Biomedical subjects
Publications and source records attributed to G Bruno.
The result of topical treatment by dimethyl sulphoxide (DMSO) in a patient with lichen amyloidosus is reported. Itching improved within five days of therapy. Remarkable flattening of the papules was obtained within two weeks. The clinical result was confirmed by histological examination which revealed partially disappearance of amyloid deposits.
As with parkinsonism, certain dystonias may involve disturbances in dopaminergic neurotransmission. The effects of bromocriptine, 18-150 mg/day (mean, 72.5), were studied in 15 patients with a variety of dystonic disorders, using a double-blind, crossover format. Of the 13 patients completing several weeks of medication, seven improved more than 10% and two worsened, on clinical ratings, while five recognized improvement in disability. Dopaminomimetic agents such as bromocriptine, used in the dose range effective for treating parkinsonism, may yield symptomatic improvement with several patterns of dystonia.
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2-(4-(2',4'-Difluorophenyl)-phenoxy)propionic acid (MR 714) is endowed with an interesting analgesic and antiinflammatory activity, while any remarkable gastro-ulcerogenic action is virtually absent. From a toxicological point of view, MR 714 orally administered to mice showed a LD50 of 848 mg/kg; an observation of general behaviour proved that the drug is free of any remarkable effect on general behaviour, food and water intake, or diuresis after single or repeated administration. An autoptic examination after single oral doses (25, 50, 100 and 200 mg/kg) or repeated oral doses (100 mg/kg/day over 5 days) did not show any adverse modification and also the Ames test didn't allow any mutagenic action to be detected. From a pharmacokinetic point of view, MR 714 given p.o. to rats was absorbed excellently and plasma levels showed a peak after 4-6 h, followed by a plateau lasting 24-36 h at a dose of 50 or 100 mg/kg and considerably less at a dosage of 25 mg/kg. This lower dose allowed a dominant half-life (t1/2) of plasma levels of 13 h to be determined. Excretion occurred only via the bile in conjugated form (acylglucuronide) which reverted easily into the parent drug. The resultant enterohepatic circulation contributes to a substantial maintenance of plasma levels and hence long-lasting activity. Among the organs examined, the uterus showed the highest ratio of organ/plasma concentration; this evidence points to a possible clinical application of MR 714 in the treatment of dysmenorrhoea. From a chemical point of view, the aryloxypropionic structure may be regarded as an interesting novelty in the field of structure-activity relationship studies on non-steroidal antiinflammatory agents.
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CDP-choline, an intermediate in the phospholipid metabolic pathway supposed to improve the functionality of the dopamine (DA) system, was administered to parkinsonian patients in a double-blind cross-over study versus placebo. All patients were already treated with L-dopa + dopa decarboxylase inhibitor. Clinical evaluations were carried out using the Webster Rating Scale (WRS), the Northwestern University Disability Scale (NUDS) and a semiquantitative rating scale for tremor, rigidity and bradykinesia. CDP-choline treatment showed a significant improvement of rigidity and bradykinesia and a less important amelioration of tremor. NUDS and WRS showed a similar positive result. Comparing the results obtained by placebo, we found that the actual clinical efficacy of CDP-choline regards mainly bradykinesia and rigidity (23 and 33% improvement, respectively). The positive effect of CDP-choline on parkinsonian patients already treated with L-dopa + dopa decarboxylase inhibitor stands for a possible action on the DA receptor through an activation of the phospholipid metabolism.
The authors studied 54 patients suffering from rheumatoid arthritis by sigma SR method. The sigma SR, unlike the ESR, often reveals inflammatory activity in patients suffering from possible or probable rheumatoid arthritis and is very useful to diagnose the disease. The sigma SR constantly increases when the disease is in active period, unlike the ESR, in patients affected by classic or definite rheumatoid arthritis. The authors conclude the sigma SR determination is useful in every case of rheumatoid arthritis, especially when the disease is at beginning and is difficult to be diagnosed, i.e. cases of possible and probable rheumatoid arthritis, and when clinical and biohumoral picture disagree.
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Apovincaminic acid (AVA) esters are eburnamenine derivatives with a vasodilating action that are mainly metabolized to AVA by enzymatic hydrolysis, in the rat in particular. In an organic solvent/water partition, AVA and AVA ester were quantitatively separated. AVA ester was then chemically hydrolysed into AVA. Unchanged AVA and AVA hydrolysed from its ester were separately methylated and quantitatively analysed by GLC. Using a flame ionisation detector, this method has a sensitivity of 20 ng making possible metabolic investigations to be carried out in vitro and in the urine and can be applied to any AVA ester. The method was applied in a preliminary investigation to MR 711, a methylene-methoxy-apovincaminic acid ester. When incubated in vitro with rat plasma, MR 711 was enzymatically converted into AVA. The urine of rats p.o. treated with 10 mg/kg of MR 711 contained AVA as the main metabolite.
In the present work it was determined the ability of non-steroidal anti-inflammatory drugs (Diflunisal and Indomethacin) to inhibit formation of "granuloma pouch" exudate induced in rats. This study shows that the combined administration of Diflunisal and Indomethacin exerts similar anti-inflammatory activity as the single drugs. There does not seem to be additive anti-inflammatory effects of the drugs in combination but, if anything, a weak antagonism. The association of the two compounds produces a reduced harmful effect on the gastric mucus.
Cultures of lymphocytes from a patient with a suppressed immune-system were set up, and a low response was seen after treatment with mitogenic substances such as PHA and ConA. Other lymphocyte cultures from the same patient were treated with Levamisole, and after this it was noted that the percentage of T-cell rosettes with sheep erythrocytes was increased.
In this work, the authors are concerned with the study of the effects of non-steroidal antiinflammatory drugs in the gastric mucosa of the rat after induced chronic inflammation with potassium permanganate.
The most satisfactory diagnostic procedure for hereditary angioneurotic oedema is the demonstration of low serum levels of C1 esterase-inhibitor. A modified method for the assay of this protein is described. It is based on the kinetic measurement of the C1 esterase-inhibitor when it inhibits the hydrolysis of N-acetyl-L-tyrosine-ethyl ester by C1 esterase. The relative C1 esterase-inhibitor concentration is based on the initial hydrolytic velocity, which can be evaluated from the pH change in a short time and within a small range. High reproducibility, cheap instrumentation and short time of analysis are some of the favorable aspects of this method in comparison with the 'end point titrimetric' method. Furthermore, this paper describes the mechanism of inhibition of C1 esterase by C1 esterase-inhibitor. The results are indicative of a non-competitive mechanism. The value of the Michaelis-Menten constant, Km, is 0.017 +/- 0.001 mol/l at 37 degrees C, in the optimum pH range 7.2-7.4. An estimate of KI in arbitrary units is also given.
The antiarrhythmic effect of metoprolol after chronic treatment has been evaluated by 24 hour Holter monitoring in 16 patients with several premature ventricular beats and in 14 patients with chronic atrial fibrillation and compared with the effect of a placebo. Metoprolol induced a mean decrease of heart rate of 14.5% in the 16 patients and reduced the mean value/min of the ventricular premature beats of the 51.2%. In addition the use of metoprolol abolished the ventricular premature beats in 9 cases, while in two cases there was an increase of their frequency. In the 14 patients with chronic atrial fibrillation metoprolol was able to reverse to sinus rhythm three of the patients and in the remaining 11 decreased the ventricular heart rate of the 33%.
The effect of metoprolol in ECG experiments induced by a treadmill exercise test, was studied in 30 patients with stable angina pectoris. The study was a simple blind cross-over between metoprolol (150 mg/die) and placebo. The evaluation of ECG recordings (V5 lead) was carried out by a computer program. In order to assess the ST-segment depression, the ST 0.8 (Depression at 80 msec after R-peak) and AST (ST area) values were used. We observed an increased exercise tolerance after administration of metoprolol (P less than 0.001) and a significant reduction of ST segment depression for ST 0.8 (P less than 0.01) and AST (P less than 0.005) at the maximal commun work load attained by every patient in the metoprolol and placebo tests. When the evaluation of ECG measurements were performed at the maximal commun double product no significant modifications were observed.
On the purpose of specifying more and more the peculiarity of the isoenzymes MBCK in regard to enzyme CK, in the diagnosis as well as in the quantitative evaluation of myocardial infarction, we examined 34 patients hospitalized in U.C.I.C. The curves of the MBCK and CK were obtained through samples taken every 2-3 hours still the 12th hour, after the enzymatic concentration have exceeded the normal level and successively every 4 hours till the enzymatic activity regains its limits. The values of I.S.MBCK and I.S.CK were compared and we obtained two correlations based on the enteric work (r = 0.79) or on selected cases (r = 0.96). We conclude, for the major practicality and usefulness of measurement of MBCK in the evaluation of size, because this measurement can be obtained on the total enumeration of cases of myocardial infarction, not takine into consideration all those factors which could produce an increase of CK; moreover the MBCK is able to show the extension of myocardial infarction that would not be detectable with CK.
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