Evolution of tool handling activity in monkeys

Main experimental data are presented which have been obtained on lower and higher monkeys. New understanding is suggested of regularities of interaction of primates with the environmental objects. The data are discussed in relation to historic and ontogenetic development of working activity in man.     

Hypotension caused by intravenous infusion of rifampicin and its relation to the administration schedule

It was shown in studies on animals that bolus administration of rifampicin induced hypotension whose severity depended on the rate of the antibiotic administration. When the antibiotic was administered in the 5-, 10- or 15-minute regimen in a dose of 10 mg/kg the maximum decrease in blood pressure was 44, 34 or 21% of the initial level and the maximum antibiotic concentration attained in the blood was 34.4, 27.2 or 22.6 micrograms/ml, respectively. With the infusion for 30 minutes, the maximum antibiotic concentration in the blood was 17.6 micrograms/ml and the blood pressure did not undergo any significant changes. When the rate of the antibiotic infusion was high there was pharmacokinetic heterogeneity of the blood serum and biophase which could lead to unpredictable results. After repeated administrations of rifampicin to the same animals pronounced tachyphylaxis to the antibiotic was noted, which manifested itself in decreasing of hypotension, though the serum antibiotic level was 1.5 to 2 times higher that the initial one. It was concluded that administration of rifampicin in the therapeutic dose equal to 10 mg/kg for 30 minutes was the most sparing regimen for the antibiotic bolus intravenous infusion. Gradual increase in the antibiotic dose and administration rate in patients is possible under careful control of blood pressure and pharmacokinetic studies.     

A model for cleavage ofO-glycosidic bonds in glycoproteins

The present work investigated the possibility of cleavage of -linkages between mannose or galactose and serine/threonine residues by -mannosidase and -galactosidase. The study was carried out initially with model synthetic compounds imitating theO-glycosidic bond in glycoproteins, and further with glucoamylase. It was shown that -mannosidase and -galactosidase can hydrolyse these linkages after proteolytic digestion of glucosamylase.     

Crystallization and preliminary X-ray study of minor glucoamylase from Aspergillus awamori variant X-100/D27.

Crystals of the reduced form of glucoamylase were obtained from polyethylene glycol 6000 solution by the hanging-drop method. The protein was treated with alpha-mannosidase to partly remove the sugar component. The crystals belong to the space group P2(1)2(1)2(1) with cell dimensions a = 116.7 A, b = 104.3 A, c = 48.5 A and diffract beyond 2.5 A resolution.     

Crystal structure of glucoamylase from Aspergillus awamori var. X100 to 2.2-A resolution.

The crystal structure of a catalytically active fragment of glucoamylase-I from Aspergillus awamori var. X100 has been determined to a resolution of 2.2 A. Twelve of its 13 alpha-helices are arranged into an "alpha/alpha-barrel." An inner core of six mutually parallel alpha-helices are connected to each other through a peripheral set of six alpha-helices. The peripheral helices are parallel to each other, but approximately antiparallel to the inner core of alpha-helices. The putative active site lies in the packing void of the inner set of helices. The last 30 residues of the enzyme comprise a separate domain containing 10 sites of O-glycosylation. Each instance of O-glycosylation involves a serine or threonine side chain linked to the alpha-anomer of a single mannosyl residue. The O-glycosylated domain is in an extended conformation, wrapping around the "waist" of the alpha/alpha-barrel. Two additional sites of N-glycosylation contribute well ordered glycosyl chains that lie in proximity to the belt of O-glycosylation. The model developed for glucoamylase is a rare and valuable structural example of a glycoprotein and an exo-acting amylolytic enzyme.     

Erythromycin pharmacokinetics in children after rectal and oral administration

Pharmacokinetics of erythromycin base was studied clinically in children not older than 14 years treated with new children dosage forms of the antibiotic i. e. 0.1 and 0.25 g enteric coated tablets and 0.06 and 0.125 g suppositories. It was noted that the new dosage forms were characterized by higher availability which was 2.5-3 times higher than that after using the erythromycin base tablets without the coating. Systematic increasing of erythromycin availability after the use of the rectal suppositories was observed with increasing of the children age. Absolute absorption in newborns, sucklings and children over 1 year amounted to 28, 36 and 54 per cent respectively.     

Effect of x-ray contrast agents on the deformation properties of human erythrocytes

Using the ectacytometric method the authors observed that the contrast agents: bilimin, triombrast 76%, iodamide-380, bilignost 20%, bilignost 50%, metrizamide decrease red cell deformability. This effect of the contrast agents depends on their osmolality and chemical structure.     

Small proline-rich protein 1A is a gp130 pathway- and stress-inducible cardioprotective protein

The interleukin-6 cytokines, acting via gp130 receptor pathways, play a pivotal role in the reduction of cardiac injury induced by mechanical stress or ischemia and in promoting subsequent adaptive remodeling of the heart. We have now identified the small proline-rich repeat proteins (SPRR) 1A and 2A as downstream targets of gp130 signaling that are strongly induced in cardiomyocytes responding to biomechanical/ischemic stress. Upregulation of SPRR1A and 2A was markedly reduced in the gp130 cardiomyocyte-restricted knockout mice. In cardiomyocytes, MEK1/2 inhibitors prevented SPRR1A upregulation by gp130 cytokines. Furthermore, binding of NF-IL6 (C/EBPbeta) and c-Jun to the SPRR1A promoter was observed after CT-1 stimulation. Histological analysis revealed that SPRR1A induction after mechanical stress of pressure overload was restricted to myocytes surrounding piecemeal necrotic lesions. A similar expression pattern was found in postinfarcted rat hearts. Both in vitro and in vivo ectopic overexpression of SPRR1A protected cardiomyocytes against ischemic injury. Thus, this study identifies SPRR1A as a novel stress-inducible downstream mediator of gp130 cytokines in cardiomyocytes and documents its cardioprotective effect against ischemic stress.