The reactivity and mechanism of action of triazenes (review)

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 28, No. 10, pp. 4–18, October 1994.     

Mechanism of the antiulcer action of oxyferriscorbon

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 28, No. 7, pp. 3–6, July, 1994.     

Synthesis and pharmacological activity of derivatives of 3-aminomethylenindolin-2-one

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 28, No. 4, pp. 22–26, April, 1994.     

Steroidal spirooxetanes. I. Synthesis and antiandrogenic properties of some 17-spirooxetanoandrostanes

Pharmaceutical Chemistry Journal -     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Contact angles of substances used for internal tamponade in retinal detachment surgery

In order to ascertain the tamponade effect of air and silicone oil we examined the contact angles subtended by ex vivo human retina, Teflon and Perspex to find a suitable experimental material which would mimic the surface properties of the retina at a three-phase interface. Using the captive bubble technique to measure the contact angle, it was found that air subtended a larger contact angle (38.8°) with the retina than did silicone oil (18.2°). On coating the Perspex surface with protein (PCP), it was observed that the surface properties were modified such that PCP subtended contact angles with air (43.0°) and silicone oil (16.4°) similar to those subtended by ex vivo human retina. Using PCP as an experimental material that mimics ex vivo human retina, spherical chambers were employed in order to examine qualitatively and to quantify the arc of contact obtained with air and silicone oil. It was found that air gave a greater arc of contact for the same percentage fill than silicone oil.     

Retinopathy of prematurity in infants less than 29 weeks' gestation at birth

From January 1986 to December 1991 we examined the eyes of 206 infants born at Westmead Hospital, Neonatal Intensive Care Unit who were less than 29 weeks' gestation at birth to determine the incidence of retinopathy of prematurity. Eighty-five infants (41.3%) had no retinopathy of prematurity (ROP) in either eye, 82 infants had stages 1 or 2 ROP (39.8%), 29 had stage 3 ROP (14.1%) and 11 had stage 4 ROP (5.3%). Of these, cryotherapy was performed in 18; six now have bilateral retinal detachment and are blind The more severe stages of ROP were significantly associated with an increase in the number of days of oxygen supplementation, an increase in the number of days of mechanical ventilation and the presence of patent ductus arteriosus. Infants receiving steroids for mechanical ventilator dependence had a significantly greater chance of requiring cryotherapy (11 or 22 receiving steroids versus seven of 43 without steroids; P < 0.01).     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.     

Abolition of flow-dependent EDRF release before that evoked by agonists in hypercholesterolaemic rabbits.

1. We have used a pulsatile cascade bioassay system to investigate the effects of dietary-induced hypercholesterolaemia on EDRF release evoked by acetylcholine and by the oscillatory and time-averaged components of flow, in isolated segments of rabbit abdominal aorta. 2. Flow pulsatility (frequency range 0.1-10 Hz) was studied with constant flow (9 ml min-1) at a pulse pressure amplitude of 2 mmHg. Frequency-related EDRF release, maximal at 6 Hz, was slightly attenuated after 4 weeks and abolished after 8 weeks of cholesterol feeding. 3. Time-averaged shear stress was manipulated with dextran (1-4% w/v, 80000 mol. wt.), to increase perfusate viscosity. EDRF release induced by increased perfusate viscosity was unaffected after 4 weeks but abolished after 8 weeks of cholesterol feeding. 4. Endothelium-dependent relaxations to acetylcholine (0.1-10 microM) were not influenced after 4 weeks and only partially attenuated (by 60% of the maximal response, EC50 unchanged at 6.45 +/- 0.04 vs. 6.4 +/- 0.1 microM) after 8 weeks of cholesterol feeding. 5. Blood cholesterol levels were significantly (P < 0.001) increased after 4 weeks (26 +/- 3.6 vs 2.6 +/- 0.6 mmol l-1) and 8 weeks (56.2 +/- 3.8 vs 1.3 +/- 0.1 mmol l-1) of cholesterol feeding but after 8 weeks plasma L-arginine levels were not significantly different from the age-matched controls (0.2 +/- 0.05 vs. 0.19 +/- 0.04 mmol l-1). 6. We conclude that hypercholesterolaemia impairs flow-related (pulsatile- and time-averaged shear-induced) EDRF release earlier than acetylcholine-induced relaxation in rabbit aorta.(ABSTRACT TRUNCATED AT 250 WORDS)