Drugs for epilepsy.
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Biomedical subjects
Publications and source records attributed to D F Smith.
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The hindlimb extensor reflex of reserpinized, spinal rats was used to determine whether tranylcypromine (dl-TCP) and its stereoisomers (d-TCP and l-TCP) after tryptaminergic neurotransmission. dl-TCP and d-TCP caused an extensor reflex while l-TCP failed to cause a reliable extensor reflex. Neither H 22/54 nor nialamide affected the extensor reflex in rats given dl-TCP, while H 22/54 reduced the reflex in rats given d-TCP. The results suggest that dl-TCP and d-TCP have direct as well as indirect actions on tryptaminergic neurotransmission.
Male albino rats given a bilateral injection of Baclofen (Lioresal) (12 micrograms/rat) in the cerebral ventricles showed a behavioral syndrome of activation + ataxia, paddling, tail-pinch hyperresponse and anesthesia. The phase of activation + ataxia was reduced by pretreatment of rats with H 44/68, FLA 63, reserpine, pimozide, phenoxybenzamine, oxypertine or chlorpromazine. The phase of paddling was reduced by pretreatment with FLA 63, reserpine, phenoxybenzamine, oxypertine, chlorpromazine, pimozide + phenoxybenzamine or apomorphine, while administration of clonidine instead of Baclofen caused paddling in non-pretreated rats. The phase of tail-pinch hyperresponse was reduced by reserpine, oxypertine, chlorpromazine or pimozide + phenoxybenzamine, while none of the pretreatments affected Baclofen-induced anesthesia. Drugs which affect mainly tryptaminergic or GABA-ergic functions failed to affect Baclofen-induced behaviors consistently. The findings suggest that dopaminergic and noradrenergic functions play a role in the central effects of Baclofen on behavior of rats.
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A 1700 nucleotide DNA sequence derived from Xenopus vitellogenin mRNA has been cloned in the bacterial plasmid pBR322. The identity of the cloned sequence was verified in two ways. Firstly, the plasmid DNA was shown to hybridise to an RNA of the correct size (6,700 nucleotides). This was shown by in situ hybridisation to electrophoretically separated RNA and also by the formation of "R-loops" with purified vitellogenin mRNA. Then, using a novel procedure in which plasmid DNA covalently bound to diazotised paper is used to select complementary mRNA sequences, the cloned sequence was shown to hybridise to an mRNA which directed the synthesis of vitellogenin when translated in a reticulocyte lysate cell-free system.
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A recent study by Kling et al (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intraperitoneal injection (2 mmol lithium kg-1) of lithium orotate as a slurry than of lithium carbonate in solution. The authors suggested that lithium orotate might offer advantages in the treatment of patients. We repeated the experiments of Kling et al but in addition examined the kidney function of the rats. Glomerular filtration rate and urine flow were markedly lower in rats given lithium orotate than in rats given lithium carbonate, sodium chloride or a sham injection. The renal lithium clearance was significantly lower, the kidney weight and the lithium concentrations in serum, kidney and heart significantly higher after injection of lithium orotate than after injection of lithium carbonate. The higher lithium concentrations could be accounted for by the lower kidney function. It seems inadvisable to use lithium orotate for the treatment of patients.
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Adult male Wistar rats given an i.p. injection (3 ml/kg) of a 2-phenylcyclopropylamine (59 mumol/kg) were tested 3--5 h later for shock-induced aggression, jump threshold, stereotypic movement, rearing and ambulation. Shock-induced aggression was facilitated by trans-1-2-phenylcyclopropylamine (1-TPCP) and was suppressed by trans-d-2-phenylcyclopropylamine (d-TPCP). Neither drug affected jump threshold. The effects of 1-TPCP and d-TPCP on irritable aggression are discussed in terms of the effects of the drugs on monoaminergic mechanisms. A behavioral syndrome of increased stereotypic behavior of the serotonin-dependent type as well as decreased rearing and ambulation occurred in rats given d-TPCP, trans-dl-2-phenylcyclopropylamine, 2-(4-chlorophenyl)-cyclopropylamine and 2-(3,4-dichlorophenyl)-cyclopropylamine, but not in rats given 1-TPCP, cis-dl-2-phenylcyclopropylamine, 2-(2-chlorophenyl)-cyclopropylamine or 2-(2,5-dichlorophenyl)-cyclopropylamine. The findings suggest that the behavioral syndrome depended in part on the absence of a chlorine substitution in the ortho position of the phenyl ring.
The effects of an i.p. injection of 0.15 M LiCl resembled closely the effects of another toxic substance, 0.005 M PbCl2, on conditioned aversion to saccharin and rearing movements in male rats. The findings suggest that nonspecific aversive after-effects of a LiCl injection can account fully for prompt effects of LiCl on rearing behavior.
1. Oestradiol-17beta induces livers of Xenopus laevis (South African clawed toad) to synthesize and secrete into the serum large quantities of the egg-yolk-protein precursor, vitellogenin. The peak of this response occurs 9-16 days after hormone treatment [Dolphin, Ansari, Lazier, Munday & Akhtar (1971) Biochem. J.124, 751-758]. It is now shown that 6 days after hormone treatment a 120-160-fold stimulation of the synthesis of cholesterol and fatty acid compared with control values occurred. 2. A cell-free system, derived from Xenopus liver, which synthesizes squalene and fatty acid is described. By using this system, several hundredfold stimulation of incorporation of [(14)C]acetate into squalene was recorded 6 days after the administration of oestradiol-17beta, compared with a 3-4-fold stimulation of incorporation of [(3)H]mevalonate compared with control values. It is argued that oestradiol-17beta must affect enzyme(s) catalysing step(s) between acetate and mevalonate in the biosynthetic pathway to cholesterol. 3. In incubation of liver slices in vitro, most of the lipid and cholesterol synthesized in response to the steroid hormone was associated with those subcellular fractions that contained membranes. Moreover, pulse-labelling experiments in vivo showed that 70% of this lipid and cholesterol was retained in the liver. The remainder appeared in the serum, where it was equally distributed between vitellogenin and vitellogenin-free serum. 4. G.l.c. analyses of the cholesterol content of liver microsomal fractions of Xenopus laevis indicated that the cholesterol content was at least 50% higher in microsomal fractions obtained from livers that had been exposed to oestradiol-17beta. Meanwhile, g.l.c. analysis of the lipid moiety of secreted vitellogenin showed that up to 35% of its lipid was cholesterol.
A retrospective analysis was made of 100 cases of surgically corrected right-side torsion of the abomasum (RTA) in dairy cows. A classification for degrees of severity of RTA was developed, based on the amount of fluid sequestered in the abomasum. Serum concentrations of Na+, K+, AND Cl- decreased with increasing severity of RTA. Cows in the most severely affected classification were markedly hypochloremic and hypokalemic. The PCV, plasma protein concentration, and pulse rate increased with increasing severity of RTA. Statistically significant correlations were observed between postsurgical outcome and classifications of RTA, serum Cl- concentration, and pulse rate. The outcome was not statistically related to serum concentrations of Na+ or K+, PCV, or plasma protein concentration.
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