D-aspartate binding to the glutamate uptake site in human brain tissue — effects of leucotomy

Summary Binding of [3 H]D-aspartate, as an indicator of glutamate uptake sites, was investigated in post-mortem human brain tissue by use of a centrifugation assay to separate free and bound ligand. Binding was displaceable, apparently saturable and to a single site, with mean K_D and Bmax values of 2.3 M and 40.3 nmol/g tissue in the frontal cortex. The method was applied to the study of tissue from frontal and temporal cortices and the caudate nucleus of five psychiatric patients who had undergone a frontal leucotomy. The effects of this neurosurgical procedure were to diminish by almost 50% the density of D-aspartate binding sites in the frontal cortex and caudate nucleus, while the temporal cortex was less affected. It is concluded that the method provides a potentially useful correlate of glutamatergic innervation in human brain tissue.     

Cation exchange contribution to the retention of specific quaternary ammonium compounds in reversed-phase high-performance liquid chromatography

The influence of electrolytes on the retention of organic cationic solutes in reversed-phase high-performance liquid chromatography (RP-HPLC) has been investigated. The effects of the nature and concentration of electrolytes and mobile phase pH on the retention of two model quaternary ammonium compounds were studied on mu-Bondapak C18 stationary phase with aqueous methanolic eluents. The nature and concentration of inorganic cations added to the mobile phase modified the retention of the solutes. The counter anion of the added electrolyte did not perceptibly influence solute retention at constant mobile phase pH, although it did significantly influence solute retention when the electrolytes were added to unbuffered mobile phases. The retention data are consistent with the inclusion of an ion exchange contribution to the retention of cationic solutes in the systems investigated.     

Estimates of radiation absorbed dose for intraperitoneally administered iodine-131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses

Using a newly available model for determining estimates of radiation absorbed dose of radioisotopes administered intraperitoneally, we have calculated absorbed dose to tumor and normal tissues based on a surgically controlled study of radiolabeled antibody distribution. Ten patients with peritoneal carcinomatosis received intraperitoneal injections of the murine monoclonal antibody B72.3 radiolabeled with 131I. Biodistribution studies were performed using nuclear medicine methods until laparotomy at 4-14 days after injection. Surgical biopsies of normal tissues and tumor were obtained. The marrow was predicted to be the critical organ, with maximum tolerated dose [200 rad (2 Gy) to marrow] expected at about 200 mCi (7.4 GBq). In patients with large intraperitoneal tumor deposits, the tumor itself is an important source tissue for radiation exposure to normal tissues. Local "hot-spots" for tumor-absorbed dose were observed, with maximum tumor-absorbed dose calculated at 11,000 rad (11 Gy) per 100 mCi (3.7 GBq) administered intraperitoneal; however, tumor rad dose varied considerably. This may pose serious problems for curative therapy, especially in patients with large tumor burdens.     

Extending epidural blockade for emergency caesarean section. Evaluation of 2% lignocaine with adrenaline

Pre-existing epidural analgesia was rapidly extended in 36 consecutive patients presenting for emergency caesarean section by using 20 ml of 2% lignocaine + 1/200,000 adrenaline freshly prepared given by slow bolus injection. Despite a wide range of initial analgesic sensory levels the technique produced blocks that were dense with adequate anaesthesia for surgery in all patients within 12.5 min. The plasma local anaesthetic concentrations were well below the toxic range. Neonatal condition was good.     

Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver

Dichloroacetic acid (DCA) is a chlorination byproduct found in finished drinking water. When administered in drinking water this chemical has been shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over the animal's lifetime. In this study, we investigated whether mutant frequencies were increased in mouse liver using treatment protocols that yielded significant tumor induction. DCA was administered continuously at either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice harboring the bacterial lacI gene. Groups of five or six animals were killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of treatment, there was no significant difference in mutant frequency between the treated and control animals at either dose level. At 60 weeks, mice treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60 weeks had a 2.3-fold increase in mutant frequency over the concurrent controls (P = 0.002). The mutation spectrum recovered from mice treated with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%) and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T transitions comprised 53.19% of the recovered mutants among control animals. Although only 19.15% of mutations among the controls were at T:A sites, 32.79% of the mutations from DCA-treated animals were at T:A sites. This is consistent with the previous observation that the proportion of mutations at T:A sites in codon 61 of the H-ras gene was increased in DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates DCA-associated mutagenicity in the mouse liver under conditions in which DCA produces hepatic tumors.      

Fatty acid balance studies in term infants fed formula milk containing long-chain polyunsaturated fatty acids

Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP ( n = 20) and standard Aptamil ( n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group ( n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg⁻¹) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil ( p < 0:01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between.