Decrease In Tissue Resistance Research Articles

Researches of the assortment of drugs for the treatment of diabetes II type оn the pharmaceutical market of Ukraine

Type II diabetes is a global pandemic, as evidenced by data from a study by the International Diabetes Federation. The disease is a chronic, progressive process with a special metabolic condition that is characterized by hyperglycemia. Therapeutic effects should be aimed at eliminating the main causes of type II diabetes mellitus: insulin secretion dysfunction, a decrease in tissue resistance to insulin, or a combination of these. The aim of the work was to study the range of oral antidiabetic drugs on the pharmaceutical market of Ukraine for the treatment of type II diabetes. The objects of study were drugs used in the treatment of type II diabetes. Studies were conducted using content analysis of official sources of information. In the course of the work, the range of antidiabetic drugs, classification, mechanism of action, cost, main advantages and disadvantages of use were established. It is established that the most common dosage form for the treatment of diabetes are tablets, which occupy more than 90% of the total range of drugs. The lack of modern types of dosage forms in the group A10B is the basis for the creation of new drugs with improved biopharmaceutical and consumer properties.
 The data obtained indicate a strong dependence of the pharmaceutical market of antidiabetic drugs of Ukraine on imports, with the exception of insulin (А10В). The share of imports in the market in quantitative terms for the period under review amounted to more than 75.86% of the total market volume.
 It has been established that the use of drugs of the A10B A, A10B F groups with an affordable cost with active therapy contributes to a lower rate of development of diabetes mellitus type II and a high degree of regression to normal glucose, without affecting the fluctuations in body weight. Preparations of the new generation (A10B H, A10B J, A10B X) are highly effective with an insufficient safety profile. The high cost of drugs of these groups makes them inaccessible to the general population. It has been shown that only metformin and voglibosis have a positive effect on body mass fluctuation rates, which will ensure safe and effective glycemic control with minimal risk of hypoglycemia and without weight gain in the treatment of type II diabetes.

Epidermal growth factor protects mouse ileal mucosa from Triton X-100-induced injury

Luminal exposure of mouse ileal mucosal sheets in vitro to 0.3% Triton X-100 for 10 min resulted in a 45.3 ± 4.4% decrease in tissue resistance (Rt). Luminal pretreatment of tissue with epidermal growth factor (EGF, 30 nM) reduced the Triton X-100-induced decrease in Rt to 10.2 ± 3.5%. This effect of luminal EGF was concentration-related with an A50 value of 7.4 nM. EGF applied to the basal buffer also produced a similar protective effect, but it was 5.3-fold less potent than luminal EGF. Morphological analysis indicated the formation of denudations at villi tips by Triton X-100 which was prevented by EGF pretreatment. These results suggest that EGF may play a role in the protection of ilegal mucosal integrity.

137 ATTACHING AND EFFACING BACTERIA INDUCE AN INCREASE IN TISSUE PERMEABILITY THAT IS SPECIES-SPECIFIC

Introduction. A three-steps of Enteropathogenie Escherichia coli (EPEC) pathogenicity include a fimbrial-mediated loose adherence to the enterocyte apical membrane (step. 1), followed by intimate adherence with formation of characteristic attaching and affacing (A/E) lesions (step 2). The genetic elements necessary for step 2 are clustered in a 35kb region called Locus for Enterocyte Effacement (LEE). Finally, step 3 involves an intracellular signalling cascade that seems to mediate ion secretion. Other data shows that EPEC decrease tissue resistance and increase transepithelial flux of mannitol, which may be a complementary mechanism of diarrhea. Aim. We investigated whether the decrease in tissue resistance is species-specific and whether intimate adherence is necessary for the resistance drop to occur. Methods. Stripped rabbit ileal mucosa was mounted in Ussing chambers, batheds with Ringer's solution, gassed with 95%O2-5%CO2 and potential difference (PD) and short-cirtcuit current (Isc) were monitored after challenging the tissue with PBS-resuspended cultures of wild type A/E forming bacteria and genetically derived strains. Tissue resistance (Rt) was calculated from PD and Isc according to Ohm's law and its variation (ΔRt) was expressed as percentage of the basal Rt value obtained ca 10 min after mounting the tissue. Results and conclusions. Rabbit specific A/E strain RDEC-1 induced a ΔRt of -17% (±3) while negative control (i.e. no fimbria, no A/E formation) strain DH5α induced a decrease of -7% (±2). Wild type, human specific EPEC strain E2348/69 did not induce a significant Δrt while transforming it with the plasmid (pM5) containing RDEC-1 fimbria gene evokes a ΔRt of -27% (±4). No significant ΔRt were noted transforming pM5 into a negative control strain. Finally, cloning RDEC-1 LEE and pM5, but not the LEE alone, into DH5α induced a ΔRt comparable to wild type RDEC-1. In summary, our data show that the ability of decreasing Rt is dependent on species-specific step 1 adherence. However, fimbrial adherence per se is not sufficient to give this effect, since elements contained in the LEE, most likely involved in A/E lesion formation, are required. Using optical and electron microscopy we are currently looking for a morphologic correlation between A/E lesions and decreased Rt. We are also engineering more selective genetic constructs to find out which gene(s) in the LEE is (are) involved in the process.

Electrical response to acid across the dorsal epithelium of the frog tongue

Acid stimulation produced a change in trans-epithelial potential difference across isolated dorsal epithelium of frog tongue. The responses to acetic acid, tartaric acid and citric acid were significantly greater than those to hydrochloric acid and nitric acid at the same pH. Metabolic inhibitors had no effect on the response, but local anaesthetics reversibly depressed it. The induced response was associated with a decrease in tissue resistance. Positive polarization on the mucosa increased the response, which was decreased or reversed under negative polarization. These responses may be caused by diffusion of H-ions through the tissue, and may influence sour reception in the frog.

The secretory action of barium chloride in rat colon.

BaCl2, applied serosally, caused a rise in the p.d. and short-circuit current (s.c.c), and a decrease in tissue resistance in stripped sheets of rat colon. This response was dose dependent. Mucosal application of BaCl2 was without effect. The BaCl2-induced rise in s.c.c. was inhibited by reducing the serosal Na+ concentration to 25 mM. Lowering the mucosal Na+ concentration was without effect. Ouabain (10(-3) M in serosal fluid) and furosemide (10(-3) M in serosal fluid) both reduced the rise in s.c.c. induced by BaCl2. Flux determinations indicated that BaCl2 inhibited Na+ absorption and stimulated Cl- secretion by the colon. In vivo, BaCl2 increased fluid accumulation within the colonic lumen, an effect that was associated with a rise in the transcolonic p.d. Increasing the serosal K+ concentration to 20 mM reduced the responses to BaCl2, acetylcholine and theophylline, and this could not be entirely accounted for by the concomitant reduction in the serosal Na+ concentration. As high serosal K+ did not mimic the secretory response it would appear that BaCl2 does not act by blocking K+ channels. The rise in s.c.c. induced by BaCl2 was not reduced by Ca2+-free conditions, but it was inhibited by 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) and trifluoperazine. BaCl2 did not alter cyclic AMP production by colonic scrapes. It is concluded that BaCl2 induces colonic secretion by the release of intracellular Ca2+, which then combines with calmodulin to activate the secretory process.

Effect of cotton bracts extract on canine tracheal epithelium and shunt pathway.

The effects of increasing concentrations (5 to 100 microliters) of an aqueous extract of cotton bracts (CBE) on the electrophysiologic properties and paracellular pathway of the canine trachea mounted in Ussing chambers were examined. The CBE produced a 50% decrease in short-circuit current and a dose-dependent decrease in transepithelial potential difference and tissue resistance when added to the mucosal bathing solution. The decrease in tissue resistance after exposure to 25 and 100 microliters was followed by an increase in mannitol flux, suggesting an effect on the paracellular pathway. No significant effect on mannitol flux was seen after 5 microliters CBE, when results were compared with control tissues from the same dog. The effects of 5 microliters CBE but not higher concentrations were reversible. Submucosal CBE had no effect on the electrophysiologic properties of the canine trachea or on mannitol flux. We conclude that in the canine tracheal epithelium, CBE inhibits active ion transport, alters the paracellular pathway, and acts only from the luminal surface.