Wedensky phenomenon by d-tubocurarine or prostigmine in the isolated rat diaphragm. Effects of the medium cooling and of changes in the Ca++-concentration.
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Biomedical subjects
Publications and source records attributed to L Munari.
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Previous observations had shown that, in the isolated rat preparations, calcitonin facilitates the excitement transmission from autonomic nerve-endings to smooth muscle. The present research, was designed to verify whether this facilitation effect could be present in somatic nerve-endings too. For this reason, we used the isolated frog "sciatic nerve-gastrocnemius muscle" preparation where the calcitonin influence on the beginning of a complete tetanic response was studied. The motor nerve-endings were stimulated at different frequencies. It was observed that the added calcitonin and/or an increased [Ca++] medium induced a complete tetanic response also at stimulating frequencies that, in the controls, provoked only a clonic response. Moreover, both the calcitonin and the increased [Ca++] medium frequently induced an increase in the mechanical muscle tension developed. These facilitating effects were reduced or even abolished with inhibition of Ca++-passage through the cell membrane by nifedipine. Therefore, we could hypothesize that the added calcitonin causes increased Ach-release from the somatic nerve-endings and that this action depends on facilitated Ca++-passage through the cell membrane of the nerve-endings and of the muscle fibres too.
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In 122 patients aged between 14 and 58 years with different degrees of hypertension, mean 24-h ambulatory blood pressure (BP) and casual BP were measured to evaluate the relationship with hypertensive target organ damage. The following results were obtained: (1) In agreement with previous reports, this study found a better relationship between target organ damage and mean ambulatory BP than with causal BP, although the correlation coefficients were similar for both. (2) A higher degree of cardiovascular complications occurred in patients with higher variability in BP. These data emphasize the superiority of BP monitoring over causal BP for the study of hypertension and its complications.
As suggested by literature about the carnitine's choline-mimetic effects, it has been studied the influence of this substance on the response to Ach of the isolated coronary arteries. It has been seen that Ach has often induced the contraction of the preparation that was preceded or abolished by atropine or prifinium bromide, or reduced by fendiline and verapamil. It resulted also that carnitine has always increased the entity of the contraction of the preparation treated with Ach and that the raising was abolished by fendiline or verapamil. Taking such results and suggestions from the literature as a basis, it has been concluded that the carnitine increased the response of the preparation to Ach, sensitizing muscarinic receptors which cause the entry of Ca++ throught the cell membrane.
Since it is known that PLP inhibits "in vitro" the COMT much more than pyridoxine; the influence of pyridoxine to the response of hepatic arteries isolated to AD has been compared to the influence of PLP to the same arteries. As for as the increase in percent is concerned, the result is that PLP gives rise to a greater answer to AD than pyridoxine. Such effects lacked when pyrogallol, a powerful COMT inhibitor, was present. Taking such results as a basis, it has been concluded that the mechanism of action of pyridoxine and of PLP was metabolic and that it was based on the COMT inhibition, even for the hepatic arteries. It was been also deduced that the higher efficiency of PLP compared to the pyridoxine's was due to its greater capacity to inhibit the COMT.
Previous observations have shown that the 4-Methylesculetin (4ME) and the calcium provoke an increased response when the motor somatic and autonomic nerve-endings are stimolated. In the present research, we have studied the influence of the bioflavonoid and of an increased medium [Ca++] on the tetanic responses obtained from the isolated frog "sciatic nerve-gastrocnemius muscle" preparation. The 4ME has always facilitated the beginning of a complete tetanic response and has also frequently increased the developed mechanical tension. These effects appeared more evident when the bioflavonoid was employed together with the ascorbic acid. Moreover, an increased medium [Ca++] has induced similar effects. The nifedipine and the flunarizine, well-known Ca++ -antagonists, have constantly reduced or even abolished the facilitating effect induced by the bioflavonoid. On the basis of these results, we could hypothize that these observed facilitating effects are dependent on both an increased Ach-release and an increased muscle mechanical efficiency. Our previous results and also some literature data suggest that these effects could be due to an increased Ca++-passage through the cell membrane of the motor nervendings and of the muscle fibres too.
The aim of this work is to study the mechanism by which 4-Methylesculetin (4-ME) causes the relaxation or inhibits the Angiotensin II (ATN 2) induced contraction in the smooth muscle. The effect of 4-Me, alone or associated with Ascorbic Acid, on basal tone and ATN 2 induced contraction of isolated coronary strips have been studied. Experiments have been carried out in presence of Lysine Acetylsalicylate (LAS) and Indomethacin (IN), known inhibitors of prostaglandin-synthetase. Both LAS and IN decrease but not abolish, the 4-ME induced relaxation and suppressed the depressive effect of 4-ME on the ATN 2 dependent contraction. From R.I.A. tests results that 6-Keto PGF1 alpha (prostacyclines stable metabolite) concentration increased with the addition of 4-ME to the bath. 6-Keto PGF1 alpha concentration was drastically reduced after IN and LAS use. Therefore, it seems reasonable to conclude that 4-ME influence could be mediated by prostacyclines release in the smooth muscle.
The administration of large doses (5 mg/kg b.wt./day) of ethynylestradiol to adult female hamsters did not induce cholestasis or modifications of bile lipid composition. These findings are in contrast with the data of other authors who in different experimental conditions described the sensitivity of hamsters to the estrogen-induced hepatobiliary toxicity. Ascorbic acid alone or added to ethynylestradiol did not impair bile secretion. However, it significantly increased the plasma levels of radioactivity tested 24 hours after the oral administration of a tracer dose of radiolabelled ethynylestradiol. These results confirm previous data showing in humans the capability of ascorbic acid to favour the rise of plasma concentrations of ethynylestradiol.
Doses and schedules for treatment of malignant glial tumors, using IFN are still uncertain and controversial. In this study preliminary results of treatment of 10 glioblastoma multiforme patients are shown. Six patients were treated with local injection of beta-IFN through an Ommaya reservoir: 4 with beta-IFN followed by systemic chemotherapy (CDDP-VP16); we found that IFN alone was ineffective. Results were improved when local immunotherapy was associated with systemic chemotherapy. New drugs and investigation of possible pharmacological synergism are needed.
In this preliminary study twenty-nine malignant glioma patients after surgery were treated using Cis-platin (CDDP) combined with etoposide (VP16). Superfractionated radiation therapy comes into chemotherapy. The time to tumor progression in GBM patients is encouraging result to continue in this treatment.
Adherent lymphokine-activated killer (A-LAK) activity has been recently differentiated in recombinant interleukin-2 (rIL-2) activated PBL. A pilot study on A-LAK + rIL-2 injection into the post-surgical cavity of glioblastoma-operated patients is ongoing. Preliminary data support the feasibility of this technique, which may improve the antitumor response of the host.
Activation of the SPergic pathway may be responsible for the starting of both painful and autonomic symptoms during a typical cluster headache (CH) attack. We utilized Brainstem Auditory Evoked Potentials (BAEPs) and Visual Evoked Potentials (VEPs) to evaluate the possibility of underlying asymmetries in central functions in CH attacks. We studied 14 CH (7 right and 7 left cluster) and 14 normal subjects. All the CH patients showed a significant VEP asymmetry; the mean P 100 amplitude was significantly reduced on the side of the pain and I-V latency of BAEP was increased on the symptomatic side. No check was made for any significant variation underlying asymmetries in the normal subjects. We postulate that such an asymmetry in VEP and BAEP responses could suggest a neurotransmitters disorder with a different manifestation in each hemisphere.
To characterize autonomic imbalance in migraine, we compared the cardiovascular reflex responses of 10 migraineurs and 10 healthy subjects after pharmacological noradrenergic stimulation or inhibition. A battery of 5 autonomic tests was administered on basal conditions as well as after pretreatment with drugs acting at different levels on the noradrenergic pathway: pseudoephedrine, clonidine, guanethidine, indenolol, prazosin. Our data confirm a predominantly sympathetic hypofunction in migraine and provide evidence for an impairment of the central autonomic control.
To investigate the involvement of the autonomic nervous system in Cluster Headache (CH) patients, we compared the cardiovascular reflex responses in a group of CH subjects and a group of controls. We considered five tests: 1) deep breathing test (DB); 2) lying to standing test; 3) heart rate response to Valsalva manoeuvre; 4) blood pressure response to standing; 5) blood pressure response to sustained handgrip. Our data confirm an autonomic dysfunction in CH, particularly regarding the parasympathetic system. Alternative interpretations of these results are discussed.