Multiple sources of calcium for contraction of the human urinary bladder muscle.

1. KCl, carbachol, neurokinin A and endothelin produced concentration-dependent contractions of mucosa-free muscle strips from the dome of the human urinary bladder. The maximal response to carbachol or neurokinin A exceeded that to KCl, while the maximal response to endothelin approached that to KCl. 2. Nifedipine (1 microM) abolished the response to KCl, reduced the response to carbachol or neurokinin A but had no effect on the response to endothelin. Bay K 8644 (1 microM) markedly potentiated the response to KCl but had little or no effect on the response produced by the other stimulants. 3. Superfusion of the strips with a nominally calcium (Ca)-free medium containing EDTA (1 mM) for 30 min markedly reduced the response to carbachol, neurokinin A and endothelin, although a small response was still evident at high concentrations. Likewise, after a prolonged (60 min) superfusion of the strips with a high K (80 mM) Ca-free medium plus EDTA (1 mM) these three agonists still produced a small contractile response. 4. The nifedipine (1 microM) resistant response to carbachol, neurokinin A or endothelin was markedly depressed by LaCl3 (1 mM). In contrast, the nifedipine-(1 microM) resistant response to carbachol was not modified by NiCl2 (0.1 mM) or omega-conotoxin (0.1 microM). 5. Caffeine produced divergent effects depending upon the temperature of incubation: a relaxation at 37 degrees C and a concentration-dependent (2.5-20 mM) contraction at 25 degrees C. The latter was markedly inhibited by procaine (3 mM) but unaffected by nifedipine (1 microM). 6. After a prolonged (60 min) superfusion with a high K, Ca-free medium containing EDTA the response to carbachol (100 microM) was abolished by previous exposure to procaine (3 mM). Conversely, the response to endothelin (1 microM) was unaffected by procaine. The response to endothelin in these experimental conditions was also resistant to LaCl3 (1 mM). 7. These findings indicate that multiple sources of Ca are mobilized for contraction of the human bladder muscle by different stimulants. Dihydropyridine- and voltage-sensitive Ca channels provide the major if not the sole source of Ca for the response to KCl, play some role in the response to muscarinic (carbachol) or NK-2 tachykinin receptor stimulation but are not involved in the response to endothelin. Carbachol, neurokinin A and endothelin all mobilize a Ca pool (either extracellular or located at membrane level) which is LaCl3-sensitive but nifedipine-resistant. Neither T- nor N-type channels appear to be involved in the response to carbachol.(ABSTRACT TRUNCATED AT 400 WORDS)     

Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy

BACKGROUND: Vitiligo is the most common pigmentary disorder with a global incidence from 0.1% to 2% in different geographical areas. Histopathology and histochemistry have shown the reduction of melanocytes in achromic patches, but microscopic changes of lesional and non-lesional skin are still not completely understood. Reflectance confocal microscopy (RCM), based on the different light reflectance index of cutaneous structures, allowed in vivo, en face microscopic evaluation of superficial skin layers with a resolution similar to skin histology. AIM: The purpose of this study was to evaluate RCM features of lesional and non-lesional skin of vitiligo patients. Moreover, re-pigmented areas were taken into consideration in order to evaluate melanocyte response to ultraviolet B (UVB) radiation. SUBJECTS AND METHODS: Sixteen patients of different phototypes affected by active non-segmental vitiligo and 10 controls were enrolled in the study. In vivo skin imaging was done using a commercially available RCM (Lucid, Vivascope 1500. Re-pigmented areas from 6 to 16 patients (after UVB narrow-band therapy) were also examined. RESULTS: Vitiligo lesions showed the disappearance of the bright rings normally seen at the dermo-epidermal junction. Moreover, non-lesional skin of vitiligo patients showed unexpected changes as the presence of half-rings or scalloped border-like features of the bright papillary rings. In re-pigmented areas after UVB narrow band therapy, the presence of activated, dendritic melanocytes was seen. CONCLUSIONS: Considering our results, and following further studies, RCM clinical applications could be used in the therapeutic monitoring and evaluation of the evolution of vitiligo.     

Desipramine and nortriptyline antagonize apomorphine and reserpine hypothermia by a different mechanism

The reversal of hypothermia, induced by reserpine or by a high (16 mg) dose of apomorphine, in male Swiss mice, does not seem to utilize a common mechanism. Desipramine (20 mg kg-1 i.p., 60 min) or nortriptyline (8 mg kg-1 i.p., 60 min) increased temperature in both reserpine (2.5 mg kg-1 s.c., 18-19 h) and apomorphine (16 mg kg-1 s.c., 30 min) treated mice. In apomorphine-treated animals the effect of both drugs was reversed by the mixed dopaminergic D1- D2-antagonist haloperidol (1 mg kg-1 i.p., 90 min), the D1-receptor blocking drug SCH 23390 (0.05 mg kg-1 s.c., 30 min), the alpha 1-adrenoceptor blocking drugs prazosin (3 mg kg-1 s.c., 90 min) and phenoxybenzamine (20 mg kg-1 i.p., 65 min), the beta-adrenoceptor blocking drug (+/-)-propranolol (10 mg kg-1 i.p., 120 min), and the opioid antagonist naloxone (2 mg kg-1 i.p., 15 min). In contrast the selective D2-antagonist (+/-)-sulpiride (100 mg kg-1 i.p., 90 min), and the alpha 2-antagonist yohimbine (2 mg kg-1 i.p., 75 min), failed to effect the reversal of apomorphine hypothermia brought about by desipramine or nortriptyline. Their temperature effects in reserpinized mice were not modified by any of the antagonists tested.     

Effect of psychotomimetics and some putative anxiolytics on stress-induced hyperthermia

Summary Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip). At higher dose, CL 218872 (100 mg/kg, os) and tracazolate (12.5 mg/kg, ip) lose their activity.PK 9084 (5–40 mg/kg, ip) and CGS 9896 (2–20 mg/kg, both ip and os) were also ineffective in preventing SIH. The anti-hyperthermic effect of CL 218872 (25 mg/kg) and tracazolate (7.5 mg/kg) was blocked by the benzodiazepine antagonist Ro 15–1788 (15 mg/kg). CGS 9896 (10 mg/kg, os) also reversed the effect of CL 218872 (25 mg/kg) on SIH.Differently from anxiolytics, MK-801 (0.5–1 mg/kg, os), PCP (2.5 mg/kg, ip) and d-amphetamine (10 mg/kg, ip) evoked hyperthermia in the first set of mice and prevented a further stress-induced rise of body temperature in the last set of mice.     

Coronary permeability and left ventricular function following thrombolytic therapy

We study 40 patients, 55 +/- 7 years old with acute myocardial infarction treated early by thrombolytic therapy (20 STK and 20 rt-PA). All patients were angiographically studied in the following conditions: 1) baseline, before initiating therapy. 2) Three hours after treatment. 3) Twenty four hours later. 4) Before discharge. The infarct related artery was patent 24 hours after treatment in 31 patients (78%); five of them were patent before treatment, and we observed an early reperfusion in 20 patients (57%) and late reperfusion in 6 patients (17%). The number of patients with angiographic evidence of intraluminal thrombus decreased progressively through conditions while the grade TIMI of coronary perfusion increased in the absence of reocclusion. Final regional wall motion of infarct related myocardial zones and their degree of recovery were significantly higher in recanalized patients, as compared with non-reperfused patients. Similarly, left ventricular functional recovery was higher in patients with antegrade of collateral flow to the infarct area, as compared with totally occluded patients.     

Collection efficiency of an ionisation chamber in a pulsed swept beam: chamber size effects

Boag's theory for the collection efficiency of a small ionisation chamber in a pulsed swept beam is generalised by taking chamber size into account. The collection efficiency is given in terms of the chamber radius, the Gaussian scale constant of the stationary beam, and the maximum distance between beam and chamber centres. It is shown that, for cases of practical interest, collection efficiency is independent of chamber size.