HORMONE PROFILE IN PREMENSTRUAL TENSION: EFFECTS OF BROMOCRIPTINE AND DIURETICS

Plasma levels of prolactin, FSH, LH, progesterone and 17-beta-oestradiol in twenty women with premenstrual tension were compared with those in twenty controls. The former group was studied also during treatment with bromocriptine. The mean prolactin level in the PMT group was lower in the follicular phase than in the luteal phase (P less than 0.01), but there was no difference between the PMT and control group in the luteal phase. No differences were found between the controls and the PMT group in FSH,LH, 17-beta-oestradiol and progesterone levels in the luteal phase. Bromocriptine suppressed prolactin concentrations (P less than 0.01), but had no effect on the FSH, LH, 17-B-oestradiol or progesterone levels.     

Metabolic responses in ischemic myocardium after inhalation of carbon monoxide

Background: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO.
Methods: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate.
Results: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups.
Conclusions: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection.     

HORMONAL TREATMENT BEFORE RADICAL PROSTATECTOMY: A 3-YEAR FOLLOWUP

Purpose

Hormonal treatment administered before radical prostatectomy has been shown to decrease the rate of positive surgical margins. We determine whether preoperative hormonal treatment has any impact on the subsequent failure rate.

Materials and Methods

We prospectively evaluated 122 patients with stages T1bNxM0 to T3aNxM0, grades 1 to 3 prostate cancer, including 64 randomly assigned to immediate radical retropubic prostatectomy and 58 randomly assigned to radical retropubic prostatectomy preceded by 3 months of pretreatment with a gonadotropin-releasing hormone agonist. We performed intention to treat analysis on the data with failure defined as lymph node involvement, serum prostate specific antigen greater than 0.5 ng./ml., or the need for postoperative hormonal or radiation adjuvant treatment.

Results

The positive margin rate was 23.6 versus 45.5% in the pretreatment plus prostatectomy versus prostatectomy only groups (p = 0.016). There were 20 failures (34.5%) in the pretreatment plus prostatectomy subgroup and 26 (40.6%) in the prostatectomy only group (p = 0.48). A negative surgical margin was associated with a significantly lower risk of progression than a positive surgical margin (20.8 versus 50.0%, p = 0.0016), and progression was delayed by approximately 1 year after hormonal pretreatment. However, at a median followup of 38 months there was no difference in progression-free survival (p = 0.57).

Conclusions

Although hormonal pretreatment significantly decreased the positive margin rate, it did not result in any difference in progression-free survival when followup exceeded 3 years. Thus, our current results do not support the routine administration of hormonal treatment before radical prostatectomy.     

Cyclic AMP potentiates glucose-induced insulin release from mouse pancreatic islets without increasing cytosolic free Ca2

RORSMAN P. & ABRAHAMSSON, H. 1985. Cyclic AMP potentiates glucose-induced insulin release from mouse pancreatic islets without increasing cytosolic free Ca²⁺. Acta Physiol Scand 125 , 639–647. Received 18 March 1985, accepted 28 May 1985. ISSN 0001–6772. Department of Medical Cell Biology, Biomedicum, University of Uppsala, Sweden. The effects of various stimulants of insulin release on cytosolic free Ca²⁺, [Ca²⁺]i, in dispersed and cultured pancreatic β-cells from ob/ob-mice were studied using the indicator quin-2, which in itself has only slight effects on the glucose-induced insulin release and the metabolism of the sugar. The resting [Ca²⁺]_i was 158 ± 7 nM. After increasing glucose to 20 mM there was a lag-period of 1–2 min before [Ca²⁺]_i gradually rose, reaching a new plateau 60% higher after 5–6 min. Increasing intracellular cyclic AMP by adding forskolin did not further increase [Ca²⁺]_i; on the contrary there was a slight temporary reduction despite a doubling of insulin secretion. The maintenance of the β-cell function was evident from a marked increase of cytosolic [Ca²⁺]_i after depolarization evoked by high extracellular K⁺. Also dibutyryl cyclic AMP and theophylline lacked the ability to raise [Ca²⁺]_i beyond that obtained by glucose. The results suggest that cyclic AMP potentiates glucose-induced insulin release by sensitizing the secretory machinery to changes of [Ca²⁺]_i rather than by increasing the cytosolic concentration of the ion.     

Endogenous NPY acting on the Y1 receptor accounts for the long-lasting part of the sympathetic contraction in guinea-pig cava: evidence using SR 120107A

The role of cholinergic nerves in the cyclic activation of interdigestive motility and secretion was studied in 23 healthy volunteers. Net fluid transport in a distal duodenal segment and the release of pancreaticobiliary secretions into the duodenal lumen, were measured with a triple lumen perfusion technique. Interdigestive motor activity was recorded with a low-compliance pneumohydraulic system, and the transmural potential difference (PD) was measured as an on-line marker of electrogenic anion secretion. Transport parameters were related to the migrating motor complex (MMC) in the control situation and after the administration of atropine (0.01 mg kg^-1 body wt, i.v.). The early part of the MMC cycle was characterized by low motor activity, low release of bile and pancreatic juice into the duodenal lumen, a slightly lumen positive transmural PD, and a non-significant net fluid absorption (‘absorptive mode’)- Under control conditions, motor activity and pancreaticobiliary secretions subsequently increased and there was a shift in net fluid transport and transmural PD in the secretory direction (‘secretory mode’). Furthermore, there was a significant correlation between contraction frequency, a more lumen negative PD, and the magnitude of net fluid secretion. After the administration of atropine, the secretory mode was abolished, but there was still a significant correlation between contraction frequency and transmural PD. In conclusion, cholinergic neurones seem to mediate the shift from the absorptive to the secretory mode in the human distal duodenum. The antisecretory effect of atropine may be the result of inhibition of motilin release, reduced activation of tension-sensitive intramural secretory pathways, or blockade of cholinergic neurones to the secreting epithelium.     

Lidocaine and Nisoldipine Attenuate Almokalant-Induced Dispersion of Repolarization and Early Afterdepolarizations In Vitro

Attenuation of Almokalant-Induced Proarrhythmias In Vitro. Introduction: Treatment with Class III antiarrhythmic agents may lead to increased dispersion or repolarization and early afterdepolarizations (EADs), which are both likely substrates for torsades de pointes. Recent studies in vivo have shown that the prevalence of proarrhythmias induced by Class III agents may be reduced by Na⁺ or Ca²⁺-blocking agents. In the present study, tentative mechanisms for this protective effect were investigated in vitro. Methods and Results: Transmembrane action potentials were recorded simultaneously from rabbit isolated ventricular muscle (VM) and Purkinje fibers (PF). At a basic cycle length (BCL) of 500 msec, the Class III agent almokalant (0.1 μM) increased the dispersion by prolonging the action potential duration (APD) significantly more in the PF (33%± 4.2%, n = 18) than in the VM (17%± 5.9%, n = 18. P < 0.05). In six of the preparations, addition of 1, 5, and 25 μM lidocaine reduced the almokalant-induced prolongation in a concentration-dependent manner mainly in the PF, thereby decreasing the dispersion. At 5 μM lidocaine, the remaining prolongation was 7%± 12.2% (P < 0.05 vs time controls) in the PF and 14%± 6.4% in the VM, respectively. In six other preparations, the addition of 0.01, 0.05, and 0.25 μM nisoldipine did not reduce the almokalant-induced prolongation in the PF and VM, hut attenuated the spike-and-dome appearance of the action potential in the PF. In separate experiments performed at a BCL of 1000 msec, EADs developed in 2 of 6 and 5 of 6 PF during superfusion with almokalant (0.3 and 1 μM, respectively) at an API) of 828 ± 41.4 msec. In six separate preparations pretreated with lidocaine (5 μ) the almokalant-induced prolongation in the PF was less pronounced and EADs were not observed. Pretreatment with nisoldipine (0.05 μM) did not influence the response to almokalant, and in 4 of 6 preparations the APD exceeded 1000 msec. Despite this extensive prolongation, EADs did not appear. Conclusion: At concentrations that did not affect the APD in the VM hut reduced the APD in the PE. lidocaine suppressed almokalant-induced dispersion and the development of EADs. Nisoldipine, (m the other hand, inhibited almokalant-induced EADs directly. Hence, (he primary APD-prolonging effect of a Class III agent may he preserved, but the risk of proarrhythmary reduced, during concomitant treatment with low concentrations of a Na⁺- or Ca²⁺ blocking agent.     

Activity of dopamine-β-hydroxylase (DBH) and phenylethanolamine-N-methyl transferase (PNMT) in heart,lung and chromaffin tissue from the Florida spotted gar,Lepisosteus platyrhincus (Holostei)

The activities of dopamine-β-hydroxylase (DBH; E.C. 1.14.17.1) and phenylethanolamine-N-methyl transferase (PNMT; E.C. 2.1.1.10) were estimated in homogenates from the heart. the lung and the posterior cardinal veins from Lepisosteus platyrhincus. Both enzymes could be detected in all three tissues, the activity being highest in the chromaffin tissue of the posterior cardinal veins. The activity of DBH estimated in the present in vitro experiments was about 100-fold higher than the PNMT activity. Preliminary experiments with substrate specificity for the PNMT shows a low (heart) or undetectable (lung and cardinal veins) methylation of phenylethylamine, and the specific PNMT inhibitor SK&F 64139 (1μM) lowered the PNMT activity in all three tissues by 55–75%. The presence of PNMT in the adrenergically innervated tissues puts Lepisosteus with the teleosts and the amphibians among vertebrates with capacity for truly adrenergic, as opposed to noradrenergic, transmission.     

Axonal transport of adrenaline,noradrenaline and phenylethanolamine-N-methyl transferase (PNMT) in sympathetic neurons of the cod,Gadus morhua

The axonal transport of adrenaline, noradrenaline and phenylethanolamine-N-methyl transferase (PNMT) has been studied in vivo in sympathetic neurons of the splanchnic nerve in the cod, Gadus morhua. Adrenaline and noradrenaline are transported at a mean axonal transport rate of 16 mm/day. After correction for a non-mobile fraction of adrenaline and noradrenaline, which does not contribute to the amine accumulation proximal to a ligature, a maximal rate of transport was calculated to about 45 mm/day for both amines. The increased level of catecholamines in front of a ligature could be depleted by reserpine treatment, which strongly suggests that both amines are stored in granules. PNMT is transported at a slow rate of 2 mm/day. The subcellular distribution of the cod PNMT was exclusively non-particular. The cod PNMT was further characterized by studying substrate specificity, temperature and pH optima. It is concluded that adrenaline and noradrenaline, stored in granules, are transported in a proximo-distal direction at a high rate compared to PNMT.