[Complement componenets, C3 and factors B, in the blood of patients with acute ischemic stroke].

Several studies suggest that activation of compliment cascade contributes to the development of the inflammatory immune response in ischemic stroke and results in tissue injury by initiating apoptosis and necrosis. It is proposed that suppression of the compliment activation may have positive effect on stroke severity and outcome. However, the majority of data relevant to involvement of the compliment in the pathogenethic mechanisms of stroke have been obtained in animal models of stroke that does not allow to extrapolate these data to humans. Our previous studies were the first ones demonstrated the involvement of both the classical and the alternative complement activation pathways in the pathogenetic mechanisms of generation and development of stroke in humans. In the present work, using immunoblotting, we determined the levels of key components of the classical and alternative pathways of complement activation, C3 and factor B, in the blood of patients with ischemic stroke. Comparing to healthy controls, patients with ischemic stroke are characterized by the increased level of C3 and decreased level of factor B.

[Influence of mental and emotional stress on the levels of electrolytes in the saliva of senior schoolchildren]. / Vliianie umstvenno-émotsial'nogo napriazheniia na soderzhanie élektrolitov v sliune starsheklassnikov.

Salivary Na+,K+-excretory function was studied in senior schoolchildren-entrants during an academic year and entrance examinations. The time course of changes in the salivary levels of Na+ and K+ in entrants during an academic year was undulating. In late October that is coincident with the beginning of lessons given by tutors, the salivary content of Na+ reduced while that of K+ increased. The second peak of decreased excretion rates for Na+ and increased excretion rates for K+ and that of less Na+/K+ ratios was observed in May on the eve of entrance examinations. On the eve of the examinations, 70% were observed to have tachycardia, elevated levels of integral parameters of cardiac rhythm regulation, a considerable reduction in the concentration of Na+, and an increase in the level of K+ with less Na+/K+ ratios. The pattern of the observed changes also retained in the postexamination period. On the eve of the examinations, 30% were found to have lowered levels of integral parameters of cardiac rhythm regulation and elevated levels of Na+. After an examination, there was a reduction in Na+ excretion which did not yet achieve the initial level. The mechanisms responsible for ionic shifts in the composition of saliva during psychoemotional stress are discussed.

Dynamics of polymorphonuclear leukocyte accumulation in acute cerebral infarction and their correlation with brain tissue damage.

BACKGROUND AND PURPOSE: This study was performed to study the dynamics of polymorphonuclear leukocyte (PMNL) accumulation in human cerebral infarction and its association with neurological outcome and brain lesion. METHODS: A total of 88 patients diagnosed as having hemispheric ischemic stroke were examined. PMNL accumulation was studied using technetium-99m hexamethylpropyleneamine oxime (99mTc HMPAO)-labeled leukocyte brain single-photon emission computed tomography (SPECT). Volume of brain infarction was evaluated by CT scan. The Mathew Scale was used for neurological assessment. Dynamics of PMNL accumulation was studied at 3 to 6, 6 to 12, and 12 to 24 hours and 6 to 9, 28 to 30, and 90 days after stroke onset. In parallel, at admission, at 6 to 9 days, and at 28 to 30 days neurological outcome and infarction volume were evaluated. RESULTS: Generally, PMNL accumulation progressively increased during 6 to 24 hours after stroke, remained at a high level up to 6 to 9 days and then declined. With the use of cluster analysis, all patients were subdivided into three groups: patients with severe PMNL accumulation that dramatically increased within 12 hours after stroke onset and persisted even at 28 to 30 days (group A); those with moderate PMNL accumulation that significantly decreased at 30 days (group B); and those with mild PMNL accumulation that decreased at 6 to 9 days (group C). Baseline neurological deficit and brain tissue damage at admission appear to be at a similar level for all groups of patients. In dynamics, however, in patients with severe PMNL accumulation, neurological outcome was worse and infarction volume larger than in patients with less marked PMNL accumulation. CONCLUSIONS: The present clinical study confirms that PMNLs intensively accumulate in the regions of cerebral infarction. The present study revealed that this accumulation correlated with the severity of the brain tissue damage and poor neurological outcome.

Nifedipine kinetics and dynamics in hypertensive patients: a new approach.

Nifedipine tablet in a 20 mg dose was administered orally to 44 patients with arterial hypertension. Nifedipine pharmacokinetics showed wide interindividual variation, for instance maximal concentration varied from 10-90 ng/ml, elimination half-life from 2-9 hours, etc. Cluster analysis classified all variants of nifedipine concentration profiles into 3 more homogeneous groups. Group A was characterized by small maximal nifedipine concentrations and its fast elimination; in group C nifedipine concentration reached high level in plasma and elimination half-life was more than 5.5 hours; in group B intermediate variants of nifedipine concentration profiles were separated. Nifedipine effects on mean blood pressure and platelet aggregation differed between these groups significantly. There were no changes in these parameters in patients from group A whereas in group C nifedipine produced profound and long-term reduction of both blood pressure and platelet aggregation. Using cluster analysis it appears to be possible to objectively classify a variant of nifedipine concentration profile to one of these homogeneous groups using only 3 measurements of nifedipine concentration in plasma at 1, 2 and 3 hours after the administration. It has been suggested that this approach simplifies the estimation of nifedipine pharmacokinetics and it might be useful for introducing the pharmacokinetic investigations to clinical practice.

Dynamic component of internal carotid artery stenosis in patients with cerebrovascular disease: effects of nifedipine.

By means of Doppler spectral analysis, it was shown that internal carotid artery stenosis has a dynamic component that determines the possibility of changes in the area of stenosis under various influences. It was demonstrated that cold pressor test may increase the area of stenosis in some patients for up to 3-5 hours. In such cases, reduction of volume blood flow in the commun carotid artery and decrease of cerebral blood flow in the ipsilateral hemisphere of the stenosis are observed. Such a response was effectively prevented by nifedipine. At the same time, nifedipine can itself change the area of stenosis in some patients examined. In 31 cases it decreased the area by 22.9 +/- 5.9% and in 11 cases it increased it by 26.4 + 7.7%. When the decrease in the area of stenosis was observed, nifedipine enhanced cerebral blood flow. However, it provoked a depression of cerebral blood flow in the patients in whom the area of stenosis was increased. The data obtained disclose one of the reasons of the variability of therapeutic effects of vasodilators in patients with cerebrovascular disorders.

Cerebral blood flow and effects of cerebrospinal fluid on calcium transport in patients with cerebral infarction.

BACKGROUND AND PURPOSE: In this study we investigated whether cerebrospinal fluid in patients with brain infarction possesses an activity that contributes to the evolution of brain ischemia. As a test, the effect of cerebrospinal fluid on Ca2+ influx into the intracellular space was chosen because this process is a mechanism for vasospasm, platelet aggregation as thrombi, and neuron damage. METHODS: Effects of cerebrospinal fluid taken from 48 patients with cerebral hemispheric infarction on the concentration of cytosolic free Ca2+ in platelets were studied using the fluorescent probe quin-2. Hemispheric cerebral blood flow was measured using 133Xe intravenous injection. RESULTS: Cerebrospinal fluid in 19 of 48 patients with cerebral hemispheric infarction increased the level of cytosolic free Ca2+ in platelets. The course of the disease in the patients who showed a positive effect of cerebrospinal fluid on Ca2+, when compared with that of patients who showed a negative effect, was characterized by a more severe clinical manifestation and mortality. The decrease in hemispheric cerebral blood flow was more marked in both ischemic and contralateral hemispheres in patients with positive effects of cerebrospinal fluid on the level of Ca2+. CONCLUSIONS: These data suggest that the ability of cerebrospinal fluid to evoke Ca2+ influx into the intracellular space in patients with brain infarction is a factor that aggravates ischemic brain damage.

Dose-dependent aspirin hydrolysis and platelet aggregation in patients with atherosclerosis.

In a double blind, randomized trial, the effects of aspirin (1, 5, and 15 mg/kg) were compared with the changes in platelet aggregation at 6 and 24 hours after dosage. It is found that there is a negative correlation between aspirin hydrolysis velocity in blood and capability of aspirin to decrease platelet aggregation with ADP and collagen in patients with atherosclerosis. Relationship between these parameters depends on aspirin dosage. The correlation was more marked for low doses of aspirin. It is suggested that the effect of aspirin in low dosage on platelet aggregation might be ineffective in many patients without control of aspirin hydrolysis velocity in blood.

[The characteristics of the cerebral circulation in arterial hypertension]. / Osobennosti tserebral'noi tsirkuliatsii pri arterial'noi gipertenzii.

In arterial hypertension, cerebral blood flow (CBF) in patients with chronic cerebrovascular diseases is lower than in patients without hypertension. In stenosis of internal carotid arteries, hypertension leads to the disturbance of the response of resisting cerebral vessels compensating the decrease of perfusion pressure at the expense of vessel dilation. As compared with patients without hypertension, the difference between the values of regional CBF (rCBF) in various regions of the brain is more obvious with the appearance of alternate hypoemic and hyperemic regions. After nifedipine, both an increase and a decrease of hemispheric CBF is possible in these patients. In many of them such changes in CBF are combined with further increase of the difference between rCBF values in various parts of the brain with the formation of well marked zones with relative ischemia and hyperemia.

["Dynamic" component of carotid artery stenosis in patients with cerebrovascular disorders]. / O "dinamicheskom" komponente stenozov sonnykh arterii u bol'nykh s tserebrovaskuliarnymi zabolevaniiami.

Nifedipine is shown to abolish contraction of the vessel at the site of the internal carotid artery stenosis induced by a cold test. It can furthermore produce a direct 5-40% reduction of the stenosis, the effect being dependent both on the drug plasma level and the ability to rise such levels of prostacyclin. In some patients there is a possibility of nifedipine contrary action when it promotes stenosis (up to 5-30% increase) and leads to disturbances of cerebral circulation. Consequently, to make optimal therapeutic measures in relevant patients nifedipine should be tried for stenosis-directed action.

[Pharmacodynamic approach to the optimal use of calcium antagonists in patients with cerebrovascular disorders]. / Farmakodinamicheskie podkhody k optimizatsii primeneniia antagonistov kal'tsiia u bol'nykh s tserebrovaskuliarnymi zabolevaniiami.

Three hours after administration of a single 20 mg dose of nifedipine the platelet, leucocyte and red blood cells aggregation was inhibited with the red blood cells and leucocytes deformability increased. This effect proved sensitive to the plasma nifedipine concentration disappearing with its concentrations below 25 ng/ml. The nifedipine sensitivity of the blood cells was the second factor influencing its effect. This was closely related to prostacyclin. The blood cells sensitivity to the latter, and its plasma concentration and decay rates were major determinants of the nifedipine capability of inhibiting the leucocyte, red blood cells and especially platelet inhibition.

[Status of the prostacyclin-thromboxane balance in patients with cerebrovascular disorders and the effect of the treatment with nifedipine]. / Sostoianie prostatsiklin-tromboksanovogo balansa u bol'nykh s narusheniiami mozgovogo krovoobrashcheniia i vliianie na nego terapii nifedipinom.

It is shown that in patients with cerebral circulatory disorders, the prostacyclin -thromboxane balance is replaced toward the latter one. As a result of nifedipine administration part of the test subjects demonstrate a rise of the content of prostacyclin and a decline of the concentration of thromboxane. This effect of nifedipine is ascertained to be in a good agreement with its action on blood inflow to the brain and platelet aggregation. It is concluded that the efficacy of nifedipine can be raised if it is combined with the drugs that enhance the synthesis of prostacyclins in the body.

[Pharmacokinetics of nifedipine after a single oral dose in patients with disorders of cerebral circulation]. / Issledovanie farmakokinetiki nifedipina pri ego odnokratnom prieme vnutr' u bol'nykh s narusheniiami mozgovogo krovoobrashcheniia.

The pharmacokinetics of nifedipine was studied in 44 patients with disorders of cerebral circulation. A significant variability of the pharmacokinetic parameters in different patients was revealed. According to the results of the cluster-analysis, the main types (classes) of nifedipine pharmacokinetics were established and the possibility of regarding the patient examined as having this or that type during the measurement of the blood nifedipine concentration 2, 3 and 4 hours after administration of the drug was shown. The relationship between the type of nifedipine pharmacokinetics and its antiaggregatory effect was established.