Increased BAEP latency and reduced brain cytochrome c oxidase activity observed in the Suzuki model of Alzheimer's disease [abstract]

Cytochrome c oxidase (COX), the terminal respiratory enzyme, is reported to be deficient and to exhibit reduced activity in a number of neurodegenerative disorders. The Alzheimer's rabbit model is based on the intracerebral injection of Holt's adjuvant, an aluminum salt solution. This model was used to compare the brain activity and the activity of brain COX in treated and controlled rabbits. Of a total of 26 New Zealand white rabbits, thirteen were injected intracerebrally with Holt's adjuvant solution, five with physiologically saline solution and the remainder were kept as controls. The auditory responses (BAEP) of the rabbits were monitored for 14 days before injections and 14 days thereafter. The animals were then sacrificed and brain mitochondrial extracts were used for SDS-PAGE analysis, difference spectra spectrophotometry and polarographic assays. The results of SDS-PAGE showed that there were no differences in the protein composition of the brain mitochondria of the three groups. Similarly, difference spectra (reduced minus oxidized, 400-630 nm) from both treated groups were identical to that of the control with characteristic maxima centered around 434, 550 and 604 nm. Polarographic assays, however, showed that while the enzyme from both treated groups displayed the characteristic biphasic kinetics, there was reduced activity in the enzymes from the brain of rabbits receiving the adjuvant but not the saline solution. This result is significant in light of the fact that several researchers have reported reduced activity of COX from Alzheimer's disease (AD) patients. Of particular significance, BAEP results reveal an increase in the interpeak latency between peaks III and V of the Holt's injected but not the saline injected or control rabbits. This latter result suggests that monitoring the BAEP might provide a simple non-invasive method for confirming AD. (AU)

Osseointegration of the bone-anchored prosthesis

This is the first of three articles reviewing the biomechanical features, histology and clinical results of the Osteo-Ti dental implant system. The second and third papers will describe surgical and prosthetic protocols, respectively (AU)

Strongyloides stercoralis: characterization of immunodiagnostic larval antigens

Forty-one-, 31-, and 28-kDa proteins of strongyloides stercoralis filariform larvae have previously been demonstrated to be sensitively and specifically recognized by serum IgG in individuals with strongyloidiasis. Characteristics of these proteins, their immunodominant epitopes, and reactive antibodies are described here. The proteins are soluble is aqueous as well as detergent extracts. The immunodominant epitopes are present in S. stercoralis but not in S. cebus or S. ratti. Epitopes on the three proteins are not shared, as determined by cross-absorption of serum with each of the size components on nitrocellulose. In most sera from strongyloidiasis patients there was reactivity to each of the proteins by IgG1 and IgG4, but reactivity by IgG2 or IgG3 was detectable only in a minority. A rabbit antiserum raised to a 41-kDa size fraction of S. stercoralis larvae reacted against a doublet of 41-kDa which was distinct from the immunodiagnostic 41-kDa protein.(AU)

Isolation of branched chain alpha-keto acid dehydrogenase from rabbit liver

An enzyme catalysing a series of reactions resulting in the oxidative decarboxylation of branched chain alpha-keto acids and production of NADH, was extracted from rabbit liver mitochondria with the aid of NaClO4. Purification yielded a product which appeared homogeneous on alpha-ketoisocaproate, alpha-keto-beta-methyl valerate, and alpha-ketoisovalerate. (AU)

The influence of canasol on various tissues including the eye and the modification of the ocular effect by several alpha adrenoceptor antagonists

Canasol solution is an ophthalmic drop prepared from Cannabis sativa and contains 0.3 percent of active solid. The solution produced vasoconstriction in the auricular artery and in the rabbit's ear, inhibited the pendular movement of the rabbit jejunum. and produced a marked lowering of the intra ocular pressure in the dog. The response in the eye is localized in that it does not produce consensual responses in the centralateral eye. Both the vascular and the ocular responses to canasol acts by stimulating alpha adrenoceptor (Summary)

The treatment of glaucoma using a non-psychoactive preparation of cannabis sativa

A non-psychotropic, ophthalmic preparation from cannabis sativa produced a significant fall in intraocular pressure both in the dog and in glaucoma patients. The preparation is non-toxic and compared favourably with pilocarpine in the dog. It is concluded, from our observations, that cannabis sativa contains an active principle which is non-psychotic and which has a significant effect in lowering the intraocular pressure (AU)

Insulin and growth hormone inter-relationships in vitro and in vivo - abstract

The effect of growth hormone on insulin release was observed in rabbit pancreas in vitro. Isolated islets and pancreas slices were incubated with varying concentrations of human growth hormone. Insulin released in the medium was measured by double antibody immunoassay. Human growth harmone stimulated insulin release in both pancreas preparations (p=.01). However the response was concentration dependent in that insulin release was inhibited at high concentrations of growth hormone. These observations support the concept that growth hormone plays a physiological role in the control of insulin release. Correlation between insulin and growth hormone levels in vivo was investigated in infants recovering from malnutrition. Plasma immunoreactive insulin was measured by a specially modified assay which descriminated between 0, 3, 6 and 12 uu/ml (P=.01). Growth hormone assay was equally sensitive, detecting 0.16 uu/ml. Fasting hormone levels were observed during acute malnutrition, rapid catch-up growth and recovery. In 19 acutely malnourished children insulin levels were low (2.3ñ0.3 uu/ml) (mean ñ SEM) while growth hormone levels were high (32.5 ñ 7.1). During the phase of rapid growth, insulin levels were significantly increased (4.5 ñ 0.6) (p = 0.025) while growth hormone level was 21.7 ñ 4.1. When growth curves plateaued with recovery, mean insulin level was 2.8 ñ 0.3 while growth hormone was 17.6 ñ 3.4. It is concluded that rapid catch-up after protein-calorie malnutrition is associated with a significant elevation of plasma insulin (AU)

Studies of Patois group arboviruses in Mexico, Guatemala, Honduras, and British Honduras

Patois, Zegla, and Shark River-like arboviruses in the Patois group were isolaed in Mexico, Guatemala, Honduras, and British Honduras during 1963 to 1968. Twenty-three Patois viruses came from mosquitoes, sentinel hamsters, and suckling mice, 21 Zegla viruses from sentinel hamsters and mice and from a wild cotton rat, and two Shark River-like viruses from sentinel hamsters. Hemagglutination-inhibition(HI) and neutralizing antibody tests with Patois virus were positive with human sera from each country, and HI antibody tests were positive with sera from pigs in Mexico, Guatemala, and British Honduras and from small wild mammals, wild birds, and cattle in Mexico.(AU)

Comparison of two human pathogenic strains with a commensal strain of Herpes Simplex virus isolated at the University Hospital of the West Indies

Comparision has been made between two human "neuropathogenic" and one "commensal" strains of herpes simplex virus. These terms are assigned to these viruses on the basis of their origin. The first two were related from patients with encephalitis and the third from a benign recurrent lesion. A number of physiochemical characteristics of these three strains were studied. The major differences observed between the "pathogens" and the "commensal" virus are: 1. The ability of the commensal herpes virus to infect adult mice while the pathogenic herpes could not. 2. The commensal herpes virus could not be neutralized by the hyperimmune sera of the pathogenic herpes and vice versa, although all crossreacted in complement fixation tests. 3. The commensal virus was significantly inactivated by chloroform, while the pathogens were not significantly affected under the same conditions. 4. Freezing and thawing followed by differential centrifugation rendered the commensal herpes vulnerable to inactivation of DNAse. Inactivation of the pathogens by this enzyme could only be acheived after chromatography on the anion exchanger, Diethyl aminoethyl. 5. The absorbtion spectrum gave a maximum peak at wave lenghts between 260-270 mu for the pathogenic virus. The peak absorption of the commensal herpes was at 280 mu. The peak at 260-270 mu by the pathogens is most likely due to the presence of nucleic acid. The peak absorption of the commensal virus is similar to that given by a typical protein. The relatively high concentration of protein which accompanies the commensal virus might account for the behaviour of this virus. 6. The "pathogenic" and "commensal" strains could be distinguished with respect to susceptibility to interferon. The commensal strain being more susceptible and also more effective in inducing interferon synthesis. 7. The method of comparision used in this investigation, and the results which reflect the marked difference between the strains of herpes simplex studied here produce some methods which may be used for differentiating between pathogenic and commensal strains of herpes simplex virus. It would appear that the methods used here are valuable to the study of viral genetics and the physiochemical study of herpes viruses. Evidence has been presented to show that there is molecular structural difference between the pathogenic and the commensal strains of herpes simplex virus. Such a difference or such differences may provide tools to probe into the pathogenic physiology of infected cells, or help to elucidate the factors responsible for neurotropicity and commensalism in herpes virus. The author is convinced that the differences cited above are genetically based. However, until further investigations are carried out, it is a subjective choice whether to consider the differences as sufficient basis for the subgrouping of herpes simplex virus. No claim is made that the distinction cited are attributes of other strains associated with encephalitis or limited lesions of recurrent herpes (AU)

Phosphoenolpyruvate carboxykinase of kidney

A method for the assay of phosphoenolpyruvate carboxykinase is presented, based on the enzymic determination of the phosphoenolpyruvate produced by the enzyme reaction. The subcellular distribution of phosphoenolpyruvate carboxykinase in the kidney of several animal species resembled the distribution in the liver. The rise in enzyme activity in the kidney cortex of rats made acidotic by feeding with ammonium chloride was not prevented by the administration of ethionine or actinomycin. The possibility is suggested that in the kidney acidosis causes activation of an inactive form of the enzyme already present. (AU)

The cardiovascular effects of a crude solid from the bark of anacardium occidentale - abstract

The bark of Anacardium occidentale (cashew tree) is used widely in Jamaica as an aqueous extract for the control of diabetes mellitus. No antidiabetic properties were observed when aqueous and alcoholic extractives of this bark were given intraperitonealy to fed and fasted rats. However, when a crude solid from the same extract was given intravenously at a dose of 5mg/Kg body weight to the pentobarbitone anaesthetised dog or cat, there was a full fall in blood presure followed by a prolonged slowing of the heart, together with an increase in force of contraction. This cardiac response was also observed on the isolated perfused rabbit and frog heart. Injection of 100 gm/Kg body weight of this crude solid in white mice weighing approximately 20 gm did not cause death in 24 hours. When the same dose was given daily for five days the death rate was one out of six. There were no deaths among the control. In experiments with the open chest dog ventricular fibrillation was observed when a lethal dose of the crude solid was injected intraperitoneally. It is concluded from the present study that the bark of Anacardium occidentale has no antidiabetic property, but has a marked effect on the heart similar to digitalis. Further work is being done on the chemical and pharmacological nature of this solid (AU)

Teratogenicity of hypoglycin-A: some morphological and biochemical aspects

Hypoglycin-A is a toxic, non-proteinogenic amino acid of considerable biochemical interest. It is obtained fron the fruit of Blighia sapida K., and is the causative factor of the Jamaican "vomiting sickness". The toxicity of hypoglycin-A is attributed to the formation of a metabolic methylenecycclopropaneacetic acid which inhibits the oxidation of long-chain fatty acids. Hypoglycin-A induced in pregnant rats a significantly high incidence of congenital abnormalities and reabsorption. It did not reduce the fertility in mice, malformations were absent and only a small increase in reabsorption sites was observed after the adminstration of large doses. Hypoglycin-A administered to pregnant rabbits resulted in a high incidence of foetal reabsorption and overall stunting. Injected into the yolk sac of 24 and 48 hour chick embryos, hypoglycin-A was not teratogenic. Leucine, administered to pregnant rats simutaneously with hypoglycin-A, afforded no protection against the teratogenic action of hypoglycin-A. Leucine was shown to be highly teratogenic and exaggerated the teratogenicity of riboflavin and hypoglycin-A to pregnant rats the occurrence of congenital abnormalities. Inhibition of long-chain fatty acid oxidation may represent a basic cellular mechanism involved in the teratogenicity of hypoglycin-A, because of its influence on oxidative phosphorylation and the electron transport system. Reversal of the hypoglycin-induced teratogenic effects by riboflavin, suggests that inhibition of the acyl dehydrogenase flavin-dependent-oxidation reaction, occurring during the degradation of fatty acids, is the site of action of hypoglycin-A (AU)