Prodrugs of 5-Iodo-2′-Deoxyuridine for Enhanced Ocular Transport

Problems associated with the use of 5-iodo-2content/h43253x75183t67x/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-deoxyundine (IDU) in the treatment of herpes simplex keratitis can be attributed largely to the polar nature of IDU resulting in its poor permeability across the lipoidal epithelial layer of the corneal membrane. Five aliphatic 5content/h43253x75183t67x/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-esters of IDU were synthesized and evaluated as prodrugs for potential use in the treatment of deep ocular infections such as stromal keratitis, iritis, and even retinitis. A parabolic relationship between in vitro corneal membrane permeability and carbon chain length of prodrugs is evident. For a given prodrug, enzymatic hydrolysis proceeded most readily in iris–ciliary body, followed by cornea and aqueous humor. An increase in carbon chain length made the prodrugs more enzymatically labile but more resistant to chemical hydrolysis at pH 7.4 and 34°C. The 5content/h43253x75183t67x/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-butyryl ester of IDU exhibited an approximately fourfold increase in aqueous humor IDU concentration relative to IDU at 25 min following instillation of 25-µl 5 mM solutions.     

Compartmentation of cardiac adenine nucleotides and formation of adenosine

Summary After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either¹⁴C-adenine or¹⁴C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 3content/q35p152u31241151/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">5content/q35p152u31241151/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substance. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart.Our findings provide evidence that at least two different adenine nucleotide compartments of the heart serve as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine.A preliminary report of part of this work appeared in content/q35p152u31241151/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia and Infarctioncontent/q35p152u31241151/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0"> Vol. 7 of content/q35p152u31241151/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">Recent advances in studies on cardiac structure and metabolismcontent/q35p152u31241151/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0">. (P. Harris, R. J. Bing, A. Fleckenstein, eds.), pp. 171–175. München: Urban & Schwarzenberg 1976A preliminary report of part of this work appeared in content/q35p152u31241151/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">Biochemistry and Pharmacology of Myocardial Hypertrophy, Hypoxia and Infarctioncontent/q35p152u31241151/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0"> Vol. 7 of content/q35p152u31241151/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">Recent advances in studies on cardiac structure and metabolismcontent/q35p152u31241151/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0">. (P. Harris, R. J. Bing, A. Fleckenstein, eds.), pp. 171–175. München: Urban & Schwarzenberg 1976     

Temperature stabilizing effect of tocopherol on rhodopsin in the pressure of fatty acids studied by differential scanning calorimetry

Institute of Cytology, Academy of Sciences of the USSR. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Institute of Physiology, Bulgarian Academy of Sciences, Sofia. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. A. Vladimirov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 8, pp. 160–171, August, 1989.     

Electron-cytochemical investigation of the brain mitochondria at various times after death

An electron-cytochemical investigation was made of oxidation of 3,3content/p3373271133jt2gj/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-diaminobenzidine (DAB) in the brain of rats and man at different times after death. The oxidation product of DAB was localized in the mitochondria, lipofuscin granules, and erythrocytes. Oxidation of DAB by rat and human brain mitochondria was shown to be only very slightly depressed even 2 days after death.Laboratory of Experimental Pathology and Pathomorphology of the Brain, Institute of Psychiatry, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Snezhnevskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 6, pp. 757–759, June, 1976.     

The effect of intravenously administered salbutamol on serum potassium in asthmatic and nonasthmatic atopic subjects

The role of adrenergic mechanism in the pathogenesis of allergic disease is controversial. Recent experimental and clinical reports have suggested that content/hx31l707771501v7/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenergic blockade impairs and content/hx31l707771501v7/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> stimulation enhances extrarenal potassium uptake in humans. This led us to study the effect of the intravenous administration of salbutamol, a specific content/hx31l707771501v7/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-2-adrenergic agonist, on serum potassium in 9 healthy subjects and in 23 patients with allergic asthma and/or rhinitis. Serum potassium fell significantly and reached a peak decline at the end of venous infusion in all the normal subjects. Seventeen atopic subjects showed a lower or absent serum K⁺ decrement: there was no difference between asthmatic and rhinitic patients. There was no relation among the salbutamol-induced serum potassium decrement, serum glucose increment, blood pressure and heart-rate changes, and nonspecific bronchial reactivity. These findings suggest that content/hx31l707771501v7/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-2-adrenergic hyporesponsiveness is present only in some allergic patients.     

鼻咽癌旁上皮细胞核DNA含量分析

应用显微分光光度计测定15例鼻咽癌19处癌旁病变的上皮细胞核DNA含量并与浸润癌相比较。中、重度异型增生上皮细胞核DI及超过2.5c细胞的百分数处于单纯增生+轻度异型增生与浸润癌之间,3组DI及超过2.5c细胞的百分数差异显著。中、重度异型增生以非整倍体为主,其细胞核DNA含量组方图相似于浸润癌。从细胞核DNA含量角度来看,中、重度异型增生是重要的癌前病变。     

Ultrastructure and membrane permeability of cultured pancreaticβ-cells exposed to alloxan or 6-hydroxydopamine

Summary Stereological techniques on electron microscopy micrographs were used to evaluate the morphological changes of cultured isletcontent/l223u721370wwu32/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> cells that had been exposed to alloxan or 6-hydroxydopamine.Trypan Blue exclusion by cells cultured for 3 days indicated that the cells were 100% viable. Electron microscopy revealed that nearly all of the surviving cultured cells werecontent/l223u721370wwu32/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> cells.Exposure to 5 mmol/l alloxan or 1–5 mmol/l 6-hydroxydopamine for 10 or 30 min caused a general swelling of the cultured cells with a concomitant swelling of mitochondria and nuclei. The size of the secretory granules was not affected by the drugs. Only 3–10% of the cells excluded Trypan Blue after exposure to 5 mmol/l alloxan or 6-hydroxydopamine.The data conform with the hypothesis that a primary action of alloxan and 6-hydroxydopamine is at the plasma membrane level ofcontent/l223u721370wwu32/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> cells.Abbreviations and definitions A _cell Cell profile area (µm²), surface area of one cell section surface - V _n Nuclear volume density (%), number of points over the nucleus divided by the number of points over the total cell area × 100 - V _m Mitochondrial volume density (%), number of points over mitochondria divided by hits over the cytoplasm (points over the cell minus points over the nucleus) × 100 - V _g Granular volume density (%), number of points over granules divided by hits over the cytoplasm × 100     

Adenosine and adenine nucleotides are independently released from both the nerve terminals and the muscle fibres upon electrical stimulation of the innervated skeletal muscle of the frog

The independent release of adenosine and adenine nucleotides upon electrical stimulation was studied in the innervated sartorius muscle of the frog after blockade of the extracellular catabolism of adenosine monophosphate (AMP) through exo-AMP deaminase and ecto-5content/x422u304072255x7/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-nucleotidase. Nerve stimulation (30 min, 0.2Hz) induced the release of both adenosine (19±3 pmol) and adenine nucleotides (101±7 pmol). Experiments performed in the presence of tubocurarine (5 content/x422u304072255x7/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">M) to prevent purine release due to nerve-evoked muscle twitching, or under direct stimulation of the muscle in low calcium solutions to prevent pre-synaptic release of purines, showed that there was an evoked release of adenosine and adenine nucleotides both from the nerve endings and from the twitching muscle fibres. Removal of ecto-5content/x422u304072255x7/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-nucleotidase inhibition shows that the catabolism of adenine nucleotides released during stimulation contributes in about 50% to the amount of endogenous extracellular adenosine. When only one of the enzymes catabolizing AMP (ecto-5content/x422u304072255x7/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-nucleotidase or exo-AMP deaminase) was inhibited, the evoked release of adenine nucleotides was undetectable, suggesting that each enzyme is able to catabolize all the AMP formed from adenine nucleotides released upon stimulation. It is concluded that the concentration of endogenous extracellular adenosine is under the control of the relative activities of exo-AMP deaminase and ecto-5content/x422u304072255x7/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-nucleotidase.Brief accounts of some of the results in this study have been published previously (refs. [6, 7]).