[Pandemic influenza in Russia: specific features of clinical course and the absence of early etiotropic therapy as a risk factor of severe forms of the disease].

AIM: To assess efficacy and safety of ingavirin in the treatment of the flu caused by pandemic virus of flu A (H1N1) sw1 in hospitalized patients compared with oseltamivir. MATERIAL AND METHODS: A population-based comparative multicenter trial included 194 patients with verified diagnosis of the flu aged 18-60 years with marked clinical symptoms, body temperature over 38 degrees C and duration of the disease 48 hours maximum. The patients were randomized into 2 groups: group 1 (n=152) received ingavirin (90 mg once a day), group 2 received oseltamivir (n=42) in a dose 150 mg twice a day. Duration of the course was 5 days. RESULTS: Ingavirin and oseltamivir normalized body temperature within treatment hours 24-36 if therapy was initiated in the first disease hours 27.0 +/- 10.0 and 31.9 +/- 10.4. Mean duration of the fever for ingavirin was 35.1 +/- 14.5 hours, for oseltamivir--26.3 +/- 13.0 hours (p < 0.817). The antiviral medicines significantly reduced duration of intoxication (head ache, weakness), catarrhal symptoms (cough, tracheitis, rhinitis), rate of complication vs. patients untreated with antivirus drugs (n=30). CONCLUSION: The results of the treatment show safety and efficacy of ingavirin in uncomplicated flu caused by pandemic virus of flu A (H1N1) sw1 in inpatients. Early etiotropic therapy is a basic treatment policy able to reduce the number of severe complications and lethality.

Photosynthesis of previtamin D3 in human skin and the physiologic consequences.

Photosynthesis of previtamin D3 can occur throughout the epidermis in the dermis when hypopigmented Caucasian skin is exposed to solar ultraviolet radiation. Once previtamin D3 is formed in the skin, it undergoes a temperature-dependent thermal isomerization that takes at least 3 days to complete. The vitamin D-binding protein preferentially translocates the thermal product, vitamin D3, into the circulation. These processes suggest a unique mechanism for the synthesis, storage, and slow, steady release of vitamin D3 from the skin into the circulation.

['Masks' of acute neuroinfections and markers of differencial diagnosis]. / 'Maski' ostrykh neiroinfektsii i markery differentsial'noi diagnostiki.

AIM: To compare thе medical history, clinical features, composition of cerebrospinal fluid (CSF), results of laboratory and instrumental examinations of patients with acute neuroinfections and differentiable diseases including a pseudoinflammatory variant of the acute stage of uncomplicated subarachnoid hemorrhage (SAH), consequences of traumatic brain injury (traumatic SAH, SAN combination with secondary purulent meningitis, posttraumatic nasal liquorrhea, intracerebral hematomas), abscesses and tumors of the brain, lymphoma with proven CNS. These diagnoses were mistakenly made to patients admitted to an infectious department. MATERIAL AND METHODS: Forty-six patients, aged from 18 to 83 years, hospitalized in the Department of neuroinfections and intensive care in 2010-2016 were examined. Conventional clinical neurological, laboratory, instrumental (including MRI) examinations of patients, comprehensive examination of CSF samples, the study of markers of inflammation (C - reactive protein, CSF lactate), immunophenotyping of CSF cells were performed. RESULTS AND CONCLUSION: The misdiagnosis can be explained by the overestimation of such symptoms as the acute (in most cases) onset of the disease with increased body temperature to febrile levels, presence of meningeal syndrome, disorders of consciousness and focal symptoms of varying severity. The authors showed the errors and difficulties in the diagnosis, the role and importance of an integrated, interdisciplinary approach taking into account history, clinical data, results of CSF study, conventional and special methods of laboratory and instrumental examination of patients.

Lipid self-assembled structures for reactivity control in food.

Lipid self-assembled structures (SASs) have recently gained considerable interest for their potential applications, especially for sustained nutrient release and protein crystallization. An additional property, which is underexploited, is their ability to control chemical reactions in food products. Here, we concentrate on SASs formed by phospholipids (PLs) and monoglycerides (MGs), those compounds being the most natural surfactants and therefore, the best compatible with food products, in view of providing new functionalities through the formation of SASs. In this work, the phase behaviour of these amphiphiles when mixed with oil and water is described and compared. Subsequently, we address the influence of these structures to the oxidation and Maillard-type reactions. Finally, we show that SASs formed by MGs can strongly increase the yield of key aroma impact compounds generated by Maillard-type reactions when compared with the reaction performed in aqueous precursor solutions. Various SASs are compared. In particular, addition of oil to a reversed bicontinuous structure formed by MG leads to a reversed microemulsion, which, considering its low viscosity, is particularly suitable for food products and act as a very efficient reactor system. The influence of oil and precursors on phase behaviour is discussed and related to the efficiency of the Maillard reactions.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'.

[Enterovirus infections and meningitis in children].

OBJECTIVE: To compare clinical characteristics in children with enterovirus infections (EVI) and meningitis with detailed characteristics of the changes in the content of cerebrospinal fluid (CSF) confirmed in the laboratory. MATERIAL AND METHODS: The results of examinations of 97 children, aged from 2.5 to 15 years, 3 adolescents and 1 adult female patient with EVI were analyzed. Enterovirus RNA isolation and detection in feces and CSF was performed using PCR. RESULTS AND CONCLUSION: Enterovirus RNA in CSF was detected in 44 children, including 3 patients with cytosis (5-7-19 cells in 3 mm3). The frequency and severity of symptoms in 42 patients with EVI and meningitis, 14 children with EVI without meningitis and 8 patients with ICD-10 «Meningitis unspecified¼ are presented. The initial CSF pleocytosis in 1-3 day (4-5 day for two-wave course) in EVI and meningitis was <100 in 4, from 100 to 1000 in 33, >1000 (max 3036) cells in 3 mm3 in 5 patients, including 15 with the predominance of neutrophils (from 77 to 97% in cytosis 114-2300 cells in 3 mm(3)). In the peripheral blood, leukocytosis 10.9-13.8×10(9)/л was noted in 12 children and leukocytosis 14.4-18.7×10(9)/л with the «left shift¼ in 7. Most of the children (n=37) with EVI and meningitis were discharged from the hospital within 10-17 days. The authors suggest the importance of including the variety of clinical presentations of EVI in the additional item «B10 Enterovirus infections¼ in upcoming ICD-11.

Mechanisms of acrylamide formation: Maillard-induced transformation of asparagine.

The formation of acrylamide (AA) from L-asparagine was studied in Maillard model systems under pyrolysis conditions. While the early Maillard intermediate N-glucosylasparagine generated approximately 2.4 mmol/mol AA, the Amadori compound was a less efficient precursor (0.1 mmol/mol). Reaction with alpha-dicarbonyls resulted in relatively low AA amounts (0.2-0.5 mmol/mol), suggesting that the Strecker aldehyde pathway is of limited relevance. Similarly, the Strecker alcohol 3-hydroxypropanamide generated low amounts of AA (0.2 mmol/mol). On the other hand, hydroxyacetone afforded more than 4 mmol/mol AA, indicating that alpha-hydroxycarbonyls are more efficient than alpha-dicarbonyls in transforming asparagine into AA. The experimental results are consistent with the reaction mechanism proposed, i.e. (i) Strecker-type degradation of the Schiff base leading to azomethine ylides, followed by (ii) beta-elimination of the decarboxylated Amadori compound to release AA. The functional group in beta-position on both sides of the nitrogen atom is crucial. Rearrangement of the azomethine ylide to the decarboxylated Amadori compound is the key step, which is favored if the carbonyl moiety contains a hydroxyl group in beta-position to the N-atom. The beta-elimination step in the amino acid moiety was demonstrated by reacting under pyrolysis conditions decarboxylated model Amadori compounds obtained by synthesis.

[Cerebrospinal fluid in clinical aspects of tuberculosis of the central nervous system].

OBJECTIVE: To identify clinical features of tuberculosis of the meninges and central nervous system (TM) with detailed characterization of changes in the composition of cerebrospinal fluid (CSF) in the initial period of the disease. MATERIAL AND METHODS: We analyzed the results of the examination of 42 patients, aged from 17 to 49 years, who were hospitalized in 2005-2014. RESULTS AND CONCLUSION: Most of the patients were admitted in the hospital in early acute disease onset. Along with the description of inflectional and cerebral symptoms, meningeal signs, disorders of consciousness and focal symptoms, we presented cell count values, protein and glucose concentrations at initial examination of CSF as well as the results of additional examination and specific therapy issues. The importance of combining treatment standards and individualization of therapy of TM patients is emphasized.

Industry-funded dermatologic research within academia in the United States: fiscal and ethical considerations.

Private-sector funding of biomedical research within academia may come from industry, foundations, the dermatologists themselves, and the public at large. Industry-funding is of benefit to both academia and industry. Industry may fund clinical and basic research and product testing. Industry is more willing to fund product testing and clinical research than basic research. Funds for dermatologic research may be obtained from manufacturers of drugs, medical devices, cosmetics, soaps, and detergents. Questions of academic freedom arise when research is funded by industry. The results of academic research are in the public domain; the results of intramural industry research are often proprietary, i.e., "trade secrets." When there is industry funding within academia, any restraints on publication should be held to a minimum and be temporary. Publication should occur in a timely fashion, although recognizing the need for delayed publication if the results concern patentable material. When there is a consultantship, pre-arranged terms of agreement may restrict communication. Patents usually are held by the investigator's institution. The funding company may be granted world-wide, royalty-bearing licenses. Conflicts of interest may arise during any research endeavor; this warrants close attention when the research is industry funded. Stock ownership, speaker fees, blind contracts, etc., should be avoided. In any communication, funding agreements should be stated. Indirect costs are a "necessary evil." There are non-research expenditures associated with all research projects for which the institution is justified in requesting compensation. Indirect costs must have definite connections to a project. As industrial funding of research within academia increases, various facets of the academia-industry relationship are receiving increasing attention. Several aspects of conflicts of interest and indirect costs must yet be resolved. When faced openly and directly, all of these issues are manageable and need not reduce the benefits to both industry and academia that are inherent in this relationship. Federal funding of academic research uses tax dollars; industry funding comes from private capital. Academia will benefit from the funding of academic biomedical research by industry. The ultimate beneficiary of the funding of academic research by industry, however, will be society at large as the medical advances derived from sound biomedical research and carefully controlled clinical trials aid patients. A solidly established academia-industry relationship is essential to the effective funding by industry of biomedical research within academia.

Effects of UVA (320-400 nm) on the barrier characteristics of the skin.

The stratum corneum serves as the major barrier to the entrance of most molecules into the skin. In the studies presented here, the effects of UVA radiation (320-400 nm) on the barrier capacity of human stratum corneum were examined. Penetration of a homologous series of primary alcohols through unirradiated (control) and UVA-irradiated (test) human epidermis was determined in vitro. Permeability constants, kp, were calculated. Mean ratios of permeability constants for UVA-irradiated and unirradiated epidermis (mean kp test)/(mean kp control) ranged from 2.3 to 3.0 for methanol and from 2.2 to 2.5 for ethanol. These mean ratios were determined using different pieces of epidermis from the same piece of skin for test and control samples. When kp control and kp test were determined on the same piece of epidermis on successive days, the ratios (kp test/kp control) were similar to the mean ratios determined on different pieces of epidermis. For other primary alcohols, propanol, butanol, hexanol, and heptanol, UVA radiation did not alter their permeability constants significantly. Partition coefficients, Km, were determined for ethanol and heptanol using UVA-irradiated and unirradiated stratum corneum. For ethanol, irradiation resulted in a 1.5 to 2.6 times increase in Km. For heptanol, irradiation caused no change in Km. These results demonstrate that the barrier capacity of stratum corneum for small, polar, primary alcohols is diminished (permeability increases) and for higher molecular weight less polar alcohols, is unaffected by small doses of UVA radiation. This increased permeability of small polar alcohols through human skin may be due to enhanced partitioning into UVA-irradiated stratum corneum, which was not apparent for a higher molecular weight less polar alcohol.

Penetration of benzene through human skin.

Although it is known that benzene may be absorbed from inhaled air, the amount that may enter the system by percutaneous absorption is less well established. We have measured the penetration of benzene through human abdominal skin in vitro from solutions in water, gasoline, hexadecane, and isooctane and found permeability constants which averaged 111.0, 1.4, 0.9, and 3.7 X 10(-3) cm X h-1, respectively. The stratum corneum/water partition coefficient for benzene has been measured and averages 30.0. The partition coefficients for the other vehicles are very low and cannot be measured by the method used for water. A new method is presented for calculating these coefficients, however, and they are 0.11, 0.14, 0.17, and 0.19 for gasoline, hexane, isooctane, and hexadecane. The flux of benzene through epidermis in vitro from air saturated with benzene at 31 degrees C averages 1.0 microliter cm-2 X h-1. Solvents may alter the barrier characteristics of the stratum corneum. Polar and nonpolar molecules probably traverse the stratum corneum via different pathways. By measuring the change in the permeability constants for tritiated water (a polar molecule) and for benzene (a relatively nonpolar molecule) before and after exposure to different solvents, alterations of the polar and nonpolar pathways have been shown to differ. Since benzene penetrates normal intact human skin more rapidly than many small organic molecules, and is potentially toxic, the skin should be considered a portal of entry for benzene. Good hygiene should be maintained and care taken to avoid lengthy exposure to solvents containing benzene.

Observations on the mechanism of the protective action of sunscreens.

A method is described for measuring the entrance into excised skin of ultraviolet radiation absorbing chemicals (UVRACs) following their application to the cutaneous surface in volatile, partially volatile or nonvolatile vehicles. Also a method is presented for observing changes in optical density (OD) of a sheet of stratum corneum subsequent to the application of an UVRAC and then washing it from the surface. Using these methods, p-aminobenzoic acid (PABA) and 2-ethylhexyl p-dimethyl aminobenzoate (O-PABA) have been studied. In the presence or absence of the nonvolatile vehicle, isopropyl myristate (IM), significant amounts of PABA enter the skin but almost all of the O-PABA remains on the surface. Nevertheless subsequently PABA is more easily removed by water than is O-PABA. When either UVRAC is applied to excised stratum corneum, the OD of the tissue increases immediately; only with PABA is there a further increase as it enters the skin. In vivo, delayed erythemal responses to 280-400 nm radiation of persons to whom the UVRACs are applied correlate well with the observations made on excised skin.

Controlled removal of human stratum corneum by pulsed laser.

A new method is presented for controlled removal of the stratum corneum of human skin. An excimer laser (193 nm wavelength, 14 ns pulsewidth) was used to remove stratum corneum from in vitro human skin samples by an ablative process. The tritiated water (3H2O) permeability constant and electrical resistance of skin samples were measured in a diffusion chamber apparatus to quantify the enhancement of skin permeability. Each laser pulse ablates about a micrometer of stratum corneum, which allows controlled removal of tissue. The maximum specific enhancement of the 3H2O permeability constant obtained after complete stratum corneum removal depends on the laser pulse energy used. The most gentle laser ablation, achieved with a radiant exposure of 70 mJ/cm2 per pulse, produced a 124-fold enhancement, which is comparable to that achieved after stratum corneum removal by tape-stripping or removal of epidermis by mild heat treatment. Rapid tissue ablation occurred at higher radiant exposures of 170-480 mJ/cm2 per pulse, but only a 45-fold enhancement of permeability was achieved. The precision with which stratum corneum can be ablated using excimer laser pulses may allow further basic research on the internal structure of stratum corneum and on the re-epithelization in controlled wounds. The technique may prove useful clinically to enhance percutaneous transport in applications such as topical delivery of drugs, patch testing, and percutaneous blood gas monitoring.

The diffusion of water across the stratum corneum as a function of its water content.

The flux of tritiated water (HTO) through pieces of stratum corneum at four different levels of hydration has been measured. The concentration of water in the stratum corneum, the concentration of HTO in the presenting solution, and the thickness, density, and weight per unit area of the dry stratum corneum are known. The thickness of the hydrated stratum corneum and the permeability and diffusion constants of HTO were calculated. From these in vitro data it is possible to calculate the in vivo thickness of the stratum corneum, its water concentration profile, and the flux of water (transepidermal water loss) at environments of different relative humidities. Both the transepidermal water loss and the water concentration profile change very little as the environmental relative humidity increases from 0 to 80%. The small decrease in the water concentration of the surface layers of cells as the relative humidity becomes very low, however, may cause an observable alteration in the physical characteristics of the surface layers.

Prolonged hemodynamic effect of a slow-release nitroglycerin ointment.

Nitroglycerin (NTG) ointment has been shown to be effective in the treatment of angina pectoris and congestive heart failure. Its duration of action is usually 4 to 6 hours. This study presents data that show that a new slow-release NTG ointment produces hemodynamic improvement over at least 24 hours. Twenty patients with coronary artery disease were tested with serial gated equilibrium radionuclide ventriculography before and at various stages of continuous, once-a-day use of slow-release NTG ointment and 4 days after cessation of therapy. NTG ointment significantly (p less than 0.005) decreased left ventricular end-diastolic and end-systolic volumes both at rest (23% and 33%) and during handgrip exercise (22% and 32%) when examined after continuous usage of at least 24 hours. Ejection fraction increased 21% at rest, from 0.42 +/- 0.15 to 0.51 +/- -0.18, p less than 0.0005). The ratio of peak systolic pressure to end-systolic volume increased 85% at rest (p less than 0.05) and 54% during exercise (p less than 0.01). All values had returned to baseline 4 days after cessation of treatment. Thus, slow-release NTG ointment may be useful in the treatment of angina pectoris and congestive heart failure on a once-a-day basis.

Efficiency of opaque photoprotective agents in the visible light range.

"Opaque" physical sunscreens are important for photoprotection of individuals with visible light and UV-A photosensitivity such as those with porphyria, drug photoallergy, and polymorphous light eruption. Diffuse spectral transmittance of various thicknesses of opaque sunscreen formulations were measured from 350- to 800-nm range using a spectrophotometer equipped with an integrating sphere. Transmission through 20% zinc oxide paste was high and decreased minimally despite large increases in the sunscreen layer thickness. Adding a visible light absorber such as iron oxide to scattering sunscreens, however, substantially lowered transmittance below that predicted by the product of the transmittances for each component alone. Opaque sunscreens protected against hematoporphyrin derivative photosensitization of albino guinea pig skin; these results were quantitatively consistent with the in vitro findings. Poor photoprotection against visible light is obtained with white paste sunscreens, even if thick layers are applied. The addition of pigments to such sunscreens, however, greatly enhances photoprotection and cosmetic acceptability.

Piloplex, a new long-acting pilocarpine polymer salt. A: Long-term study.

Thirty eyes of 15 patients with open-angle glaucoma were followed up for a period of up to 1 year while being treated with Piloplex eye drops containg a new long-acting pilocarpine polymer salt. Average morning intraocular pressure (IOP) values during treatment with pilocarpine hydrochloride administered 4 times daily was 20.5 mmHg. Average morning IOP values during Piloplex medication administered only twice daily were 19.8 to 18.2 mmHg (range of averages on 14 sessions). These findings indicate the lower average pressure during Piloplex medication and show its prolonged hypotensive effect. Both medications contained an equivalent total daily amount of pilocarpine. Throughout the 1-year study period no adverse side effects were reported, and only 1 patient complained of local sensitivity reaction. Visual disturbances characteristic of pilocarpine eye drops were reduced from 3 times a day on pilocarpine hydrochloride 4 times daily to once a day on Piloplex twice daily.

Identification of potent odorants formed by autoxidation of arachidonic acid: structure elucidation and synthesis of (E,Z,Z)-2,4,7-tridecatrienal.

The aroma composition of autoxidized arachidonic acid was characterized by aroma extract dilution analysis. The most potent odorant was trans-4,5-epoxy-(E)-2-decenal followed by 1-octen-3-one, (E,Z)-2,4-decadienal, (E,Z,Z)-2,4,7-tridecatrienal, (E,E)-2,4-decadienal, and hexanal. (E,Z,Z)-2,4,7-Tridecatrienal was unequivocally identified by mass spectrometry and nuclear magnetic resonance (NMR) data. The stereochemistry of its extended double-bond system was elucidated on the basis of NMR measurements. The target compound was synthesized in four steps starting with bromination of 2-octyn-1-ol, followed by copper-catalyzed coupling of the bromide with ethylmagnesium bromide and (E)-2-penten-4-yn-1-ol. Partial hydrogenation of the resulting C(13)-compound with triple bonds in the positions C-4 and C-7 gave rise to (E,Z,Z)-2,4,7-tridecatrien-1-ol, which was finally oxidized to the target compound. It exhibits a typical egg-white-like, marine-like odor at low concentrations, and an intense orange-citrus, animal-like odor at higher concentrations. Its odor threshold was estimated by gas chromatography-olfactometry to be 0.07 ng/L air, which is of the same order of magnitude as that reported for 1-octen-3-one and (E,E)-2,4-decadienal.

Synthesis of deuterated volatile lipid degradation products to be used as internal standards in isotope dilution assays. 1. Aldehydes.

The isotopically labeled compounds [5,6-(2)H(2)]hexanal (d-I), [2, 3-(2)H(2)]-(E)-2-nonenal (d-II), [3,4-(2)H(2)]-(E,E)-2,4-nonadienal (d-III), and [3,4-(2)H(2)]-(E,E)-2,4-decadienal (d-IV) were prepared in good yields using new or improved synthesis procedures. Labeling position, chemical purity, and isotopic distribution of the compounds were characterized by various MS and NMR techniques. These molecules are used as internal standards in quantification experiments based on isotope dilution assay. Synthesis of d-I, d-III, and d-IV has not yet been reported in the literature.

Synthesis of deuterated volatile lipid degradation products to be used as internal standards in isotope dilution assays. 2. Vinyl ketones.

The isotopically labeled compounds [5,6-(2)H(2)]-(Z)-1, 5-octadien-3-one (d-I) and [1-(2)H(1;2),2-(2)H(1;1)]-1-octen-3-one (d-II), as well as the unlabeled reference compound (Z)-1, 5-octadien-3-one (I) were prepared by improved synthesis procedures. Labeling position, chemical purity, and isotopic distribution of the compounds were characterized by various MS and NMR techniques. These molecules are used as internal standards in quantification experiments based on isotope dilution assay. The newly prepared compound d-II was synthesized in a simple two-step procedure, and formation of the main isotopomers was studied in model systems.

Synthesis of trans-4,5-epoxy-(E)-2-decenal and its deuterated analog used for the development of a sensitive and selective quantification method based on isotope dilution assay with negative chemical ionization.

The volatile compound trans-4,5-epoxy-(E)-2-decenal (1) was synthesized in two steps with good overall yields. The newly developed method is based on trans-epoxidation of (E)-2-octenal with alkaline hydrogen peroxide followed by a Wittig-type chain elongation with the ylide formylmethylene triphenylphosphorane. For the synthesis of [4,5-2H2]-trans-4,5-epoxy-(E)-2-decenal (d-1), [2,3-2H2]-(E)-2-octenal was prepared by reduction of 2-octyn-1-ol with lithium aluminum deuteride and subsequent oxidation of [2,3-2H2]-(E)-2-octen-1-ol with manganese oxide. Compound d1 was used as internal standard for the quantification of 1 by isotope dilution assay. Among various mass spectrometry (MS) ionization techniques tested, negative chemical ionization with ammonia as reagent gas gave best results with respect to both sensitivity and selectivity. The detection limit was found to be at about 1 pg of the analyte introduced into the gas chromatography-MS system.