Increased platelet aggregability in young patients with stroke. Diagnosis and therapy.

Four patients ages 20 to 38 years had repeated cerebrovascular occlusions. Three of the four patients had vascular headaches (classical migraine in two) for some years before their first occlusive event occurred. When first seen at the time of their major cerebrovascular occlusion, all had evidence of plasma hyper-coagulability, and two of the women were receiving birth control pills. Many months later, while off the "pill" and on warfarin sodium (Coumadin) therapy, two women and one man continued to have new cerebrovascular symptoms. For the first time, their platelet aggregability was tested to several biological substances known to come in contact with platelets in vivo. At this time, all four patients were found to have platelet hyperaggregability. The three symptomatic patients also had a shortened platelet survival time. Long-term management of these patients with chronic platelet aggregability and chronic plasma hyper-coagulability is described.

Pyridinolcarbamate and experimental atherosclerosis. Correlation of hypocholesterolemic and antiatherogenic effects.

Rabbits were maintained for 12 weeks on either a control or hypercholesteremic dietary regime, or on comparable diets supplemented with pyridinolcarbamate (PDC) at a level of 30 mg/kg body weight/day. Blood was obtained from all rabbits prior to study and at two-week intervals for analysis of serum cholesterol, phospholipid phosphorus and triglycerides. Animals from each group were sacrificed at 4-week intervals for quantitative assessment of the degree of atherosclerotic involvement of the aorta. All animals in the four groups consumed their entire daily allowance (100 g) of their respective diets, and weight gains throughout the feeding period were comparable in the 4 groups. PDC given with the control chow diet had no effect on serum cholesterol levels but did result in persistent decrease in serum triglycerides and a variable decrease in serum phospholipids during the 12-week feeding period. None of the rabbits on the chow diet, with or without PDC, had any evidence of aortic lesions during the experimental period. Rabbits fed 1% cholesterol administered with chow exhibited markedly elevated levels of serum cholesterol and phospholipids, while serum triglycerides were not significantly different than in the control group. In these animals there was a rapid and progressive increase in aortic atherosclerosis throughout the study, and at 12 weeks plaque involvement was 74 +/- 8% of the aortic surface. Addition of PDC to the 1% cholesterol--chow diet resulted in significantly lowered levels of serum cholesterol and phospholipids, but these remained elevated compared to the control levels. There was also a dramatic reduction in the rate and extent of aortic plaque formation. Thus, after 12 weeks on diet, only 27 +/- 6% of the aortic surface showed evidence of atheroma. The data suggest that PDC significantly decreases the hypercholesteremia resulting from feeding 1% cholesterol to rabbits, and that this may be largely responsible for the antiatherogenic effect of this drug.

Anti-proliferative effect of pyridinolcarbamate and of aspirin in the early stages of atherogenesis in swine.

When young swine are fed a suitable hyperlipidemic (HL) diet the number of cells in intimal cell masses (ICM) of large and medium-sized arteries begins to increase in number; by 90 days on the diet the cell increase is several-fold compared to no significant increase in cell numbers in ICM of mash-fed controls. The objective of the current study was to see if the cell increase associated with the HL diet could be reduced by pyridinolcarbamate or aspirin. Arteries studied were the abdominal aorta and the coronaries; time on HL diet was 90 days. Both drugs resulted in significant reductions in the increases in cells in ICM associated with the HL diet in both of the arterial beds that were studied. The reduction was most prominent in the abdominal aorta where the increase in ICM cells in the untreated HL diet-fed swine was from an average of 242 +/- 50 cells per cross-section in the mash-fed controls to 1925 +/- 556; in the pyridinolcarbamate-treated swine the increase was only to 641 +/- 214 and in the aspirin-treated group to 770 +/- 146.

Progression of occlusive atherosclerosis. Long-term administration of pyridinol carbamate.

The effects of pyridinol carbamate, a drug with demonstrated capacity to inhibit development of atherosclerotic plaques in the rabbit, were studied in humans with symptoms of arterial occlusive disease in the lower extremities. Microcirculation, perfusion, claudication distance, peripheral pulsations, and angiographic appearances were supplemented by clinical impressions over a two-year period. Although the drug was discontinued in several patients from a larger group because of gastrointestinal tract symptoms, and for other reasons, seven of eight patients receiving it showed no progression of their disease, whereas all 15 patients receiving identical-appearing placebos did. Although the number of patients is not sufficient to warrant statistical conclusions, the observations were totally objective and strongly encourage further control of studies.

A multiclinic double-blind trial of pyridinolcarbamate and inositol niacinate in ischemic ulcer due to chronic arterial occlusion.

A double-blind multiclinic trial compared the efficacies of pyridinolcarbamate and inositol niacinate in the patients with the ischemic ulcer due to chronic arterial occlusion. A thrice-daily dose of 1.5 g of pyridinolcarbamate or 1.2 g of inositol niacinate was given at random to the patients during cold seasons, and the effectiveness of treatment was assessed mainly on the basis of the clinical course of the ischemic ulcer and the rest pain. The patients were classified into 4- and 6-week groups. Beneficial results were recorded in 16 of 32 cases (50.0%) of the 4-week pyridinolcarbamate group, and in 24 of 42 cases (57.1%) of the 4-week inositol niacinate group. In the 6-week group favorable results were observed in 54 of 79 cases (68.4%) on pyridinolcarbamate, and in 36 of 74 cases (48.6%) on inositol niacinate. Although sympathectomy is currently indicated for these ischemic lesions, long-term treatment with pyridinolcarbamate is recommended on the basis of the finding that the 6-week treatment appears superior to the 4-week treatment and also to the 6-week treatment with inositiol niacinate.

[The efficacy of pyridonolcarbamate in diabetic angiopathy]. / L'efficacia del piridinolcarbamato nell'angiopatia diabetica

A group of atherosclerotic patients, some of whom were diabetics with clinical and instrumental signs of angiopathy, was treated with pyridinolcarbamate which was found to be elective for diabetic angiopathy. This was seen in the improvement in haemocoagulative alterations (platelet adhesiveness and clumping), that in certain lipidico-plasmatic alterations (normalization or reduction of glycoproteins) and in anatomofunctional modifications at wall level (rheographic modifications and changes in the diffusion curves with Alb labelled with I 131). These improvements were not observed in atherosclerotic subjects.

[Therapeutic efficacy of pyridinolcarbamate (Anginin) in patients with combined cerebral and peripheral arteriosclerosis]. / Stosowanie Angininy w skojarzonej miazdzycy naczyn mózgu i dolnych konczyn.

A group of 20 patients (average age 55.5 yrs) with advanced arterioscleorosis obliterans and cerebral thrombosis were treated with pyridinolcarbamate. Anginin was given for 6 months, 1,5--2 g. per day. Observation period before, during and after the treatment lasted 2 yrs. Medical and psychological examinations were performed; laboratory test included: sphigmooscylography, photoplethysmography, EKG, EEG, cholesterol, triglyceridis and other routine biochemical blood tests. All data are statistically evaluated. Results. During Anginin treatment clinical improvement was noted in 8 cases, in 9 there was no change in neurological examination; 3 cases--deteriorated. Control examination 6 to 12 months after discontinuation of the treatment revealed no changes in 13 patients; 1 patient deteriorated and 6--died. There was improvement in blood circulation as shown by plethysmography and sphigmooscylography in patients with less advanced vascular changes and no change in cases with more advanced disease. In 75% of the patients there was statistically significant (p less than 0.001) decrease of cholesterol and in 50% of triglicerids (not statistically significant). In patients with advanced disease there was no clinical and EEG improvement, on the contrary 1/3 of them deteriorated clinically and in EEG. In cases with less advanced disease clinical improvement was recorded. Anginin seems to be a good drug for patients with moderately advanced combined peripheral and central arteriosclerosis.

[Clinical and rheoencephalographical evaluation of prodectin in the treatment of cerebral arteriosclerosis]. / Kliniczna i reoencefalograficzna ocena dzialania prodectinu w miazdzycy naczyn mózgowych.

The reported investigations were carried out in a group of patients with evidence of cerebral circulatory disturbances aged from 43 to 72 years treated with Prodectin for 5-7 weeks. The dynamics of the clinical manifestations and REG curves were analysed before and after treatment. REG investigations were done using a II type rheograph with Fc-M leads. The basic parameters of the REG waves and reaction to nitroglycerin were evaluated. The results of REG were compared with the results of similar investigations in an age-matched control group. In nearly half the patients a tendency was observed for REG tracing normalization wit clinical improvement. Most frequently shortening of the ascending part of the REG wave was observed.

[Comparison of the effectiveness of anginin and stugeron treatment of cerebral arteriosclerosis]. / Porównanie skutecznosci leczenia anginina i stugeronem w miazdzycy naczyn mózgowych.

Using the method of double-blind trial the effectiveness of treatment with Anginin (pyrridinolcarbamate) and Stugeron (cinnarizine) was evaluated. The somatic and mental condition and the results of motor rehabilitation of the patients were estimated. In all the evaluated elements the results of Stugeron treatment were better. The results were assessed in two groups of 20 cases each of patients with cerebral atherosclerosis observed during two months.

[Evaluation of anginine in the treatment of cerebrovascular disorders (preliminary report)]. / Ocena dzialania angininy w chorobach naczyniowych mózgu (doniesienie wstepne)

The effect of Anginin was assessed in 10 patients with cerebrovascular diseases. Anginin was administered in daily doses of 1.5 g. during a mean time of 5.25 months. The duration of follow-up before, during and after treatment was 2 years. A favourable effect of Anginin was observed on such symptoms as dizziness, disturbances of recent memory, mental fatiguability, difficulties in concentration and irritability. EEG investigations demonstrated a rise in the index of alpha waves, increased frequency and amplitude of alpha waves, and normalization of tracings in cases with pathological abnormalities. The basic laboratory investigations failed to reveal any significant changes. Side effects included transient dyspeptic symptoms were in 5 patients.

[Anginin effect in cerebovascular disorders in the light of psychological studies]. / Ocena dzialania angininy w chorobach naczyniowych mózgu w swietle badan psychologicznych.

Seventeen patients aged 40 to 69 years with cerebral atherosclerosis and peripheral atherosclerotic changes treated for 6 months with Anginin were investigated psychologically. The purpose of the investigation was assessment of the effects of Anginin on certain higher psychic functions and motor fitness, duration of drug effects, and the influence of patients' attitude on health improvement. The investigations comprised a set of 10 psychometric tests assessing objectively the state of different kinds of memory and motor fitness, that is those functions which are most frequently disturbed in cerebral atherosclerosis, and evaluation of the symptoms associated with the disease (in the light of interviews). Each patient was investigated 4 times with parallel sets of tests: before starting treatment, after 3--4 months of treatment, 6 months after the beginnning of treatment, and 6 months after completion of treatment. Seven patients received placebo during the first 2 months. Statistically analysed results showed that during the treatment immediate and delayed visual and auditory memory increased, visumotor coordination improved and disturbances of attention concentration and motor fitness were alleviated. After 3--4 months of treatment the results of the tests for these functions improved further. The effect of Anginin lasted for 6 months after comletion of treatment showing only a slight tendency for decrease. The analysis of symptoms and comparison of the placebo group with the drug group demonstrated a high influence of the attitude of the patient on health improvement, and the psychotherapeutic effect of the drug was considerable. The good effects were obtained in cases with moderately severe and slight intensity of disturbances.

[Psychophysiological aspect of the therapeutic use of pyridinolcarbamate]. / Psikhofiziologicheskii aspekt lechebnogo deistviia piridinokarbamata.

The effect of prodectin was examined in 79 patients with coronary disease after a course of treatment, and in 16 normal subjects. A series of electrocardiographic and hemodynamic parameters were investigated at rest and during bicycle ergometric exercise. Resultant psycho-physiologic shifts were reviewed with the aid of the information test recording the time of response, errors and vegetative changes in response to colour and mathematical stimuli. Pyridinol carbamate was found to produce a psychostimulating effect, with information processing and vegetative control improved significantly. Therefore the drug appears to be advisable for patients with coronary disease exposed to increased information inflow which requires greater concentration of their attention in short time.

[Effect of antikinin agents on the course of experimental myocarditis]. / Deistvie antikininovykh veshchestv na techenie eksperimental'nogo miokardita

The therapeutic action of 5 preparations: specific antikinin substances -- anginin and contrical, and nonspecific -- epsilon-aminocapronic acid, aspirin and indometacine, was tested in 71 rabbits with allergic myocarditis. It has been concluded that in the allergic distruction of the myocardium plasma kinins, which are formed and accumulated in large quantities, take part in the pathogenesis of the disease serving as mediators of the tissue distruction, therefore specific antagonists of kinins and inhibitors of the kinin system should be included as pathogenetic agents into the complex of allergic myocarditis treatment.

[Pharmacotherapy of peripheral arteriosclerosis]. / Farmakoterapiia perifericheskogo ateroskleroza.

Peripheral atherosclerosis was treated in 178 patients: 90 were given pyridinol carbamate for 2--4 months, 40 pentoxyphylline, 30 cetedil, and 18 received butalamine. in intermittent claudication pyridinol carbamate and trental proved most effective, cetedil (straten) was less effective. The favourable effect of pyridinol carbamate is associated with its action both on the state of microcirculation and on the content of lipids. A significant decrease in the level of blood triglycerides was observed during treatment with pyridinol carbamate. Pentoxyphylline reduced blood viscosity and platelet aggregation in patients with peripheral atherosclerosis but had no effect on the blood lipid content. Cetedil did not reduce blood viscosity although it decreased the aggregation of erythrocytes and inhibited the second phase of platelet aggregation. The objective criterion for the improvement of circulation in the affected extremities was increased tolerance to load, particularly in medication with pyridinol carbamate and trental.

[Pharmacological action on the thrombocyte link in hemostasis in the treatment of ischemic heart disease]. / Farmakologischeskoe vozdeistvie na trombotsitarnyoe zveno gemostaza pri lechenii bol'nykh ishemicheskoi bolezn'iu serdtsa.

The expediency of using agents inhibiting the functional property of blood platelets for the treatment and prevention of thrombus formation in the system of arteries is substantiated theoretically and by the findings of experimental and clinical study. Data are cited on the clinical use of acetylsalicylic acid, dipyridamole, clofibrat, and also of such preparations as pyridinol carbamate, nonachlasine, pentoxyphylline, cetedil, heparin, streptokinase and anti-vitamins K for the treatment of patients with ischemic heart disease. The correlations of the clinical effect and the influence of these drugs on various aspects of the functional blood platelet activity is analysed.

[Mechanism of action and clinical effectiveness of the new Soviet-made drug parmidin in the treatment of arteriosclerosis and ischemic heart disease]. / O mekhanizme deistviia i klinicheskoi effektivnosti novogo otechestvennogo preparata parmidina u bol'nykh aterosklerozom i ishemicheskoi bolezn'iu serdtsa.

The pharmacodynamics and efficacy of the new Soviet drug parmidin depending on the state of the coronary reserve are discussed on the basis of the results of observation over 176 patients suffering from chronic ischemic heart disease with affection of the peripheral arteries of the lower extremities. The activity of the drug in patients with atherosclerotic and diabetic affection of the arterial vessels is shown. The pharmacokinetics of parmidin in patients after the administration of a single 1.0 g dose was studied by determining its content in blood and urine 1, 2, 4, 8, 12, and 24 hours later. The effect of parmidin on the blood kinin system in patients with chronic ischemic heart disease was studied.

[The effect of ximedon on cholesterol metabolism and experimental atherosclerosis in rabbits]. / Vliianie ksimedona na metabolizm kholesterina i éksperimental'nyi ateroskleroz u krolikov.

The effects produced by the two pyrimidine derivatives pyridinol carbamate (parmidine) and xymedon on cholesterol metabolism and experimental atherosclerosis were comparatively studied in rabbits. The rabbits were fed either a chow containing cholesterol (200 mg/kg body weight) or the same diet also containing xymedon (30 mg/kg body weight) or pyridinol carbamate (30 mg/kg body weight). Total plasma cholesterol showed 5.5- and 4.7-fold increases in the rabbits receiving only cholesterol or cholesterol + pyridinol carbamate, respectively, as compared with that in the animals on a standard laboratory chow. In the rabbits given cholesterol+xymedon, cholesterol levels were 24% less than that in the animals taking cholesterol alone. In these animals, the aortic atherosclerotic damage index (ADI) was equal to 24.1%, which was 1.8-fold less than that in the cholesterol-fed rabbits. In the rabbits given cholesterol+pyridinol carbamate, ADI was decreased by 1.7 times, but it did not differ from that in the hypocholesterolemic rabbits. At the same time xymidone and pyridinol carbamate reduced the hepatic levels of total and esterified cholesterol. To elucidate the mechanism of action of xymedon, it was studied for effects on cholesterol metabolism in cultured rabbit hepatocytes and murine macrophage J774. Xymedon did not alter the esterification and other parameters of cholesterol metabolism in the cultured hepatocytes. It is suggested that the hypocholesterolemic effect was realized at the level of intestinal rather than hepatic cholesterol metabolic changes. The investigations made on the murine macrophage J744 showed that xymedone reduced cholesterol esterification in macrophages, evidently by inhibiting the activity of the enzyme acyl-CoA: cholesterol acyltransferase. The anti-atherosclerotic effect of xymedon seems to result from reductions in plasma cholesterol levels and cholesterol esterification in blood vascular cells.

[Evaluation of the therapeutic effect of hyperbaric oxygenation and anginin in peptic ulcer]. / Otsenka terapevticheskogo éffekta giperbaricheskoi oksigenatsii i anginina pri iazvennoi bolezni zheludka i dvenadtsatiperstnoi kishki.

Hyperbaric oxygenation (HBO) and pyridinolcarbamat were mainly applied in the treatment of elderly patients with peptic ulcer attended by coronary heart disease and atherosclerosis. To evaluate the condition of intracellular regulators after the treatment, a study was made of the time-course of changes in the content of cyclic nucleotides in blood plasma and gastric mucosa. The use of HBO in the treatment of peptic ulcer raised the efficacy of the multimodality therapy and accelerated the epithelization of erosive and ulcerative defects. The use of pyridinolcarbamat turned to produce a beneficial therapeutic effect and to be protective with respect to the gastric mucosa. Thus it was found desirable to apply the drug to the treatment of ulcers mainly occurring in the stomach. The changes in the content of cyclic nucleotides in blood plasma and gastric mucosa may play an important role in the realization of positive metabolic changes in gastric mucosa, induced by pyridinolcarbamat and HBO in peptic ulcer patients.

[Disorders of organic hemodynamics of the liver and their correction in suppurative cholangitis]. / Narusheniia organnoi gemodinamiki pecheni i ikh korrektsiia pri gnoinom kholangite.

The blood flow in the portal vein and hepatic artery was studied by means of ultrasonic Doppler flow measurement to investigate organic and regional hemodynamics of the liver in purulent cholangitis. The blood flow in the portal vein was found to be significantly diminished in patients with acute cholangitis and hepatic failure. Hepatic microcirculation was studied on a experimental model of obstructive jaundice and obstructive purulent cholangitis in rats by polarographic measurement of hydrogen clearance. Considerable reduction of the volume rate of the local blood flow was noted, and the degree of the reduction was related to the severity and duration of the disease. Decompression of the biliary tract by external drainage improved the local blood flow rate which, however, diminished again in prolonged external drainage. The use of pharmacological agents for correction of microcirculation in decompression of the biliary tract led to total and rapid correction of the volume rate of the local blood flow.

[Pathogenetic basis for using prodectin and teonicol, redergin and aescuzan in complex treatment of chronic gastritis]. / Patogeneticheskie osnovy primeneniia prodektina i teonikola, redergina i éskuzana pri kompleksnom lechenii khronicheskogo gastrita.

The study of the microvessels in bioptates of gastric mucosa and micro haemocirculation in the conjunctiva of 254 patients with chronic gastritis revealed that exacerbation of the gastric process is going on the background of hard terminal bloodstream disorders. They have the generalized character and picture of the typical chronic relapsing trombohaemorrhagic syndrome. The use of Prodectin (250 mg), Teonicolum (150 mg), Redergin (1 tab.) and Aescuzan (25 dr.) 4 times per day during 3 weeks helps to eliminate the microcirculatory disorders and exacerbation of the chronic gastritis.