A new photoelectric method for measuring hemodynamic changes in a thin layer of cerebral tissue in situ is described. The apparatus consists of a miniature lamp of 0.7 mm OD and a photodiode with a color filter having maximum light transmission at 548 nm. The lamp was chronically or acutely implanted into the brain tissue of animals as a light source, and the intensity of the light transmitted through the cerebral tissue was monitored with the photodiode from the brain surface. The intensity of the transmitted light was quantified for cerebral blood volume (CBV). The mean transit time of blood (t) was obtained from tissue hemodilution curves produced by saline injection into the carotid artery. The regional blood flow was calculated from the values of CBV and t according to the Stewart-Hamilton equation. The apparatus was shown to be stable, rapid in response, easy to operate, and to give reproducible results. Possible sources of error are discussed.

Substrate specificity on the reduction of bicyclic diketones with a yeast strain, Torulaspora delbrueckii IFO10921, was investigated. Although this yeast efficiently reduces the isolated carbonyl group involved in the (S)-enantiomer of Wieland± Miescher ketone with high enantioselectivity (E 126), the introduction of a substituent on the octahydronaphthalene skeleton as well as the structural change into an octahydroindene skeleton retarded the enzymatic reduction and the enantioselectivity fell to E 5 ± 16. Further structural variation into a bicyclo[3.3.0] skeleton led to an exclusive 1,4-conjugate reduction of the a,b-unsaturated carbonyl group, and the above results suggested the participation of plural oxidoreductive enzymes in the whole cell. In turn, among the 2,2-disubstituted cycloalkanediones there were found good substrates to give the corresponding hydroxy ketone equivalents by yeast-mediated reduction. The products were isolated as cyclic hemiacetals, such as (1S,6S)-3-ethyl-3-hydroxy-6-methyl-2-oxabicyclo[4.4.0]decan-7-one and (1S,6S)-3-hydroxy-3,6-dimethyl-2-oxabicyclo[4.3.0]nonan-7-one. In addition, the reduction worked well with use of an air-dried, long-term preservable cell preparation. The subsequent chemical transformation warranted the stereochemistry and the stereochemical purity of the products, which are related to octahydronaphthalenone and octahydroindenone systems that, in turn, are of considerable value as starting materials for terpenoid synthesis.

A formal synthesis of (+)-madindoline A was achieved. The Sunazuka's key intermediate (4 R,5 S)-(–)-3-butyl-4-( tert-butyldimethylsiloxy)-5-methoxycarbonyl-2,5-dimethyl-2-cyclopentenone was synthesized from easily available (2 S,3 S)-3-acetoxy-2-ethenyl-2-methylcyclopentanone. The starting material was reliably supplied by a chemo-enzymatic procedure in enantiomerically pure form. The synthesis was performed by straightforward transformations involving enone formation and regioselective introduction of the two alkyl side chains.

1 Sumatriptan, a 5-hydroxytryptamine (5-HT)1-like receptor agonist, is effective against the headache of migraine. The effects of sumatriptan injected via the carotid artery on the cerebral microcirculation were studied in 10 anaesthetized cats. 2 The local cerebral blood volume (CBV), mean transit time of blood (MTT) and cerebral blood flow (CBF) in the parieto-temporal cortex were measured by a photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels.3 Sumatriptan at 5 and 50 g,g kg-' had no significant effects on the CBV, MTT, CBF, and mean arterial blood pressure (MABP); 500 tg kg-' of sumatriptan reduced the CBV, prolonged the MTT, and decreased the CBF (approximately -20%) without affecting the MABP. Sumatriptan, 5 mg kg', elicited transient reductions in CBV and CBF, which were attributable to the rapid and marked falls of MABP seen with this dose.4 Thus, while a high dose of sumatriptan (500 Stg kg-') exhibits direct vasoconstrictor actions on the cerebral vessels, low doses of sumatriptan, within the therapeutic range, elicit no vasoconstriction. The data do not support a vasoconstrictor action of sumatriptan playing a primary role in reversing the headache of migraine.

Summary:The photoelectric method using carbon black as a nondiffusible tracer of blood was compared with the hydrogen clearance (H2) method in nine anesthetized cats. A photoelectric apparatus and H2 electrode were applied to a small region of the cerebral cortex (left ecto sylvian gyrus) for simultaneous measurement of the re gional CBF. The values of CBF(H2) and CBF(photoelec tric) were 50.7 ± 19.2 and 52.1 ± 14.5 ml' 100 g-I . min-I, respectively. CBF(H2) and CBF(photoelec tric) were found to correlate well (r = 0.588, p < 0.01) when changes in CBF were induced by CO2 inhalation, exsanguination, hyperventilation, and occlusion of the middle cerebral artery. The correlation between CBF(H2) and CBF(photoelectric) was much better in the case of For measuring the cortical blood flow of the brain in experimental animals, numerous techniques, e.g., the inert gas clearance technique, microsphere method, autoradiographic technique, thermistor method, dynamic recording of isotopically labeled substances injected into the bloodstream, etc., have been reported. However, none of these methods is feasible for quantitatively measuring time-to-time changes in CBF. To meet the require ment of better temporal resolution, we developed a photoelectric method (Tomita et aI., 1978a(Tomita et aI., , 1983 that permits frequent determinations of cortical blood flow together with continuous recording of the blood volume of the cortex. Employing this Manuscript received January 26, 1988; accepted March 28, 1988.Address correspondence and reprint requests to Dr. M. To mita at Department of Neurology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan.Abbreviations used: CBV, cerebral blood volume; H2, hy drogen clearance; MCA, middle cerebral artery; SP D, silicone photodiode. 727intraindividual comparisons (r = 0.957, p < 0.01). In ad dition to its merits in common with the H2 clearance method, such as handiness, low cost, and strict regional ity, the photoelectric method displayed the following ad vantages: time-to-time measurements of CBF «20 s), immediate display of the microcirculatory flow pattern, and simultaneous monitoring of cerebral blood volume. However, measurements from deep structures of the brain are better performed by the H2 method despite the disadvantage of the use of a potentially explosive gas. Key Words: Photoelectric method-Hydrogen clearance method-Cerebral blood flow-Cerebral blood volume -Mean transit time of blood-Carbon black.photoelectric method, some new insights into the brain under pathophysiological conditions have been obtained (Tomita et aI., 1978b(Tomita et aI., , 1980(Tomita et aI., , 1983 To mita, 1988). However, strict objective verification of the validity of the photoelectric method has not yet been carried out. This article therefore attempts to compare two flow values measured simultaneously in the same area of the cerebral cortex in nine cats using our photoelectric method and the hydrogen clearance (H2) method. The results are discussed in relation to t...