Clinical effect of terodiline hydrochloride (TD-758) in patients with urinary disturbances

We evaluated the efficacy of terodiline hydrochloride (TD-758) in 23 patients with psychosomatic bladder, chronic prostatitis and chronic cystitis. The drug was administered at a dose of 24 mg once a day for 4 weeks. In 78% of the patients the symptoms such as urinary frequency and sense of residual urine improved. Only mild side effects such as thirst were noted. We concluded that terodiline hydrochloride was effective in this trial.     

Amplification of IMR-32 clones 8, G21, and N-myc in human neuroblastoma xenografts

Amplification of clones 8, G21, and N-myc, which were derived from human neuroblastoma cell lines IMR-32 and NB-19, were studied in nine neuroblastoma xenografts. N-myc was amplified from 50- to 120-fold in eight of nine xenografts, clone 8 was amplified in five of the xenografts, and clone G21 was amplified in four of these five. Each of these clones was localized by in situ hybridization to homogeneously staining regions in metaphase spreads of xenograft chromosomes. In one xenograft a DNA rearrangement of clone 8 was observed, and only two of the sequences detected by G21 were amplified. Restriction enzyme mapping indicated that the rearrangement within clone 8 occurred at a position close to the rearrangement previously noted in neuroblastoma cell line NB-9.     

Antenatal diagnosis of congenital heart disease and fetal arrhythmia by ultrasound: prospective study

Fetal echocardiographic and Doppler ultrasonographic prospective studies were performed in utero on 299 babies delivered at Hirata Municipal Hospital, Shimane, Japan, from May 1984 to June 1986. Two or three ultrasonographic examinations were performed on each fetus from 20 weeks of gestation to term. Three congenital heart anomalies and 12 fetal arrhythmias were diagnosed antenatally, but 3 heart anomalies (2 small ventricular septal defects and 1 moderate pulmonary stenosis) were not detected in utero. Routine echocardiographic screening appears to be a useful diagnostic tool to detect congenital heart anomalies and fetal arrhythmia antenatally.     

Inhibition of shock-elicited ultrasonic vocalization by opioid peptides in the rat: a psychotropic effect

Following three series of electric footshocks (10 shocks/day), one out of three rats in most cages were brought to emit ultrasonic vocalization for several minutes after a single shock. The characteristics of shock-elicited ultrasound were pure tone pulses of a frequency between 22 and 28 kHz, with duration longer than 300 msec. The same type of ultrasound is produced by subordinate male rats during agonistic behavior. The intracerebroventricular injection of beta-endorphin, dynorphin, methionine-enkephalin or leucine-enkephalin attenuated the shock-elicited ultrasonic vocalization. Psychotropic drugs such as diazepam and chlorpromazine also attenuated the shock-elicited ultrasonic vocalization. A test utilizing ultrasonic vocalization in rodents can provide useful data for studying the psychotropic properties of neuropeptides.     

'Ischemic tolerance' phenomenon detected in various brain regions.

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the 'ischemic tolerance' phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of 'ischemic tolerance'.     

Enzyme immunoassay of free thyroxin in dried blood samples on filter paper

We describe a double-antibody enzyme immunoassay for determination of free thyroxin (FT4) in dried blood samples on filter paper, with use of a T4-beta-D-galactosidase complex. The measurable range of FT4 concentration in two 3-mm blood discs, each of which contained about 2.7 microL of blood, was 1.9 to 93 ng/L, as determined by comparison with concentrations of FT4 in known serum standards. FT4 in blood samples dried on filter paper was stable for at least four weeks when kept dry at -20 degrees C, room temperature, or 37 degrees C. The mean coefficients of variation were 7.6% (within assay) and 6.4% (between assays). Results for FT4 by this method correlated well with those for serum determined by radioimmunoassay (r = 0.98). The proposed method can be used to differentiate persons with hyper- and hypothyroidism from normal subjects and those with abnormal concentrations of thyroxin-binding globulin. The procedure seems suited for screening studies.     

Intratumoral blood flow analysis in ovarian cancer: what does it mean?

The objective of this study is to evaluate the significance of intratumoral blood flow in ovarian cancer. Forty-seven patients with histologically proved ovarian cancer underwent transvaginal gray scale sonography, and color and Doppler sonography before surgery. Intratumoral blood flow velocity waveforms obtained from architecture within the tumor were recorded, and resistive index and peak systolic velocity were calculated. Neither resistive index values nor peak systolic velocity values differed significantly among the histological diagnoses, regardless of stage (including metastatic tumor) or morphologic classification of tumor. These results suggest that intratumoral blood flow analysis in ovarian cancer cannot provide information on individual tumor characteristics.     

Cardiovascular effects of the new generation calcium antagonist 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitropheny l) octyl ester.

The cardiovascular effects of 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitro phenyl) oxtyl ester (NP-252, CAS 132031-81-3) were examined in anesthetized closed- or open-chest dogs and Langendorff perfused rabbit hearts, and compared with those of nifedipine (NF) and nicardipine (NC). In anesthetized closed- and open-chest dogs, NP-252 (i.v.) selectively increased vertebral and coronary blood flow with a fall in mean blood pressure (MBP). These effects were nearly equipotent with those of NF and NC, but more durable. A similar effect was obtained by intraduodenal administration of NP-252. Also, NP-252 (i.v.) decreased MBP, total peripheral resistance (TPR), left ventricular pressure and dLVP/dtmax while cardiac output (CO) and stroke volume (SV) increased without apparent changes in heart rate and myocardial contractility index. Decreases in MBP and TPR by NP-252 were equipotent with NF and NC, whereas increases in CO and SV were more potent than those of the two drugs. These actions of NP-252 were longer than those of the reference agents. Further, in perfused rabbit hearts, NO-252 increased coronary perfusion flow (CPF), accompanying a slight negative inotropy. Its effect in CPF was equipotent with NF and 2 times less than that of NC, however the duration was much longer than those of the reference drugs. On the other hand, the negative inotropic effect of NP-252 was less than NF, but greater than that of NC. In the preparations controlled by pacing, NP-252 and NF lengthened atrio-His bundle conduction time, without affecting His bundle-ventricular conduction time. Lengthening effect of NP-252 was about 4 times less than that of NF. These results suggest that NP-252 acts more selectively on vascular smooth muscle than cardiac muscle, and has almost equipotent but markedly longer vasodilating actions as compared to NF and NC. It may be expected that NP-252 is a new generation of tissue specific and long acting Ca2+ antagonist.