Examination of geniculate ganglion cells contributing sensory fibers to the rat facial ‘motor’ nerve

Using a method to visualize HRP- containing cells in the geniculate ganglion (GG) in situ after decalcifying surrounding bone, we found that about 30% of the total (about 1000) GG cells contributed sensory fibers to the posterior auricular branch of the facial motor nerve. These cells are relatively large for GG cells in general. The remaining facial motor nerve branches, including those involved in vibrissal movement, contained few sensory afferent fibers originating from GG cells.     

Biosynthesis of phospholipids and sphingolipids from acetoacetate and glucose in different regions of developing brain in vivo

The incorporation of ¹⁴C-label from subcutaneously injected [3-¹⁴C]acetoacetate and [U-¹⁴C]glucose into phospholipids and sphingolipids in different regions of developing rat brain was determined. In all regions, phosphatidylcholine was the lipid synthesized most readily from either substrate. The percentages of radioactivity in other phospholipids and most sphingolipids remained relatively constant throughout postnatal development. An exceptional increase in the percentage of radioactivity incorporated into cerebroside, coinciding with a decrease of incorporation into phosphatidylcholine, was first noted on day 12 and continued until a maximal level was reached between days 18 and 20 of postnatal age. These developmental changes in preferential synthesis of lipids were associated with increased demands for phospholipids and cerebroside during the early and late postnatal stages, respectively. There was no difference in accumulation of radioactivity from acetoacetate, expressed as dpm of [¹⁴C]acetoacetate recovered in phospholipids plus sphingolipids per g of tissue, among all brain regions during the first 5 days of life. During active myelination (12 to 20 days of age); however, the amount of ¹⁴C-label was highest in brain stem, ranging from 1.9- to 2.3-fold greater than values for cerebrum and thalamus. The region with the next highest accumulation was cerebellum, followed by midbrain. During the same period, brain stem was likewise the most active site of accumulation of radioactivity from ¹⁴C-labeled glucose. Higher amounts of [¹⁴C]acetoacetate label accumulated in lipids of brain stem and cerebellum, relative to midbrain, thalamus, and cerebrum, coincide with evidence that active myelination begins in the hindbrain and proceeds rostrally toward the forebrain. Ketone bodies could therefore serve as a potential source of phospholipids and sphingolipids for brain growth and maturation.     

Results of 110 vitrectomies with a portable vitrectomy system

Filtration surgery was performed with a pressure-sensitive, unidirectional valve implant in 79 eyes with neovascular glaucoma. The device consisted of an open Supramid tube (outside diameter 0.58 mm) sealed to a Silastic tube with a slit valve. The Supramid tube was inserted at the corneoscleral limbus 1 to 4 mm into the anterior chamber. The Silastic portion was located under a scleral flap. Of the 79 eyes, 53 had postoperative intraocular pressures less than or equal to 24 mm Hg after a mean follow-up period of 23.7 +/- 10.9 months. Bleb revision for external scarring was required in ten of these 53 eyes and postoperative medical therapy was required in 26. The valve implant failed to control intraocular pressure in 26 of the 79 eyes. Failure was secondary to scarring of the external bleb in 18 eyes and to closure of the internal Supramid tube in five eyes. Mortality during the follow-up period was high: 12 of the 53 successfully treated patients and five of the unsuccessfully treated patients died.     

Bioavailability assessment under quasi- and nonsteady-state conditions II: study designs.

The flexibility of bioavailability assessment at quasi-and nonsteady state is demonstrated by systematically removing experimental constraints from the study design. Mathematical expressions are derived to describe each design variation. From the resultant solutions, it is evident that the proposed method can accommodate nonuniformities in dose, dosage interval, dosage regimen, dosing cycle, sampling interval, plasma half-life, washout period, and protocol adherence. Nominal requirements for the method are linear kinetics and mean plasma concentrations estimated over time intervals beginning and ending in the log-linear region.     

N-depyridination and N-dedimethylaminoethylation of tripelennamine and pyrilamine in the rat. New metabolic pathways

N-(2-Dimethylaminoethyl)benzylamine and 2-benzylaminopyridine were identified as two new urinary metabolites of tripelennamine in the rat by GC/MS. 2-(4-Methoxybenzylamino)-pyridine and N-(dimethylaminoethyl)-4-hydroxybenzylamine were identified as new urinary metabolites of pyrilamine by GC/MS. Thus, in addition to N- and O-demethylation, hydroxylation, and glucuronidation, N-debenzylation, N-depyridination and N-dedimethylaminoethylation were shown to be novel pathways for metabolism of tripelennamine and pyrilamine. The mechanism for N-depyridination and N-dealkylation is discussed.     

Metabolism of meperidine in several animal species

Four new meperidine metabolites were identified by GC-MS in the urine of rats, guinea pigs, rabbits, cats, and dogs. In addition to known meperidine metabolites, 4-ethoxycarbonyl-4-phenyl-1,2,3,4-tetrapyridine (dehydronormeperidine; IV, the N-hydroxydehydro derivative of normeperidine (X), the dihydroxy derivative of meperidine (XII), and the dihydroxy derivative of normeperidine (XIII) were identified. The possible role of the N-hydroxy derivative of normeperidine (IX) in the pharmacological interaction of meperidine (I) with MAO inhibitors, seen selectively in the rabbit (and humans), is discussed. Following the administration of the p-hydroxy derivative of meperidine (VII), the major metabolite was conjugated VII. Trace amounts of the p-hydroxy derivative of normeperidine (VIII), the methoxy hydroxy derivative of meperidine (XI), XII, and XIII also were detected as metabolites of VII. The degree of N-demethylation of VII, both in vitro and in vivo, was small.     

Doppler atrial shunt flow patterns in patients with secundum atrial septal defect: determinants, limitations, and pitfalls

Fifteen patients with uncomplicated secundum atrial septal defect underwent studies with real-time color-coded two dimensional flow imaging, pulsed Doppler echocardiographic examination, and simultaneous pressure recordings from the left and right atrium to determine the flow-pressure dynamics of the atrial shunt flow. In all 15 patients both the color flow mapping and pulsed Doppler studies revealed that the shunt flow was mainly from left to right, occurring both during ventricular systole and diastole. It started in early systole, reached a peak in late systole to early diastole, and lasted throughout diastole with an accentuation in late diastole during atrial contraction. The amplitude of the flow velocity, the direction, and the magnitude of the shunt flow, however, changed from phase to phase during the cardiac cycle. It correlated well with the phasic variation of the interatrial pressure difference, which usually revealed a peak pressure gradient that occurred in early systole between the x descent and v wave and during the period of v wave and a wave of the left atrial pressure tracing. Right to left shunt was not detected in any of the 15 patients by color flow mapping studies. A minor reversal of the shunt flow, however, was frequently detected at the beginning of ventricular systole and sometimes also in the middle of diastole by pulsed Doppler echocardiography. The reversal of shunt flow correlated with the minor reversal of pressure gradient that occurred during the z point, x descent, and y descent of the left atrial pressure tracing. In conclusion, left to right shunt flow occurs both during ventricular systole and diastole in uncomplicated secundum atrial septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noradrenergic potentiation of cerebellar Purkinje cell responses to GABA: evidence for mediation through the β-adrenoceptor-coupled cyclic AMP system

Previous in vivo studies from our laboratory have consistently shown that iontophoretically applied norepinephrine (NE) can potentiate γ-aminobutyric acid (GABA)-induced depressant responses of cerebrocortical, cerebellar and hypothalamic neurons. Additional experiments have further suggested that this noradrenergic facilitating action is specific for GABA and results from the activation of a β-type adrenoceptor. The goal of the present studies was to determine if the cAMP second messenger system might also be a component of the mechanism responsible for this NE modulatory action on GABA-mediated inhibition. In one set of in vitro experiments, we examined cerebellar neuronal responses to GABA before, during and after iontophoretic application of NE, 8-bromo3′,5′-cylic AMP (BcAMP) or 3-isobutyl-1-methyl xanthine (IBMX) or bath application of forskolin (10–30 μM). In a second group of in vivo studies, extracellularly recorded responses of individual cerebellar Purkinje (P) cells to iontophoretic pulses of GABA or β-alanine were examined before, during and after NE or BcAMP microiontophoresis. In 20 of 25 cerebellar cells recorded from tissue slices, iontophoretically applied NE markedly enhanced responses to GABA in a manner similar to that observed previously in vivo. In these in vitro preprarations, bath application of forskolin was also capable of potentiating GABA-induced inhibition in each of 4 cases tested whereas dideoxy-forskolin was not. Iontophoretic application of IBMX further enhanced the facilitating effects of NE on GABA-induced inhibition in 10 of 11 cases tested. Furthermore, under in vitro conditions, BcAMP augmented inhibitory responses to GABA in all cerebellar neurons tested. In the intact rat brain, iontophoretic administration of BcAMP caused a marked NE-like augmentation of P-cell responses to GABA in 73% of the cells tested. As with NE, BcAMP was ineffective in enhancing P-cell inhibitory responses to β-alanine, an agent which like GABA causes hyperpolarization, by increasing Cl⁻ conductance. In summary, these results indicate that a membrane permeant analog of cAMP, a phosphodiesterase inhibitor and an agent which directly activates adenyl cyclase can mimic the previously observed GABA-potentiating actions of NE. Thus, these findings provide further support for the contention that noradrenergic enhancement of GABA inhibition results from a cascade of transmembrane events which includes β-receptor activation, adenyl cyclase stimulation and increased intracellular production of cAMP.     

Anterior interhemispheric approach to aneurysms of the anterior communicating artery

A modified anterior interhemispheric approach for clipping aneurysms of the anterior communicating artery is described. This approach is preferred on anatomical grounds because the anterior circle of Willis can be fully visualized with minimal manipulation of the frontal lobes and anterior cerebral arteries. The advantages of this approach are minimal traction, reduced operative time, and preservation of the olfactory nerve.