Analgesic action of loperamide,an opioid agonist,and its blocking action on voltage-dependent Ca2+ channels

We investigated the relationship between the antinociceptive effect of the opiate agonist loperamide at the spinal level and its inhibitory effect on calcium influx. Intrathecal administration of loperamide showed a significant antinociceptive effect in the formalin test, which was not prevented by naloxone. On the other hand, no significant effects were observed by nicardipine, an L-type specific blocker, or by BAY K8644, an L-type specific agonist, suggesting no significant role of L-type calcium channels in nociceptive signal transduction. Loperamide suppressed the calcium influx in dorsal root ganglion neurons. As the antinociceptive effect of loperamide was not affected by naloxone or other calcium channel blocking toxins, and loperamide showed a direct inhibitory effect on calcium-influx, the analgesic effect of intrathecally injected loperamide might be due to its blockade of the voltage-dependent calcium channels at the terminals of the primary afferent fibers.     

A novel translocation involving chromosomes 2, 9, 14, and 22 in chronic myeloid leukemia

A 46-year-old man with chronic myelogenous leukemia was found to have a new complex translocation. In chronic phase, all of the bone marrow cells had a rearrangement of a t(2;9;14;22) (p21;q34;q32;q11). Southern blot analysis of leukocyte DNA revealed rearrangement of the breakpoint cluster region (bcr) within the 5.8-Kb bcr. The patient eventually died in blast crisis 28 months later. The cytogenetic findings of bone marrow cells showed a 46,XY,t(2;9;14;22)(p21;q34;q32;qll),add(lp),del(3q) karyotype in blast crisis.     

Prevention of hypertensive crisis with ATP during anesthesia for pheochromcytoma

In the anesthetic management of five patients undergoing excision of pheochromocytoma, adenosine triphosphate (ATP) was used for the purpose of regulating systemic arterial pressure during the period of tumor manipulation. ATP was administered at doses of 0.05–0.4mg/kg/min. Systemic arterial pressure showed a significant decrease from 162 ± 17/103 ± 11mmHg before manipulation to 136 ± 21/81 ± 10mmHg during the manipulation period. The plasma catecholamine levels showed significant increases in this period. Immediately after excision, the systemic arterial pressure was maintained at normal levels (118 ± 13/75 ± 16mmHg) by fluid replacement and discontinuation of ATP administration, subsequently becoming 129 ± 19/79 ± 16mmHg. The heart rate was very stable and tachycardia did not ocurr during the manipulation period. Only one arrhythmic episode ocurred in one patient. The systemic vascular resistance index was significantly lower during the manipulation period than before it. It was therefore considered that ATP was useful as an agent for controlling arterial pressue during the anesthesia for pheochromocytoma.(Murata K, Sodeyama O, Ikeda K et al.: Prevention of hypertensive crisis with ATP during anesthesia for pheochromocytoma. J Anesth 1: 162–167, 1987)     

The association between renal elasticity evaluated by Real-time tissue elastography and renal fibrosis

Clinical and Experimental Nephrology - The progression of chronic kidney disease (CKD) depends on the extent of fibrosis in the kidneys; however, a renal biopsy is necessary to evaluate the...     

Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037.     

Determination of diquat in biological materials by electron spin resonance spectroscopy

Summary An electron spin resonance (ESR) method already in use for the quantitative analysis of paraquat was applied to the analysis of diquat in blood, serum, urine, tissue homogenates and several drinks without purification of the samples. The diquat radical produced with ascorbic acid at alkaline pH was much more stable than that produced with the commonly used sodium dithionite. Radical decay in solutions covered with n-hexane was less than 5% after 60 min over a wide range of ascorbic acid concentrations. In 0.2N NaOH solution 85% of the radicals was present even after 24h. The limit of detection was 0.3 g/ml and the required amount of sample was 0.1 ml. When both diquat and paraquat were present in a sample the diquat was first extracted with 1-butanol prior to the ESR measurement, because both species were converted to the radicals.     

Effect of a lysyl hydroxylase inhibitor,minoxidil, on ultrastructure and behavior of cultured rabbit subconjunctival fibroblasts

Background: Minoxidil is an inhibitor of lysyl hydroxylase, an enzyme involved in collagen production, and decreases collagen production in vitro. We investigated the in vitro effects of minoxidil on behavior such as proliferation and migration of rabbit subconjunctival fibroblasts (SCFs). The ultrastructural effect of the drug on SCFs was also examined. Methods: Proliferation of SCFs and closure of the defect produced in monolayer cultures in the presence or absence of minoxidil was studied. The ultrastructure of SCFs treated with minoxidil was also examined. Results: Minoxidil inhibited SCF proliferation and the closure of the defect produced in monolayer cell sheets. Ultrastructural observations revealed extensive areas of irregularly dilated endoplasmic reticulum in cells treated with minoxidil, indicating the accumulation of protein, probably underhydroxylated collagen precursors, in the cisternae of endoplasmic reticulum. Conclusions: The results indicated that minoxidil attenuated cellular activities of SCFs such as proliferation and migration in vitro. The exact mechanism of the inhibitory effects of minoxidil on these cellular activities is unknown. The findings suggest that the drug might help to prevent bleb scarring after glaucoma filtering surgery.     

Role of reactive oxygen in phospholipase A2 activation by ischemia/reperfusion of the rat kidney

Purpose. To investigate the role of phospholipase A₂ (PLA₂) in reperfusion injury of the kidney in an in vivo animal model, renal mitochondrial PLA₂ activity was measured under three different conditions. Methods. Male Wistar rats (n = 72) anesthetized with pentobarbital underwent renal ischemia surgically for 45 min and were reperfused for the indicated time (renal ischemia/reperfusion). Treatments included reperfusion for various predetermined periods (phase 1), exposure to hyperbaric oxygen (phase 2), and administration of reactive oxygen species (ROS) scavenger (phase 3). Thereafter, each kidney was harvested, and mitochondrial PLA₂ activity was measured by a radioisotope technique. Results. Ischemia/reperfusion resulted in time-related PLA₂ activation in the renal mitochondria up to 48 h of reperfusion after renal ischemia. Renal mitochondrial PLA₂ activity was further augmented by hyperbaric oxygen exposure prior to reperfusion, whereas administration of the ROS scavengers suppressed mitochondrial PLA₂ activity. Conclusion. These data suggest that ROS may play an important role in the in vivo activation of PLA₂ associated with renal ischemia/reperfusion. Received for publication on July 6, 1998; accepted on November 30, 1998     

Pulmonary small cell carcinoma associated with sarcoid reactions: Report of a case

A 45-year-old male was admitted to our hospital for investigation of a nodular shadow in segment 5 of the right lung on a chest computed tomogram. A right middle lobectomy with mediastinal lymph node dissection was performed under a diagnosis of lung cancer, and histologic examination confirmed small cell carcinoma. There were sarcoid reactions in the resected lymph nodes and the lung parenchyma, but no signs of systemic sarcoidosis were evident. Sarcoid reactions are rarely observed in the regional lymph nodes draining malignant tumors. Moreover, while they are most common in squamous cell carcinoma of the lung, they extremely rare in small cell carcinoma. To our knowledge, this is only the third report of this unusual entity in the English and Japanese literature.