Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide

Using a combinatorial chemistry approach, we identified a tetrameric tripeptide, denoted Protein A Mimetic (PAM) or TG19318, able to bind to immunoglobulins of different classes and species. The inverso variant, with the tripeptide in the all-D configuration (D-PAM or TG19320), is described as retaining binding properties to Ig. This peptide has now been assayed as a binder for E class immunoglobulins, in linear and competitive ELISA experiments, dot-blot and surface plasmon resonance (SPR) analyses. We show that D-PAM binds IgE with high specificity and selectivity, the interaction being sufficient to inhibit anaphylactic release of beta-hexosaminidase from RBL 2H3 cells, with an IC50 value of 10 microg/mL. Intradermal administration of D-PAM suppresses PCA in the rat, with an IC50 of 1.25 microg/kg dose of peptide, while its intraperitoneal injection inhibits mouse PCA with an IC50 of about 7 mg/kg and an efficacy comparable to that of ketotifen. Similarly, D-PAM inhibits ACA in the mouse, with 50% suppression at 10 mg/kg. The results presented here show that the peptide is active on the studied models, with effective doses below toxicity level, hence the molecule is a promising candidate for development of a new class of anti-allergic drugs.     

The effect of a new 9-aminoacridine derivative on working and long-term memory in rats

The effects of Vp, a new 9-aminoacridine derivative, on the radial maze performance of intact and scopolamine-treated rats were compared with those of amiridin and tacrine. In intact rats Vp improved the formation of long-term spatial memory and has a positive effect on working memory at the initial stage of training. In scopolamine-treated rats Vp reduced the amnesic effects of scopolamine on both kinds of memory. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 202–204, February 1999     

Immunostimulant activities of a lipophilic muramyl dipeptide derivative and of desmuramyl peptidolipid analogs.

The immunostimulant properties of a new muramyl dipeptide (MDP) derivative bearing a lipophilic moiety on the C-terminal end of the peptide chain are described. It is shown, in particular, that 1,O-(acetylmuramyl-L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate had increased immunostimulant activity in comparison with MDP. It induced hypersensitivity even when administered with an antigen in saline, and it gave higher protection against bacterial infections than did MDP. A quite unexpected finding was obtained with the corresponding desmuramyl compound 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate, which had no activity in producing humoral antibodies but was just as active as the muramic acid-containing compound in stimulating nonspecific resistance to bacterial infections. It was not pyrogenic. Modifications of the peptide moiety or the lipid moiety of this peptidolipid led to decrease, or even loss, of activity. These results show the importance of the N-acetylmuramyl moiety in MDP for humoral antibody production. The peptidolipid 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate is the first member of a new category of nonspecific immunostimulants.     

Coupling daunorubicin to monoclonal antialphafoetoprotein with a new activated derivative.

We report the synthesis of daunorubicin antialphafoetoprotein conjugates, using a new coupling method. At equimolar concentrations on AFP producing cells in vitro, these conjugates were found three times as cytotoxic as the free drug.     

Radiopaque acrylic cements prepared with a new acrylic derivative of iodo-quinoline.

A novel iodine-containing methacrylate, 2,5-diiodo-8-quinolyl methacrylate, has been synthesized and used in the preparation of acrylic radiopaque cements. The effect of incorporation of this monomer to the self-curing resins, on the curing parameters, swelling behaviour and mechanical properties was studied. The incorporation of the radiopaque compound 2,5-diiodo-8-hydroxyquinoline to the solid phase was also carried out for comparative experiments. A decrease in the peak temperature and an increase in the setting time was observed with the addition of the radiopaque monomer, however, the curing parameters did not appreciably change with the addition of the radiopaque compound to the solid phase. Swelling of the modified cements was in the same range as that of the radiolucent cement; however, the diffusion coefficients calculated according to the Fick's law were higher for the iodine-containing materials. The addition of 5 wt% of the iodine-containing methacrylate provided a significant increase in the tensile properties with respect to either control radiolucent formulations or BaSO4-containing formulations. Biocompatibility of the modified cements was studied by implantation of rods of the cements into rats and histological analysis of the surrounding tissue.     

Anti-ischemic effect of a new oxynicotinic acid derivative

The effect of a new derivative of oxynicotinic acid (KONA) on experimental cerebral ischemia is examined in rats. It is demonstrated that a single dose of the preparation (30 mg/kg) significantly decreases the severity of ischemic damage and increases the survival of the animals after bilateral ligation of the common carotid arteries. Comparison with xanthinol-nicotinate shows the advantages of the new preparation. Although KONA does not inhibit free-radical oxidationin vitro, it does lower the content of free-radical oxidation products in rat blood plasma to the normal level. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 7, pp. 49–51, July, 1994 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

Anti-allergic activity of formoterol, a new beta-adrenoceptor stimulant, and salbutamol in human leukocytes and human lung tissue

Formoterol and salbutamol were compared for in vitro inhibition of allergen-induced histamine release from allergic leukocytes and human lung tissue passively sensitized with allergic serum. Formoterol inhibited the release of histamine from leukocytes but salbutamol showed little inhibiting effect. When combined with theophylline, formoterol was a more potent inhibitor of the release of histamine from leukocytes in allergic patients than salbutamol. In fragments of human lung sensitized with allergic serum, the concentration required to inhibit histamine release by 50% was 2 × 10⁻¹¹ M for formoterol and 8.5 × 10⁻⁹ M for salbutamol. The potency of salbutamol and formoterol in blocking specific 3 H-dihydroalprenolol binding to beta-adrenoceptors on guinea pig lung membranes revealed that formoterol had higher affinity for beta-adrenoceptors than salbutamol, and the concentration required for half-maximum stimulation of adenylate cyclase was approximately 200-fold higher for salbutamol than for formoterol.     

The effect of a new phenylalkyl taurine derivative on the size of the necrotic area in experimental myocardial infarct in rats

The study of an anti-ischemic action of a new phenilalkyl taurin derivative TAU-60 has discovered that this drug attenuates ECG signs of myocardial infarction and reduces the size of necrosis zone on the anterior wall of the left ventricular myocardium in rats with experimental myocardial infarction.     

Therapeutic effects of a new taurine derivative in chronic hepatic diseases

Therapeutic properties of a novel taurin N-phenylakyl derivative (TAU-15) in a dose 25 mg/kg were studied in male rats on models of chronic toxic hepatitis and partial hepatectomy. A hepatoprotective action of TAU-15 was established which is due to antioxidative action of TAU-15 and its ability to normalize protein-synthetizing activity of hepatocytes.     

Barrier protective activities of curcumin and its derivative

Aim and objective  

Curcumin, a poly-phenolic compound, possesses diverse pharmacologic activities. However, the barrier protective functions of curcumin or its derivative have not yet been studied. The objective of this study was to investigate the barrier protective activities of curcumin and its derivative (bisdemethoxycurcumin, BDMC) on lipopolysaccharide (LPS) barrier disruption in human umbilical vein endothelial cells (HUVECs) were investigated.     

Cerebroprotective effect of a new taurine derivative during cerebral ischemia

A new taurine derivative chlorohydrate-N-isopropylamide-2-(1-phenylethyl)aminoethanesulfonic acid normalized energy metabolism, inhibited lipid peroxidation, and reactivated antioxidant enzymes in the brain of rats exposed to ischemia. This taurine derivative decreased the mortality rate of animals with ischemic changes in cerebral circulation. The test compound was more potent than piracetam in producing the cerebroprotective effect. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 1, pp. 49–52, January, 2006     

新型核苷衍生物十八烷氧乙基替诺福韦酯的体内外抗乙型肝炎病毒作用研究

目的 评价新型核苷衍生物十八烷氧乙基替诺福韦酯(ODE-TFV)在体外及体内的抗乙型肝炎病毒的活性并研究其改善肝脏病理的作用.方法 分别以乙型肝炎病毒基因转染的人肝癌2.2.15细胞和DHBV感染的1日龄北京鸭为体外和体内模型,评价ODE-TFV抑制乙型肝炎病毒复制的活性.结果 2.2.15细胞培养法实验结果显示,ODE-TFV抑制HBV DNA复制的IC50值为(0.38±0.18)μmol/L,抑制活性较阳性药TFV-DF和3TC分别强约18倍和13倍;ODE-TFV 100 mg/kg和200 mg/kg组,在给药7d和停药3d显示有显著性的DHBV-DNA抑制活性(P＜ 0.01、P＜0.05);在鸭体内模型中,ODE-TFV 100 mg/kg和200 mg/kg能够明显改善DHBV引起的肝细胞坏死和炎细胞浸润,有一定量效关系.结论 ODE-TFV不仅在2.2.15细胞内对HBV-DNA有抑制活性,而且能有效地抑制鸭体内DHBV-DNA的复制,并具有改善肝脏病理的作用.     

Pharmacological approach of a new isoquinoline derivative (458 L)

A new derivative of benzylisoquinoline (458 L) inhibited kidney histidine decarboxylase and decreased the passive anaphylactic bronchospasm in guinea pigs. In rats, the gastric hypersecretion induced by reserpine was inhibited. In mice, the catatonic reactions due to seretonin accumulation were highly reduced.