[Adrenal cortical carcinoma: an autopsy case].

In the review are available literature data about different types of adrenal cortical carcinomas. The case described for the first time diagnosed incidentaloma in an 86-year-old man has been characterized. This observation is valuable because of the rarity of pathology and the difficulties of clinical diagnostics.

Proton pump inhibitors reduce mycophenolate exposure in heart transplant recipients-a prospective case-controlled study.

This prospective study investigates the impact of proton pump inhibitors (PPI) on mycophenolic acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and tacrolimus. MPA plasma concentrations at baseline (C(0 h)), 30 min (C(0.5 h)), 1(C(1 h)) and 2 h (C(2 h)) were obtained by high-performance liquid chromatography (HPLC) in 22 patients treated with pantoprazole 40 mg and MMF 2000 mg. Measurements were repeated 1 month after pantoprazole withdrawal. A four-point limited-sampling strategy was applied to calculate the MPA area under the curve (MPA-AUC). Predose MPA concentrations with PPI were 2.6 +/- 1.6 mg/L versus 3.4 +/- 2.7 mg/L without PPI (p = ns). Postdose MPA concentrations were lower with PPI at C(0.5 h) (8.3 +/- 5.7 mg/L vs. 18.3 +/- 11.3 mg/L, p = 0.001) and C(1 h) (10.0 +/- 5.6 mg/L vs. 15.8 +/- 8.4 mg/L, p = 0.004), without significant differences at C(2 h) (8.3 +/- 6.5 mg/L vs. 7.6 +/- 3.9 mg/L). The MPA-AUC was significantly lower with PPI medication (51.2 +/- 26.6 mg x h/L vs. 68.7 +/- 30.3 mg x h/L; p = 0.003). The maximum concentration of MPA (MPA-C(max)) was lower (12.2 +/- 7.5 mg/L vs. 20.6 +/- 9.3 mg/L; p = 0.001) and the time to reach MPA-C(max) (t(max)) was longer with PPI (60.0 +/- 27.8 min vs. 46.4 +/- 22.2 min; p = 0.05). This is the first study to document an important drug interaction between a widely used immunosuppressive agent and a class of drugs frequently used in transplant patients. This interaction results in a decreased MMF drug exposure which may lead to patients having a higher risk for acute rejection and transplant vasculopathy.

Combined electronic-topological and neural networks study of some hydroxysemicarbazides as potential antitumor agents.

Structure-activity relationships study was performed for a series of Schiff bases hydroxysemicarbazide as potential antitumor agents by using the electronic-topological method combined with neural networks (ETM-NN). Data for the approach were obtained from conformational and quantum-chemical calculations and arranged first as matrices called electronic-topological matrices of contiguity, by one for each compound. Then specific molecular fragments were found for active compounds ('activity features') from the ETM application. After this, a system of prognosis was developed as the result of training the Kohonen self-organizing maps (SOM) by the most significant fragments.

The structure-inhibitory activity relationships study in a series of cyclooxygenase-2 inhibitors: a combined electronic-topological and neural networks approach.

Structure-activity relationships study was performed for a few series of cyclooxygenase-2 (COX-2) inhibitors by using the Electronic-Topological Method combined with Neural Networks (ETM-NN). Specific molecular fragments were found for active compounds ('activity features') from both series by the ETM application. After this, a system of prognosis was developed as the result of training Kohonen's self-organizing maps (SOM) by the fragments. From the detailed analysis of all compounds under study, requirements necessary for a compound to be COX-2 inhibitor were formulated. The analysis showed that any requirements violation for a molecule resulted in a considerable decrease or even complete loss of its activity. The found activity features identified correctly different marketed drugs and new compounds that had passed pre-clinical and clinical trials; this fact confirms the workability of the system developed for the COX-2 inhibitory activity prediction.

Electronic-topological study of structurally diverse cyclooxygenase-2 inhibitors.

A large series of cyclooxygenase-2 (COX-2) inhibitors with diverse skeletons were investigated by means of the Electronic-Topological Method. A system for the COX-2 inhibitor activity prognostication was built with 6 pharmacophores and 6 anti-pharmacophores. The forecasting ability of the system was also tested on different structures, which differ from those that characterize the series studied.

Electronic-topological study of the structure-activity relationships in a series of piperidine morphinomimetics.

Structure-activity relationships (SAR) are studied in the series of 4,4-disubstituted piperidine morphinomimetics (42 compounds) by means of the Electronic-Topological Method (ETM). In the frameworks of this approach, its input data were taken as the results of conformational and quantum-mechanical calculations. These calculations had been carried out for all compounds from the series under study, taking into account their neutral and protonated by the nitrogen of piperidine cycle forms. The ETM application resulted in a set of pharmacophores and anti-pharmacophores, which formed a basis of a system used to predict analgesic activity. First of all, the system was tested on known analgesics. Testing has shown a good agreement with the experimental data. Then, the system was applied to a few compounds with similar structures but unknown activity. The results of the study could be used for computer screening and design of novel compounds with analgesics properties as new potential drugs.

[Monitoring of arterial pressure in the efficacy assessment of combined drug therapy selection for hypotension]. / Monitoring arterial'nogo davleniia v otsenke effektivnosti vybora kombinirovannoi terapii gipotenzivnymi sredstvami.

A study was made of indices for a long-term monitoring of arterial pressure in patients presenting with moderately severe essential hypertension prior to treatment and against the background of administration of a combined pharmacotherapy. There was an improvement in male subjects with hyperkinetic type circulation on a combination of two drug preparations (atenolol and enalapril maleate) while female subjects derived benefit from three drugs (atenolol and enalapril maleate, hydrochlorothiazide) irrespective of the hemodynamic type of circulation.

[Combination hypotensive therapy in patients with essential hypertension]. / Kombinovana gipotenzyvna terapiia khvorykh na esentsial'nu giperterziiu.

In men and women with moderately severe essential hypertension (EH), efficiency has been analyzed of different schemes of combined hypotensive drug therapy depending on the hemodynamic type of circulation with taking account of basic indices for the 24-hour profile of arterial pressure (AP). It is shown that the baseline indices for a long-term AP monitoring (1-3 days) determine the choice of individualized differentiated therapy consisting of a combination of two (atenolol and enalapril maleate) or three (atenolol, enalapril maleate, hydrochlorothiazide) hypotensive drug preparations. Individual schemes of the above drug therapy permitted not only the correction of identified disturbances in the 24-hour AP profile but also contributed to the improvement of hemodynamic maintenance of graded physical loads, favouring positive changes in the structural-and-functional status of the myocardium, which facts suggest indirectly an improvement of prognosis in EH patients.

[The histamine and serotonin levels in the blood plasma of diabetic patients]. / Soderzhanie gistamina i serotonina v plazme krovi bol'nykh sakharnym diabetom.

Fluorometry was done in 52 patients with diabetes mellitus to determine the blood plasma content of free histamine and free serotonin. The control group was 29 essentially healthy subjects. Significant increase was found out in free histamine during the stage of decompensation of diabetes mellitus (P < 0.01). With compensation of diabetes mellitus setting in, the content of histamine returns to normal (P < 0.01). The blood plasma level of free histamine can be used as an additional criterion in the assessment of compensation of diabetes mellitus. Free histamine is supposed to play an active part in the pathogenesis of diabetic angiopathies.

Structure-odour relationships: results of an applied electron-topological approach.

Relationships between odour and chemical structure of compounds are studied by means of the electron-topological method developed for structure/activity research especially. A brief explanation is given for distinguished features of the method. Application examples are demonstrated for sandalwood, ambergris odour, garlic aroma and meat keynotes in food additives. The structural fragments affecting the odour appearance are revealed and discussed with respect to their electronic and topological peculiarities. The latter are formulated as rules for activity prediction of new compounds with special properties.

[The effect of hepatoprotectors on the level of blood lipid peroxidation in patients with chronic hepatitis]. / Vplyv hepatoprotektoriv na riven' perekysnoho okyslennia lipidiv krovi u khvorykh na khronichnyi hepatyt.

The article addresses the issue of comparative efficacy of those drug preparations having hepatoprotective action (hepatofalk, ursofalk, lipin, lavalon) by parameters characterizing lipid peroxidation (LPO). The above drug preparations enhance resistance of brush membranes, lower LPO processes. It was hepatofalk and lipin that had the most pronounced positive effect on LPO processes in patients with chronic toxic and postviral hepatitis.

Explorative and drinking behavior after prolonged access to alcohol and following chronic piracetam administration in mice.

Male mice with free access to food, water, and alcohol for 44 weeks were deprived of alcohol for 3 days and then segregated into two groups having (HD) and lacking (LD) the alcohol deprivation-induced elevation in intake. On week 47, the HD and LD groups (divided into subgroups matched for drinking) received either vehicle or piracetam (400 mg/kg) for 10 days. On the last treatment day, alcohol was again withheld. Cross-maze exploration and drinking pattern were evaluated on the first and third postinjection days. Control mice, having had no previous access to alcohol, were subjected to the same treatment and tests. There were a greater number of vehicle-treated HDs displaying arm reentries than LDs or alcohol-naive control mice. Further, the control mice drank less alcohol than HDs during the first 1.5 h of renewal access, and more water than the HD or LD group during the remaining 22.5 h. Piracetam improved maze patrolling and arm reentries in alcohol-naive mice, but did not change these measures in HDs and LDs. No effect of piracetam on drinking parameters was revealed.

Effect of chronic piracetam on age-related changes of cross-maze exploration in mice.

Normal aging is known to deteriorate memory, spatial orientation, and perceptual recognition. Experiment 1 examined behavioral manifestations of aging by using a cross-maze exploration test in 2-, 6-, and 10-month-old hybrid mice (CBA x C57BL). A decrease in explorative patrolling and an increase in arm reentries, a latency to start and a total time of exploration were found in 10-month-old mice. In Experiment 2, administration of the cognition enhancer piracetam (2-oxo-1-pirrolidone acetamide) (400 mg/kg, IP, once a day for 10 days) enhanced arm patrolling and decreased reentries in 10-month-old mice to the level displayed by the 2-month-old animals. The results suggest that the cross-maze test may be useful for a preliminary screening of antisenescent drugs.

[Disordered trace element content of the erythrocytes in diabetes mellitus]. / Narushenie soderzhaniia mikroélementov v éritrotsitakh pri sakharnom diabete.

Content of chemical elements (CE) in washed out erythrocytes was studied by nuclear-absorptive spectroscopy in 26 patients with insulin-dependent diabetes mellitus (IDDM), 26 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 29 healthy subjects. It was established that erythrocytes in IDDM contain significantly less amounts of cuprum, manganese and cobalt than in healthy subjects, content of zinc being increased. Contents of iron, cuprum, manganese and zinc were found to be decreased in patients with NIDDM as compared to the control. During the conventional treatment erythrocytes of patients with IDDM revealed increase of cuprum content while in NIDDM rise in amounts of iron, manganese, cobalt and zinc was observed. Changes of erythrocytes CE content in diabetes mellitus are supposed to be of compensatory-adaptive nature, for decompensation of IDDM and NIDDM is associated with more pronounced CE dysbalance. Increased erythrocyte content of zinc in IDDM may be explained by uptake of prolonged insulin used for substituting treatment.

[Changes in the trace element content of the blood in chronic hepatitis]. / Izmenenie soderzhaniia mikroélementov v krovi pri khronicheskom gepatite.

Trace elements were examined spectrophotometrically in 45 patients with chronic hepatitis (persisting--31; chronic--14). Lead and cadmium showed a significant increase both in the healthy and hepatitis patients. A reduction of zinc and increase of copper was found in patients with chronic hepatitis. Changes in the content of microelements depended on the severity of the disease.

[The metabolic and phagocytic activities of the neutrophilic granulocytes in patients with nonspecific ulcerative colitis nd Crohn's disease]. / Metabolicheskaia i fagotsitarnaia aktivnost' neitrofil'nykh granulotsitov u bol'nykh nespetsificheskim iazvennym kolitom i bolezn'iu Krona.

Immune homeostasis is of importance in the pathogenesis of unspecific inflammatory diseases of the colon. The authors studied the state of unspecific resistance of patients with unspecific ulcerative colitis (UUC) and Crohn's disease (KD); 27 with UUC and 21 KD patients with chronic relapsing forms of the disease were examined. Patients in the acute form of the disease showed an activation of the metabolic processes in the neutrophil granulocytes that was more pronounced in UUC and a reduction of the phagocytic activity in KD. During the period of early remission these values were practically normal evidencing the prognostic value of factors of unspecific defense in unspecific inflammatory diseases of the intestine.

[The relationship of immunological reactivity to blood groups]. / Sviaz' immunologicheskoi reaktivnosti s gruppami krovi.

The relationship of blood groups and level of immunological reactivity was studied in 500 patients with different diseases and 246 healthy subjects. Distribution of genetic markers of blood groups in the healthy and patients showed certain characteristic features. It was found that the A (11) blood group in the healthy may be considered a marker of high levels of immunological reactivity resulting in a milder course of diseases in persons of this blood group. It was shown that different pathological states are characterized by variations of immunological reactivity depending on the blood group--on the content of populations and subpopulations of lymphocytes, immunoglobulin of different classes, normal antibodies, grade of immunodeficiency.

[Characteristics of the antioxidant activity of the blood plasma in patients with hypertension]. / Osobennosti antioksidantnoi aktivnosti plazmy krovi u bol'nykh gipertonicheskoi bolezn'iu.

A study of the peroxidation of lipids of erythrocytic membranes and blood plasma, antioxidant activity of the blood plasma in 59 patients with hypertensive disease revealed that the initial stages of the disease exacerbation increase of the antioxidant activity is caused by an intensification of peroxidation of cell membrane lipids. A less distinct increase of the antioxidant activity during remission may be due to changes of the blood plasma lipid composition.

[Determination, by the electro-optical method, of the number of undamaged bacterial cells after extreme exposures]. / Opredelenie élektroopticheskim metodom chisla nepovrezhdennykh bakterial'nykh kletok posle ékstremal'nykh vozdeistvii.

The results of electro-optical measurements can be used to determine rapidly how the number of intact cells decreases before and after the action of certain extreme factors. The experiments were conducted with suspensions of Escherichia coli and Bacillus thuringiensis cells subjected to the action of heat, toluene, ethanol, and freezing. Electro-optical measurements can make it possible to assay the relative number of cells with both lethal and sublethal damages.