[Treatment of elderly patients with combination of coronary artery disease and aortic valve pathology].

Increasingly, there are patients with concomitant coronary artery disease and aortic valve, especially in elderly patients, who often have severe comorbidities and high surgical risk, which is undoubtedly a certain effect on the choice of method and tactics of treatment. Today, there are several approaches to the treatment of patients in this category, and all of them have certain advantages and disadvantages.

[DIRECT REVASCULIZATION OF THE MYOCARDIUM FROM LEFT-SIDE MINITHORACOTOMY - MODERN PERFORMANCE OF THE OPERATION NAMED AFTER V.I. KOLESOV].

The article provides the results of minimally invasive direct revasculization of myocardium at the period from 2012 to 2014. Given method was used in 49 interventions. There weren't any lethal cases or myocardial infarctions. A mean hospital stay consisted of 8,6±2,7. Computer thomographic coronary bypass angiography was carried out after operation in terms of 6-48 months. The occlusion of mammary coronary shunt was revealed in 3 patients with minimally invasive revasculization of the myocardium in terms up to 48 months. There were noted a decrease' of hospital stay, bleeding during surgery and in early postoperative period, duration of artificial pulmonary ventilation, length of stay in intensive care unit for this group of patients.

Effect of flexibility and cis residues in single-molecule FRET studies of polyproline.

Polyproline has recently been used as a spacer between donor and acceptor chromophores to help establish the accuracy of distances determined from single-molecule Förster resonance energy transfer (FRET) measurements. This work showed that the FRET efficiency in water is higher than expected for a rigid spacer and was attributed to the flexibility of the polypeptide. Here, we investigate this issue further, using a combination of single-molecule fluorescence intensity and lifetime measurements, NMR, theory, and molecular dynamics simulations of polyproline-20 that include the dyes and their linkers to the polypeptide. NMR shows that in water approximately 30% of the molecules contain internal cis prolines, whereas none are detectable in trifluoroethanol. Simulations suggest that the all-trans form of polyproline is relatively stiff, with persistence lengths of 9-13 nm using different established force fields, and that the kinks arising from internal cis prolines are primarily responsible for the higher mean FRET efficiency in water. We show that the observed efficiency histograms and distributions of donor fluorescence lifetimes are explained by the presence of multiple species with efficiencies consistent with the simulations and populations determined by NMR. In calculating FRET efficiencies from the simulation, we find that the fluctuations of the chromophores, attached to long flexible linkers, also play an important role. A similar simulation approach suggests that the flexibility of the chromophore linkers is largely responsible for the previously unexplained high value of R(0) required to fit the data in the classic study of Stryer and Haugland.

Applicability of DPI formulations for novel neurokinin receptor antagonist.

A novel triple neurokinin receptor antagonist (TNRA) could have pharmaceutical efficacy for asthma and/or chronic obstructive pulmonary disease. TNRA is potentially developed as inhalation medicine. The aim of this investigation was to evaluate the applicability of dry powder inhaler (DPI) formulation for TNRA. DPI formulation containing lactose was used for this feasibility study. Mechanofusion process for surface modification was applied on lactose particles to prepare four different DPI formulations. The mixture of TNRA and lactose was administered to rats intratracheally using an insufflator. The deposition pattern and blood concentration profile of TNRA were evaluated. Although there was no significant difference in deposition on deep lungs between the four formulations, DPI formulations containing mechanofusion-processed lactose showed longer T(max) and t(1/2) and higher AUC(0-infinity) and MRT compared to that containing intact lactose. On the other hand, the contact angle measurement showed that the mechanofusion process decreased the polar part of the surface energy of the lactose. Therefore, the prolongation of the wetting of the formulated powder mixture seemed to delay the dissolution of TNRA deposited in respiratory tract. It was concluded that DPI formulation containing mechanofusion-processed lactose could be suitable for inhalation of TNRA.

Ultrafast dynamics of myoglobin without the distal histidine: stimulated vibrational echo experiments and molecular dynamics simulations.

Ultrafast protein dynamics of the CO adduct of a myoglobin mutant with the polar distal histidine replaced by a nonpolar valine (H64V) have been investigated by spectrally resolved infrared stimulated vibrational echo experiments and molecular dynamics (MD) simulations. In aqueous solution at room temperature, the vibrational dephasing rate of CO in the mutant is reduced by approximately 50% relative to the native protein. This finding confirms that the dephasing of the CO vibration in the native protein is sensitive to the interaction between the ligand and the distal histidine. The stimulated vibrational echo observable is calculated from MD simulations of H64V within a model in which vibrational dephasing is driven by electrostatic forces. In agreement with experiment, calculated vibrational echoes show slower dephasing for the mutant than for the native protein. However, vibrational echoes calculated for H64V do not show the quantitative agreement with measurements demonstrated previously for the native protein.

Management of acute and chronic open wounds: the importance of moist environment in optimal wound healing.

The history of wound care and management closely parallels that of military surgery which has laid down the principles and dictated the practices of wound cleansing, debridement and coverage. From a treatment standpoint, there are essentially two types of wounds: those characterized by loss of tissue and those in which no tissue has been lost. In the event of tissue loss it is critical to determine whether vital structures such as bone, tendons, nerves and vessels have been exposed. It is also important to determine the amount of soft tissue contusion and contamination. In any case primary wound healing by early closure either primarily or with the help of grafts or flaps is preferred to secondary healing and wound contraction with subsequent contractures which interfere with range of motion and function. Whether the wound is acute or chronic, essential principles of wound care must be observed in order to avoid wound sepsis and achieve rapid and optimal wound healing. - Tissues must be handled gently. - Caustic solutions capable of sterilizing the skin should never be applied to the wound. It is desirable never to put anything in the wound that cannot be tolerated comfortably in the conjunctival sac. - All devitalized tissues must be debrided either hydrodynamically, chemically, mechanically or surgically. - All dead space must be obliterated. - Exposed vital structures must be covered by well vascularized tissues. An essential part of any wound management protocol is wound dressing. It cannot be too strongly emphasized that a wound dressing may have a profound influence on healing particularly of secondary type healing, a critical feature being the extent to which such dressing restricts the evaporation of water from the wound surface. A review of available dressing materials is reported with emphasis on the newly developed concept of moist environment for optimal healing. a practical guide for dressing selection is also proposed.

High-resolution LC/MS for analysis of minor components in complex mixtures: negative ion ESI for identification of impurities and degradation products of a novel oligosaccharide antibiotic.

High-resolution mass spectrometry has been routinely used for structural confirmation and identification; however, it has mostly been applied to relatively pure samples. Exact mass measurement of minor components such as impurities, degradation products or metabolites in complex mixtures has been difficult without prior separation and isolation. Here we report the utilization of on-line liquid chromatography in combination with high-resolution mass spectrometry for the identification of impurities and base degradation products of Sch 27899, a member of the everninomicin class of antibiotics. Nine Sch 27899-related impurities and degradation products were detected by negative ion electrospray ionization using a magnetic sector mass spectrometer. Exact mass measurements were obtained at a resolution of 5000 using polyethylene glycol (PEG) sulfates as internal standards. Corresponding elemental compositions were determined within a 2 ppm error tolerance and structures were proposed for all components.

Factors influencing the diffusion-controlled release of papaverine from poly (L-lactic acid) matrix.

Effects of drug content and medium pH on the release of papaverine (PAP) from biodegradable poly(l-lactic acid) [P(L)LA] matrix were investigated to reveal the predominant factors affecting the two-stage diffusion-controlled release mechanism. A drug-dissolved cylindrical matrix (rod; 10 mmx1 mm diameter) was prepared by heat compression method. In the case of a PAP content below 10%, pH was found to have a strong effect on the release rate, and drug content was found to have no effect on the release profile. The release profile consisted of two sequential diffusion stages due to P(L)LA transformation from amorphous to the semicrystalline state prior to release. In the first release stage PAP diffused through the swollen matrix. The release accelerated with increasing medium pH due to an increase in water content in the acidic P(L)LA rod. In the second release stage PAP diffused through the water-filled micropores developed as a result of the polymer crystallization. On the assumption that the drug partition between the polymer and the medium in the micropores affects the diffusion and the partition is controlled by pH, we derived a modified diffusion kinetic equation. The observation that the release decelerated with increasing medium pH can be explained by the derived equation as resulting from the increase in the drug partition to the polymer. In the case where the rods contained more than 15% of PAP, the drug precipitated out as crystals during release. Accordingly, these rods showed a slower release.

Evaluation of the mechanical destructive force in the stomach of dog.

Orally administered dosage forms receive a destructive force in the gastrointestinal (GI) tract due to peristalsis. In this study, the destructive force was measured with a 'destructive force-dependent release system' (DDRS). DDRS is a press-coated tablet with an extremely brittle outer layer composed of highly hydrophobic Teflon(R) powder, which is molded with a weak compression force. Teflon(R) powder forms a porous but water-impermeable layer around the core tablet. A marker drug contained in the core tablet is released only when the tablet receives a force larger than its pre-determined crushing strength. A comparison of the physiological conditions in the GI tract of dogs with those of humans, including the destructive force against tablets in the stomach, helps us to understand their difference in bioavailability of oral dosage forms. With DDRS, it is possible to evaluate the destructive force of both human and dog stomach using the same method. Therefore, the destructive force data from human and dog can be directly compared. The destructive force in the dog stomach was evaluated to be 3.2 N, which was considerably stronger than that of humans.

A unique dosage form to evaluate the mechanical destructive force in the gastrointestinal tract.

The purpose of this study was to prepare tablets that could evaluate the destructive force in the gastrointestinal (GI) tract. Many factors are known to affect in vivo drug release from oral dosage forms. There is still relatively little information on the mechanical destructive force in the GI tract. Press-coated tablets with an extremely brittle outer layer were developed using a unique, highly hydrophobic Teflon powder that could be shaped with weak compression force. A marker drug contained in the tablets was released only when the tablets received a force larger than its predetermined crushing strength. We referred to this type of tablet as a 'destructive force dependent release system' (DDRS). A total of nine healthy, male subjects were orally administered the tablets under fed and/or fasting conditions. Tablets with a predetermined crushing strength of 1.50 N were crushed by all of the four subjects who took them under fed conditions and two of the five subjects under fasting conditions. Tablets with a crushing strength of 1.89 N were crushed by two of the six subjects who took them under fed conditions and none of the five subjects under fasting conditions. The range of mechanical destructive force in the human stomach was obtained.

Definitive repair of the unilateral cleft lip nasal deformity.

The majority of patients with a unilateral cleft nasal deformity still benefit from additional nasal surgery in their teenage years, despite having undergone a primary nasal repair. However, the secondary nasal deformity of these patients stands in sharp contrast to those of children who have not benefited from primary repair. The authors' algorithm for the definitive correction of these secondary deformities considers the differences in these two patient groups and defines their indications for rib cartilage grafts and their method of using septal and ear cartilage in the repair. Balancing the muscle forces on the septum and alar cartilage is emphasized in both the primary and secondary repair. Both cartilage malposition and hypoplasia of the lower lateral cartilage complex have been identified as factors contributing to the deformity.

Characterizing the unfolded states of proteins using single-molecule FRET spectroscopy and molecular simulations.

To obtain quantitative information on the size and dynamics of unfolded proteins we combined single-molecule lifetime and intensity FRET measurements with molecular simulations. We compared the unfolded states of the 64-residue, alpha/beta protein L and the 66-residue, all-beta cold-shock protein CspTm. The average radius of gyration (Rg) calculated from FRET data on freely diffusing molecules was identical for the two unfolded proteins at guanidinium chloride concentrations >3 M, and the FRET-derived Rg of protein L agreed well with the Rg previously measured by equilibrium small-angle x-ray scattering. As the denaturant concentration was lowered, the mean FRET efficiency of the unfolded subpopulation increased, signaling collapse of the polypeptide chain, with protein L being slightly more compact than CspTm. A decrease in Rg with decreasing denaturant was also observed in all-atom molecular dynamics calculations in explicit water/urea solvent, and Langevin simulations of a simplified representation of the polypeptide suggest that collapse can result from either increased interresidue attraction or decreased excluded volume. In contrast to both the FRET and simulation results, previous time-resolved small-angle x-ray scattering experiments showed no collapse for protein L. Analysis of the donor fluorescence decay of the unfolded subpopulation of both proteins gives information about the end-to-end chain distribution and suggests that chain dynamics is slow compared with the donor life-time of approximately 2 ns, whereas the bin-size independence of the small excess width above the shot noise for the FRET efficiency distributions may result from incomplete conformational averaging on even the 1-ms time scale.

Surgical repair of unidirectional palatopharyngeal epignathus: Case report and review of literature.

Epignathus is an extremely rare, benign, congenital teratoma that arises from within the oral cavity and may be attached to the mandible, palate, or base of the skull. Because of its location, it can cause airway and feeding problems, as well as secondary defects due to the presence of an intraoral tumor. This tumor usually causes death in neonates, due to airway obstruction. Surgical removal is usually impossible, especially in large tumors (Stone, 1951; Bennett, 1970). A patient with a neonatally diagnosed nonobstructive palatopharyngeal epignathus is described. It was associated with a shortened palate, cleft uvula, and velopharyngeal insufficiency, and was successfully excised surgically.

Extensive facial adenoma sebaceum: successful treatment with mechanical dermabrasion: case report.

This report documents the successful elimination of disfiguring sebaceous adenomas from the face of a 21-year-old male patient with mechanical dermabrasion.

Core treatment for improving microencapsulability in simple gelatin coacervation method.

In microencapsulation by way of simple coacervation by gelatin, some core materials are encapsulated easily, whilst others are difficult to encapsulate or show an encapsulability dependent on the coacervation-inducing agent. The treatment of core materials to improve encapsulability was studied. It was found that core particle encapsulability can be improved by recrystallization from aqueous solution of an ionic polymer. Electrophoresis, microscopical observation and pH dependency of encapsulability of recrystallized cores revealed that the electrostatic attractive force between gelatin molecules in solution and a polymer attached to the core particle cause gelatin adsorption on the core surface to result in a great improvement in encapsulability.

Factors affecting microencapsulability in simple gelatin coacervation method.

Microencapsulation by way of simple coacervation by gelatin was examined. Five kinds of core material and six kinds of coacervation-inducing agent (CIA) were chosen and the encapsulability of each combination was studied. Some core materials are easily encapsulated, others are difficult to encapsulate, and some show a dependency of encapsulability on the CIA. Electrophoresis and gelatin adsorption studies revealed that encapsulation by way of simple coacervation by gelatin is caused by the affinity between core and coacervate resulting from gelatin adsorption on the core surface. These studies further revealed that cores onto which a large amount of gelatin has been adsorbed before coacervation can be encapsulated.

Direct determination of opium alkaloid-bovine serum albumin conjugate by matrix-assisted laser desorption/ionization mass spectrometry.

Opium alkaloids (thebaine, codeine and morphine) have been conjugated with bovine serum albumin (BSA) to give individual antigen conjugates which are analyzed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. It became clear that 9 molecules of thebaine were contained in a thebaine-BSA conjugate. Codeine and morphine contents in individual conjugates were determined to be 12 and 6 molecules, respectively.