Jeffery W. Gerst

The Electroencephalographic Pattern during Electroconvulsive Therapy II. Preliminary Analysis of Spectral Energy

Computer assisted energy-spectral analyses were obtained on EEG recordings of unilateral non-dominant hemisphere ECT-induced seizures using the different pre-ECT anesthetic agents methohexital (Brevital), Innovar, and ketamine (Ketalar). The previously postulated predominance of electrical energy over the stimulated (right) hemisphere early in ECT-induced seizures is confirmed. There appears to be marked reduction in total seizure energy with methohexital anesthesia, whereas ketamine anesthesia appears to be associated with increased overall seizure energy. The greatest right to left energy transfer during the seizure occurred with Innovar anesthesia.

The Electroencephalographic Pattern during Electroconvulsive Therapy: V. Observations on the Origins of Phase III Delta Energy and the Mechanism of Action of ECT

The generation of the spike-wave activity of Phase III of ECT seizures is attributed to the recurrence of synchronized, prolonged periods of intense inhibitory current flow (hyperpolarization), and associated rebound spike bursts, produced by the inhibitory circuit relationships and intrinsic electrophysiological properties of thalamic neurons. An anatomical and neurophysiological model of the development of generalized, synchronous 3-Hz spike-wave seizure activity is proposed which outlines the origin, maintenance, slowing, and termination of this fundamental seizure rhythm. Phase III inhibitory current flow (delta energy) and/or spike bursts may bring about therapeutic benefit by initiating a chain of agonist-independent and agonist-dependent events which results in long-term augmentation of serotonergic and noradrenergic neurotransmission and diminution of cholinergic neurotransmission in the forebrain. A specific anatomical and functional model of the mechanism of action of ECT is proposed, in which: (1) adrenergic and cholinergic pathways in the forebrain are assumed to be massively stimulated during ECT seizures, whereas serotonergic pathways are assumed to be inhibited during these seizures; (2) the beneficial effects of ECT are considered to be more dependent upon ECT-induced changes in 5-HT neurotransmission than upon alteration of noradrenergic function; (3) these beneficial effects involve up-regulation of 5-HT2 and down-regulation of M1- and M2-muscarinic receptor densities by both agonist-independent and agonist-dependent mechanisms, coupled with functional augmentation of noradrenergic neurotransmission; and (4) these effects may be brought about by Phase III inhibitory current flow- and/or spike burst-induced alteration of the function of second-messenger generator systems.

Biliary secretion of 14C and identification of 5,6-dihydro-5,6-dihydroxycarbaryl glucuronide as a biliary metabolite of [14C]carbaryl in the rat☆☆☆

Abstract The biliary secretion of 14 C was observed in conscious, bile-fistulated rats given single oral doses of [ 14 C]carbaryl (1.5, 30, and 300 mg/kg). Over 94% of the 14 C was absorbed after 12 hr. From 15 to 46% of the 14 C was secreted in bile, 10–40% in urine, and less than 1% in feces 12 hr after dosing. Three metabolites were isolated from bile and identified by mass and/or NMR spectrometric methods. These metabolites were: 5,6-dihydro-5,6-dihydroxycarbaryl glucuronide (12–18% of the biliary 14 C), a conjugate(s) of carbaryl (12% of the biliary 14 C), and conjugated isomers of hydroxy-carbaryl (2% of the biliary 14 C). The majority of the biliary 14 C remains to be identified.

6-Hydroxydopamine Retardation of Ovarian Development in the Housefly, Musca Domestica L.

Drug treatments affecting biogenic amine systems interfere with the processes of vitellogenesis and egg maturation in dipterans. 6-hydroxydopamine (6-OHDA) acts as a “chemical castrator” in female Sarcophaga bullata (De Loof et al., 1981) presumably by inhibiting the release of a gonadotrophic factor (Huybrechts and De Loof, 1981). Musca domestica were treated with 6-OHDA to assess the drug’s overall effects on ovarian development.

Brumback and Gerst reply

Mitochondrial calcium overload has _-been suggested as the general mechanism for cell necrosis in muscle disease.2 There is excess calcium entry into the cell as well as a failure of calcium removal. Prostaglandin El is well known for its bell-shaped dose response curve with very low and very high levels having the same effect. Very high levels of Prostaglandin El can inhibit ,Thromboxane A2 (TXA2) activity which is involved in both calcium release and calcium removal. A substantial overproduction of Prostaglandin El has been proposed to exist in myotonic dystrophy as it explains the presence in myotonia of weakness, reproductive abnormalities, reduced glucose tolerance, increased ,.metabolic effect of growth hormone, and anatomical motor end plate abnormalities.4 Finally, lithium inhibits the production of Prostaglandin El by an opiate-like effect and has, in fact, been suggested by Horrobin4 to improve the clinical state in myotonic dystrophy.

Enterohepatic circulation and biliary secretion of 5,6-dihydro-5,6-dihydroxy[14C]carbaryl glucuronide in the rat☆☆☆

Abstract Intestinal absorption (enterohepatic circulation) and biliary secretion of 14 C from a metabolite of carbaryl isolated from rat bile, 5,6-dihydro-5,6-dihydroxy[ 14 C]carbaryl glucuronide, and its aglycone were observed: Lincomycin and kanamycin sulfate were also given to rats to determine the effect of an altered intestinal microflora on the above processes. Net absorption of 14 C from the glucuronide occurred in the small intestine and cecum of control rats (68.5%); 10% of the infused 14 C was secreted in the bile. Antibiotic treatment affected the site of absorption and the biliary secretion of 14 C from the glucuronide since net 14 C absorption occurred only in the small intestine of antibiotic-treated rats (32.5%) and biliary secretion accounted for less than 1% of the infused 14 C. The site of absorption of 14 C from the aglycone and biliary secretion of 14 C (17%, control rats; 14%, antibiotic-treated rats) were not affected by antibiotic treatment. Carbon-14 from the aglycone was absorbed primarily in the small intestine (89.3%, control rats; 84.2%, antibiotic-treated rats). The results indicate that the intestinal microflora influence the enterohepatic circulation and biliary secretion of the glucuronic acid conjugate of 5,6-dihydro-5,6-dihydroxycarbaryl.