Evaluation of E-721B, an indigenous herbal combination in experimental models of immediate hypersensitivity.

E-721B, an indigenous herbal combination was investigated for its usefulness in immediate hypersensitivity using different animal models. The drug inhibited the mast cell degranulation induced both by antigen and compound 48/80, the Schultz-Dale response in sensitized guinea pig ileum smooth muscle preparation and the production of precipitating antibodies in 50% of tested rats. It also inhibited the mast cell degranulation in passively sensitized rats indicating its suppressive action on production of reaginic antibody (IgE). However, the drug did not inhibit the 48 hours passive cutaneous anaphylaxis reaction in rats, indicating that a single dose of the drug does not have cromoglycate like properties. All the above results indicate the inhibitory effect of E-721B on immediate hypersensitive reactions such as asthma.

2, 4-dichloro phenoxy acetic acid alters monoamine levels, acetylcholinesterase activity & operant learning in rats.

2, 4-Dichloro phenoxy acetic acid (2, 4-D) was given at 100 mg/kg body weight per day by oral intubation from postnatal days 2 to 25 to assess its effect on the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in olfactory bulb (OB), hippocampus (HI), visual cortex (VC), cerebellum (CB) and brainstem (BS). NE levels were increased in OB, HI, VC and BS at 10 days of age. However, by 25 days, NE levels were decreased in OB, HI and VC. DA levels were also increased in OB, HI, VC and CB at 10 days of age and again decreased by 25 days in OB, HI and VC. 5-HT levels were increased in HI, CB and BS at 10 days and in VC and CB at 25 days of age. Reduced acetylcholinesterase (AChE) activity in OB and HI and monoamines in different brain regions at 25 days of age might be responsible for the observed deficits in both acquisition and rate of pedal press response when animals were exposed chronically to 2, 4-D during postnatal brain development.

Subordination induced decrease in 5-hydroxytryptamine and dopamine levels in the frontal cortex--a study using worker-parasite relationship in rats as a model.

Competition for a limited resource appears to be an important factor in natural selection. Such competition when elicited experimentally, leads to the establishment of dominant-subordinate (D-S) relationship between the competitors. The present study was carried out to analyse the effect of D-S relationship on the levels of monoamines, namely, dopamine (DA), 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in various brain regions. The model of D-S relationship selected for this work was a modified worker-parasite paradigm in adult male Wistar rats. The levels of monoamines were estimated in the frontal cortex, the entorhinal cortex, the hippocampus and the septum of the two competitors and a non-competitor control, using high pressure liquid chromatography (HPLC). Levels of DA and 5-HT, but not NE, were found to be lower (P < 0.05) only in the frontal cortex of the subordinate as compared to that of the dominant or the control. These findings are comparable with similar neurochemical changes reported to be caused by some of the known stressors.

Synthetic peptides related to laminin pentapeptide (YIGSR) fragment.

The synthetic laminin pentapeptide amide fragment (LF), Tyr-Ile-Gly-Ser-Arg-NH2 corresponding to a part of B1 chain of the glycoprotein, laminin, and six of its analogues having structural modifications at positions 1, 3 and 4 were synthesized by solid phase method employing mainly 9-fluorenylmethoxycarbonyl-amino acid trichlorophenyl esters as coupling agents and Merrifield resin as the solid support. Their biological activities were studied in vivo by lung tumor colonization assay and in vitro by cell adhesion assay. The activity of synthetic LF was found to correlate with the earlier reported results in both in vivo and in vitro assays. Among the analogues made, [Tyr4] LF and [Thr4]LF were found to inhibit the lung tumor colonies more efficiently than LF itself in the in vivo assay whereas [D- Ser4]LF exhibited almost the same inhibition as LF.

Synthetic peptides related to the delta-receptor agonist, dermorphin gene associated peptide.

The delta-receptor selective dermorphin gen associated peptide (DGAP) and five of its analogues having structural modifications at positions 2, 4 and 5 were synthesized by the solid phase method using 9-fluorenylmethoxycarbonyl amino acid trichlorophenyl esters as coupling agents and rho-benzyloxybenzyl alcohol resin as the solid support. The delta-receptor selectivity of these peptides was determined by guinea pig ileum and mouse vas deferens assays. The latter assay was carried out using modified Kreb's solution aerated with pure oxygen instead of carbogen. All the synthetic peptides were found to be delta-receptor selective.