Protective effect of prostaglandins D2, E1 and I2 against cerebral hypoxia/anoxia in mice

The protective effect of prostaglandins (PGs) against cerebral hypoxia/anoxia was investigated with a variety of experimental models in relation to their CNS depressant effects in mice. Furthermore, the effect of PGs on the changes of cerebral energy metabolites and cyclic nucleotide was examined in hypoxic mice. Mice were given s.c. doses of PGs 30 min before tests. Among the PGs tested, treatment with PGD2, PGE1 and PGI2 Na showed a consistent and dose-dependent protection against cerebral anoxia induced by all models studied: histotoxic anoxia by KCN, hypobaric hypoxia, normobaric hypoxia and decapitation-induced gasping. However, PGA1, PGA2, PGB1, PGB2, PGE2, PGF1 alpha, PGF2 alpha and 6-keto-PGF1 alpha at a dose of 3 mg/kg were without effect against normobaric hypoxia and gasping duration. The three PGs, i.e. PGD2, PGE1 and PGI2 which showed anti-hypoxic effects decreased locomotor activity and potentiated hexobarbital-induced sleep. On the other hand, PGE2, PGA1, PGA2 and PGB2 also caused a decrease in locomotor activity. Similarly, PGE2 and PGA1 caused a potentiation of hexobarbital-induced sleep, but interestingly they did not cause clear-cut increase in cerebral resistance to hypoxia, in contrast with the former three PGs. Thus general depression of CNS function appears not to be responsible for the PGD2-, PGE1- and PGI2-induced increase in cerebral resistance to hypoxia. The levels of Cr-P and ATP were significantly reduced and those of ADP and AMP were markedly elevated in hypoxic brain, resulting in a decrease in a calculated energy charge potential. The lactate level and lactate/pyruvate ratio increased and the glucose level decreased markedly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential modulation of the short- and long-latency somatosensory evoked potentials in a forewarned reaction time task.

OBJECTIVE: We investigated modulation of the short- and long-latency somatosensory evoked potentials (SEPs) in a forewarned reaction time task. METHODS: A pair of warning (auditory) and imperative stimuli (somatosensory) was presented with a 2 s interstimulus interval. In movement condition, subjects responded by grip movement with the ipsilateral hand to the somatosensory stimulation when the imperative stimulus was presented. In counting condition, they silently counted the number of imperative stimuli. The SEPs in response to the imperative stimuli were recorded. RESULTS: Frontal N30 and central N60 amplitudes were significantly smaller in the movement than in the counting or rest conditions. None of the short-latency components differed between the counting and rest conditions. In contrast to the short-latency components, P80 was significantly larger in the counting than in the rest condition, and showed a further increase from the counting to the movement condition. The N140 amplitude was significantly larger in the movement than the rest condition, but was not changed between the counting and the rest conditions. CONCLUSIONS: The attenuation of the frontal N30 and central N60, and the enhancement of the P80 and possibly the N140 resulted from the centrifugal mechanism. The present findings may show the different effects of voluntary movement on the early and subsequent cortical processing of the relevant somatosensory information requiring a behavioral response. SIGNIFICANCE: The present study demonstrated the differential modulation of short- and long-latency components of SEPs in a forewarned reaction time task.     

Basic and clinical studies on imipenem/cilastatin sodium in the pediatric field

Basic and clinical studies have been performed on imipenem/cilastatin sodium (MK-0787/MK-0791) in the pediatric field. Antibacterial activities of MK-0787 against 14 clinical isolates of S. aureus and 67 isolates of E. coli were determined. The MIC of MK-0787 was 0.10 microgram/ml or less against all 14 strains of S. aureus. The MIC of MK-0787 was 0.39 microgram/ml or less against all 67 strains of E. coli. The pharmacokinetics of MK-0787/MK-0791 was studied at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg. The peak serum levels of MK-0787 achieved approximately 1 hour after the administration of 10 mg/10 mg/kg and 20 mg/20 mg/kg doses were 38.6 micrograms/ml and 36.2 micrograms/ml, respectively. The serum half-lives were 0.8 hour and 0.9 hour, respectively. The total 6-hour urinary excretions were 82.1% and 66.7%, respectively. The MK-0787/MK-0791 was administered to 13 children with bacterial infections. The clinical results were excellent or good in all cases. The overall efficacy rate was 100%. As a side effect, diarrhea was observed in 1 patient. Abnormalities in laboratory findings observed were elevation of direct bilirubin in 1 patient, thrombocytosis in 2, and a prolonged prothrombin time in 1 patient. Based on the above results, it can be concluded that MK-0787/MK-0791 is a safe and effective drug to use for the treatment of pediatric infections.     

Effect of cystathionine beta-synthase variant 844ins68bp and methylenetetrahydrofolate reductase A1298C polymorphisms in xenografts on 5-FU efficacy and doubling time

The association of MTHFR and CBS variants with the doubling time and responsiveness to several chemodrugs was analyzed in 26 human cancer xenografts. The tumors homozygous for the absence of insertion (NN) for the CBS 844ins68bp were more chemosensitive than those with insertion (NI) to TS-1 (P=0.0048), suggesting a potential effect of this variant on fluoropyrimidine efficacy. Furthermore, the doubling time of tumors with a variant C allele (AC or CC) in MTHFR-A1298C was significantly longer than that of tumors with a normal allele (AA) (P=0.0008). Twenty-nine cellular proliferation-related genes were associated with MTHFR-A1298C genotyping and with the doubling time.     

A case of polycythemia vera complicated by chronic renal failure under hemodialysis requiring parathyroidectomy for secondary hyperparathyroidisim

A case of polycythemia vera complicated by chronic renal failure under maintenance hemodialysis requiring parathyroidectory (PTH) for secondary hyperparathyroidism (2° HPT) is reported. A 62 year old female presented with 75000 white blood cells (WBC)/μl, 703×10⁴ red blood cells (RBC)/μl, 23×10⁴ platelets (PLT)/μl, hyperuricemia and hypertension in 1970 and the diagnosis of polycythemia vera was made. Hemodialysis was started in October 1974 for chronic renal failure. Blood cells in peripheral blood rapidly decreased in number after the beginning of dialysis, reaching the level of 10000∼20000 WBC/μl, and 150∼250×10⁴RBC/μl. In August 1988, marked bone resorption in X-ray picture and high serum alkaline phosphatase and parathyroid hormone (PTH) noted along with 17400 WBC/μl, 370×10⁴RBC/μl and 35.9×10⁴PLT/μl. After subtotal PTX removing 3.21g parathyroid gland, serum PTH rapidly fell. At 3 months after PTX, WBC rose to 23600/μl, RBC 372×10⁴/μl and PLT 94.0×10⁴/μl. At 6 months, WBC was to 31000/μl, RBC 429×10⁴/μl and PLT 78.0×10⁴/μl, suggesting an inhibitory action of PTH on not only RBC, but also WBC and PLT.     

Immediate changes in subcellular structures of transplanted tumors following photodynamic and laser hyperthermic therapy

Background and Objective: To further understand the precise process of the tumor cell degeneration after photodynamic therapy (PDT), laser hyperthermic therapy (LH), and combined treatments using an Nd:YAG laser. It is important to examine initial morphological alteration of tumor cells after these treatments. Study Design/Materials and Methods: In this study, nude mice bearing HeLa cell tumors were treated with PDT, LH, and combined treatments of the two. Tumor tissues obtained immediately after these treatments were analyzed using electron microscopy and morphometry. Results: In the combined treatments, which produced more severe effects on tumor cells, morphological features of apoptosis such as cytoplasmic condensation, blebs, and apoptotic bodies appeared in the cells, although the typical alteration in the nuclear chromatin was not seen. Conclusion: Cytoplasmic alterations may proceed more rapidly than nuclear alterations in the cellular degeneration induced by the single or combined treatments of PDT and LH.     

Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer

Angiogenesis is an independent prognostic indicator in breast cancer. In this report, the relationship between expression of vascular endothclial growth factor (VEGF; a selective mitogen for endothelial cells) and the microvessel density was examined in 103 primary breast cancers. The expression of VEGF was evaluated by immunocytochemical staining using anti-VEGF antibody. The microvessel density, which was determined by immunostaining for factor VIII antigen, in VEGF-rich tumors was clearly higher than that in VEGF-poor tumors ( P <0.01). There was a good correlation between VEGF expression and the increment of microvessel density. Furthermore, postoperative survey demonstrated that the relapse-free survival rate of VEGF-rich tumors was significantly worse than that of VEGF-poor tumors. It was suggested that the expression of VEGF is closely associated with the promotion of angiogenesis and with early relapse in primary breast cancer.     

Primary malignant lymphoma of the rectum with distant metastasis to the stomach: Report of a case

Primary extranodal malignant lymphoma frequently occurs in the gastrointestinal tract; however, it is rarely encountered in the rectum. We report herein the case of an 85-year-old man who underwent abdominoperineal resection for primary malignant lymphoma of the rectum, and 1 year later, developed hematemesis caused by gastric metastasis. To our knowledge this is the first case report of such distant metastasis developing from malignant lymphoma of the rectum.     

Virtual endoscopic images by 3D FASE cisternography for neurovascular compression.

Three-dimensional fast asymmetric spin echo (3D FASE) cisternography provides high spatial resolution and excellent contrast as a water image acquisition technique. It is also useful for the evaluation of various anatomical regions. This study investigated the usefulness and limitations of virtual endoscopic images obtained by 3D FASE MR cisternography in the preoperative evaluation of patients with neurovascular compression. The study included 12 patients with neurovascular compression: 10 with hemifacial spasm and two with trigeminal neuralgia. The diagnosis was surgically confirmed in all patients. The virtual endoscopic images obtained were judged to be of acceptable quality for interpretation in all cases. The areas of compression identified in preoperative diagnosis with virtual endoscopic images showed good agreement with those observed from surgery, except in one case in which the common trunk of the anterior inferior cerebellar artery and posterior inferior cerebellar artery (AICA-PICA) bifurcated near the root exit zone of the facial nerve. The veins are displayed in some cases but not in others. The main advantage of generating virtual endoscopic images is that such images can be used for surgical simulation, allowing the neurosurgeon to perform surgical procedures with greater confidence.     

A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions.

Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be elucidated. Accumulating genetic evidence supports that DISC1 is associated with some aspects of cognitive functions relevant to SZ and BP. Here, we provide a summary of the current updates in biological studies of DISC1. Disrupted-In-Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms with potential posttranslational modifications. Disrupted-In-Schizophrenia-1 protein occurs in multiple subcellular compartments, which include the centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal fractions, the mitochondria, and the nucleus. Recent studies have clarified that DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP. Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed.