Yoshiro Takaoka

In vivo aspects of progesterone distribution and metabolism

The end-organ response of any hormone is the result of many factors which precede the event, including biosynthesis, secretion, transport, distribution, and metabolism. These factors vary among different species. The metabolic clearance rate (MCR) of progesterone varies between 40 and 180 L./day/Kg. in man (60 to 70), monkey (40 to 50), rabbit (55 to 60), sheep (110), rat (120), and guinea pig (180). Major sites of clearance include liver, brain, and uterus. Specific metabolites of progesterone include 20 alpha-hydroxypregn-4-en-3-one (20 alphaOHP) and alpha-pregnan-3,20-dione (5 alpha-DPH). Liver, brain, and uterine clearances, extractions, and conversions of progesterone to these metabolites have been studied in various species under apparent steady-state conditions. A specific hormone action of progesterone, the appearance of uteroglobin in the rabbit uterus, has also been studied in varying horomonal states (estrogen, estrogen plus progesterone, and progesterone alone). These have all been used as examples of progesterone distribution and metabolism.

In situ Estradiol and Progestin (R5020) Localization in the Vascularly Separated and Isolated Hypothalamus of the Rhesus Monkey

A neurosurgical procedure has been developed for vascular isolation of the hypothalamus-thalamus region of the rhesus monkey brain. Utilizing this preparation, the left and right halves of the hypothalamus were perfused simultaneously, but separately, with a dextran-blood solution. Radiolabeled steroids were directly perfused in the dextran-blood into either the left or right half of the hypothalamus. Studies with radiolabeled gonadal steroids indicate that the majority of the carotid circulation is confined to the hypothalamus-thalamus area in this brain preparation and the cross-circulation of labelled steroids between the left and right sides of the hypothalamus is less than 10%. The usefulness of the preparation is illustrated by an autoradiographic study of the in situ hypothalamic distribution of (3H)estradiol in ovariectomized rhesus monkeys and of the synthetic progestin(3H)R5020 in estrogen-primed, ovariectomized rhesus monkeys. The direct perfusion of the (3H) steroids into the hypothalamus greatly increases the sensitivity of such compared to systemic administration of the (3H) steroids. The perfusion of one-half of the hypothalamus with )3H) steroid and the other half with (3H) steroids. The perfusion of one-half of the hypothalamus with (3H) steroid and the other half with (3H) steroids. The perfusion of one-half of the hypothalamus with (3H) steroid and the other half with (3H)steroid plus radioinert steroids permits in 1 animal, acting as its own control, the examination of a saturable distribution of a gonadal steroid in the rhesus monkey hypothalamus.

A PICA communicating artery aneurysm : case report

We present an unusual case of an aneurysm of the distal posterior inferior cerebellar artery (PICA). The aneurysm was associated with a unilateral PICA that supplied both cerebellar hemispheres and arose from an anastomotic vessel to the contralateral circulation, a branch of the contralateral PICA. Such an aneurysm has not been reported previously. The associated of vascular anomalies with aneurysms of the PICA is discussed.

Autoradiographic Analysis of Progestin-Concentrating Cells in the Isolated Rhesus Monkey Hypothalamus

The in situ hypothalamic distribution of (3Η)progesterone was studied in the vascularly separated and isolated hypothalamus of estrogen-treated, ovariectomized rhesus monkeys. The distribution of (3H)progesterone in one half of the hypothalamus was compared with the distribution of the synthetic progestin (3H)R5020 in the contralateral half of the same hypothalamus. As an indication of the patency of the arterial circulation to, and throughout, the hypothalamus and to histologically identify the half of the hypothalamus perfused with (3H)progesterone, 15-μm radioinert microspheres were injected into one of the carotid arteries approximately 5 min before stopping the perfusion. The observed microsphere distribution confirmed the efficiency of the in situ perfusion system to deliver (3H)progestin throughout the preoptic area and hypothalamus. The hypothalamic distribution of (3H)progesterone and/or its metabolites was similar to that of (3H)R5020 although the cellular labeling by (3H)R5020 was more intense and more neurons within specific nuclei were labeled. The (3H)progestin-concentrating cells were localized along the midline of the medial preoptic area (sparse labeling), within the suprachiasmatic nucleus (sparse labeling), along the periventricular (PERI)-ventromedial nuclear borders in the mid-hypo thalamus, as well as in the ventromedial, infundibular (arcuate), premammillary and medial mammillary nuclei. Radio inert progesterone infused with the (3H)progesterone greatly diminished the intensity of labeling in all areas except for that localized in the PERI region. Radioinert cortisol infused with the (3H)progesterone also apparently decreased but did not eliminate the labeling. The results support the use of the synthetic progestin (3H)R5020 to evaluate the hypothalamic distri bution of progesterone in the rhesus monkey and also indicate a nonsaturable progestin labeling of the midhypothalamic periventricular-ventromedial border region.

Autoradiographic localization of estradiol- and progesterone-concentrating neurons in the isolated rhesus monkey hypothalamus

Progesterone- and estradiol-concentrating neurons were autoradiographically localized in the in situ, vascularly isolated, rhesus monkey hypothalamus. Estradiol-concentrating neurons were dispersed throughout the hypothalamus, their density being greatest in the medial preoptic (MPOA) and medial basal hypothalamic nuclei (viz. dorsomedial, ventromedial (VMH) and infundibular nuclei). In contrast, progesterone-concentrating neurons were less densely localized in the medial preoptic, ventromedial (medial division) and infundibular nuclei. There was a virtual absence of progestin-concentrating cells in the anterior and posterior hypothalamic zones. This localization of cells was not attributed to the perfusion pattern of the isolated hypothalamus since a complete distribution of injected microspheres was found throughout the hypothalamus. The results of these studies indicate that a possible division between estradiol- and progesterone-concentrating neurons exists within the MPOA-medial basal hypothalamic nuclei of the rhesus monkey.

Anterior sacral meningocele

A case of anterior sacral meningocele is presented emphasizing early diagnosis based on recurring functional complaints and employing appropriate radiological studies. The appropriate use of computerized tomography (CT) scanning and the proper surgical management utilizing laminectomy and obliteration of the communicating channel of the meningocele are discussed.

In situ Subcellular Distribution and Metabolism of Progesterone, Estradiol and Androstenedione in the Vascularly Separated and Isolated Hypothalamus of the Female Rhesus Monkey

A neurosurgical procedure has been developed for the vascular isolation of the hypothalamus-thalamus region of the rhesus monkey brain. The circulation to the left and right halves of the hypothalamus was also isolated and each half of the hypothalamus was perfused simultaneously, but separately, with a dextran-blood solution which contained radioactive gonadal steroids. The hypothalamus in situ efficiently converted [3H]androstenedione to [3H]estrone and this aromatization was inhibited by the presence of androsta-1,4,6-triene-3,17-dione (ATD) in the perfusate. [3H]Progesterone was metabolized predominantly to 5 alpha-pregnane-3,20-dione (5 alpha-DHP) and 20 alpha-hydroxypregn-4-ene-3-one (20 alpha-OHP). Subcellular fractionation of the hypothalamus after the in situ perfusion with [3H]-progestin or [3H]estradiol to the hypothalamus of estrogen-treated ovariectomized monkeys or oil-treated ovariectomized monkeys, respectively, indicated that the retention of [3H]estradiol in the nucleus was a saturable, limited-capacity phenomenon. No saturable subcellular distribution of [3H]progesterone or [3H]R 5020 was observed. This latter observation might be attributable to the presence of a progesterone receptor in too small a concentration to be detected by the methods used.

A high performance isolated rat brain preparation part I: Operative technique and recipient extracorporeal perfusion

The microsurgical preparation and high level performance with extracorporeal recipient perfusion of a stable, totally isolated rat brain model is presented. Emphasis has been placed on the use of the operating microscope, bipolar cautery and mechanical fixation units to affect a complete ablation of all non-osseous cephalic and vertebral tissues with minimal physiological disturbance of the animal as a whole. The simplified technique of recipient support circulation of the isolated brain organ achieves at least 5 h of tissue viability and function as measured by electrocortical activity, A-Vo2 differences and morphological appearance. To date, no other isolated rodent brain model has been described which is truly anatomically separated from all cephalic tissues. Additionally, other surgical attempts at isolation have required the use of abnormal physiological states, including deep hypothermia and circulatory arrest.

Deep brain hypothermia by means of high-flow biventricular cooling

Abstract A simple technique of rapidly inducing profound reductions in brain temperature in rhesus monkeys, utilizing bilateral ventricular perfusion with ice-cold saline, is presented. The expected dramatic reductions in cardiac rate and arterial pressure along with the development of an isoelectric state as the brain enters the deep hypothermic state are documented. Careful neurological follow-up has demonstrated full recovery in all animals.

A high performance isolated rat brain preparation part II. Cerebral blood flow in relation to perfusion pressure and cerebral hypothermia

The effects of changes of perfusion pressure and hypothermia on the cerebral blood flow of a new isolated rat brain preparation have been studied in 7 animals. The cerebral blood flow was extremely sensitive to the mean arterial pressure of perfusion, showing little evidence of autoregulation at low pressure, and only slight evidence in hypertension. The cerebral blood flow was lower in hypothermia. The preparation maintained good electroencephalographic activity throughout, and arteriovenous differences persisted up to 1 h after it became isoelectric.