Analysis of Urinary Retention Caused by Selective ß 3-adrenoceptor Agonists Using the Japanese Adverse Drug Event Report Database (JADER).

Overactive bladder (OAB) is a frequent chronic disorder which impairs quality of life by frequent, uncontrollable urination. Newly developed selectiveß 3-adrenoceptor agonists (sß 3-agonists) have the same efficacy in treating OAB but significantly fewer side effects than the traditionally used anti-muscarinics. However, safety data on these compounds are scarce. In this study, we analysed the occurrence of adverse effects in patients taking sß 3-agonists and their characteristics using the JADER database. The most frequently reported adverse effect associated with the use of sß 3-agonists was urinary retention [mirabegron; crude reporting odds ratios (ROR): 62.1, 95% confidence interval (CI): 52.0-73.6, P<0.001, vibegron; crude ROR: 250, 95% CI : 134-483, P<0.001]. Data from patients with urinary retention were stratified by sex. In both men and women, the rate of urinary retention was higher when using the mirabegron/anti-muscarinic drug when compared to mirabegron monotherapy; its occurrence was higher in men with a history of benign prostatic hypertrophy than in those without. Weibull analysis showed that approximately 50% of sß 3 agonist-induced urinary retention occurred within 15 days after initiation of treatment, and then gradually decreased. Although sß 3-agonists are useful against OAB, they may induce several side effects, especially urinary retention, which can further evolve into more severe conditions. Urinary retention occurs more frequently in patients concomitantly taking medication that either increases urethral resistance or has organic factors that block the urethra. When using sß 3-agonists, the concomitantly used medications and underlying diseases should be thoroughly reviewed, and safety monitoring should be instituted early during the treatment.

Pharmacist Interventions for Adverse Drug Reactions in Palliative Care: A Multicentre Pilot Study.

This study aimed to investigate adverse reactions to medications administered during palliative care and compare the responses of Board-Certified Pharmacists in Palliative Pharmacy (BCPPP) and non-BCPPP professionals. Methods: This multicentre prospective survey included hospital and community pharmacists who are members of the Japanese Society for Pharmaceutical Palliative Care and Sciences. Study participants included patients who experienced new drug reactions during the study period and responded to the requested survey items. The follow-up period for each eligible patient began on the day the pharmacists initiated the intervention and ended at discharge, death, or after one month of intervention. The primary endpoint was the impact of pharmacist intervention on adverse drug reactions. The pharmacists included in the study evaluated the severity of adverse drug reactions to assess the effect of their intervention using an integrated palliative care outcome scale before and after the intervention. Key findings: During the survey period, 79 adverse drug reaction intervention reports from 69 patients were obtained from 54 pharmacists (28 certified and 26 non-certified). The response rate was 1.62% (54/3,343). The management of palliative pharmacotherapy side effects by BCPPP and non-BCPPP significantly improved the patients' activities of daily living (P < 0.001). The BCPPP group intervened for significantly more patients with adverse drug reactions and overall adverse drug reactions than the non-BCPPP group (P < 0.023 and P < 0.013, respectively). Conclusion: BCPPP interventions can improve symptom management.

Size control of sol-gel-synthesized ZnO quantum dots using photo-induced desorption.

We developed a sol-gel method using photo-induced desorption for size-controlled ZnO quantum dots (QDs). This method successfully controlled the size and size variance of ZnO QDs, and size fluctuations decreased from 23% to 18% depending on the illuminated light intensity. The sol-gel synthesis effectively reduced the number of defect levels that originated from oxygen defects.

In situ real-time monitoring of changes in the surface roughness during nonadiabatic optical near-field etching.

We performed in situ real-time monitoring of the change in surface roughness during self-organized optical near-field etching. During near-field etching of a silica substrate, we detected the scattered light intensity from a continuum wave (CW) laser (lambda = 633 nm) in addition to the etching CW laser (lambda = 532 nm) light source. We discovered that near-field etching not only decreases surface roughness, but also increases the number of scatterers, as was confirmed by analyzing the AFM image. These approaches provide optimization criteria for the etching parameter and hence for further decreases in surface roughness.

Early detection of Niemann-pick disease type C with cataplexy and orexin levels: continuous observation with and without Miglustat.

STUDY OBJECTIVES: Niemann-Pick type C (NPC) is an autosomal recessive and congenital neurological disorder characterized by the accumulation of cholesterol and glycosphingolipids. Symptoms include hepatosplenomegaly, vertical supranuclear saccadic palsy, ataxia, dystonia, and dementia. Some cases frequently display narcolepsy-like symptoms, including cataplexy which was reported in 26% of all NPC patients and was more often recorded among late-infantile onset (50%) and juvenile onset (38%) patients. In this current study, we examined CSF orexin levels in the 10 patients of NPC with and without cataplexy, which supports previous findings. METHODS: Ten patients with NPC were included in the study (5 males and 5 females). NPC diagnosis was biochemically confirmed in all 10 patients, from which 8 patients with NPC1 gene were identified. We compared CSF orexin levels among NPC, narcoleptic and idiopathic hypersomnia patients. RESULTS: Six NPC patients with cataplexy had low or intermediate orexin levels. In 4 cases without cataplexy, their orexin levels were normal. In 5 cases with Miglustat treatment, their symptoms stabilized or improved. For cases without Miglustat treatment, their conditions worsened generally. The CSF orexin levels of NPC patients were significantly higher than those of patients with narcolepsy-cataplexy and lower than those of patients with idiopathic hypersomnia, which was considered as the control group with normal CSF orexin levels. DISCUSSION: Our study indicates that orexin level measurements can be an early alert of potential NPC. Low or intermediate orexin levels could further decrease due to reduction in the neuronal function in the orexin system, accelerating the patients' NPC pathophysiology. However with Miglustat treatment, the orexin levels stabilized or improved, along with other general symptoms. Although the circuitry is unclear, this supports that orexin system is indeed involved in narcolepsy-cataplexy in NPC patients. CONCLUSION: The NPC patients with cataplexy had low or intermediate orexin levels. In the cases without cataplexy, their orexin levels were normal. Our study suggests that orexin measurements can serve as an early alert for potential NPC; furthermore, they could be a marker of therapy monitoring during a treatment.

Generation of pressures over 40 GPa using Kawai-type multi-anvil press with tungsten carbide anvils.

We have generated over 40 GPa pressures, namely, 43 and 44 GPa, at ambient temperature and 2000 K, respectively, using Kawai-type multi-anvil presses (KMAP) with tungsten carbide anvils for the first time. These high-pressure generations were achieved by combining the following pressure-generation techniques: (1) precisely aligned guide block systems, (2) high hardness of tungsten carbide, (3) tapering of second-stage anvil faces, (4) materials with high bulk modulus in a high-pressure cell, and (5) high heating efficiency.

Acute production of vascular superoxide by angiotensin II but not by catecholamines.

OBJECTIVE: To determine whether vascular superoxide is rapidly released by angiotensin II and is involved in vascular contraction. DESIGN: The effect of superoxide dismutase (SOD) on angiotensin II induced elevation of mean arterial blood pressure was measured. Subsequently, acute production of vascular superoxide by angiotensin II and its effect on isometric tension were measured in rat aortic rings. The effects of catecholamines were concomitantly measured. METHODS AND RESULTS: The acute pressor effects of angiotensin II were significantly reduced when rats were pretreated intravenously with SOD. When angiotensin II was added on aortic segments in the presence of Cypridina luciferin analog, immediate elevations of chemiluminescence were observed which were inhibited by SOD. Furthermore, angiotensin II-induced elevations of isometric tension in aortic rings were significantly reduced by SOD. The effects of epinephrine and norepinephrine were concomitantly measured and were not significant CONCLUSIONS: The acute superoxide producing effect is likely to be specific to angiotensin II, because such a significant modification of the effects was not observed for catecholamines. Our results suggest that angiotensin II causes acute vascular superoxide production, which may be involved in the acute pressor effects.

The effects of an incisal bite plane on rat sublingual glands.

Application of an incisal bite plane for as little as three d caused a significant increase in the size of the sublingual glands of rats, with some evidence of hyperplasia and hypertrophy of the acinar cells. The enlargement had few effects on salivary secretion, and the gland changes were reversible.

The effects of an incisal bite plane on rat submandibular glands.

The submandibular glands of rats subjected to application of an incisal bite plane became slightly, but not significantly, enlarged. However, in comparison with control animals, they secreted additional proteins identical with those secreted by glands enlarged by periodic incisor amputation or chronic isoproterenol treatment.

Influences of roxithromycin on cell-mediated immune responses.

We investigated the effects of roxithromycin (RXM), a synthesized macrolide antibiotic on murine cellular immune responses by examining the in vitro proliferative response of lymphocytes, interleukin 1 (IL-1) production and interleukin 2 (IL-2) production. RXM was orally administered to BALB/c mice at a dose of 5 mg/kg once a day for 42 days. Spontaneous blastic activity of lymphocytes prepared from mice administered with RXM for 7 days was higher than those from control mice. The activity peaked at the 14th day, and then decreased gradually to control levels by the 42nd day. Time kinetics of lymphocyte blastogenesis to concanavalin A showed a pattern similar to that observed in spontaneous blastic activity. Oral administration of RXM also influenced cytokine production; short-term (for 14 days) administration of RXM enhanced both IL-1 and IL-2 production but long-term (for 42 days) administration inhibited them.

Mechanism for splenocyte-mitogenesis induced in mice by water-extract of coniferous slash pine.

A water extract of wood chips of coniferous slash pine induced appreciable splenocyte-mitogenesis in healthy adult, aged, and also tumour-bearing mice. Mitogenesis was induced mainly in B-cell subset of splenocytes. The induction was not mediated by IL-2 or IFN gamma released from the activated helper T-cell. It may be worth noting that this extract could be included in a new type of immunomodulator for promotion of the host defense mechanism.

Involvement of superoxide in acute reaction of angiotensin II in mesenteric microcirculation.

Superfusion of angiotensin II (Ang II) ceased blood flow in rat mesenteric microcirculation, however, successive reflow occurred. When nitric oxide synthase inhibitor was present, the stoppage of flow occurred by the lower concentration of Ang II. Superoxide dismutase (SOD) significantly delayed the stoppage by Ang II and restored the successive reflow earlier. The acute reaction between Ang II and mesenteric artery induced immediate superoxide (O(2)(-)) production when observed by a chemiluminescence method using the Cypridina luciferin analog. The acute vascular O(2)(-) production on the addition of Ang II contributed to in vitro vascular contraction as it was significantly attenuated by SOD. The acute superoxide-producing effect is likely to be specific to Ang II because such significant modification by SOD was not observed for norepinephrine.

Reduction of burn-induced gastric mucosal injury by an endothelin receptor antagonist in rats.

Burn-induced stress ulcers may be a major complication in critically burned patients. The pathophysiology of gastric mucosal ulceration is relatively unknown, however reduced gastric mucosal blood flow is one contributing factor. Endothelin (ET) is a well known vasoconstrictor peptide produced by vascular endothelial cells. Endothelin has been reported to have a fundamental role in the regulation of the systemic circulation. The plasma ET level is increased by burn injury, which also causes thrombosis and vessel occlusion. Endothelin has potent ulcerogenic and vasoconstrictor actions in the stomach where it induces gastric mucosal damage and increases gastric vascular tone. In the present study, we examined the effects of a new non-selective ET receptor antagonist, TAK-044, on burn-induced gastric mucosal injury in rats. Twenty male Sprague-Dawley rats weighting an average of 400 g were burned with hot water (90 degrees C) and then divided into two equal groups. The treatment group received 1 mg/kg of TAK-044 via the dorsal vein of the penis immediately after burn trauma, while the control group received the same volume of saline. Gastric mucosal blood flow was measured with a laser Doppler flowmeter and the area of mucosal necrosis was also determined macroscopically and histologically. Inhibition of ET activity by TAK-044 after burn injury significantly improved microvascular perfusion in the gastric mucosa and prevented the progression of mucosal damage in the stomach (P < 0.05). The present study supports the role of ET in burn-induced gastric ulceration (Curling's ulcer).

Reduction of progressive burn injury by a stable prostaglandin I2 analogue, beraprost sodium (Procylin): an experimental study in rats.

Beraprost sodium is a chemically stable prostaglandin I2 analogue with antiplatelet and vasodilator actions. Burn injury causes thrombosis and vessel occlusion by increasing the blood viscosity and by thermal damage to the vascular network in the dermis. A vascular response also occurs in the uninjured dermis surrounding the site of injury. Diminished blood flow and spreading tissue oedema lead to progressive ischaemia and necrosis around the burn site (zone of stasis), with the final necrotic tissue area being larger than the initial one. If blood flow could be restored in the zone of stasis, secondary tissue damage would be minimized. In this study, we examined the effects of a prostaglandin I2 analogue, beraprost sodium (Procylin, Kaken Pharmaceutical Company, Tokyo, Japan) on burn injury in rats. Twenty male Sprague-Dawley rats weighing an average of 450 g were burned with a comb-shaped brass probe that produced a row of three burns measuring 10 x 30 mm each and two intervening unburned areas measuring 5 x 30 mm each. The rats were divided into two groups of 10 animals. One group received 0.015 mg of beraprost sodium intraperitoneally immediately after burn injury, while the control group received the same volume of saline. Skin blood flow was measured with a laser Doppler flowmeter, and the development of oedema as well as the area of necrotic tissue were also determined. The extent of skin necrosis and oedema were significantly reduced in the beraprost sodium-treated rats, and blood flow in the zone of stasis was increased. These findings demonstrate that prostaglandin I2 plays an important role in burn injury and that beraprost sodium can reduce secondary necrosis in the zone of stasis.

Effect of a prostaglandin I2 analogue, beraprost sodium, on burn-induced gastric mucosal injury in rats.

Stress ulcers still have a high mortality in critically burned patients and the pathophysiology remains relatively unknown. Impaired gastric mucosal perfusion is one of the factors contributing to gastric mucosal ulceration. Burn injury causes thrombosis and vascular occlusion by increasing the blood viscosity, resulting in decreased organ perfusion. Reduced blood flow is one of the most important factors in gastric mucosal ulceration. Beraprost sodium is a chemically stable prostaglandin I2 (PGI2) analogue with antiplatelet, vasodilator and cytoprotective actions. In the present study, we examined the effects of a PGI2 analogue, beraprost sodium (Procylin, Kaken Pharmaceutical Company, Tokyo, Japan) on burn-induced gastric mucosal changes in rats. Twenty male Sprague-Dawley rats weighing an average of 400 g were burned with hot water (90 degree C) and then divided into two groups of 10 animals. One group received 0.015 mg of beraprost sodium intraperitoneally immediately after burn injury, while the control group received the same volume of saline. Gastric mucosal blood flow was measured with a laser Doppler flowmeter and the area of mucosal necrosis was also determined macroscopically and histologically. Gastric mucosal damage was significantly reduced in the beraprost sodium-treated rats and gastric mucosal blood flow was significantly improved (p < 0.05). These findings demonstrate that PGI2 plays a very important role in the pathophysiology of burn-induced Curling's ulcer and that beraprost sodium can improve gastric mucosal blood flow and reduce mucosal damage.

Reduction of progressive burn injury by using a new nonselective endothelin-A and endothelin-B receptor antagonist, TAK-044: an experimental study in rats.

Endothelins are well-known vasoconstrictor peptides produced by vascular endothelial cells that have been reported to have a fundamental role in regulation of the systemic blood circulation. Plasma levels of endothelins are increased by burn injury, which also causes thrombosis and occlusion of vessels in the dermis as well as a vascular response in the adjacent uninjured dermis. Diminished blood flow leads to progressive ischemia and necrosis of the dermis beneath and around the burn (zone of stasis). If blood flow could be restored in this zone, secondary tissue damage would be minimized. In this study we examined the effects of a new nonselective endothelin receptor antagonist, TAK-044 (Takeda Chemical Industries, Ltd., Osaka, Japan), on burn trauma in rats. Fifty male Sprague-Dawley rats weighing an average of 450 gm were burned with a brass probe that produced a row of three burns 10 x 30 mm in size and two intervening unburned areas 5 x 30 mm in size. Rats were divided into five groups of 10 animals. Four groups received 0.01, 0.1, 1 or 10 mg/kg of TAK-044 via the dorsal vein of the penis immediately after burn trauma, while the control group received the same volume of saline. Skin blood flow was measured with a laser-Doppler flowmeter, and the development of edema and the area of necrotic tissue also were determined. Inhibition of endothelin activity by TAK-044 after burn injury improved microvascular perfusion in the zone of stasis and prevented the progression of tissue damage in this zone. This supports the role of endothelins in the progression of burn injury in the zone of stasis. TAK-044 was most effective in preventing progressive burn damage at a dose of 1 mg/kg. The extent of necrosis and edema was reduced significantly, and blood flow in the zone of stasis was increased in the treated rats.

Application of mechanical mobility of periodontal tissues to tooth mobility examination.

Tooth mobility examination is important in planning dental treatment, as it may give an indication of alveolar bone loss and the condition of the periodontal ligament. In clinical dental diagnosis a manual tooth mobility examination is useful. However, its determination of tooth mobility is subjective and depends on the skill and experience of the clinician. The authors have previously reported on a device for measuring the biomechanical properties of human periodontium using an impedance head. Using this device, the mechanical mobility of periodontium can be measured and the mechanical parameters of the periodontal physical model are obtained. Tooth mobility is defined objectively on the basis of discriminant scores of mechanical parameters, and a mobility triangle (MT) figure is drawn as a record for visual interpretation. The paper describes the validation of the mechanical mobility measurements and their interpretation using mobility parameters and a personal computer to produce a mobility triangle figure. The method is compared favourably with clinical mobility measurement. The relationship of the model to underlying pathology is tested by measurements performed on various tooth model systems.

[Fundamental study on ceftriaxone].

Ceftriaxone (CTRX) was examined in the blood level and urinary excretion between a healthy group of 2 persons receiving 1 g CTRX for 1 day and the other of 3 patients with renal failure receiving 1 g for 3 days, both by intravenous injection or intravenous drip infusion. In the healthy group, the blood half-life time of CTRX was 6.0 hours in 1 person and 8.2 hours in the other, being 7.1 hours on average. The mean blood level in the healthy group was 199 micrograms/ml at peak and was 13 micrograms/ml at 24 hours after administration. In patients with renal failure, the peak blood level ranged from 136.8 to 161.1 micrograms/ml on the 1st day, from 163.1 to 217.0 micrograms/ml on the 2nd day and from 156.4 to 189.7 micrograms/ml on the 3rd day, showing no tendency of getting higher, while the bottom level did from 15.2 to 47.4 micrograms/ml on the 1st day, from 23.3 to 67.9 micrograms/ml on the 2nd day and from 10.9 to 72.6 micrograms/ml on the 3rd day. The urinary excretion rate was 54.6 +/- 3.7% on average in the healthy group while it ranged from 13.7 +/- 1.8 to 27.9 +/- 7.9% in the patient group. CTRX was effective especially against E. coli among the strains clinically isolated from the patients with renal failure. No side effects were observed in any case.

[The recent trend in preoperative fasting].

It has been generally practiced that patients are restrained from any foods and water 4-6 hr prior to anesthesia. Recent trends of anesthesiologist, however, are to permit the patients to take fluid until 2-3 hr before inducing anesthesia, as described in the guidelines from Canadian Anaesthetists' Society in 1990, and in the authoritative textbooks of anesthesia. We compared effects of the preoperative fasting between age-matched groups of patients constrained to: 1) 6 hr absolute preoperative fasting, and 2) 6 hr fasting but free for taking clear fluid until 2 hr before operation. Residual gastric volume and pH immediately after inducing anesthesia were monitored. In the respective age groups from infant to the aged, no significant changes were observed between 1) and 2). Considering that light meal leaves the stomach in 1.5-3 hr and clear fluid almost immediately, these results accurately explain and support relevance of the current concept concerning the preoperative fasting. Furthermore, since actual incidence of aspiration pneumonia during anesthesia is sufficiently low, strict preoperative fasting may be unreasonable. We consider that reducing the fasting time may not increase the risk of pulmonary aspiration and recommend our practical method consisting of preoperative 6 hr withholding solid foods while allowing clear fluid ingestion until 2-3 hr before inducing anesthesia.

[A review of correlation between transfusion rate of irradiated blood and potassium load].

Transfusion of the irradiated blood has become popular in Japan to prevent the graft-versus-host disease. Case reports, however, of hyperkalemic death or lethal ECG change have been increasing since the irradiated blood was introduced nation-wide. The potassium concentration of the supernatant of irradiated blood becomes about 60 mEq.l-1 by the end of storage period. If the potassium concentration is 60 mEq.l-1, the estimated safe transfusion rate would be 6 ml.min-1 and this can not be agreed with by clinicians who transfuse daily in cases of massive bleeding. The calculated safe transfusion rate (10 mEq.hr-1 of potassium load) ranges from 6 to 72 ml.min-1 considering the storage period from the day of gathering and irradiation. This difference could affect the survival rate. On the other hand, only the difference of the potassium concentration in the supernatant between the irradiated blood and the non-irradiated blood could not explain the increasing number of hyperkalemic case report. The mechanical factors may be related to hemolysis that causes extreme hyperkalemia. Control studies of proper transfusion rate of irradiated blood should be performed to establish a safety guideline for rapid transfusion of irradiated blood.