Effects of castration on apoptosis and transforming growth factor-beta 1 mRNA in the neonatal mouse seminal vesicles

BACKGROUND: In the adult male rat prostate, castration induces apoptosis of epithelial cells concomitant with the increase in transforming growth factor-beta 1 (TGF-beta 1). In the present study, we investigated the effects of castration on apoptosis and TGF-beta 1 mRNA in neonatal mouse seminal vesicles. METHODS: 5-day-old BALB/c mice were castrated by Pfeifer's method. We estimated the weight, 3H-thymidine uptake by whole seminal vesicles, the amount of TGF-beta 1 mRNA by RT-PCR method, and the apoptotic index of both epithelium and mesenchyme. RESULTS: The castration of 5-day-old neonatal mice resulted in much less weight of seminal vesicles and DNA synthesis estimated by 3H-thymidine uptake by whole seminal vesicles compared to intact neonatal mice, indicating that the growth of neonatal mouse seminal vesicles depends on androgens secreted by the testis. The amount of TGF-beta 1 mRNA estimated by RT-PCR method increased 4 days after castration at 5 days of age. However, the castration did not induce apoptosis in the seminal vesicles. CONCLUSION: The present study indicates that castration of neonatal mice does not induce apoptosis in the seminal vesicles, although it does a transient increase in TGF-beta 1 mRNA in the seminal vesicles.     

Incidence of implantable defibrillator discharges after coronary revascularization in survivors of ischemic sudden cardiac death

Coronary revascularization has been suggested as sole therapy for secondary prevention of sudden cardiac arrest associated with ischemia. The use of implantable defibrillators (ICD) in combination with coronary revascularization for this patient population is unclear. Among 412 consecutive patients receiving an ICD, 23 (6%) were identified as sudden cardiac arrest survivors who were noninducible with programmed stimulation and had unstable angina or ischemia on a functional study; they underwent successful coronary revascularization. During a follow-up of 34 +/- 18 months, 10 (43%) of the 23 patients received ICD shocks (8 +/- 8 per patient, range 1 to 22 shocks), and nine of the 10 patients had syncope/presyncope associated with at least one ICD discharge. Patients with ICD discharges were compared with those without ICD discharges, and no clinical characteristics were statistically different between the two groups. In conclusion, revascularization alone may be inadequate therapy for survivors of sudden cardiac arrest associated with ischemia who are noninducible with programmed stimulation, and clinical variables cannot predict which patients are likely to have recurrent malignant ventricular arrhythmias.     

MIBI-scintigraphy. A simple and reliable method for localization of pathological parathyroid glands

99Tcm-sestamibi scintigraphy was used to localise enlarged parathyroid glands in 25 patients with primary hyperparathyroidism previously operated in the neck, 20 of whom had recurrent disease and five had previously undergone surgery for thyroid disorders. Of the 18 patients for whom positive scans were obtained, nine were operated on the scan findings being confirmed. Crucial information was provided in two cases of intrathyroidal and one case of intramediastinal localisation of the pathological gland were not operated on as the hypercalcaemia was only marginal or the symptoms were vague. Though preoperative localisation of pathological parathyroid glands is a prerequisite for neck exploration in patients with persistent or recurrent hypercalcaemia due to primary (or secondary) hyperparathyroidism, the procedure is not cost-effective before the initial operation.     

Analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione: structure-activity relationship at N-methyl-D-aspartate receptor glycine sites

A series of aromatic and azepine ring-modified analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione (HBAD) were synthesized and evaluated as antagonists at NMDA receptor glycine sites. Aromatic ring-modified HBADs were generally prepared via a Schmidt reaction with substituted 2-methoxynaphthalene-1,4-diones followed by demethylation. Electrophilic aromatic substitution of benzazepine 3-methyl ethers gave 7-substituted analogs. The preparation of multiply substituted 2-methoxynaphthalene-1,4-diones was effected via Diels-Alder methodology utilizing substituted butadienes with 2-methoxybenzoquinones followed by aromatization. Structural modifications, such as elimination of the aromatic ring, removal of the 3-hydroxyl group, and transfer of the hydroxyl group from C-3 to C-4, were also studied. An initial evaluation of NMDA antagonism was performed using a [3H]MK801 binding assay. HBADs demonstrating NMDA antagonist activity as indicated by inhibition of [3H]MK801 binding were further evaluated employing a [3H]-5,7-dichlorokynurenic acid (DCKA) glycine site binding assay. Selected HBADs were characterized for functional antagonism of NMDA and AMPA receptors using electrophysiological assays in Xenopus oocytes and cultured rat cortical neurons. Antagonist potency of HBADs showed good correlation between the different assay systems. HBADs substituted at the 8-position possessed the highest potency with the 8-methyl (5), 8-chloro (6), and 8-bromo (7) analogs being the most active. For HBAD 6, the IC50 in [3H]-DCKA binding assays was 0.013 microM and the Kb values for antagonism of NMDA receptors in oocytes (NR1a/2C) and cortical neurons were 0.026 and 0.048 microM, respectively. HBADs also antagonized AMPA-preferring non-NMDA receptors expressed in oocytes but at a lower potency than corresponding inhibition of NMDA receptors. HBADs demonstrating a high potency for NMDA glycine sites showed the highest steady-state selectivity index relative to AMPA receptors. Substitution at the 6-, 7-, and 9-positions generally reduced or eliminated glycine site affinity. Moving the hydroxyl group from C-3 to C-4 reduced receptor affinity, and potency was eliminated by the removal of the aromatic ring or the hydroxyl group. These data indicate that the HBAD series has specific structural requirements for high receptor affinity. With the exception of substitution at C-8, modified HBADs generally have a lower affinity at NMDA receptor glycine sites than the parent compound 3. Mouse maximum electroshock-induced seizure studies show that the three HBADs selected for testing have in vivo potency with the 6,8-dimethyl analog (52) being the most potent (ED50 = 3.9 mg/kg, iv).     

Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa

Sputum isolation of Pseudomonas aeruginosa (PA) is associated with extensive disease in bronchiectasis. It is not known, however, whether infection with P. aeruginosa is the result or the cause of severe disease. We compared spirometry in patients with bronchiectasis before and after infection with P. aeruginosa, with that of patients infected by other organisms. All patients (n=12) with chronic colonization by P. aeruginosa (PA group) were studied. These were compared with other patients with bronchiectasis with no isolations of P. aeruginosa (n=37, non-PA group). In the PA group, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were lower than in the non-PA group. The PA group, however, also had lower values at the time of initial colonization with P. aeruginosa than the current values for the non-PA group. Change in FEV1 and FVC over time was faster in the PA group than in the non-PA group. Reduction of FEV1 and FVC over time in the PA group prior to P. aeruginosa colonization was intermediate, not being statistically different from either value above. Our results confirm the association of chronic P. aeruginosa colonization with poor lung function, but conclude that patients with bronchiectasis who become colonized by P. aeruginosa have poorer lung function when first colonized than those colonized by other organisms. Decline in lung function is faster in those chronically colonized by P. aeruginosa than in those colonized by other organisms. It is not clear whether chronic P. aeruginosa colonization causes an accelerated decline in lung function or whether it is simply a marker of those whose lung function is already declining rapidly.     

Deciphering polycythemia

Most causes of an elevated hematocrit can be determined with a simple workup that includes a complete blood count and chest x-ray. However, measurement of red blood cell mass and plasma volume is required to differentiate primary, secondary, and combined polycythemia. Phlebotomy is customary for primary disease and some secondary cases in which the underlying cause cannot be removed.     

Effect of lipoxygenase derivatives of linoleic acid on functional activity of neutrophils

The effect of lipoxygenase derivatives of 13-hydroperoxylinoleic acid (13-HPODE) and 13-hydroxylinoleic acid (13-HODE) on zymosan-induced chemiluminescence of rat neutrophils in vitro was evaluated. It was found that both derivatives inhibit functional activity of neutrophils. The extent of inhibition was changed by preincubation of neutrophils with arachidonic or linoleic acid. On the other hand, in experiments with dogs it was shown that the extent of such inhibition considerably increases after ischemia and reperfusion of myocardium. Thus we assume that the ratio of lipoxygenase derivatives of arachidonic and linoleic acid play the regulative role in functional activity of neutrophils. It was concluded, that lipoxygenase derivatives of linoleic acid inhibited the neutrophils functional activity.