Pindolol as an antihypertensive agent

26 hypertensive patients groupded according to the severity-index and the WHO-index were treated with pindolol (monotherapy, 15 mg daily). The response of blood pressure depression was statistically significant, although not always sufficient when judged by clinical parameters. Plasma renin activity responded variably to the treatment in different patients and different groups. In 18 patients a statistically significant increase of serum potassium could be observed. No major side effects of therapy were encountered.     

Comparison of hexadecylphosphocholine with fish oil as an antitumor agent

Hexadecylphosphocholine (HePC) reduced the growth of the human mammary tumor, MX-1, in the athymic nude mouse similar to the fish oil, MaxEPA. When used together, HePC and MaxEPA were additive towards reducing tumor growth. An unsaturated alkylphosphocholine mixture, ShisoPC, was not as effective as HePC in reducing tumor growth. MaxEPA reduced tumor PGE2 levels greater than 90%, while HePC and the ShisoPC only reduced tumor PGE2 40-60% with HePC being slightly better than ShisoPC. MaxEPA markedly increased the cellular omega 3 fatty acids and decreased 20:4 omega 6, the substrate for PGE2. HePC did not alter the tumor fatty acid composition, but it significantly lowered the total fatty acid concentration of the tumor by about 47%. In addition, phosphatidylcholine and sphingomyelin decreased in tumors from animals treated with HePC, and alterations in other phospholipids also were noted. These data suggest that different mechanisms exist for HePC and fish oil in reducing tumor growth.     

The validity of melatonin as an oncostatic agent

The validity of melatonin as a prominent, naturally occurring oncostatic agent is examined in terms of its putative oncostatic mechanism of action, the correlation between melatonin levels and neoplastic activity, and the outcome of therapeutically administered melatonin in clinical trials. Melatonin's mechanism of action is summarized in a brief analysis of its actions at the cellular level, its antioxidative functions, and its indirect immunostimulatory effects. The difficulties of interpreting melatonin levels as a diagnostic or prognostic aid in cancer is illustrated by referral to breast cancer, the most frequently studied neoplasm in trials regarding melatonin. Trials in which melatonin was used therapeutically are reviewed, i.e., early studies using melatonin alone, trials of melatonin in combination with interleukin-2, and controlled studies comparing routine therapy to therapy in combination with melatonin. A table compiling the studies in which melatonin was used in the treatment of cancer in humans is presented according to the type of neoplasm. Melatonin's suitability in combination chemotherapy, where it augments the anticancer effect of other chemotherapeutic drugs while decreasing some of the toxic side effects, is described. Based on the evidence derived from melatonin's antiproliferative, antioxidative, and immunostimulatory mechanisms of action, from its abnormal levels in cancer patients and from clinical trials in which melatonin was administered, it is concluded that melatonin could indeed be considered a physiological anticancer substance. Further well-controlled trials should, however, be performed in order to find the link between its observed effects and the underlying mechanisms of action and to define its significance as a therapeutic oncostatic agent.     

Heparin as an antithrombotic agent. Low-dose prophylaxis

We report the first case of a tumorlike hyperplasia of the juxtaoral organ in man.     

Formation of hemichrome during reaction of hemoglobin with polar phosphatidylcholine derivatives

Polar phosphatidylcholine derivatives [1-acyl-2-lyso-sn-glycero-3-phosphocholine, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor), 1-acyl-2-glutaryl-sn-glycero-3-phosphocholine, and 1-acyl-2-azelaoyl-sn-glycero-3-phosphocholine], which are formed in biological structures by enzymatic and free-radical reactions, were studied as effectors of the conversion of methemoglobin and oxyhemoglobin into an oxidized low-spin form referred to as hemichrome. It is shown that all these phosphatidylcholine derivatives act as effectors in the course of the transition of met- and oxyhemoglobin to hemichrome. Among the compounds studied, phosphatidylcholine derivatives containing glutaric and azelaic acids residues have the greatest effect on the rate of hemichrome formation.     

Increased thrombosis incidence in a family with an inherited protein S deficiency and a high oxygen affinity hemoglobin variant

Inherited protein S deficiency and the presence of a rare high oxygen affinity hemoglobin variant: Hb Rainier [beta 145 (HC2) Tyr-->Cys] were found in a family. Among 16 studied members, nine were found as carriers of protein S deficiency (type I with decrease of total, free, and activity levels). Six subjects carried the high-affinity hemoglobin variant, which displayed an increase of blood viscosity. Four members combined both abnormalities. Three had thrombotic accidents before the age of 30. We suggest the combination of protein S deficiency and the presence of this hemoglobin variant can lead to a severe primary hypercoagulable state with pathological consequences compared to each genetic defect alone.     

Time-resolved spectroscopy of hemoglobin and its complexes with subpicosecond optical pulses

Subpicosecond optical pulses have been used to study the photolysis of hemoglobin conplexes. Photodissociation of carboxyhemoglobin is found to occur in less than 0.5 picosecond. In hemoglobin and oxyhemoglobin a nondissociative excited state recovery in 2.5 picoseconds is observed.     

Arterial blood pressure responses to cell-free hemoglobin solutions and the reaction with nitric oxide

Changes in mean arterial pressure were monitored in rats following 50% isovolemic exchange transfusion with solutions of chemically modified hemoglobins. Blood pressure responses fall into three categories: 1) an immediate and sustained increase, 2) an immediate yet transient increase, or 3) no significant change either during or subsequent to exchange transfusion. The reactivities of these hemoglobins with nitric monoxide (.NO) were measured to test the hypothesis that different blood pressure responses to these solutions result from differences in .NO scavenging reactions. All hemoglobins studied exhibited a value of 30 microM-1 s-1 for both .NO bimolecular association rate constants and the rate constants for .NO-induced oxidation in vitro. Only the .NO dissociation rate constants and, thus, the equilibrium dissociation constants varied. Values of equilibrium dissociation constants ranged from 2 to 14 pM and varied inversely with vasopressor response. Hemoglobin solutions that exhibited either transient or no significant increase in blood pressure showed tighter .NO binding affinities than hemoglobin solutions that exhibited sustained increases. These results suggest that blood pressure increases observed upon exchange transfusion with cell-free hemoglobin solutions can not be the result of .NO scavenging reactions at the heme, but rather must be due to alternative physiologic mechanisms.     

(+)-7-Deaza-5''-noraristeromycin as an anti-trypanosomal agent

The (+)-enantiomer of 7-deaza-5'-noraristeromycin (4) has been found to show IC50 values ranging from 0.16 to 5.3 microM against four strains of African trypanosomes, one Trypanosoma brucei brucei isolate, and several clinical isolates of Trypanosoma brucei rhodesiense (agent of east African sleeping sickness), including a multidrug resistant clone of one isolate. While this compound was originally designed to inhibit S-adenosyl-L-homocysteine hydrolase, it has been found to have no effect on this enzyme.     

Tea plant root extract (TRE) as an antineoplastic agent

The antitumour effect of tea plant root extract (TRE) has been evaluated against Ehrlich ascites carcinoma (EAC) in Balb-C mice. Significant increases of survival times of the TRE-treated, tumour-bearing mice have been confirmed repeatedly with respect to the control group. TRE inhibited the tumour cell growth and reversed the changes of haematological parameters consequent to tumour inoculation.     

Ribotyping of Chryseobacterium meningosepticum: its use as an epidemiological tool and its correlation with serovars

Despite advances in terms of chemotherapy, the prognosis for patients with advanced ovarian cancer remains poor. The issue of dose intensity remains controversial in treatment of patients with advanced ovarian cancer. This review focuses on the issues of dose intensity, particularly platinum dose intensity with regard to treatment of advanced ovarian cancer. Specific issues addressed include 1) results of the current generation of randomized trials of dose intensity in ovarian cancer; 2) the use of combination platinum strategies, focusing on attempts at paclitaxol dose intensification in the setting of advanced ovarian cancer; and 3) approaches utilizing high-dose chemotherapy both with bone marrow and progenitor self-support and the use of multiple cycle high-dose chemotherapy in patients with advanced disease.     

Dimethyl(isopropenylethynyl)carbinol as an efficient nonionogenic collector and foaming agent

The efficiency of the application of dimethyl(isopropenylethynyl)carbinol (DMIPEC) is investigated for ores of nonferrous metals of deposits in Russia, Kazakhstan, and Chili. Additional extraction is 1.2–5.8% Cu, 1.3–4.3% Mo, 10.1–20.0% Zn, and 0.9% Ni. The mechanism of adsorption of a froth reagent on sulfides is established by quantum-chemical calculations. Based on comparison of the obtained results, the assumption is made that the interaction of DMIPEC with the ore surface principally differs from both ionogenic sulfur-containing collectors and nonpolar hydrocarbons. It is revealed that the efficiency of the use of DMIPEC depends on the energy of interaction of multiple carbon-carbon bonds of the froth reagent with sulfides and on the degree of hydrophobicity of the surrounding the nonferrous metal cation.