Interaction between ethanol and low dietary zinc during gestation and lactation in the rat

Pregnant rats were fed individual liquid diets throughout gestation and lactation. The diets contained either 2 or 10 micrograms zinc/ml diet with or without 30% of the kilocalories supplied from ethanol. The low zinc diet produced a moderate zinc deficiency in dams evidenced by decreases in tissue zinc content, serum alkaline phosphatase activity and urinary zinc concentration. Despite the presence of high zinc content in the diet, ethanol antagonized the maternal zinc status to a level typical of that produced by the low zinc diet. The lowest zinc status, however, was found when low dietary zinc and ethanol were combined. The maternal interaction between ethanol and zinc also depressed offspring serum zinc and alkaline phosphatase activity in a similar manner. Ethanol, however, did not affect tissue content of calcium, magnesium or phosphorus, which indicates that ethanol is a specific antagonist of zinc utilization during gestation and lactation.     

Intraventricular hemorrhage due to aneurysms of the distal posterior inferior cerebellar artery. Report of three cases

Three cases of ruptured aneurysm of the distal posterior inferior cerebellar artery (PICA) presenting with isolated intraventricular hematoma are reported. All of the aneurysms originated from the lateral medullary segment of the PICA and ruptured into the lateral recess of the fourth ventricle. The diagnosis of distal PICA aneurysm should be considered if isolated intraventricular hematoma is found without obvious parenchymal hemorrhage or subarachnoid blood in the basal cisterns. Complete vertebral arteriography is a requisite for the recognition of this condition. The outcome in patients with these aneurysms should be good if surgical repair is performed before rebleeding occurs.     

The value of thallium and three-phase bone scans in the evaluation of bone and soft tissue sarcomas

Thirty-seven patients with newly diagnosed or treated sarcomas had 47 sets of sequential thallium scans (TS) followed by three-phase bone scan (TPBS) on the same day. The diagnosis in all patients was verified by biopsy (n=40) or long-term follow-up studies (n=7). The sensitivity, specificity, and accuracy of TS and TPBS in detecting sarcomatous lesions was calculated: TS sensitivity was 88%, specificity 69%, and accuracy 83%; blood flow (BF) and blood pool (BP) sensitivity was 91%, specificity 54%, and accuracy 81 %; delayed bone scan (DB) sensitivity was 88%, specificity 38%, and accuracy 74%. In 17 studies the flow and blood pool parts of the TPBS and TS demonstrated the soft tissue component of sarcomas, which would have been missed if only the delayed bone scan had been performed. The TS lesion to normal tissue ratio alone was not very helpful in differentiating sarcomas from benign conditions because some benign lesions are highly cellular and vascular while some malignant lesions, such as chondrosarcoma, have poor vascularity and a less cellular chondroid matrix. However, when the thallium ratio was correlated with similar ratios calculated from yhe BP image, it was found that if the TS lesion to normal tissue ratio exceeded the BP lesion to normal tissue ratio (12 patients), the specificity for detecting sarcomatous lesions was 100%. Nevertheless, the reverse was not true. The positive predictive value of this observation was 100% and the negative predictive value was 37%.     

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.