Showing papers by "Central Drug Research Institute published in 1976"

Ascorbic acid--a naturally occurring mediator of lipid peroxide formation in rat brain.

Abstract: Male albino rats (body wt. 3G50g) drawn from the CDRI Stock Colony were fasted overnight. They were decapitated and their whole brains were excised and washed with cold 150 mM-potassium chloride. Homogenates (10% w/v) were prepared in chilled 150 mwpotassium chloride and centrifuged at 80Oy for IOmin. The supernatant fluid was centrifuged at 18,000g for 15 min and the resultant supernatant fluid was centrifuged at 106,000 for 1 h to recover the organelle-free cytosol fraction. The pellet sedimenting at 18,OOOy was suspended in 150 mM-potassium chloride and washed by centrifugation and finally suspended in 150 mM-potassium chloride to a final protein concentration of 6 mg/ml. This was referred to as 'mitochondrial fraction'. Assay of lipid peroxides. Samples of 0.5 ml of the source of pro-oxidant were mixed with 0.25 ml of the mitochondrial fraction. The flasks containing the mixture were shaken in a metabolic shaker (120 strokes/min) for 3 h a t 37°C. One millilitre of 10% w/v trichloroacetic acid was added and after thorough mixing, the reaction mixture was centrifuged at 800 y for 10 min. Samples (1 ml) of the clear supernatant fluids were mixed with 1 ml 0.67% w/v 2-thiobarbituric acid and held in a boiling water bath for 10 min, cooled and diluted with 1 ml distilled water. The absorbance of the solution was read at 535nm and results expressed as malonyldialdehyde using 1.56 x lo5 as extinction coefficient (UTLEY et a/., 1967). Chemical esfimutions. Protein was estimated according to LOWRY et al. (1951), sulphydryl groups according to ELLMAN (1959), ascorbic acid according to ROE & KUENTHEK (1943) (bromine as oxidizing agent), ACh according to HESTRIN (1949) and amino acids according to MOORE & STEIN (1948). Preparation and assay of ascorbic acid oxidase (EC 1.10.3.3). The enzyme was prepared from the bottle gourd (Lagenaria siceraria) and assayed by the procedure Of LOVETT-JAMISON & NELSON (1940).

Restoration of virulence to rat of axenically grown Entamoeba histolytica by cholesterol and hamster liver passage.

Abstract: A virulent strain of Entamoeba histolytica (NIH-200) from a symptomatic human case, cultured in vitro for more than three years, was unable to infect rat caecum or hamster liver. When grown with a mixed bacterial flora, it infected rat caecum but did not produce ulceration. After passaging amoebae growing with bacteria in hamster liver, amoebic hepatic lesions were regularly produced. The amoebae from liver lesions produced ulceration in the caeca of rats. Expoxure to cholesterol of amoebae growing with bacteria or feeding rats orally with cholesterol and injecting these amoebae along with bacteria also led to the production of ulcers in rats. Thus virulent amoebae which have been cultured in vitro for a long time become attenuated but their virulence can be revived.

Radiation sensitivity of a mutant of Escherichia coli K-12 associated with DNA replication: Evidence for a new repair function

Abstract: The isolation and properties of a new radiation sensitive mutant of Escherichia coli K-12 are described which shows a correlation between radiation sensitivity and replication of irradiated DNA. The mutation, called rer, is located between argB and purD loci. The mutant, when grown in tryptone broth after irradiation, is sensitive to UV and γ-rays and incorporates little or no 3H-thymidine but in minimal glucose-salts medium both the radiation sensitivity and incorporation of 3H-thymidine remain identical to that of the parent strain. Studies with a temperature sensitive double mutant rer dnaC show that 1 hr incubation of irradiated cells at 42° C before their transfer to 30° C results in higher survival as compared to their incubation at 30° C only. It is suggested that rer controls the replication of irradiated DNA and thus regulates the coordination between replication and repair of DNA.

Haplorchoides Chen, 1949 (Haplorchinae: Heterophyidae) in freshwater fishes.

Abstract: Two metacercariae of Haplorchoides, recorded in the fingerlings of over a dozen species of freshwater fishes, are described and illustrated. Ovigerous flukes were recovered from older specimens of two species of fishes procured from the same locality. Comparison of taxonomic characters of the juveniles and adults suggests that they are conspecific. The metacercariae and adults are assigned to two new species, Haplorchoides pearsoni and H. Mehrai. The observations, presented herein, necessitated a review of the species named under this genus and a revision of the generic diagnosis. The reports on fish intermediaries of H. attenatus have been enlarged.

Studies on the mechanism of centpiperalone-induced hypoglycemia.

Abstract: The effect of centpiperalone [2-piperazino-4(3H)-quinazolinone monoacetate], a potent hypoglycemic compound on glucose and oxygen uptake, and lactic acid formation by rat hemidiaphragms suspended in glucose-phosphate buffer in Warburg bath at 37 degrees C and 80 shakes/min was studied in vitro. Although centpiperalone enhanced glucose and oxygen uptake by itself, no increment in the above parameters was seen when insulin was added simultaneously along with centpiperalone. Preincubation of hemidiaphragms with centpiperalone and their subsequent incubation with insulin did not indicate any potentiation of insulin action as indicated by uptake of oxygen and glucose. However when 16 times diluted serum from centpiperalone-treated rats was added to hemidiaphragms suspended in glucose-phosphate buffer, significant increase in glycogen content was observed compared to that seen in hemidiaphragms after addition of serum from normal untreated and alloxanized centpiperalone-fed rats. Definite degranulation of B-cells was seen in centpiperalone-fed rats using the aldehyde fuchsin staining technique. These data strongly suggest that centpiperalone induces hypoglycemia through liberation of insulin from B-cells.

Structure and stereochemistry of Coccuvine (Cocculus laurifolius DC).

Abstract: Coccuvine C17H19NO2, m.p. 137–38°, a new alkaloid fromCocculus laurifolius DC has been assigned the structure and stereochemistry as (I) on the basis of spectroscopic studies and chemical correlation.

Effect of nicotine administration into the lateral cerebral ventricles of mice provides evidence for cholinergic mechanisms in the CNS

Abstract: Numerous investigations have been carried out to elucidate cholinergic mechanisms in the central nervous system (CNS). Bhattacharya and Feldberg (1958), using perfusion of cerebral ventricles in cat, found that acetylcholine (ACh) was released into the effluent. Ryall (1963) reported that ACh is contained within synaptic endings and Curtis, Ryall and Wilkins (1965) observed the presence of ACh, cholinacetylase and cholinesterase in the CNS. Dhawan, Gupta, Dixit and Chandra (1965) showed the presence of muscarinic receptors in the CNS of dogs.

Evidence for non-dopaminergic nature of apomorphine-induced pecking in pigeons

Abstract: Apomorphine-induced pecking in pigeons was first reported by Amsler (1923), who also reported that removal of corpora striata could prevent it. Detailed observations on apomorphine-induced pecking were published independently and simultaneously by Burkmann (1960) and Dhawan and Saxena (1960).

Possible involvement of a dopaminergic link in the analgesic action of morphine

Abstract: Many workers have attempted to assign specific functions to catecholamines in the central nervous system, since Vogt (1954) demonstrated their presence in different areas of brain. Vedernikov and Afrikanov (1969) have reported that pretreatment with reserpine reduced the analgesic activity of morphine. Subsequently Vedernikov (1970) observed that prior administration of pyro­gallol, cocaine and iproniazid also potentiated the analgesic activity of morphine. On the basis of these observations noradrenaline (NA) has been suggested as playing a significant role in the analgesic activity of morphine. The possibility of NA being a neurotransmitter at the spinothalamic pathways which transmit nociceptive impulses has also been postulated. Even though in most of these experiments there is also a change in dopamine (DA) levels in the same direction, these workers have not attached much significance to changes in DA level. Recently however, DA has also been increasingly considered to have important functions at subcortical structures such as striatum and substantia nigra. In these areas, its presence in the presynaptic nerve endings has been demonstrated by histochemical methods (Dahlstrom and Fuxe, 1964). The involvement of dopaminergic mechanisms in morphine analgesia has recently been suggested by some workers (Calcutt, Doggett and Spencer, 1971; Carroll and Sharp 1972). The present study was undertaken to further investigate the possible role of DA in the antinociceptive (analgesic) activity of morphine.