西洋参茎叶皂甙对低频电刺激豚鼠乳头肌的抗缺糖缺氧作用

西洋参茎叶皂甙对豚鼠乳头肌电刺激频率在1/8～1/64Ｈｚ，可增强其收缩力（Ｐ＜０．００５）。在营养液中加入５０ｍｏ１／Ｌ葡萄糖并充以95%N₂和5%CO₂，或在营养液中无糖并充以95%N₂和5%CO₂时，在低频刺激（1/8～1/64Hz）时西洋参茎叶皂贰具有抗缺氧缺糖作用（p<0.05，p<0.01）。     

Microvascular changes in large flame burn wound in sheep

Advances in local wound management with early excisional therapy have decreased morbidity and mortality of massive third-degree burn patients. Although blood redistribution within burned tissue is of clinical interest, few studies have longitudinally determined the regional blood flow of various layers of the burn wound. We used a conscious ovine model in which animals were subjected to 40% third degree burn. Burned tissue was divided into the four layers (i.e. skin, panniculus carnosus, adipose tissue, and skeletal muscle), and regional blood flow was determined separately, with fluorescent microspheres, while measuring systemic hemodynamics and total burned tissue microvascular fluid flux. The subburn adipose tissue exhibited a remarkable biphasic alteration in regional blood flow, whereas the skin layer showed only decreased blood flow during the whole experimental period. The increase in blood flow to the adipose tissue seems to be related to a sustained fluid filtrate in the postresuscitation period, resulting in edema formation mainly located in the adipose tissue at the endpoint.     

Mutational analysis of conserved hydrophobic amino acid residues in the N-terminal region of DnaA protein

DnaA is the initiator of chromosomal DNA replication in E. coli. We previously reported that conserved hydrophobic amino acid residues in the N-terminal region of DnaA (I26 and L40) are essential for DNA replication in vivo and in vitro using mutant DnaA proteins (DnaAI26S and DnaAL40S). In this study, we introduced further random mutations to find intragenic suppressors for dnaAI26S or dnaAL40S. By direct DNA sequence, a mutation which causes substitution of the Ser (Ile, in the wild-type DnaA) with Phe (DnaAI26F or DnaAL40F) was found in all of the suppressors. Site-directed mutational analysis showed that DnaAI26L, and DnaAL40I, but not DnaAI26S or DnaAL40S, were active for oriC DNA replication in cells. Furthermore, purified DnaAI26F but not DnaAI26S was active for oriC DNA replication in a crude extract. These results strongly suggest that hydrophobic amino acid residues in these positions of DnaA (I26 and L40) are important for the function of this protein as an initiator of DNA replication both in vivo and in vitro.     

Pharmacokinetic and clinical studies on teicoplanin for sepsis by methicillin-cephem resistant Staphylococcus aureus in the pediatric and neonate field

Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrated dose for pediatrics patients was 10 mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals. 1. Pharmacokinetic results. All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60 micrograms/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8 micrograms/mL, and in pediatrics were 12.5, 12.2 and 13.1 micrograms/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients. 2. Efficacy and safety results. Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood. Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs. Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, gamma-GTP increased, GOT increased and GPT increased in 3 pediatrics. These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.     

Carotenoids in cancer chemoprevention

Various natural carotenoids, besides -carotene, were proven to have anticarcinogenic activity, and some of them showed more potent activity than -carotene. Thus, these carotenoids (-carotene, lutein, zeaxanthin, lycopene, rbeta -cryptoxanthin, fucoxanthin, astaxanthin, capsanthin, crocetin and phytoene), as well as -carotene, may be useful for cancer prevention. In the case of phytoene, the concept of 'bio-chemoprevention', which means biotechnology-assisted method for cancer chemoprevention, may be applicable. In fact, establishment of mammalian cells producing phytoene was succeeded by the introduction of crtB gene, which encodes phytoene synthase, and these cells were proven to acquire the resistance against carcinogenesis. Antioxidative phytoene-containing animal foods may be classified as a novel type of functional food, which has the preventive activity against carcinogenesis, as well as the ability to reduce the accumulation of oxidative damages, which are hazardous for human health.     

Analysis of Various Treatments for Pulmonary Aspergillomas

The objective of this study was to analyze the results of various treatments for pulmonary aspergilloma and to determine the surgical indications. A total of 41 patients with pulmonary aspergilloma hospitalized at the National Minamifukuoka Chest Hospital between 1973 and 1999 were analyzed with regard to their response to treatment and long-term prognosis. Five asymptomatic patients who were untreated demonstrated no change in the clinical status of aspergilloma. Analysis of the short-term response revealed surgery to be the most effective treatment. Systemic and intracavitary injections of antifungal drugs were not definitely effective, although they had a positive effect in some patients. A survival analysis revealed that all eight patients who underwent surgery are still alive. Using the Cox proportional hazard model, it was found that the favorable prognostic factors were the absence of symptoms, the absence of a superimposed bacterial infection, and surgery. There were ten deaths: three from lung cancer and seven related to uncontrollable superimposed bacterial infections, often resulting in hemoptysis. We conclude that patients with asymptomatic pulmonary aspergillomas should be clinically observed for signs of the development of lung cancer, but do not require active treatment. On the other hand, patients who are symptomatic and have uncontrollable superimposed bacterial infection will benefit from surgery. Received: August 24, 2000 / Accepted: March 6, 2001     

Intrinsic factors involved in the depression of neuronal activity induced by temperature increase in rat hippocampal neurons

The intrinsic factors involved in the temperature-dependent impairment of neuronal activity in hippocampal CA2-CA1 regions were investigated using optical recording techniques. At 32 degrees C, stimulation of the Schaffer collaterals in the hippocampal CA2 region evoked depolarizing optical responses that spread toward the CA1 region. The optical response was characterized by fast and slow components that were mainly related to the presynaptic action potentials and excitatory postsynaptic response, respectively. The increase of the temperature to 38 degrees C was associated with a reversible depression of the neuronal activity in the hippocampal brain preparations. The depression of neuronal activity was irreversible when the temperature was increased to 40 degrees C. In the presence of 22 mM glucose, the depression of the neuronal activity at 38 degrees C was significantly attenuated. Pyruvate (22 mM), but not lactate (22 mM), also improved the depression of neuronal activity induced by the temperature increase. Adenosine (200 microM) strongly depressed the excitatory postsynaptic response, but not presynaptic action potentials. 8-Cyclopentyl-1,3-dimethylxanthine (8-CPT) (10 microM), an adenosine A1 receptor blocker, attenuated the adenosine-induced depression of the excitatory postsynaptic response. 8-CPT (10 microM) prevented the impairment of the excitatory postsynaptic response induced by the increase of the temperature to 38 degrees C. In contrast, the depression of presynaptic action potential at 38 degrees C was not prevented by 8-CPT (10 microM). N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, and methylcobalamin (10 microM), a vitamin B12 analogue, attenuated the inhibition of pre- and postsynaptic activities induced by the increase of the temperature to 38 degrees C. Glibenclamide, a KATP channel blocker, did not protect neuronal activity from the effects of the increase of the temperature. These results suggest that the heat-induced depression of neuronal activity is mediated by multiple factors, such as impairment of energy metabolism and increase in extracellular adenosine and nitric oxide (NO) levels in hippocampal neurons.     

A New Indole Alkaloid Glycoside from the Leaves of Palicourea marcgravii

A new indole alkaloid glucoside, named palicoside, has been isolated from the leaves of PALICOUREA MARCGRAVII (Rubiaceae) collected in Brazil. The structure was established by spectroscopic methods and its chemical conversion to strictosamide.     

Four cases of therapy-related leukemia in multiple myeloma

We have experienced 4 cases of therapy-related leukemia (TRL) in 119 patients with multiple myeloma (MM) who had received combination chemotherapy including alkylating agents between 1988 and 1998. All 4 cases were acute myelogenous leukemia, 3 were males and 1 was female. Median age at diagnosis of MM was 60 years, and median time to TRL from diagnosis of MM was 5.5 years. The chromosome abnormalities were found in 3 of those cases. All 4 cases were resistant to antileukemic chemotherapy, and median survival time from TRL was only 5.5 months. The TRL in MM is thought to be a more important problem, because recently the treatment for this disease has become more intensive, including high-dose chemotherapy supported by autologous stem cell transplantation.     

Sodium orthovanadate enhances proliferation of progenitor cells in the adult rat subventricular zone after focal cerebral ischemia

Neuronal progenitor cells able to produce new neuron and glia persist in the adult central nervous system (CNS). Their proliferation is up-regulated by growth factors or cytokines under some pathological conditions, including ischemia. Because sodium orthovanadate (SOV), a protein tyrosine phosphatase inhibitor, can up-regulate tyrosine kinase-linked growth factor receptor signaling via the inhibition of tyrosine residue dephosphorylation, it may be capable of enhancing progenitor cells. To investigate the effect of SOV on progenitor cells in the subventricular zone (SVZ), we injected rats intraperitoneally with 50 mg/kg bromodeoxyuridine (BrdU) and 12.5 or 25 mM SOV or BrdU and saline (control) on days 1 to 7 after middle cerebral artery occlusion. The density of BrdU-positive cells in the ipsilateral SVZ showed a significant SOV dose-dependent increase. This effect was found only in the ipsilateral and not contralateral SVZ, and it was not found in nonischemic rats. Double immunolabeling with BrdU and double cortin, a marker of migrating neuroblast, revealed that the density of double-positive cells increased significantly in an SOV dose-dependent manner. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining suggested that the SOV-induced increase was not due to antiapoptotic effects. Treatment with SOV also significantly increased the density of cells positive for BrdU and phosphorylated Akt and BrdU and phosphorylated extracellular signal-regulated kinase (ERK). We postulate that ischemia triggers off the proliferation of SVZ cells by bioactive factors such as growth factors and that SOV enhances the proliferation of only triggered-off SVZ cells with Akt and ERK activation. Our findings suggest that SOV may aid in the self-repair of the postischemic CNS.