L-2-oxothiazolidine-4-carboxylate as a cysteine precursor: efficacy for growth and hepatic glutathione synthesis in chicks and rats

Chick and rat experiments were conducted to determine the efficacy of L-2-oxothiazolidine-4-carboxylate (OTC) as a cysteine (Cys) precursor for growth and hepatic glutathione (GSH) biosynthesis. Isosulfurous graded increments of OTC and Cys were added to Cys-free purified amino acid diets that were adequate in methionine. Curvilinear responses to both Cys and OTC for chicks and rats were obtained. Hepatic GSH accumulated in chicks only at dietary Cys levels above 0.10%. In rats, hepatic GSH increased linearly as dietary Cys content increased from deficient to adequate and from adequate to excessive. Utilization of OTC by chicks was as efficacious as isosulfurous levels of Cys for growth and hepatic GSH biosynthesis. In rats, OTC was slightly inferior to Cys for growth and hepatic GSH biosynthesis. Exponential regression slope-ratio growth efficacy values for OTC were 78.5% for chicks and 70.2% for rats; multiple linear regression slope-ratio GSH biosynthesis efficacy values were 80.3% for chicks and 83.7% for rats. It is concluded that orally administered OTC is active as a Cys precursor.     

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.     

Rigid contact lens decentration: a risk factor for corneal warpage

Clinically significant contact lens induced corneal warpage is seen in a small proportion of soft and rigid contact lens wearers. Previous studies using the keratometer have found no correlation between the fit of the lens and the induced topographic changes. In this study, using computer-assisted topographic analysis, seven eyes (four patients) with rigid contact lens-induced corneal warpage were noted to have topographic abnormalities that correlated with the decentered resting position of the contact lens on the cornea. The warpage topography for each of these corneas was characterized by a relative flattening of the cornea underlying the resting position of the contact lens. Lenses that rode high, for example, produced flattening superiorly and resulted in a relatively steeper contour inferiorly that simulated the topography of early keratoconus patients who had not worn contact lenses. After discontinuing contact lenses the corneal topography returned to a normal pattern in five eyes. Two eyes retained asymmetry that is not characteristic of normal corneas. Up to 6 months was required for the corneas to return to a stable topography after contact lens wear was discontinued.     

Effect of Yag-laser anterior capsulotomy on the biochemical content of aqueous humor

Elevation of prostaglandins and protein in the aqueous humor is an immediate response to Yag-laser anterior capsulotomy. There was a significant correlation between prostaglandins and thromboxane to the elevation of intraocular pressure. The elevation of protein concentration was proportional to the elevation of prostaglandin F1, but not to thromboxane. The biochemical changes in the aqueous humor were more severe as laser power was increased above 3 mj. While the role of prostaglandins in the elevation of intraocular pressure is uncertain, the present data recommend the selection of laser power below 3 mj to avoid pressure rise instead of inhibition of all prostaglandin synthesis by medication.     

Conjunctival involvement of lymphomatoid granulomatosis

Lymphomatoid granulomatosis is an angiocentric and angiodestructive lympho-proliferative disorder involving multisystems but rarely conjunctiva. We present a 62-year-old Chinese female with lymphomatoid granulomatosis who had an ulcerative conjunctival nodule. Conjunctival biopsy revealed pathological findings important for diagnosis and indicating progression of disease severity. To our knowledge, this is the first report to demonstrate pathological findings characteristic of lymphomatoid granulomatosis with conjunctival involvement.     

Deletion of aldose reductase leads to protection against cerebral ischemic injury.

Previously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR(-/-) brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR(-/-) brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron- and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury.     

纸质病案保存期限的思考

本文作者比较了不同时期的纸质病案的使用率,讨论了旧病案的缺点,如难于保存,占用空间及实用价值不大.作者提出了改进保存病案的办法.