bladder may have different inhibitory effects on non‐neuronal ATP release.