Glial cell line-derived neurotrophic factor protects against delayed neuronal death after transient forebrain ischemia in rats

Glial cell line-derived neurotrophic factor, a member of the transforming growth factor-beta superfamily, is a potent neurotrophic factor, which has a variety of biological activities that affect several types of neurons in both the central and peripheral nervous systems. In this study, we examined the effects of glial cell line-derived neurotrophic factor on delayed neuronal death in the hippocampal CA1 region of rats after transient forebrain ischemia. In the control rats pretreated with the vehicle, transient forebrain ischemia-induced delayed neuronal death in the hippocampal CA1 region was observed seven days after reperfusion. Pretreatment with glial cell line-derived neurotrophic factor (1.0 microg), which was directly microinjected into the right hippocampal CA1 region, gave significant protection against the delayed hippocampal neuronal death. On the contralateral side of the hippocampus, which was not injected with glial cell line-derived neurotrophic factor, delayed neuronal death similar to that seen in vehicle-treated control animals was observed. Intracerebroventricular glial cell line-derived neurotrophic factor (2.5 microg) injection also protected against delayed neuronal death. In addition, pretreatment with glial cell line-derived neurotrophic factor gave significant protection against apoptotic cell death induced by brain ischemia in the hippocampal CA1 region, as determined by in situ staining for DNA fragmentation. These findings suggest that glial cell line-derived neurotrophic factor plays an important role in delayed neuronal death induced by brain ischemia.     

Three cases of acute pulmonary thromboembolism diagnosed by transesophageal echocardiography

We report 3 cases of acute pulmonary thromboembolism (PTE) diagnosed by transesophageal echocardiography (TEE). In all these cases, cardiovascular state of the patient was unstable and therefore computerized tomography and catheterization of the pulmonary artery for diagnosis of PTE could not be performed. TEE was useful for diagnosis of acute PTE. All three patients passed away eventually and we had a difficult experience for treatment of acute PTE. We should take various measures against deep vein thrombosis for prevention of acute PTE.     

Attenuation of nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine in streptozotocin-treated rats

Diabetes alters retinal hemodynamics, but little is known about the impact of diabetes on the role of endothelium-derived hyperpolarizing factor (EDHF) in the regulation of retinal circulation. Therefore, we examined how diabetes affects the nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine. Male Wistar rats were treated with streptozotocin (80 mg/kg, i.p.) and experiments were performed 6-8 weeks later. Under artificial ventilation, rats were treated with tetrodotoxin (100 microg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye. Methoxamine was used to maintain adequate systemic circulation. Fundus images were captured by a digital camera that was equipped with a special objective lens. The vasodilator responses of retinal arterioles were assessed by measuring changes in diameters of the vessels. In streptozotocin-induced diabetic rats and the age-matched controls, acetylcholine increased diameters of retinal arterioles in a dose-dependent manner. The vasodilator responses to acetylcholine in diabetic rats were smaller than those in control rats. The nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles observed under treatment with combination of N(G)-nitro-l-arginine methyl ester (30 mg/kg, i.v.) and indomethacin (5 mg/kg, i.v.) were also attenuated by diabetes. Diabetes did not alter the dilator responses of retinal arterioles to sodium nitroprusside and forskolin. These results suggest that diabetes impairs EDHF-mediated vasodilation of retinal arterioles induced by acetylcholine. The impaired EDHF-mediated vasodilation may contribute to alteration of retinal hemodynamics in diabetes.     

Virtual microscopy for cytology proficiency testing: are we there yet?

BACKGROUND: The objective of this study was to investigate the potential of virtual microscopy (VM) as an avenue for the delivery of mandatory cytology proficiency tests). METHODS: Three senior cytotechnologists and 2 board-certified cytopathologists participated in 3 virtual proficiency tests. Each set consisted of 10 ThinPrep slides that were digitized by an Aperio T3 ScanScope. The cytologic diagnoses covered the range of interpretive guidelines provided by the Centers for Medicare and Medicaid Services (CMS). Each cytotechnologist followed the requirement of a primary screener with the cytopathologists utilizing the secondary screener option. RESULTS: Analysis of the diagnostic interpretation of the first proficiency test showed correct classification of 100% of normal and abnormal cells for primary and secondary screeners. The second proficiency test analysis revealed a 93.3% correct classification (100% using CMS guidelines) among the primary screeners. The secondary screeners gave a 100% correct classification. The final proficiency test had primary screeners and secondary screeners with 100% correct classification. CONCLUSIONS: The current results confirmed the feasibility of VM for proficiency tests with 2 main problems noted. First, primary screeners had difficulties meeting the mandatory time allocation; however, with increased familiarity with the software, the screening times decreased. Second, the 3-dimensional nature of certain lesions made them difficult to interpret even on monolayered, liquid-based preparations. Creation of a more user-friendly software interface and better methods to capture depth of focus should make this a valid measure of cervicovaginal cytopathologic interpretive competence.     

Effects of atorvastatin on hyperlipidemia in kidney disease patients

BACKGROUND: It has been suggested that hyperlipidemia contributes to the progression of kidney disease and there are some experimental reports that support the hypothesis of lipid nephrotoxicity. The treatment of hyperlipidemia in patients with renal disease has two purposes: to prevent the development of cardiovascular disease and to prevent the progression of renal disease. However, statins, which are widely used to treat hyperlipidemia, should be used very carefully in patients with renal disease, especially in those whose serum creatinine level is more than 3 mg/dL. Atorvastatin, an HMG-CoA reductase inhibitor, is completely metabolized in the liver. Thus, we thought that atorvastatin could be used safely in hyperlipidemic patients with chronic renal disease. PATIENTS AND METHODS: Atorvastatin was administered to 84 hyperlipidemic patients with chronic renal disease(including dialysis patients) for 12 months. TC, TG, LDL-C, AST, ALT, CK, BUN, and Cr were measured at 3, 6, and 12 months during treatment. Blood pressure and renal function, as indicated by urinary protein excretion and creatinine clearance measured at 0 and 12 months during treatment, were also monitored. RESULTS: TC and LDL-C were decreased at every determination point regardless of the kidney function, which was not affected by atorvastatin. Urinary protein excretion (UP) decreased significantly during the study period in patients who had not taken any anti-hyperlipidemic drug before treatment with atorvastatin. This decrease in UP was not associated with significant Ccr change. However, the decrease in UP was not statistically significant in all the patients. The decrease in UP showed a significant positive correlation with the decrease in TC and of the mean BP. CONCLUSION: Atorvastatin can be used safely in hyperlipidemic patients with chronic renal disease including dialysis patients under periodical monitoring. Atorvastatin could contribute to prevent the progression of renal disease.     

Analysis of a nationwide survey on treatment and outcomes of congenital hydrocephalus in Japan

A nationwide questionnaire survey of congenital hydrocephalus in 2000 investigated the treatment and clinical outcomes for congenital hydrocephalus in Japan to evaluate the factors influencing clinical outcome. Surgical treatment was performed in 341 of 380 patients who survived the early neonatal period. Of 321 patients who had shunt operations, 295 (91.9%) underwent ventriculoperitoneal shunting and nine (2.8%) ventriculoatrial shunting. Programmable valves were used in 83 (33.6%) of the 247 patients at the first shunting and in 97 (39.3%) at the last shunting. The incidence of complications after the first shunting was 55.4% (46 of 83 patients) in the programmable and 61.6% (101 of 164) in the non-programmable valve groups. The types of shunt complication differed significantly between these groups (p < 0.001), as the incidence of shunt infection and malfunction was lower in the programmable valve group. Clinical outcome was generally better with later delivery stage during gestation (p < 0.02). The clinical outcome was statistically significantly better in term patients who underwent early shunt placement than in those who underwent late shunt placement (p < 0.05).     

Byelyankacin: a novel melanogenesis inhibitor produced by Enterobacter sp. B20

A novel melanogenesis inhibitor, byelyankacin (1), was isolated from the fermentation broth of a bacterial strain. The producing organism, designated B20, was identified as a member of the genus Enterobacter based on taxonomic characteristics. 1 was obtained as a white powder from the culture medium by solvent extraction and serial chromatographic purification. The structure of 1 was determined as (E)-4-(2-isocyanovinyl)phenyl alpha-L-rhamnopyranoside on the basis of spectroscopic data. 1 potently inhibited mushroom tyrosinase and melanogenesis of B16-2D2 melanoma cells with IC50 value of 2.1 nM and 30 nM, respectively.     

Stereochemistry of pladienolide B

Pladienolide B is a 12-membered macrolide isolated from Streptomyces platensis Mer-11107. It showed potent in vitro and in vivo antitumor activities and is a potential lead for novel antitumor agents. The absolute configurations at ten chiral centers were determined on the basis of spectral data of pladienolide B and its chemical transformation products.