Bone morphogenetic protein-2 and retinoic acid induce neurotrophin-3 responsiveness in developing rat sympathetic neurons

Expression of the receptor tyrosine kinase, Trk, determines the specificity of neurotrophin responsiveness of different neuronal populations during development. Recently it has become apparent that sympathetic neurons of rat superior cervical ganglia (SCG) acquire sensitivity to neurotrophin-3 (NT3) before they become dependent on the target-derived nerve growth factor (NGF) for their survival by sequential induction of TrkC and TrkA. The mechanism controlling the expression of TrkC as well as the source of NT3 at their initial developmental stage has, however, not been clarified. Here we show that the treatment of the perinatal rat SCG neurons which express high levels of trkA mRNA with bone morphogenetic protein-2 (BMP2) induced the expression of trkC mRNA. Induction of the functional TrkC receptor by BMP2 was confirmed by the enhancement of the survival response of these neurons to NT3. Treatment of SCG neurons with retinoic acid (RA) promoted the effect of BMP2 on the induction of trkC mRNA levels. BMP2 treatment, on the other hand, promoted the effect of RA on the suppressions of trkA mRNA levels and the NGF-dependent survival of the SCG neurons. Furthermore, BMP2/RA treatment induced the endogenous expression of NT3. These results indicate that specific environmental signals can regulate neurotrophin responsiveness of developing sympathetic neurons by differential alteration of the trk and neurotrophin expressions.     

Calcium channel blocker

In the treatment of coronary heart disease, augmentation of oxygen supply and reduction of oxygen demand are necessary. Calcium antagonists (CA) have potent coronary vasodilating (augmentation of oxygen supply) and hypotensive (reduction of oxygen demand) effects without serious side effects, and are most popular agents in the treatment of coronary heart disease (CHD) and hypertension. Short acting CA are reported to be risks for coronary heart disease presumably due to a steal phenomenon, a marked hypotensive effect, and an increased sympathetic nerve activity. Therefore, nowadays long acting CA are usually used in the treatment of CHD and hypertension. However, long term treatment effects of long acting CA in patients with CHD are not clear. Further clinical trials (including primary prevention) concerning long acting CA are needed.     

Protective effects of the antiparkinsonian drugs talipexole and pramipexole against 1-methyl-4-phenylpyridinium-induced apoptotic death in human neuroblastoma SH-SY5Y cells

Treatment of human neuroblastoma SH-SY5Y cells with 1 mM 1-methyl-4-phenylpyridinium (MPP+) for 3 days induced production of reactive oxygen species (ROS), followed by caspase-3 activation, cleavage of poly(ADP-ribose) polymerase (PARP), and apoptotic cell death with DNA fragmentation and characteristic morphological changes (condensed chromatin and fragmented nuclei). Simultaneous treatment with 1 mM talipexole slightly inhibited the MPP+-induced ROS production and apoptotic cell death. In contrast, pretreatment with 1 mM talipexole for 4 days markedly protected the cells against MPP+-induced apoptosis. However, this protective effect might not be mediated by dopamine receptors. The talipexole pretreatment induced an increase in antiapoptotic Bcl-2 protein level but had no effect on levels of proapoptotic Bax, Bak, and Bad. It also inhibited MPP+-induced ROS production, p53 expression, and cleavages of caspase-3 and PARP. Similarly, pramipexole pretreatment increased Bcl-2 and inhibited MPP+-induced apoptosis. Although pretreatment with bromocriptine also had a protective effect against MPP+-induced apoptosis, it had no effect on the protein levels of Bcl-2 family members. On the other hand, N6,2'-O-dibutyryl cAMP or calphostin C induced a decreased Bcl-2 level and enhanced MPP+-induced cell death. These results suggest that talipexole has dual actions: (1) it directly scavenges ROS, affording slight protection against MPP+-induced apoptosis, and (2) it induces Bcl-2 expression, thereby affording more potent protection, if it is administrated before MPP+. Pramipexole has similar effects, whereas bromocriptine seems to exhibit the former but not the latter effect.     

Survey of the sensitivities of clinical isolates to antibacterial agents (annual report)

Research groups were formed in 21 institutions nationwide to investigate carbapenem resistance. The activities of various antibacterial agents, principally carbapenems were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MIC) of 17 antibacterial agents for 1,282 strains of 11 bacterial species isolated at all institutions between October and December 1995. The results were as follows: 1. Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae. Their activities against Enterococcus faecalis were comparable to that of ABPC. Carbapenems showed low activities against MRSA. 2. OFLX exhibited the greatest antibacterial activity against Haemophilus influenzae, followed by MEPM. The antibacterial activities of the other carbapenems were comparable to those of FMOX and CTM. 3. The carbapenems showed high activities against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Bacteroides fragilis group. Their activities were greater than that exhibited by other beta-lactam antibacterial agents. The carbapenems also exhibited greater antibacterial activities against Serratia marcescens than the other beta-lactam antibacterial agents, but some resistant strains were detected. 4. The antibacterial activities of carbapenems against Pseudomonas aeruginosa were comparable to those of CAZ, AZT, AMK.     

The GABAA receptor is expressed in human neurons derived from a teratocarcinoma cell line

NT2 cells, a human teratocarcinoma cell line, are shown to be differentiated in neuron-like cells (NT2-N cells) by treatment with retinoic acid. The present study identified the neurotransmitter receptors expressed in NT2-N cells using patch-clamp recording. Voltage-sensitive Na+ currents, which are specific for neurons, were observed in NT2-N cells but not in NT2 cells, suggesting that NT2-N cells actually function as neurons. Glutamate receptor agonists, N-methyl-D-aspartate (NMDA) and kainate, evoked whole-cell currents. In addition, gamma-aminobutyric acid (GABA) evoked currents and the currents were inhibited by the selective GABAA receptor antagonist, bicuculline. In outside-out patches, GABA elicited single channel currents with two classes of the slope conductance (26 and 50 pS). No current, however, was induced by ACh, serotonin, or dopamine NT2-N cells, thus, express at least two types of the major excitatory and inhibitory neurotransmitter receptor in the central nervous system, the glutamate and GAGAA receptors, suggesting that these receptors have a crucial role in neurotransmission from the earlier stage of the brain development.     

Near-threshold fatigue crack growth properties at elevated temperature for 1Cr-1Mo-0.25V steel and 12Cr stainless steel

Near-threshold fatigue crack growth properties were investigated for a low-alloy steel 1Cr-1Mo-0.25V and a stainless steel SUS403 (13Cr) in the temperature range from 25 to 550°C. Fatigue tests were conducted at frequencies of 0.5, 5, and 50 Hz, in a manner designed to avoid crack closure. The effective value of threshold stress intensity range increased with increasing temperature and with decreasing frequency for the Cr−Mo−V steel, whereas the effective threshold stress intensity range was independent of temperature and frequency in the case of the SUS403 steel. At a given ΔK value, the fatigue crack growth rates accelerated with increasing temperature and with decreasing frequency for the Cr−Mo−V steel. However, although the rate of fatigue crack growth was independent of frequency at a given temperature for the SUS403 steel, the rate did increase with temperature. The observed threshold levels and crack growth behavior were closely related to the oxidation process of the bare surface formed at the crack tip during each load cycle.     

Determination of organophosphorous pesticides in biological samples of acute poisoning by HPLC with diode-array detector

We have studied fibrinogen levels (Clauss technique) in atherothrombotic ischemic stroke patients, in order to determine its role as a thrombogenic risk factor. Twenty nine patients (20 men and 9 women) between 25 and 79 years old were studied; they all have had a atherothrombotic stroke. They were classified into two groups according to the result of their carotid doppler ultrasonography: gl-without carotid flow reduction (n = 19) and g2-with carotid flow reduction (n = 10). The fibrinogen mean value was 269 mg/dl in gl and 353 mg/dl in g2. There were 47% of patients in gl and 80% of patients in g2 who presented levels > 300 mg/dl. The proportions of the groups were significantly different (p < 0.05). Considering the epidemiological value of 300 mg/dl, we conclude that the fibrinogen can be an independent risk factor for ischemic atherothrombotic stroke, specially in those whose carotid flow is reduced.     

A new mechanism in hydrogen-enhanced fatigue crack growth behavior of a 1900-MPa-class high-strength steel

This paper presents a new mechanism controlling the acceleration of fatigue crack growth of a hydrogen-charged high-strength steel (bearing steel SAE52100, ?? _ult?>?1, 900MPa, HV =?569). Three- dimensionally complicated shape of a primary crack and secondary cracks were observed in hydrogen- charged specimens. Marked acceleration of fatigue crack growth in the presence of hydrogen was observed particularly at low test frequency, and was attributed to the initiation and successive coalescence of secondary cracks formed ahead of primary crack. These secondary cracks were produced along prior-austenite grain boundaries and carbide boundaries, or by direct cracking of carbides. Surprisingly, secondary cracks were observed outside the ordinary plastic zone ahead of the crack tip. TEM observation elucidated that the secondary cracks outside the crack tip plastic zone were produced by hydrogen-induced deformation twins impinging on grain boundaries and carbides. These results suggest a new mechanism of the acceleration of fatigue crack growth rates in high-strength steels caused by hydrogen-induced deformation twins, rather than due to hydrogen- enhanced localized plasticity. The phenomena associated with time dependent fatigue crack growth are presumed to be correlated with the initiation and coalescence of secondary cracks in the presence of hydrogen.