ALD coated polypropylene hernia meshes for prevention of mesh-related post-surgery complications: an experimental study in animals.

In this work, thermal atomic layer deposition (ALD) was used to synthesize vanadium (V)-doped TiO2thin nanofilm on polypropylene (PP) hernia meshes. Multiple layers of (Al2O3+ TiVOx) nano-films were coated on the PP hernia mesh surface to provide a layer with a total thickness of 38 nm to improve its antibacterial properties, thereby, prevent mesh-related post-surgery complications. Highly conformal V-doped TiO2nanofilm were deposited on PP mesh at a temperature of 85 °C. Rats and rabbits have been used to evaluate the tissue reaction on coated PP hernia meshes and biomechanical testing of the healed tissue. Five rabbits and ten rats have been implanted with ALD coated and uncoated (control) PP meshes into the back of rats and abdominal wall of rabbits. Histology of the mesh-adjacent tissues and electron microscopy of the explanted mesh surface were performed to characterize host tissue response to the implanted PP meshes. The effect of V-doped TiO2coating on a living organism and fibroblast functions and bacterial activities were studied. The present results indicated that ALD coating improves adhesion properties and exhibited enhanced antibacterial activity compared to uncoated PP mesh. It was shown that V-doped TiO2coatings were highly effective in inhibitingS. aureusandE. coliadhesion and exhibited excellent antibacterial activity. We found that V-doping of TiO2, unlike bare TiO2, allows generated and further procured strong redox reactions which effectively kills bacteria under visible light. We have reported comparative analysis of the use of undoped (bare) TiO2and V-doped TiO2as a coating for PP meshes and their action in biological environment and preventing biofilms formation compared with uncoated PP meshes. The PP meshes coated with V-doped TiO2showed significantly lower shrinkage rates compared with an identical PP mesh without a coating. We have shown that ALD coatings provide non-adhesive and functional (antibacterial) properties.

[Multicenter study of the effectiveness of antiscar therapy in patients at different age periods]. / Mul'titsentrovoe issledovanie effektivnosti protivorubtsovoi terapii u patsientov razlichnykh vozrastnykh grupp.

OBJECTIVE: Was to evaluate the effectiveness of anti-scar treatment with Contractubex gel in children and adults. MATERIAL AND METHODS: A group of researchers based on clinical hospitals and university medical clinics carry out the multicenter study to evaluate the effectiveness of anti-scar treatment with Contractubex gel containing cepalin, allantoin and heparin, with its early appointment in groups of children from 12 to 18 years old and adults from 21 to 35 years old. The study included data from 216 patients. Patients of both age groups were initially divided into two: the main and control ones with an equal distribution according to the type of surgical intervention (hernia repair and appendectomy), age, gender, and anamnestic data. The dynamic observation was carried out using two rating scales - filled out by a doctor (Vancouver scale) and a patient (author's rating scale in the Scar Diary mobile application). RESULTS: Based on the results of the analysis of the data obtained, a high efficiency of the use of Contractubex gel at the early stages of scar formation among patients of the main group in comparison with the control was revealed. By 90 days, the treatment result according to the Vancouver scale was 0,16±0,1 points in the main group and 0,39±0,2 points in the control group. At the same time, with a dynamic scale for assessing the cicatricial process, there was a significant (p<0.05) improvement in the main group (0,2±0,06 points) compared with the control group (0,6±0,17 points). In addition, was noticed the strong commitment to anti-scar treatment in pediatric patients. CONCLUSIONS: The work confirms the undoubted need for anti-scar treatment in the early stages of scar formation after surgical interventions, which accelerates the psychophysical rehabilitation of patients after surgery and improves the quality of life.

[Hydronephrosis of bottom half of doubling segment of horseshoe kidney].

The article presents the clinical observation of a rare anatomical variant of congenital malformation of the upper urinary tract in 11 years old girl (horseshoe kidney, doubling of each of the halves, hydronephrosis of the bottom half of the doubling left segment of the horseshoe kidney), which was correctly diagnosed only during surgery.

[Efficacy of photon therapy in combined postoperative treatment of children with congenital obstructive uropathy and secondary pyelonephritis].

A total of 110 children aged from 5 to 15 years with different forms of congenital obstructive uropathy and secondary pyelonephritis received standard combined treatment (n = 71) or standard treatment combination with photon therapy 3 months after discharge from hospital. Postoperative combined treatment including photon therapy promoted uneventful course of the postoperative period, normalized immunological indices, achievement of persistent remission.

[Immunogenetics of congenital obstructive uropathies in children].

The authors have examined immunogenetically 136 children of east slavonic nationality aged 5-15 years with different forms of congenital obstructive uropathy. Positive and negative association was found of some HLA antigenes, their phenotypical combinations and haplotypical combinations with diseases in the group of patients with congenital obstructive uropathies and in patients with obstructive pyelonephritis. Different immunogenetic picture was seen in patients with congenital hydronephrosis and in children with pyeloectosy. Different distribution of immunogenetic markers can be used for differential diagnosis, definition of the risk of progression of hydronephrotic transformation, complication of obstructive pathology with secondary infectious process and objective validation of therapeutic policy in children with congenital obstructive uropathy.

[Immune disorders in congenital hydronephrosis complicated by obstructive pyelonephritis]. / Immunnye nausheniia pri vrozhdennom gidronefroze, oslozhnennom obstruktivnym pielonefritom.

Congenital hydronephrotic transformation complicated by obstructive pyelonephritis with intact renal function in children exhibited association with some antigens of the major histocompatibility system and their combinations, changes in immunity and nonspecific resistance. Marked and stable shifts in immune reactivity give grounds for inclusion of immunomodulating drugs in combined treatment of the above patients.

Gender differences in sympathoadrenal activity in rats at rest and in response to footshock stress.

A comparison was made of the dynamics of sympathoadrenal activity in 11 age-matched male and female rats, under basal conditions and after exposure to footshock. Rats were prepared with indwelling catheters in the tail artery 24 h before the experiment. Measurements were made of plasma corticosterone (COR), norepinephrine (NE), epinephrine (EPI), dihydroxyphenylalanine (DOPA), dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) under resting conditions, after transfer to the shock box (novelty) and at various times after footshock. Under basal conditions, males have significantly higher blood pressure and plasma DHPG/NE ratios but lower plasma levels of COR, NE and DOPAC than females. Three min after exposure to the shock chamber (novelty stress) there were significant increases in COR, EPI, NE and DHPG in both sexes, while DOPA increased only in females and DOPAC remained unchanged in both sexes. Footshock produced a further increase in EPI, NE and DOPAC within 2 min, which lasted about 15 min. There were significant sex differences in the extent and duration of the response of COR, EPI and DHPG. The data show that the female sympathoadrenal system is more reactive than that of the male to the stresses of a novel environment and footshock. The smaller DHPG/NE ratios in females at rest and after stress suggest that neuronal uptake of NE is lower in females than in males. The finding that stress produces larger increments of plasma DOPA and DOPAC in female rats indicates that tyrosine hydroxylase in the sympathetic nerve terminals and adrenal medulla may also be higher than in males.

Pharmacological evaluation of phenyl-carbamates as CNS-selective acetylcholinesterase inhibitors.

The pharmacological and clinical properties of a novel phenyl carbamate acetylcholinesterase (AChE) inhibitor, SDZ ENA 713 are described. In animals and human subjects this compound showed superior chemical stability, oral bioavailability and a longer duration of action than physostigmine. SDZ ENA 713 produced a 10-fold greater inhibition of AChE in the hippocampus and cortex than in the heart and skeletal muscle, which explains its relatively low toxicity and freedom from cholinergic side effects. The selective effect in the cortex and hippocampus may be due to its preferential inhibition of the G1 form of the enzyme, which is present in relatively higher concentrations in these brain areas. Evidence of a selective hippocampal action was obtained in normal human subjects in whom REM sleep density was increased at doses that had no effect on plasma cholinesterase. If memory impairments in AD are related to a lack of cholinergic activity in cortical and hippocampal brain areas, SDZ ENA 713 should produce significant symptomatic improvement.

Effect of cutting, phosphorus and potassium fertilization on guar plant (Cyamoposis tetragonoloba) in newly reclaimed soil in Egypt.

A two year experiment was carried out in newly reclaimed soils (sandy soils) to investigate the effect of cutting and phosphorus and potassium fertilization on the growth, yield, seed mucilage content and seed protein content of guar plant. The results revealed that different cutting treatments significantly decreased the plant weight, seed yield, seed mucilage content and seed protein content. Phosphorus fertilization up to 350 kg super-phosphate (15% P2O5)/feddan* significantly increased plant weight, seed yield, seed mucilage content and seed protein content. Fertilization with 150 kg potassium sulfate (48% K2O)/feddan was quite capable to meet guar plant potassium demands in this kind of soil. Without cutting plants, fertilization with 350 kg super-phosphate and 150 kg potassium sulfate/feddan resulted in the highest seed yield, seed muculage content and seed protein content.

Rabbits with a genetic impairment in baroreceptor reflex sensitivity show abnormal renal haemodynamics and proximal tubular sodium reabsorption in response to a saline infusion.

OBJECTIVE: To compare renal haemodynamics and proximal tubular sodium reabsorption (PTSR) in response to an acute intravenous saline infusion in rabbits bred for genetic differences in cardiac baroreflex sensitivity (BRS). Rabbits with low BRS increase their blood pressure significantly on a high-salt diet, in association with an initial delay in sodium excretion. It was hypothesized that this could occur through an impaired baroreflex regulation of renal sympathetic nerve activity. This, in turn, would alter renal blood flow and PTSR. DESIGN: Experiments were performed in two groups of normotensive male rabbits (n = 10 per group), one of which had high BRS (> 5 beats/min per mmHg; group I) and one of which had low BRS (< 4 beats/min per mmHg; group II). Effective renal plasma flow (ERPF) was measured by para-aminohippuric acid clearance, and PTSR by the lithium clearance technique. Sodium, lithium, para-aminohippuric acid and glomerular filtration rate were measured from urine samples collected every 30 min (for 90 min) via an indwelling bladder catheter, during a control infusion of glucose (30 mg/ml) NaCl (1.8 mg/ml), and for 2 h after a threefold increase in NaCl. RESULTS: Group I rabbits increased their ERPF by approximately 40%, in response to saline, and doubled their sodium and lithium clearances within the 2 h, but those in group II did not change their cation excretion or their ERPF significantly during this period. Blood pressure did not increase in either group. CONCLUSIONS: A genetic impairment in BRS may be responsible for the inadequate depression of renal sympathetic nerve activity, which results in a failure to increase ERPF and suppress sodium reabsorption in the proximal tubule in response to salt loading.

Mechanism of antagonism by physostigmine of acute flunitrazepam intoxication.

The effect of physostigmine on the loss of consciousness and respiratory depression induced in rabbits by flunitrazepam, 1 mg/kg, was studied to demonstrate whether the restoration of consciousness and respiration rate results from an increase in central cholinergic activity or from an interference by physostigmine with specific binding of flunitrazepam to its receptors. Physostigmine, 0.1-0.4 mg/kg iv, caused a dose-related reversal of consciousness and respiration rate within 15 min of its injection, which lasted 15-30 min depending on the dose. This was associated with peak inhibition of acetylcholinesterase (AChE) in the frontal cortex and medulla, at 15 min, ranging from 35-51%. The analeptic effect of physostigmine in flunitrazepam-treated rabbits was prevented by pretreatment with scopolamine, 1 mg/kg. The effective dose range for physostigmine, 3-12 mumol/kg, is close to concentrations of this agent that inhibit activity in solubilized preparations of AChE from rabbit cortex, 1-3 X 10(-8) M. However, physostigmine, 10(-9) -10(-4) M, failed to displace 3H flunitrazepam from specific binding sites on membranes prepared from rabbit cerebral cortex. It is concluded that physostigmine antagonizes the somnolence and respiratory depression induced by benzodiazepines by restoring cholinergic transmission to normal levels. The effective dose range of physostigmine is small, and serious side effects from overdose can occur as a result of excess cholinergic activity at neuromuscular synapses.

Melittin lysis of red cells.

This paper describes experiments designed to explore interactions between human red blood cell membranes and melittin, the main component of bee venom. We found that melittin binds to human red cell membranes suspended in isotonic NaCl at room temperature, with an apparent dissociation constant of 3 X 10(-8) M and maximum binding capacity of 1.8 X 10(7) molecules/cell. When about 1% of the melittin binding sites are occupied, cell lysis can be observed, and progressive, further increases in the fraction of the total sites occupied lead to progressively greater lysis in a graded manner. 50% lysis occurs when there are about 2 X 10(6) molecules bound to the cell membrane. For any particular extent of melittin binding, lysis proceeds rapidly during the first few minutes but then slows and stops so that no further lysis occurs after one hour of exposure of cells to melittin. The graded lysis of erythrocytes by melittin is due to complete lysis of some of the cells, since both the density and the hemoglobin content of surviving, intact cells in a suspension that has undergone graded melittin lysis are similar to the values observed in the same cells prior to the addition of melittin. The cells surviving graded melittin lysis have an increased Na and reduced K, proportional to the extent of occupation of the melittin binding sites. Like lysis, Na accumulation and K loss proceed rapidly during the first few minutes of exposure to melittin but then stops so that Na, K and hemoglobin content of the cells remain constant after the first hour. These kinetic characteristics of both lysis and cation movements suggest that melittin modifies the permeability of the red cell membrane only for the first few minutes after the start of the interaction. Direct observation of cells by Nomarsky optics revealed that they crenate, become swollen and lyse within 10 to 30 sec after these changes in morphology are first seen. Taken together, these results are consistent with the idea that melittin produces lysis of human red cells at room temperature by a colloid osmotic mechanism.

Kinetic tests of models for sugar transport in human erythrocytes and a comparison of fresh and cold-stored cells.

We studied the time course of the entry of galactose into human erythrocytes from an external concentration of 500 mM, and analyzed the data by an integrated rate equation treatment. We found evidence for only a single, high-affinity site for sugar at the inner face of the membrane. We studied the effect of pre-loading cells with galactose at various concentrations on the entrance of galactose into the cell from 128 mM, and compared the result we found with a previous report of a similar experiment from 500 mM external sugar. We found no evidence of other than a high affinity for sugar at the inner face of the membrane. The data reject a model in which sugar transport occurs on two asymmetric, oppositely directed carriers. We studied exchange of glucose into and out of the cells as a function of sugar concentration, taking care to minimize metabolism of sugar. We found no evidence for other than a single component for glucose exchange. Our data reject the 'allosteric pore' model for sugar transport. The explanation of the high-affinity site for sugar at the inner membrane face thus remains enigmatic. We find a very significant difference in the kinetics of glucose exchange when we compare freshly drawn and long cold-stored blood. The Km for exchange was almost twice as large for cold-stored as for fresh blood.

Uptake of arachidonic acid into membrane phospholipids: effect on chloride transport across cornea.

We demonstrate that arachidonic acid (AA) stimulation of chloride transport across frog cornea is mediated via two independent pathways: (1) stimulation of prostaglandins and cAMP synthesis, and (2) a direct physical change in the membrane produced by substitution of different phospholipid acyl chains. AA is well known as a precursor in the synthesis of prostaglandins, which have been shown to stimulate cAMP synthesis and chloride transport in frog cornea. We show that frog cornea can convert exogenous AA to PGE2, but that in the presence of 10(-5) M indomethacin both the conversion to PGE2 and stimulation of cAMP are completely blocked. However, with indomethacin the action of AA to stimulate chloride transport (as measured by SCC) remains, but peak height of the response is reduced to 57% of that found when AA alone is given. Similarly, we show that propranolol completely blocks cAMP stimulation, but stimulation of SCC is reduced to 45% of the original response. Therefore, cAMP appears to be responsible for roughly half of the observed stimulation in SCC. By gas chromatographic analysis we show that significant quantities of AA can rapidly substitute into membrane phospholipids of corneal epithelium and L929 cells following the addition of AA to the medium. Modification of membrane phospholipid structure can affect membrane viscosity, membrane-bound enzyme activity, and the distribution and lateral mobility of integral proteins. It seems likely that such alterations in the properties of the membrane may modulate the rate of chloride transport, and this may constitute the second mechanism. Upon addition of AA, both mechanisms appear to stimulate chloride transport simultaneously, and are apparently additive. We show that prolonged exposure to AA results in a large incorporation of AA into phospholipid and consequently, a perturbation in the ratio of unsaturated to saturated fatty acids. We also find evidence of a compensatory cellular mechanism that alters the ratio of endogenously synthesized fatty acids and tends to reduce the membrane-perturbing effect of AA.U

The anion-transfer system of erythrocyte membranes. N-(7-Nitrobenzofurazan-4-yl)taurine, a fluorescent substrate-analogue of the system.

The fluorescent probe Nbd-Tau [N-(7-nitrobenzofurazan-4-yl)taurine] was synthesized and evaluated as a potential substrate of the anion-transport system of human erythrocyte membrane. The probe inhibited Cl- exchange in a competitive manner from either surface of the membrane, displaying Ki values in the mM range at the inner surface and in the microM range at the outer surface. Inhibition from within cells was via interaction with Cl--transport sites, whereas from it was via interaction with sites of unidentified nature. Nbd-Tau efflux from cells was monitored fluorimetrically in a continuous mode by a novel method that circumvents separation of the cells from the medium. Using this method, it is shown that Nbd-Tau efflux fulfils the following criteria of a substrate of the anion transport system: (a) susceptibility to classical and specific inhibitors of the system; (b) competitive inhibition with Cl- for anion-transport sites; and (c) temperature coefficient comparable with that of Cl- exchange. The fluorometric method is highly sensitive, versatile, and kinetically informative. With minor modifications it can be used for measuring anion transport across "ghost" and isolated membrane vesicles.

Fusion of liposomes with planar lipid bilayers.

The fusion of liposomes with planar lipid bilayers was monitored by two different methods. (a) Liposomes consisting of phospholipids and cholesterol were added to the aqueous phase bathing the cholesterol-deficient planar lipid bilayers in the presence of nystatin. The resulting increase in the planar lipid bilayer's electrical conductance was considered indicative of fusion. (b) Transplanar lipid bilayer injection of 35SO24- trapped inside the liposomes. It is shown by both methods that fusion is specifically dependent on the presence of negatively charged phospholipids both in the liposomes and the planar lipid bilayers and on Ca2+ in the aqueous phase of the fusion system.