Pharmacological evidence of distinct alpha 1-adrenoceptor subtypes mediating the contraction of human prostatic urethra and peripheral artery.

1. The alpha 1-adrenoceptor subtypes mediating contractions of the smooth muscle in human prostatic urethra and branches of internal iliac artery were characterized in isometric contraction experiments. 2. Phenylephrine produced concentration-dependent contractions in both the urethra and artery. These responses were competitively inhibited by prazosin, WB4101 and 5-methyl-urapidil, and the slopes of Schild plots for all these antagonists were close to unity. 3. The pA2 values for prazosin were not significantly different between the urethra (9.42 +/- 0.11; mean +/- s.d.) and artery (9.50 +/- 0.27), while the pA2 values for WB4101 and 5-methyl-urapidil in the human prostatic urethra (8.94 +/- 0.19 and 8.42 +/- 0.14, respectively) were significantly greater than in the branches of human internal iliac artery (7.94 +/- 0.21 and 7.43 +/- 0.22, respectively; P < 0.01). 4. Pretreatment with chlorethylclonidine (CEC) at concentrations ranging from 0.1 microM to 100 microM attenuated the maximum contraction to phenylephrine in a concentration-dependent manner in both the urethra and artery. However, the urethra was significantly less affected by CEC than the artery. The pD'2 values (negative logarithm of the molar concentration of antagonist which reduced the maximum contraction to one half) in the urethra and artery were 4.35 +/- 0.27 and 5.20 +/- 0.37, respectively (P < 0.01). 5. The present results indicate that there are distinct populations of alpha 1-adrenoceptor subtypes in the human prostatic urethra and branches of the internal iliac artery. The alpha 1-adrenoceptors responsible for the contraction of the human internal iliac artery branches are predominantly alpha 1 B-subtype, whereas those in the human prostatic urethra are considered to be not alpha 1 B, but alpha 1 c or possibly alpha 1 A or alpha 1A/D-subtype.

The alpha-adrenoceptor antagonist properties of the enantiomers of doxazosin in the human prostate.

The alpha-adrenoceptor antagonist properties of doxazosin and its enantiomers were characterized using human prostate tissue and cell membranes isolated from rat-1 fibroblast expressing each of the cloned human alpha 1-adrenoceptor subtypes. In the alpha 1-adrenoceptor-binding studies on the human prostate with [3H]doxazosin and 2-{[beta-(3-[125I],4-hydroxyphenyl)ethyl]aminomethyl}-l-tetralone ([125I]HEAT), no significant differences were observed between racemic doxazosin, R-doxazosin and S-doxazosin (mean -log Ki (pKi) values were 8.60-8.63, 8.47-8.55 and 8.61-8.65, respectively), whereas the alpha 2-adrenoceptor-binding studies with [3H]rauwolscine and [3H]clonidine revealed that the alpha 2-adrenoceptor-binding affinity of S-doxazosin (pKi = 5.91-5.94) was slightly (3- or 4-fold), but significantly lower than that of R-doxazosin (pKi = 6.47-6.54). Studies in phenylephrine-contracted prostatic tissue showed no significant difference in alpha 1-adrenoceptor antagonist potency between racemic doxazosin, R-doxazosin and S-doxazosin (pA2 values were 8.43 +/- 0.28, 8.64 +/- 0.56 and 8.75 +/- 0.38, respectively). In the binding studies with cloned alpha 1-adrenoceptor subtypes using [3H]prazosin and [125I]HEAT, racemic doxazosin, R-doxazosin and S-doxazosin showed no selectivity for the alpha 1-adrenoceptor subtypes. The present study demonstrated that doxazosin and its enantiomers are highly selective alpha 1-adrenoceptor antagonists and that there is no evidence suggesting differential alpha 1-adrenoceptor antagonist effects of doxazosin and its enantiomers in the human prostate. Doxazosin, therefore, could be described as displaying balanced activity across all three alpha 1-adrenoceptor subtypes.

Effects of sea water pollution on chicken embryos.

Organic matter and heavy metal contamination in sea water obstruct vital functions of chicken embryos and interrupt their growth. Histological examination of contaminated fetuses showed a menacing growth of abnormal protuberances in the lungs as well as highly impeded formation of capillaries, although the windpipes exhibited normal expansion. Compared with controls, liver tissue also showed retarded growth accompanied by decrease in liver weight. Consequently, vital metabolic functions were impaired, hydropsy and evisceration developed, and fetuses were deformed.

Chemical change involved in the oxidative-reductive depolymerization of heparin.

A solution of hog intestinal heparin (average M(r) 12,000, anti-clotting activity 168 USP units/mg) in 0.2 M phosphate buffer (pH 7.2), was incubated in the presence of Fe2+ for 20 h at 50 degrees under an O2 atmosphere to yield oxidative-reductively depolymerized heparin (ORD heparin, average M(r) 3,000, anti-clotting activity 34 USP units/mg). Chemical analysis of the ORD heparin showed a 22, 26, and 14% loss of hexosamine, uronic acid, and N-acetyl group, respectively, but no remarkable loss of both total and N-sulfate groups. 1H and 13C NMR spectroscopic analysis indicated no decrease in the amount of L-iduronic acid 2-sulfate, but a marked loss of nonsulfated uronic acid (73 and 39% loss of D-glucuronic acid and L-iduronic acids, respectively, the sum of which corresponds to the chemically determined loss of total uronic acid). The results indicated that the ORD reaction of heparin proceeds essentially by destruction of monosaccharide units, except L-iduronic acid 2-sulfate residues, due to oxygen-derived free radicals, followed by secondary hydrolytic cleavage of the resulting unstable residues.

Complement system in abnormal pregnancy and chorionic neoplasia: immunotherapy and chemotherapy of chorionic neoplasia.

In normal pregnancy, the activity of the alternate pathway elevates latently and compensatorily for the suppression of cellular immunity. Aging of the placenta becomes a trigger for the onset of labor and production of C3-a. In cases of hydatidiform mole, abruptio placentae, threatened abortion, and chorionic malignancy, the activity of the complement system is depressed, especially that of C3-activator and alternate pathway. This may in turn result from activation of complement by the pathologic lesion of the chorionic villi. In pathologic lesions of the placenta, activation of alternate pathway can lead to a number of diseases. Immunotherapy is effective in the prevention of malignant transformation of hydatidiform mole. Immunotherapy and combination chemotherapy are markedly effective for treatment of metastatic chorionic malignancy.

Neurovirulent strains of herpes simplex virus type 1 are not necessarily competent for reactivatable latency.

Ability of two neurovirulent strains (F and +GC (LPV) Miyama) of herpes simplex virus type 1 (HSV-1) to establish and maintain reactivatable latency in trigeminal ganglia (TG) was compared after intranasal inoculation of mice. The +GC (LPV) Miyama strain showed a very low rate of virus reactivation in explant cultures of TG, while the F strain showed a high rate of reactivation. These data indicate that neurovirulent strains of HSV-1 are not always competent for reactivatable latency, although most virulent strains of HSV-1 thus far reported were competent for reactivatable latency.

Reactivatable latency of three avirulent strains of herpes simplex virus type 1 after intranasal inoculation in mice.

In order to elucidate the mechanism of latent infection of herpes simplex virus (HSV), reactivatable latency of three avirulent strains (SKO-1B, -GCr Miyama, SKa) of HSV type 1 was comparatively examined in a mouse latency model. The SKO-1B strain showed high rate of virus reactivation from explanted trigeminal ganglia without n-butyrate enhancement, while the other two strains showed a very low rate of virus reactivation in the absence of n-butyrate. In the presence of n-butyrate, however, the rate of the -GCr Miyama strain jumped to a comparable level with that of SKO-1B, although the rate of SKa remained at a low level. A more precise follow-up experiment changing the virus dose highlighted the difference of the ability to reactivate from the latent state between SKO-1B and -GCr Miyama. Virus titer in trigeminal ganglia during acute phase, infectivity to cell lines of neural origin, and susceptibility to acyclovir and phosphonoacetate were assayed to know the reasons for the variation in the ability of reactivatable latency among these strains. It was concluded that the reduced infectivity to neural cells, and limited ability of reactivatable latency shown by the SKa strain could mainly be attributed to the deficiency of thymidine kinase activity.

[Survey of activities of daily living in non-institutionalized elderly residents].

To investigate the states of activities of daily living (ADLs) in the elderly, non-institutionalized residents-aged 65 and over living in Azuchi (population of approximately 12,000) were interviewed. Data was collected from 1,287 subjects (509 men and 778 women; 92.1%) for the 3 years, 1990 to 1992. Differences in difficulties with the 6 basic ADLs (BADLs) and the 7 instrumental ADLs (IADLs) were analyzed according to gender and age. For the BADLs (eating, dressing, bathing, using the toilet, mobility, and incontinence), only the percentage of incontinence was significantly higher in women than in men (p < 0.01). The percentage of those fully independent in the 6 BADLs in men was 87%, which was higher than that in women (77%), but except for incontinence there were no significant differences between the sexes. The percentages of disability in the BADLs for women and for both sexes combined were higher according to age (p < 0.01), but for men, only those of dressing (p < 0.05) and of incontinence (p < 0.01) were related with age. The disability percentage for cooking was the only activity among the IADLs (cooking, using the telephone, cleaning house, walking, shopping, going up and down steps, and using transportation) which was significantly higher in men (p < 0.01), but those for walking, going up and down steps, and using transportation were higher in women (p < 0.01). The percentage of those who were fully independent was 74% in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

[Long-term results and indications of intraurethral stents in elderly patients with prostatic hypertrophy complaining of urinary retention].

Thirty-two elderly male patients with benign prostatic hypertrophy complaining of urinary retention were treated by polyurethane intraurethral stents. All of them were unfit for prostatic surgery due to the presence of several complications, and had been indwelt with a urethral balloon catheter. Cystometry before stent insertion was performed in 23 of the 32 patients. Eleven patients showed overactive bladder, 5 patients normal bladder, and 7 patients underactive bladder. Duration of stent indwelling ranged from 2 days to 22 months (mean 6.7 months), and stent could successfully function for more than 6 months in 20 of the 32 patients (62.5%). Nine of these 20 patients (45%) could keep continence of urine, and urinary tract infections improved in 7 of these 20 patients (35%). The stent failed in 4 of the 5 patients who had had previous operations for prostatic hypertrophy. In a comparison of the findings of urodynamic study prior to insertion of stent with the results of the stent, the results were significantly better in the patients with overactive or normal bladder than in those with underactive bladder (p < 0.05, chi-square test). Bladder stone formation was found in one patient and was the only complication among the 32 patients. In conclusion, stent placement without incontinence or urinary tract infection can be successful for more than 6 months in patients who do not have an underactive bladder and who had not had a previous prostatic operation.

[Application of intraurethral catheter for geriatric male patients complaining of urethral obstruction due to malignancy--comparison with benign prostatic hypertrophy].

Intraurethral catheters (IUC) were used for elderly male patients with prostatic urethral obstruction (PUO) due to malignancy (MA) and benign prostatic hypertrophy (BPH). Thirty-three men complaining of urinary retention in spite of medical therapy at the risk for prostatic surgery underwent insertion of IUC (16Fr Puroflex, Angiomed Co., Ltd., Germany). Six of 33 were patients with PUO due to MA (5 prostatic cancer, and 1 urethral invasion of rectal cancer, mean 82.7 years old), and the other 27 were patients with BPH (average 80.1 years old). Follow-up period of the former ranged from 2 to 9 (mean 6.5) months, and that of the latter ranged from 6 to 23 months. Water filling cystometry (CMG) before the insertion of IUC and fluoroscopic voiding cystourethrography (VCU) just after insertion of IUC were performed. We defined normal CMG and normal VCU as normal bladder, overactive CMG and normal VCU as overactive bladder, and normal or poor sensitive CMG and underactive VCU as underactive bladder. Five of 27 BPH patients had previous prostatic operations (TUR-P, and/or balloon dilation), but 6 MA did not. All of MA (3 normal bladder, 2 overactive bladder, and 1 underactive bladder) voided satisfactorily, and average duration of IUC in place was 6.5 months without exchange of IUC. Although sixteen of 27 (59.3%) BPH patients voided satisfactorily, and average duration of IUC in place was 12.1 months without exchange of IUC, in the other 11 of these 27 BPH patients were removed IUC, and average duration of IUC in place was 4.7 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

[Endoscopic operation of congenital anterior urethral valve. Application of flexible renoureteroscope for antegrade urethroscopy].

4 children with anterior urethral valve were treated by TUR-Valve. Before TUR, valve anatomy could be easily seen by antegrade urethroscopy through cystostomy using a 10.8Fr caliber flexible renoureteroscope and destruction of the valve could be recognized after TUR. Antegrade urethroscopy with a flexible fiberscope was so helpful to TUR-Valve and the findings of voiding cystourethrography and micturition have remarkably improved. This technique is not so difficult to apply and thought to be one of the best methods to recognize valve anatomy and degree of resection. This technique is also applicable to other lower urinary tract lesions in children.

[The effect of intra-urethral catheter for prostatic hypertrophy patients who are unfit for operation and suffer from urinary retention].

The effect of double Malecot type polyurethane intraurethral catheter (IUC) was examined in 17 benign prostatic hypertrophy patients who were unfit for operation and suffered from urinary retention. Patients were aged 68 to 90 (mean 80.5) years old and the causes of IUC insertion were cardiac, cerebrovascular, respiratory and gastrointestinal diseases, diabetes mellitus and aging. IUC was selected among three types (55, 60, 65 mm) according to the length of prostatic urethra. Insertion of IUC was carried out easily under fluoroscopic guidance without endoscopy. All patients could void by themselves just after insertion of IUC and the longest indwelling period was 10 months. The length of IUC need not be longer than that of prostatic urethra and patients with normal or hypertonic bladder could void better than those with atonic bladder. Urinary tract infection did not get worse in any patients with indwelling IUC. Double Malecot type polyurethane IUC is a safe and an effective alternative method in place of urethral balloon catheter for inoperable prostatic hypertrophy patients in urinary retention.

[Intranasal infection of ICR mice with herpes simplex virus type 1].

Intranasal inoculation of mice with herpes simplex virus (HSV) provides a model of human herpetic infection through a natural route of inoculation. Five-week-old male ICR mice were infected intranasally with various strains of herpes simplex virus type 1 (HSV-1), and the fundamental aspects of the pathogenicity of this virus were studied. Six virus strains examined showed variance in their virulence determined by lethal dose 50 (LD50) for mice. Four of the strains were revealed to be virulent, and two were shown to be attenuated. The relative degree of virulence among these strains corresponded well to that shown by intraperitoneal inoculation. When mice were inoculated with a virulent virus strain (F), virus multiplication was shown clearly in several organs tested, such as the lung, brain, olfactory bulb, trigeminal ganglion, spinal cord and adrenal gland. Viremia was also demonstrated. On the other hand, in mice inoculated with an attenuated virus strain (-GCr), virus was recovered only from the lung and adrenal gland and in much less amount than in the respective organs of mice infected with the virulent strain. No viremia was demonstrated. These data strongly suggest that the lethal effect of HSV-1 on mice is dependent upon whether or not significant virus multiplication occurs in the central nervous system, which is the critical target organ of HSV. Preinoculation of mice with an attenuated strain via the intranasal route suppressed the lethal effect of subsequent infection with any of the virulent strains by the same route of inoculation, although this protection phenomenon was not so pronounced when the virulent UNO-1A strain was used.(ABSTRACT TRUNCATED AT 250 WORDS)

[Studies on screening for hard-of-hearing children by questionnaire. 2. Comparison of response rates to individual questions in 1-year-6-month-old children with normal hearing and hearing loss using a health screening questionnaire].

We report the results of studies on responses to questions on hearing impairment, comparing 165 school children whose hearing was diagnosed as normal at the time of admission to primary school and 37 children with hearing loss attending facilities for children with this disability. These children had been covered by similar surveys as part of the health screening for 1-year-6-month-old infants conducted by municipal authorities. Significant differences between the two groups were noted in the response rates to all questions on hearing. Similar differences were noted in the responses to questions on family history of hearing impairment. There were no significant differences in the incidences of asphyxia and jaundice at birth. The most striking differences were noted in the response rates to questions 6, 7, 8, 10, 11, 16, and 18. Most useful and universally valid in this survey were questions 8, 10 and 18 in addition to the question on whether or not parents suspected infantile hearing loss.

Influence of polychlorinated biphenyls on the growth of chicken embryos.

Incubation of chicken embryos with either 0.01 or 0.03 ppm polychlorinated biphenyls (PCBs) for 12, 15, or 18 d resulted in a significant decrease in liver and body weight associated with enhanced mortality. Teratological examination revealed an increased frequency of malformations including hydrops, eventration, wry neck, and brevicollis. PCB exposure was also found to produce histologic damage to liver and cutaneous tissue. Our data demonstrate that exposure of chicks to PCBs during development results in a retardation of growth, an increased incidence of malformations, and histopathologic damage.