Protective effect of JTV519, a new 1,4-benzothiazepine derivative, on prolonged myocardial preservation

BACKGROUND: JTV519 is know to protect cardiomyocytes from calcium overloading-induced damage. The aim of this study was to investigate the potential protective effect of JTV519 on myocardium subjected to prolonged ischemia and the underlying mechanism of such protection. The effect of JTV519 was also compared with that of diltiazem, a 1,5-benzothiazepine derivative. METHODS: Isolated rat hearts were randomly divided into three groups. Control hearts were arrested with histidine-tryptophan-ketoglutarat (HTK) cardioplegic solution alone. In the JTV519 group of hearts, cardiac arrest was achieved with JTV519 (10(-3) mmol/L) in the HTK solution. Hearts in the diltiazem group were arrested with diltiazem (0.5 mmol/L) in the HTK solution. All the hearts were then subjected to 6-hour storage in HTK solution at 4 degrees C. RESULTS: After a 30-minute reperfusion, the left ventricular developed pressure in the JTV519 and diltiazem groups were improved significantly compared with the control group. There was a significantly lower left ventricular end-diastolic pressure level and higher recovery of coronary flow in the JTV519 group than in the control group. The postischemic intracellular calcium concentration was attenuated by adding JTV519 or diltiazem to HTK cardioplegia. CONCLUSION: As an adjunct to cardioplegia, JTV519 showed a significant protective effect on myocardium undergoing 6 hours of ischemia. The beneficial protective effects of JTV519 are correlated with its ability to inhibit the postischemic rise in intracellular calcium.     

Anticoagulation after valve replacement: a multicenter retrospective study

Anticoagulant therapy after cardiac valve replacement was evaluated retrospectively in 1,200 patients attending 8 cardiac surgery clinics in the Tokyo area as part of the Tokyo Area Study on Anticoagulation After Cardiac Valve Replacement Using PT-INR (TAS). A prospective trial is also in progress and will be reported later. The prothrombin time international normalized ratio (PT-INR) was determined at the time of thromboembolic and bleeding complications in 1,200 patients. During the 5 year study period, thromboembolisms occurred in 21 patients, and bleeding complications occurred in 15 patients. In 71% of patients with thromboembolism and 47% of those with bleeding complications, the PT-INR was within the range of 1.6 to 2.8, which is the accepted therapeutic range in Japan. Therefore, the correct PT-INR therapeutic range for Japanese patients with mechanical heart valves needs to be reexamined, and data from the prospective TAS trial that is currently underway will be used for this purpose.     

Denervation supersensitivity of the urethra to α-adrenergics in the chronic neurogenic bladder

Summary The response of the urethral pressure profile to the administration of various autonomic drugs was compared between a group of eight patients with chronic neurogenic bladder as evidenced by denervation supersensitivity to besacholine^R and a group of 10 control subjects. A supersensitive response to the administration of an -stimulant with a rise of maximum urethral pressure of 10 mmHg or more above the control urethral pressure was uniformly observed in the urethra of patients with chronically denervated bladders. Mechanisms of supersensitivity are postulated and the significance of -adrenergic innervation of the urethra are stressed. These results appear to add pharmacological evidence of -adrenergic predominance in the urethra which is now believed to be dually innervated.     

Complete repair of severe penoscrotal hypospadias in 1 stage: experience with urethral mobilization, wing flap-flipping urethroplasty and "glanulomeatoplasty"

We describe our experience with complete repair of severe penoscrotal hypospadias in 1 stage. The operative technique includes several innovative points, such as release of chordee by urethral mobilization (without detaching it from the glans) after penile degloving of dartos chordee, wing flap-flipping urethroplasty to the tip of the glans and incrimination of "glanulomeatoplasty" for better cosmetic and functional results. Our technique is compared to other 1-stage methods.     

Serum fluoride as an indicator of occupational hydrofluoric acid exposure

Summary To define the relationship between ionic fluoride concentration in the serum of workers and the amount of hydrofluoric acid (HF) in the work environment, pre-and postshift serum and urine samples of 142 HF workers and 270 unexposed workers were examined. The maximum and minimum concentrations of HF in the air in each workshop varied from the mean by less than 30%. The pre-exposure levels of serum and urinary fluoride in HF workers were higher (P < 0.001) than the control values. This suggests that fluoride excretion from the body continues for at least 12 h. The postshift serum and urinary fluoride concentrations of these workers were significantly higher (P < 0.001) than the preshift concentrations. A good correlation (r = 0.64) was obtained between postshift serum fluoride and postshift urine fluoride. There was a linear relationship between mean serum fluoride concentration and HF concentration in the workshop. A mean fluoride concentration of 82.3 g/l with a lower fiducial limit (95%, P = 0.05) of 57.9 g/l was estimated to correspond to an atmospheric HF concentration of 3 ppm. This is the maximum allowable environmental concentration recommended by the Japanese Association of Industrial Health, and it is also the threshold limit value suggested by the American Conference of Governmental Industrial Hygienists. The results demonstrate that exposure to HF can be monitored by determining the serum fluoride concentration.     

Ontogeny of behavioral patterns in relation to the concurrent development of central nervous system function, focusing on REM sleep, NREM sleep and waking states in the human fetus

Behavior is considered a one to one match between the manifestation of a particular individual motor activity (movement) and its correlated brain function. Each motor activity can be seen to run on its own developmental course with advance in gestation, while various movements also develop in concurrence with one another during intrauterine life, gradually integrating into complex and accommodated movements. I emphasized the present study, under real-time ultrasound observation, for investigating whether or not three states: REM (rapid eye movement) sleep, NREM (non-rapid eye movement) sleep and the waking state actually exist in utero, and if so, when the development of these states begins. 1. Examined for 30-40 minutes were 21 fetuses, including 10 from 33 to 36 weeks of gestation and 11 from 37 to 41 weeks of gestation. As parameters, the duration of each eye movement unit and the cumulative duration of this movement, from the shortest to a given duration, per individual case, were observed. A scattergram of cumulative duration vs, given duration obtained from all cases, for each age-group, were analyzed using "piecewise linear regression". Critical points were noted, with statistical significance, at 0.62 second for the earlier group and at 0.76 second for the later group. These findings reveal two different types of eye movement: rapid and slow eye movements. The fact that the rapid eye movement coexists with the slow eye movement during REM period indicates that REM sleep exists in utero at the latest at 33 weeks of gestation. 2. Observed for 60 minutes were 26 fetuses from 28 to 41 weeks of gestation. Regular mouthing movement every 300 to 600 msec concurred significantly only with the NREM period from 35 weeks of gestation onwards. Random mouthing movements were observed predominantly during REM sleep and were unrelated to the advance in gestational age. This concurrence between the NREM period and regular mouthing indicates the existence of NREM sleep in utero at this age of gestation. 3. To evaluate whether the waking state is present, 10 fetuses at 36 weeks or more of gestation were examined for a concurrence between miosis/mydriasis and the REM/NREM periods. Using pupil diameter as a parameter, miosis and mydriasis were distinguished from each other, statistically, by means of "least median of squares regression". Accordingly, the NREM period was occupied only by miosis (41.0% of total observation period), while the REM period was divided into two conditions: 52.6% with miosis and 6.4% with mydriasis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ooplasmic round spermatid nuclear injection procedures as an experimental treatment for nonobstructive azoospermia

Purpose: Our objective was to apply ooplasmic round spermatid nuclear injections for the treatment of nonobstructive azoospermia. Materials: Participants were nine azoospermic men who had previously undergone diagnostic testicular biopsy. Spermatogenetic arrest was diagnosed at the round spermatid stage (n=6) or primary spermatocyte stage (n=3). A second (therapeutic) testicular biopsy was performed and round spermatid nuclei were recovered from all the participants. Results: Forty-nine mature oocytes were successfully injected with nuclei and then cultured for 72 hr. Twenty-four embryos were transferred to nine women. No pregnancy was achieved. Conclusions: Round spermatids can be recovered from therapeutic testicular biopsy material of men negative for round spermatids in previous routine diagnostic testicular biopsy specimens. Round spermatid nuclear injections may play a role in the treatment of nonobstructive azoospermia.     

Sequence Analysis of Genes Encoding Rodent Homologues of the Human Tumor-rejection Antigen SART-1

Human SART-1 ( hSART-1 ) gene encodes a 125 kD protein with a leucine-zipper motif expressed in the nucleus of all proliferating cells, and a 43 kD protein expressed in the cytosol of most epithelial cancers. In this study, two rodent genes ( rSART-1 and mSART-1 ) homologous to hSART-1 were cloned from cDNA libraries of murine brain and a rat tumor cell line, respectively. mSART-1 and rSART-1 were highly homologous to hSART-1 with 86% and 84% identity at the nucleotide level, and 95% and 91% at the protein level, respectively. The leucine zipper domain and two basic amino acid portions that bind DNA, as well as peptide sequences recognized by human cyto-toxic T lymphocytes (CTLs), were all conserved in these rodent genes. Nuclear protein homologous to the 125 kD hSART-1₈₀₀ protein, but not to the 43 kD cytosol SART-1₂₅₉ protein, was detectable with specific antibody in the nuclear fractions of rodent tumor cell lines, and normal rodent fetal liver and testis. These rodent genes should be a novel tool for studies on the biological roles of the SART-1 gene, and also in the construction of animal models of specific immuno-therapy using SART-1 gene products.