Concentration of copper and zinc in blood of psoriatic patients treated topically with ointment containing 2-chloroethyl-3-chloropropyl sulfide.

Copper and zinc concentration in plasma, erythrocytes and whole blood was determined in a group of psoriatic patients (n = 80 ) before and after treatment with an ointment (in accordance with recommendations of the Helsinki Declaration) in which 2-chloroethyl-3-chloropropyl sulfide (CLEPS) is an active compound and in a comparative group (n = 99) of clinically healthy volunteers. The performed examinations revealed a significantly lower (by 19.1%) plasma copper concentration in patients before treatment in comparison with the control group. After treatment (CLEPS) plasma copper concentration increased significantly (p < 0.001). In comparison with the control group, in erythrocytes of psoriatic patients copper concentration was higher both before and after treatment. Plasma zinc concentration in psoriatic patients was lower before treatment, whereas in erythrocytes, compared with the control group, it was higher both before and after treatment.

Adenosine deaminase activity in blood of patients with stable angina pectoris.

The activity of adenosine deaminases (EC.3.5.4.4) in granulocytes and lymphocytes of patients with stable angina pectoris was lower by about 27% and 24%, respectively as compared with control group, whereas these values in erythrocytes and blood plasma were at the normal level.

5'-nucleotidase and adenosine deaminase activities in blood of patients with unstable angina pectoris.

During ischaemia and hypoxia adenosine is released from cardiac cells. Adenosine is the end product of 5'-nucleotidase activity. We were interested in how this enzyme activity in plasma of patients with unstable angina pectoris, causes short-term ischaemia. 5'-Nucleotidase activity in plasma was determined using a standard diagnostic kit from Sigma. Furthermore, we studied the activity of adenosine deaminase in plasma, granulocytes, lymphocytes and erythrocytes by the methods of Hopkinson [1]. It was found that 5'-nucleotidase activity was increased by about 43% in plasma. The activity of adenosine deaminase (ADA) in plasma increased by 6%, but in granulocytes, lymphocytes and erythrocytes decreased by about 24, 19 and 10.6%, respectively. We concluded that a large increase in 5'-nucleotidase activity may be caused by activation of 5'-ectonucleotidase in blood cells by ischaemia. However, the decrease in ADA activity in blood cells may be associate with the adenosine metabolism.

Red blood cell superoxide dismutase and catalase activities in patients suffering from multiple sclerosis treated with adrenocorticotropic hormone.

The purpose of this study was to determine superoxide dismutase (SOD) and catalase (CAT) activities in erythrocytes of patients with multiple sclerosis treated with ACTH. SOD activity in hemolysates was determined according to the method of Misra and Fridovich and calculated as units per gram of hemoglobin (Hb). CAT activity in hemolysates was determined with Beers and Sizer's method and expressed in IU/g Hb. SOD activity in control group was (1.61 +/- 0.45) x 10(3) U/g Hb whereas, the activity of CAT amounted to (5.88 +/- 1.36) x 10(4) U/g Hb. Before the treatment, SOD activity was decreased by approximately 20% ((1.25 +/- 0.25) x 10(3) U/g Hb) while that of CAT-by about 7.7% ((5.43 +/- 0.68) x 10(4) U/g Hb) in comparison to the normal control. After treatment with ACTH, activity of both enzymes increased: SOD-by about 34.4% to (1.68 +/- 0.38) x 10(3) U/g Hb and CAT-by about 7% to (6.29 +/- 0.55) x 10(4) U/g Hb. Results of investigations showed that ACTH caused an increase in CAT and SOD activities in erythrocytes of patients after three-week treatment.

Activity of adenosine deaminase in red blood cells of patients suffering from multiple sclerosis treated with adrenocorticotropic hormone.

Adenosine deaminase (ADA) activity was studied in red blood cells of patients suffering from multiple sclerosis treated with adrenocorticotropic hormone (ACTH). ADA activity in hemolysates was determined according to the method of Hopkinson and calculated as units per g of hemoglobin. Activity of adenosine deaminase in healthy subjects was 0.871 +/- 0.251 U/g Hb. In patients with multiple sclerosis, before treatment ADA activity was 0.765 +/- 0.131 U/g Hb and was about 15.2% lower than in the control group (p < 0.02). After treatment with ACTH, ADA activity increased to 1.005 +/- 0.211 U/g Hb (p < 0.001). We have suggested that increased activity of adenosine deaminase in red blood cells of patients suffering from multiple sclerosis after treatment with ACTH is caused by diminution of superoxide generation, and therefore its sparing effect on cell membrane and enzyme is connected with membranes.

Superoxide dismutase and catalase activity in psoriatic patients treated topically with ointment containing 2-chloroethyl-3-chloropropyl sulfide.

The purpose of this study was to determine dismutase and catalase activities in erythrocytes of psoriatic patients with psoriasis vulgaris topically treated with an ointment (in accordance with recommendations of the Helsinki Declaration), in which 2-chloroethyl-3-chloropropyl sulfide (CLEPS) is an active compound. SOD activity in hemolysates was determined according to the method of Misra and Fridovich [12] and calculated as units per g of hemoglobin. CAT activity in hemolysates was determined by Beers and Sizer method [2] and expressed in U/g Hb. SOD activity in the control group was 1.61 +/- 0.48 U/g Hb x 10(3). However, the activity of CAT was 5.72 +/- 1.17 U/g Hb x 10(4). Before treatment SOD activity was decreased by ca. 22.5% (1.25 +/- 0.53 U/g Hb x 10(3)) while that of CAT by about 7% (5.30 +/- 1.41 U/g Hb x 10(4)), in comparison with the normal control. After treatment with the ointment, activity of both enzymes increased by about 18% to 1.55 x 10(3) U/g Hb and by about 16.5% to 6.25 x 10(4) U/g Hb, respectively. The results of our investigations showed that the ointment (containing mustard gas derivative) applied on psoriatic skin, causes increased of SOD and CAT activity in erythrocytes after regression of psoriatic lesions and treatment termination.

Some pharmacological properties of perhydro-1,4-thiazepine and perhydro-1,2,5-dithiazepine derivatives.

Some newly synthesized perhydro-1,2,5-dithiazepine derivatives have antihistaminic, anticholinergic and spasmolytic properties. One perhydro-1,4-thiazepine derivative, compound 3, produces also a weak local anesthetic effect. The activity of the investigated compounds is lower than that of reference compounds; diphenhydramine, antazoline and papaverine.

Effect of dipyridamole on inosine triphosphate pyrophosphohydrolase activity and inosine triphosphate content in fresh human erythrocytes incubated with adenosine.

The activity of inosine triphosphate pyrophosphohydrolase (ITPH) in human erythrocytes was found to be 1.50 +/- 0.39 mumol of inosine triphosphate (ITP) hydrolysed x min-1 per g Hb, and no measurable amount of ITP was detected. When dipyridamole was added to the medium composed of adenosine, pyruvate and inorganic phosphate, ITPH activity was 1.18 +/- 0.41, and at the same time ITP accumulation was 0.61 +/- 0.31 mumol/g Hb. The negative correlation between ITPH activity and accumulation of ITP was r = -0.87 at P less than 0.001.

Relationship between adenosine deaminase activity (ADA) and inosinemonophosphate (IMP) accumulation in fresh erythrocytes incubated with adenosine and dipyridamole.

Fresh human erythrocytes were incubated in two media: a) adenosine (10 mM), pyruvate (10 mM), phosphate (50 mM) (APP medium); b) APP medium enriched with 100 mumol/l dipyridamole (APPD) medium. The amount of IMP in fresh erythrocytes was 0.18 +/- 0.09 mumol/g Hb, after incubation in APP medium it was 1.52 +/- 0.78 mumol/g Hb, and after incubation in APP medium it was 1.52 +/- 0.78 mumol/g Hb, and after incubation in APPD the amount was 5.28 +/- 0.94 mumol/g Hb. ADA activity was measured simultaneously. The mean activity (+/- SD) of ADA fresh red cells was 1.29 +/- 0.36 U/g Hb, after 2 h incubation in APP medium it was 1.71 +/- 0.38 U/g Hb, and after 2 h incubation in APPD medium an activity of 2.68 +/- 0.95 U/g Hb was found. A highly significant correlation between the accumulation of IMP and the activity of ADA in fresh erythrocytes (r = 0.93; p = less than 0.001) and in erythrocytes incubated in APPD medium (r = 0.97; p = less than 0.001) was found.

Studies on mutagenicity of 3-chloropropylsulfide derivatives, potential antipsoriatic agents.

The mutagenicity of three sulfides--sulfur yperites--was investigated in vitro by a method of chromosome structural aberrations and sister chromatid exchange (SCE) on metaphasic chromosomes of the peripheral blood. The study demonstrated a relatively low mutagenicity of 2-chloroethyl-3-chloropropyl sulfide and permitted initiation of clinical investigation of this compound as a potential antipsoriatic agent.

Synthesis of perhydro-1,2,5-dithiazepine derivatives of potential pharmacological activity.

New derivatives of perhydro-1,2,5-dithiazepine, 1-18, were synthesized. Compounds 1 and 16 showed spasmolytic and antihistaminic activity stronger than their analogs containing perhydro-1,4-thiazepine system.

Synthesis of perhydro-1,4-thiazepines, of expected pharmacological activity. Part III. 4-(2-hydroxyethyl)-perhydro-1,4-thiazepine esters.

New esters, derivatives or the title aminoalcohol, were obtained by three classical methods in the reaction of 4-(2-hydroxyethyl)-perhydro-1,4-thiazepine (HEPT) with chlorides (method a), acid potassium salts (method b), and sodium HEPT salts with acid chlorides (method c). Compounds 3 and 5 have weak spasmolytic properties; 5 in a dose of approx. 50 mg/kg strongly depressed the central nervous system.

Synthesis of hexahydro-1,4-thiazepine derivatives with expected pharmacological activity. Part I. N-alkyl(hydroxyalkyl)-hexahydro-1,4-thiazepines and 2-(hexahydro-1,4-thiazepinyl)-ethyl esters of phenoxyacetic acids.

New N-alkyl or N-hydroxyalkyl derivatives of hexahydro-1,4-thiazepine(compounds 1--6, Table 2) were obtained by condensation of 2-chloroethyl-3-chloropropyl sulfide with appropriate primary amines. Estrification of 2-hydroxyethylhexahydro-1,4-thiazepine by chloride of appropriate phenoxyacetic acids yielded 2-(hexahydro-1,4-thiazepinyl)-ethyl esters of phenoxyacetic acids (compounds 7--12, Table 4).