Summary: Brain edema formation during the early stages of focal cerebral ischemia is associated with an increase in both sodium content and blood-brain barrier (BBB) sodium transport. The goals of this study were to deter mine whether chloride is the principal anion that accumu lates in ischemic brain, how the rate of BBB transport of chloride compares with its rate of accumulation, and whether the stimulation seen in BBB sodium transport is also seen with other cations. Focal ischemia was pro duced by occlusion of the middle cerebral artery (MCAO) in anesthetized rats. Over the first 6 h after MCAO, the amount of brain water in the center of the ischemic cortex increased progressively at a rate of 0.15 ± 0.02 (SE) gig dry wtlh. This was accompanied by a net increase in brain sodium (48 ± 12 j.Lmol/g dry wtlh) and a loss of potassium (34 ± 7 j.Lmol/g dry wt/h). The net rate of chloride accu mulation (16 ± 1 j.Lmol/g dry wt/h) approximated the net rate of increase of cations. Three hours after MCAO, the BBB permeability to three ions e2Na, 36CI, and 86Rb) and two passive permeability tracers WH]a-aminoisobutyric Numerous studies have emphasized the impor tance of cations in the development of brain edema during focal ischemia (Ito et aI., 1979;Schuier and Hossmann, 1980; Gotoh et aI., 1985; Young et aI., 1987; Betz et aI., 1989; Menzies et aI., 1993). For example, during the first 3-6 h of ischemia, water accumulation results from a net increase in brain sodium despite a significant loss of brain potassium (Gotoh et aI., 1985; Young et aI., 1987; Betz et aI., 1989; Menzies et aI., 1993). The rate at which soReceived November 9, 1992; final revision received July 13, 1993; accepted July 16, 1993.Address correspondence and reprint requests to Dr. A. L. Betz at D3227 Medical Professional Building, University of Michigan, Ann Arbor, MI 48109-0718, U. S.A.Abbreviations used: AlB, a-aminoisobutyric acid; BBB, blood-brain barrier; MeAO, middle cerebral artery occlusion. 29acid eH]AIB) and e4C]urea} was determined. Permeabil ity to either passive tracer was not increased, indicating that the BBB was intact. The rate of 36CI influx was 3 times greater and the rate of 22Na influx 1.8 times greater than their respective net rates of accumulation in isch emic brain. The BBB permeability to 22Na relative to that of eRJAIB was significantly increased in the ischemic cortex, the relative permeability to 86Rb was significantly decreased, and the relative permeability to 36CI was un changed. These results indicate that the stimulation in BBB sodium transport is specific for sodium. Further, chloride accumulates with sodium in brain during the early stages of ischemia; however, its rate of accumula tion is low compared with its rate of transport from blood to brain. Therefore, inhibition of BBB sodium transport is more likely to reduce edema formation than is inhibition of BBB chloride transport. Key Words: Brain edema Electrolyte transport-Middle cerebral artery occlu sion-Permeability-surface area product.

The mechanism of unidirectional transport of sodium from blood to brain in pentobarbital‐anesthetized rats was examined using in situ perfusion. Sodium transport followed Michaelis‐Menten saturation kinetics with a Vmax of 50.1 nmol/g/min and a Km of 17.7 mM in the left frontal cortex. The kinetic analysis indicated that, at a physiologic sodium concentration, ∼26% of sodium transport at the blood‐brain barrier (BBB) was carrier mediated. Dimethylamiloride (25 µM), an inhibitor of Na+/H+ exchange, reduced sodium transport by 28%, whereas phenamil (25 µM), a sodium channel inhibitor, reduced the transfer constant for sodium by 22%. Bumetanide (250 µM) and hydrochlorothiazide (1.5 mM), inhibitors of Na+‐K+‐2Cl−/NaCl symport, were ineffective in reducing blood to brain sodium transport. Acetazolamide (0.25 mM), an inhibitor of carbonic anhydrase, did not change sodium transport at the BBB. Finally, a perfusate pH of 7.0 or 7.8 or a perfusate Pco2 of 86 mm Hg failed to change sodium transport. These results indicate that 50% of transcellular transport of sodium from blood to brain occurs through Na+/H+ exchange and a sodium channel in the luminal membrane of the BBB. We propose that the sodium transport systems at the luminal membrane of the BBB, in conjunction with Cl−/HCO3− exchange, lead to net NaCl secretion and obligate water transport into the brain.

Abstract:The mechanism of unidirectional transport of glutamine from blood to brain in pentobarbital-anesthetized rats was examined using in Situ perfusion. Amino acid uptake into brain across the blood-brain barrier (BBB) is classically thought to be via the Na-independent large neutral (L-system), acidic and basic amino acid transporters. In the presence of physiological concentrations of amino acids in the perfusate, which should saturate the known amino acid transporters at the BBB, the cortical transfer constant (I<~)for L-[ 14C]glutamine was 11.6 ± 1.1~tl/g/min. The addition of either 10 mM 2-amino-2-norbornanecarboxylic acid or 10 mM 2-amino-2-norbornanecarboxylic acid and 5 mM cysteine had no effect on the cortical K for L-[14C]glutamine, indicating that glutamine transport under these conditions does not occur by the L-, A-, or ASC-systems. Decreasing perfusate Na from 140 to 2.4 mM by Tris substitution reduced the cortical K, for L-[14C]glutamine by 62% (p 0.001). The Na-dependent uptake has the characteristics of Nsystem transport. It was inhibited by L-histidine and Lglutamine, both N-system substrates, and it was pH sensitive and moderately tolerant of Li substitution for Na. This putative N-system transporter at the luminal membrane of the BBB plays an important role in mediating brain glutamine uptake. Key Words: Blood-brain barrier-Transport-Glutamine-N-system-ln situ perfusion.

The environmentally friendly anionic surfactant fatty acid methyl ester sulfonate (MES) was prepared by esterification of waste cooking oil (WCO), a low-cost raw material, followed by sulfonation with chlorosulfonic acid. MES production from WCO (W-MES) gave yields up to 78 %. Such a value is only slightly lower than the one obtained from soybean oil (S-MES), 82 %, and almost the same as that from reused cooking oil (R-MES), 76 %. According to the two-phase titration results, the content of the active component, a-MES, in S-MES, R-MES and W-MES was equal to 76.82, 69.19 and 66.60 %, respectively. The disalt, RCH(CO 2 Na)SO 3 Na, contents were instead 3.2, 3.8 and 4.7 %, respectively. As proved by the results of the FTIR and NMR characterizations, the chemical structure of W-MES is almost the same as that of S-MES and R-MES. The critical micelle concentration of W-MES is 5.38 mmol/L and the corresponding surface tension is 32.3 mN/m. The hydrophile-lipophile balance value of W-MES is 12.33, which indicates that it can form oil/water emulsions. The three MES demonstrated the same adsorption efficiency, yielding a pC20 value of 3.22, and similar foam stability. Their detergency can be up to 75 % at a concentration of 400 mg/kg and the tolerance to Ca 2? is higher than the one exhibited by linear alkylbenzene sulphonic acid and alpha olefin sulfonate. Additionally, W-MES shows a considerable solubilization capacity towards polycyclic aromatic hydrocarbon as the molar solubilization ratios to pyrene, phenanthrene and acenaphthene in a 30 mmol/L solution are 1.22 9 10 -3 , 2.67 9 10 -3 and 3.81 9 10 -3 , respectively.

Four novel oxepin-containing pyrimidines, namely oxepinamides D-G (1-4), were isolated from cultures of Aspergillus puniceus F02Z-1744. The structures of 1-4 were elucidated by analyzing their spectroscopic data generated by 1D and 2D NMR and MS methods. The configurations of 1 and 2