Dexamethasone alters glucose, lactate, and insulin dyshomeostasis during endotoxicosis in the rat.

This study examined the effects of dexamethasone on the glucose, lactate, and insulin dyshomeostasis of endotoxicosis in the rat. To assess the effects of dexamethasone on carbohydrate dyshomeostasis, sequential measurements of plasma glucose and lactate were made in vivo. The effects of dexamethasone on endotoxin-induced portal and systemic hyperinsulinemia also were evaluated in vivo. The ability of dexamethasone to alter the insulin hypersecretory state of the endotoxic pancreas was evaluated by using the in vitro perfused rat pancreas. Endotoxicosis caused severe hypoglycemia and hyperlactacidemia in the pentobarbital-anesthetized rat. Dexamethasone prevented the hypoglycemia, significantly reduced the hyperlactacidemia, and prevented endotoxin-induced hyperinsulinemia in vivo. Dexamethasone reduced endotoxin-induced pancreatic hypersecretion of insulin when administered as a pretreatment 1 h prior to endotoxin treatment; however, when administered as a cotreatment with endotoxin, no significant reduction of insulin hypersecretion occurred. The results of this study suggest that the ameliorating effects of dexamethasone on glucose and lactate dyshomeostasis occur not only at the peripheral tissue level, but also through effects on insulin secretion.

Lithium prevention of amphetamine-induced 'manic' excitement and of reserpine-induced 'depression' in mice: possible role of 2-phenylethylamine.

Repeated treatment of mice with lithium chloride (45 mg/kg, i.p., daily for 8 days) reduced the jumping, fighting, stereotypies, and hyperactivity induced by d-amphetamine (5 mg/kg, i.p.). Lithium also reduced the hypoactivity observed 1--3 h after reserpine (0.75 mg/kg, i.p.). In biochemical studies we found that 8-day treatment with lithium markedly reduced (to 45% of control) the recovery from brain of labelled 2-phenylethylamine (PEA) following i.p. injection of labelled L-phenylalanine, while decreasing recovery from brain of labelled PEA following its i.p. injection of 63% of control. In saline-treated mice, d-amphetamine appeared to increase PEA synthesis and to accelerate its disposition, whereas reserpine enhanced PEA synthesis and reduced disposition; all of these effects were antagonized by lithium pretreatments. Since PEA appears to be one of the most powerful behavioral stimulants among endogenous neuroamines, and because its deaminated metabolites are behavioral depressants, such antagonism of brain PEA metabolism may significantly contribute to the prophylactic action of lithium against both manic and depressive behavior.

Metabolism of an amino acid with antidepressant properties.

The amino acid D-phenylalanine exerts antidepressant properties which are believed to be due to its metabolism to brain phenylethylamine. We now show that in mice, the increase in brain phenylethylamine levels induced by L-phenylalanine, but not D-phenylalanine, is antagonized by drugs which block the stereospecific decarboxylase enzyme. Our results show that D-phenylalanine metabolism to phenylethylamine is independent of pathways involving L-phenylalanine.

Differential membrane effects of general and local anesthetics.

The authors studied the effects of varying Na+ and Ca++ concentrations and of replacing H2O with D2O in Ringer's solution upon the actions of general and local anesthetics on isolated frog sciatic nerves. This experimental model was used to study whether general anesthetics affect excitable membranes in a manner similar to that of typical membrane stabilizers (local anesthetics). Procaine (2.5-7.5 mM), halothane (9, 18, and 36 mM), enflurane (8 mM), and ketamine (0.15 and 0.73 mM) raised threshold and lowered spike amplitude, and their effects were facilitated by reducing Na+ concentration in the Ringer's solution. The local anesthetic effects of procaine (2.5-7.5 mM) and ketamine (0.73 mM) were antagonized by Ca++, while the axonal depressant effect of halothane was facilitated by increasing Ca++ concentration in the Ringer's solution, indicating a different mode of action. General anesthetics also differed from local anesthetics in their interaction with water: replacement by D2O of H2O in the Ringer's solution selectively increased the axonal depressant effects of halothane and enflurane but not those of ketamine or procaine. Since D2O differs from H2O in its greater ice-likeness, these results are consistent with the view that general anesthetics stabilize excitable membranes via stabilization of the water-biopolymer lattice, as predicted by the hydrate-microcrystal theory of anesthesia. In contrast, local anesthetics may stabilize excitable tissues by binding to the same fixed negative charges of the membrane to which Ca++ is normally bound. (Key words: Theories of anesthesia, hydrate-microcrystal; Nerve, mode of action of anesthetics; Anesthetics, volatile, halothane; Anesthetics, volatile, enflurane; Anesthetics, local, procaine; Anesthetics, intravenous, ketamine.)

Ketamine anesthesia for laparoscopy.

PIP: A total of 57 patients were selected for ketamine anesthesia during laparoscopy. Of these 45 underwent bilateral partial salpingectomy for sterilization, 7 had diagnostic laparoscopy, and 5 a combination of dilation and curettage and sterilization. All were given meperidine HCl, 50 mg, and atropine sulfate, .4 mg, shortly before surgery. Most were also given hydroxyzine hydrochloride, 50 mg, or occasionally 75 mg. A few received valium, 10 mg, instead. Total average dose of ketamine was 431 mg, with a range of 225-1093 mg. Only 1 patient received over 1 gm. Statistical analysis of data showed that time of anesthesia rather than weight of the patient was the more important factor in determining dosage. Initial dose of ketamine was about 1 mg per pound of body weight, given iv. For maintenance, at 5-10 minute intervals amounts half the original dose were used. Average operating time was 45 minutes. Effective anesthesia was produced for the duration of the procedure. 2 patients had laryngospasm, 2 had postoperative hallucinations, 1 had postoperative confusion and irrational behavior, and 1 patient developed tachycardia. Transient elevations of blood pressure were the rule. Advantages of ketamine anesthesia are claimed to be: special selective effect on pain perception, stimulation of cardi ovascular system, antiarrhythmic properties, increase of reflexes, patent airway, and more natural appearance of the patient.^ieng