9-Nor-9-hydroxyhexahydrocannabinols. Synthesis, Some behavioral and analgesic properties, and comparison with the tetrahydrocannabinols

The racemic mixture and levo isomer of both 9-nor-9alpha-hydroxyhexahydrocannabinol and its 9beta-hydroxy isomer were prepared. Both alpha-and beta-hydroxy compounds were active in the dog ataxia test and depressed spontaneous activity in mice. However, only the beta-hydroxy compound was an analgesic in mice morphine-like potency. The behavioral and analgesic properties of these compounds may be mediated through different sites or mechanisms and may, therefore, be separable.     

Editorial. Phencyclidine: an emerging drug problem

A technique was developed for catheterization of the portal vein in rhesus monkeys (Macaca mulatta). Silicone rubber catheters (0.040 ID by 0.085 inch OD, or 0.030 ID by 0.065 inch OD) were surgically placed into the portal vein via the umbilical, inferior mesenteric, right colic, or ileocolic veins. The right colic and ileocolic veins proved to be the preferred route for catheterization. Both single end-hole and multiple end-hole catheters with 2 side holes were used. Catheter function was dependent upon proper placement within the portal vein and on maintaining patency. Single-hole catheters were successfully maintained by periodic flushing (2-3 times daily) with heparinized saline solution (1.5-4.0 units/ml), and multiple-hole catheters were best maintained by a continuous flow (1-2 ml/hour) of heparinized saline solution (1.5 units/ml). No adverse clinical effects due to the portal catheter were observed in any of the monkeys catheterized. The technique allowed placing the monkey in a restraint chair, thus enabling one to utilize the monkey in a conscious state.     

In vitro metabolism of aniline by sheep intestine

1. The major metabolite after incubating aniline with sheep intestine was acetanilide. 2. Other metabolites detected in smaller amounts were 2-aminophenol, 4-aminophenol, 2-acetamidophenol and 4-acetamidophenol. 3. The rumen, abomasum duodenum, jejunum, ileum and colon were all able to acetylate aniline. 4. 4-Aminophenol, 4-aminobenzoic acid, 4-anisidine and 4-nitroaniline were also acetylated.     

Modification of venous stasis thrombosis in the rat by platelet-active drugs and by heparin

Incubation of adenovirus type 2 infected cells at 42 degrees C resulted in an inhibition of assembly of virus particles although all the major viral structural polypeptides and virus-induced cellular polypeptides so far identified were detected by electrophoretic analysis. Selective high salt-acid-urea extraction of low mol. wt. polypeptides revealed the absence of protein VII at 42 degrees C whereas precursor polypeptide P-VII and core protein V were found. Pulse-chase and temperature shift experiments indicated that cleavage of P-VII into VII was a reversible thermosensitive process, requiring de novo protein synthesis after shift-down to 37 degrees C. Virus particles assembled at 37 degrees C after transfer from 42 to 37 degrees C contained both viral DNA and polypeptides pre-labelled during the eclipse phase at 42 degrees C, including core protein VII.     

A preplanned treatment for malignant hyperpyrexia

Vidarabin (Dr. Thilo) is an effective virostatic agent in recurring herpetic corneal lesions.     

Studies of chemical modifications of proteins by carbon 13 neuclear magnetic resonance spectroscopy. Reaction of hen egg white lysozyme with iodine

The reaction of iodine with aromatic residues of hen egg white lysozyme is examined by means of natural abundance 13C nuclear magnetic resonance spectroscopy. In the unfractionated product of the reaction at PH 5.5 (with I2/lysozyme molar ratios of 0.5, 1.0, and 2.5), the only detectably modified aromatic residues are Trp-108 and either Tyr-20 or Tyr-23 (probably the latter). The rates of reaction at the two sites are similar. The extents of modification (at each site) are approximately 25%, 50%, and approximately greater than 80% for I2/lysozyme molar ratios of 0.5, 1.0, and 2.5, respectively. At pH 4.5, the rates of reaction of both residues are about one-third or less of the rates at pH 5.5. When the reaction is carried out at pH 8.5 (with an I2/lysozyme molar ratio of 1.0), only the tyrosine residue is modified. Resonances observed in the spectra of the modified protein mixtures (but not in the spectrum of intact lysozyme) indicate that the modified Trp-108 residue is not oxindolealanine, but either delta1-hydroxytryptophan or an ester thereof. This result is consistent with previous evidence which indicates that the modified tryptophan is the Glu-35 ester of delta1-hydroxytryptophan-108 (Imoto, T., and Rupley, J.A. (1973) J. Mol. Biol. 80, 657-667; Beddell, C. R., Blake, C. C. F., and Oatley, S. J. (1975) J. Mol. Biol. 97, 643-654). The spectra also indicate that the modified tyrosine residue is predominantly monoiodinated. The spectra of modified protein samples subjected to denaturation with 6M guanidinium chloride for 24 h at 37 degrees (and the renatured) indicate that residue 108 is converted to about equal amounts of the two diastereoisomers of oxindolealanine. However, incubation in 6M guanidinium chloride for 2 h at 25 degrees does not cause measurable hydrolysis of the Glu-35 ester of delta1-hydroxytryptophan-108.     

Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases

A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome;16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block. Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites.