Canine myocardial reperfusion injury: protection by a free radical scavenger, N-2-mercaptopropionyl glycine

Oxygen-derived free radicals and their metabolites may contribute to the extension of irreversible cellular injury, which occurs on reperfusion of the previously ischemic myocardium. Therefore, therapy directed against the toxic effects of reactive oxygen species may provide protection to the ischemic myocardium, which undergoes subsequent reperfusion. We evaluated the effectiveness of N-2-mercaptopropionyl glycine (MPG), a free radical scavenger, to limit the extent of irreversible injury resulting from 90 min of ischemia followed by 6 h of reperfusion in a canine model of myocardial infarction. In three groups of dogs, MPG (20 mg/kg) was administered as a constant infusion into the left atrium. Group I received MPG for 2 h, starting 15 min before occlusion of the left circumflex coronary artery and ending 15 min after reperfusion. Group II received MPG for 1 h, starting 15 min before reperfusion. Group III received MPG for 1 h beginning 45 min after reperfusion. Each group was compared with its respective saline control group. Infarct size was reduced by 35% in Group I (32.2 +/- 5.1% vs. 47.7 +/- 3.4% of the area at risk, p less than 0.05) and Group II (31.4 +/- 3.6% vs. 47.5 +/- 5.1% of the area at risk, p less than 0.025) in comparison with the saline treated control animals. In contrast, in Group III infarct size did not differ significantly from the saline-treated control group (45.9 +/- 3.3% vs. 47.7 +/- 3.5% of the area at risk). The percent of left ventricle at risk did not differ among the groups. The beneficial effects of MPG could not be explained on the basis of hemodynamic differences. In addition, MPG did not influence regional myocardial blood flow. In vitro studies indicated that MPG effectively scavanges O2- generated by the hypoxanthine-xanthine oxidase reaction, as well as by PMA-activated polymorphonuclear leukocytes. Based on these observations, we propose that MPG exerts its beneficial effects by protecting against free radical-mediated damage during the early phase of reperfusion.     

A ubiquitous protein is the source of naturally occurring peptides that are recognized by a CD8+ T-cell clone.

We previously isolated from mouse spleen an octapeptide (LSPFPFDL) that in association with the class I major histocompatibility complex protein Ld is recognized by the antigen-specific receptor of an alloreactive CD8+ T-cell clone (2C). Guided by an assay dependent upon the same 2C T-cell receptor, we have now isolated from the same source another naturally occurring peptide. The second peptide (VAITRIEQLSPFPFDL) includes the entire octapeptide sequence and preliminary evidence suggests that it may be a natural precursor of the octapeptide. On finding extensive sequence homology between the 16-mer and part of human 2-oxoglutarate dehydrogenase, we determined the cDNA sequence of mouse 2-oxoglutarate dehydrogenase and found that the deduced amino acid sequence matches precisely the two naturally occurring peptides, indicating their origin by cellular processing of this ubiquitous self protein.     

Transsynaptic degeneration of motoneurones caudal to spinal cord lesions

We studied the effects of complete transversal section of the spinal cord, at T8-10, in adult rats, upon the number and morphology of identified motoneurones in lumbar segments L4 and L5. In observations by light and electron microscopy many lumbar motoneurones had structural abnormalities when the interval between surgery and perfusion ranged between a few hours and one week. We found also that as many as 25% of the motoneurones distal to a cord transection disappeared as a consequence of the lesions. We did not find comparable changes in the spinal cord at C6 after transection at T8-10. Complete removal of the cerebellum did not reduce the lumbar motoneurone counts. Bilateral ablation of the "motor" cortex did cause a reduction of motoneurone counts at L4-5; these animals showed normal or near normal spontaneous locomotor activity beginning a few days after the lesion was placed. Motoneurone counts were significantly reduced after partial cord lesions that spared the dorsal funiculi (where the corticospinal tract travels in the rat), but in this case the rats were paraplegic as a result of the lesion. Cord transection at 7 days of postnatal age resulted in reduced motoneurone counts when the rats reached adulthood. Intraspinal or subarachnoid administration of colchicine led to reduced motoneurone counts. Prolonged infusion of a GABA agonist, muscimol, into the lumbar CSF did not prevent the loss of motoneurones produced by cord transection. Pretreatment of animals with a Ca2+ channel blocker (nimodipine) did not prevent the effects of cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decrease of potassium permeability by intracellular application of sodium ions in snail neurons

In the identified neurons B1, B2 and B3 of Helix pomatia an intracellular injection of Na+ induced an outward current in 10% and an inward current in 90% of the experiments. The outward current was associated with an increase and the inward current with a decrease of the membrane conductance. Both currents reversed at membrane potentials of between -60 and -70 mV. Inward currents were also elicited by intracellular Li+ or tris-[hydroxymethyl]-aminomethane (Tris+) injection. All inward currents were reduced by extracellular administration of tetraethylammonium or quinine. It is suggested that the outward current represents a calcium-activated potassium current and that the inward current is due to a blockade of potassium channels from the intracellular side.     

Paroxysmal neuronal depolarizations in the rat motor cortex in vivo: intracellular injection of the calcium agonist BAY K 8644

Summary Epileptic activity was elicited in the rat's motor cortex by local application of penicillin. At the neuronal level it consisted of typical paroxysmal depolarization shifts. The calcium agonist BAY K 8644 was injected into neurons showing such a discharge pattern. The application of this drug increased amplitude and afterdepolarization of paroxysmal neuronal depolarizations.     

Psychometric properties of the Boston Qualitative Scoring System for the Rey-Osterrieth Complex Figure

Interrater and internal consistency reliabilities were computed for the Boston Qualitative Scoring System, a newly developed system for scoring the Rey-Osterrieth Complex Figure. Subjects (N = 108) included males with right hemisphere stroke (n = 46), left hemisphere stroke (n = 20), dementia (n = 21), and normal controls (n = 21). Interrater reliability coefficients for all scales except asymmetry, which had a reliability coefficient of .2013, ranged from .6342 to .9919, with most in the good to excellent range. Internal consistency reliabilities ranged from .7774 to .9128, also with most in the good to excellent range. Discriminant indices of visuospatial accuracy scales found the scoring system to be useful in distinguishing between individuals based on visuospatial scores.     

The first radiation accident in America: a centennial account of the x-ray photograph made in 1890

On February 22, 1890, Dr Arthur Goodspeed and William Jennings made the first x-ray photograph, in the physical lecture room of the University of Pennsylvania. On that evening, Goodspeed and Jennings had been making brush electrographs of coins and brass weights. After they finished their experiments, Jennings stacked all of the photographic plates; two coins--either left from the experiments or Jennings' trolley fare--were placed on top of the plates. Goodspeed then demonstrated to Jennings the university's collection of Crookes tubes, with the idea of photographing the glow from the tube. While the two men were talking, however, the Crookes tube was emitting x radiation that affected the nearby plates. After the plates were developed, Jennings noted that one had the shawdow(s) of a disk(s) on it; neither man could explain the image. On hearing of Roentgen's work in 1896, Goodspeed and Jennigns retrieved the original plate and reproduced their "accident." The glass plate was subsequently lost among library archives.     

Parasitic diseases. Other roundworms. Trichuris, hookworm, and Strongyloides

Trichuriasis may be asymptomatic or, in heavy infection, lead to profuse, bloody diarrhea and rectal prolapse. Diagnosis is made by finding the distinctive barrel shaped eggs in the stool or in the heavily infested patient, by anoscopy and identification of worms attached to reddened and ulcerated rectal mucosa. Mebendazole is the drug of choice in treatment. Capillariasis, a parasitic infection encountered mainly in the Philippine Islands, is of interest in that the eggs may be confused with the eggs of trichuris. Hookworm disease is generally asymptomatic, but in heavy infection, leads to iron deficiency and hypochromic, microcytic anemia. Diagnosis is made by finding the characteristic hookworm eggs on a examination of a direct fecal film. Accidental invasion of humans by dog and cat hookworm leads to cutaneous larva migrans, also known as "creeping eruption." Human hookworm is treated most effectively with mebendazole, while the rash produced by creeping eruption responds to topical thiabendazole. Strongyloides is fairly common in rural areas of the southeastern United States and may be seen in the urban setting among inmates of mental institutions, prisons, and in immigrants who formerly resided in endemic tropical regions. Because of its remarkable capacity for dissemination of larvae throughout the body, this parasite is now recognized as a serious problem for the patient who is immunocompromised. Diagnosis is made by finding larvae in the stool or by the Enterotest. All infected patients should be treated with thiabendazole. I consider the issue on Drugs For Parasitic Infections, published annually or biannually by The Medical Letter on Drugs and Therapeutics, to be the single best source of information on the treatment of parasitic diseases for primary care physicians.