[Intraoperative fluorescence diagnostics upon recurrent operations for brain gliomas].

UNLABELLED: The method of fluorescent diagnosis (FD) using 5-ALA has been widely employed in surgery of primary intracerebral tumors over the last years. The issue of FD application in surgery of gliomas with continued growth has remained less studied. OBJECTIVE: To investigate the efficacy of using FD with 5-ALA and laser spectral analysis in surgery of brain gliomas with continued growth. MATERIAL AND METHODS: 19 patients with Grade II-IV (WHO) gliomas with continued growth of different localization were studied. All tumors localized supratentorially. 5-Aminolevulinic acid hydrochloride "Alasens" (SSC "NIOPIK", Moscow, Russia) was used in the study. The equipment used during surgery included an operating microscope with an attachment for fluorescent navigation. Apart from expert qualitative assessment of a fluorescence extent, computer analysis of the fluorescence and light scattering (diffuse reflection) spectra was performed on a LESA-01-BIOSPEK spectrum analyzer (Russia). RESULTS: Detectable fluorescence was obtained in all the cases. PP IX fluorescence indices from 9.05 to 53.97 (the study was conducted in 12 cases) were determined by quantitative analysis of the spectrograms. The analysis of light scattering revealed its inverse relationship with respect to the fluorescence index. High sensitivity of the method in surgery of gliomas with continued growth requires clarification of method specificity because non-specific accumulation of PP IX in the area of post-radiation necrosis may occur in these patients. CONCLUSIONS: The FD method can be used for intraoperative demarcation of tumor resection boundaries in surgery of cerebral gliomas with continued growth. However, it is necessary to be critical of the high sensitivity of the method in patients with postradiation pathomorphism due to possible non-specific accumulation of PP IX in tissues. A light scattering study may provide additional information about the structure of tissues in the surgical wound.

[Development of the system of dietary nutrition in the Armed Forces of the Russian Federation].

The analysis of the existing system of organization dietary personnel in the Armed Forces has been done. The new system of improvement of dietary nutrition for military personnel was developed. This system is based on scientifically proven food rationings that provide a balance of nutrients and mechanical and chemical sparing of GI tract. For the purpose of evalution of the given system the research was conducted. Two test groups were formed. First group (control) got dietary nutrition according to the current system; second group (experimental) got dietary nutrition according to the developed system. In 3 months, experimental group showed the significant improvement of health record. Control group had no significant changes. Obtained results show the prospects of developed dietary nutrition.

A new modified cut standard straw vitrification technique reduces the apoptosis of mouse blastocysts and generates more live mouse offspring.

Effects of freezing on apoptosis and autophagy in embryos are poorly understood. This study introduces a simple and successful method (modified cut standard straw, M-CSS) for cryopreservation of mouse zygotes. Apoptosis and autophagy were investigated in cultured mouse blastocysts derived from vitrified zygotes using two vitrification containers (M-CSS vs 0.25-ml straw). The percentages of zygotes that survived and developed into blastocysts and the number of cells per blastocyst were higher in the M-CSS group than in the 0.25 ml straw group; whereas the rate of apoptosis in blastocysts was significantly lower in the M-CSS group than in the 0.25-ml straw group. The expression of the apoptosis-related gene Caspase 3 in blastocysts was higher in the 0.25-ml straw group than in the M-CSS group; however, there were no significant differences in autophagy between these two groups. Vitrified-thawed mouse zygotes were transferred into recipients. The percentage of recipients that became pregnant and the percentage of transferred zygotes that developed into live offspring were significantly lower in the 0.25-ml straw group than in the M-CSS (10.2% vs. 17.5%). In conclusion, the novel M-CSS procedure improves oocyte and embryo vitrification. The standard 0.25-ml straw vitrification procedure induces mitochondrial apoptosis in zygotes in an autophagy-independent manner.

[Intraoperative combined spectroscopy (optical biopsy) of cerebral gliomas]. / Intraoperatsionnaia kombinirovannaia spektroskopiia (opti-cheskaia biopsiia) gliom golovnogo mozga.

Clinical studies have revealed high selectivity of 5-ALA-induced protoporphyrin IX accumulation in different brain tumors. Modern methods of evaluation of tissues visible fluorescence are based on the qualitative analysis of the images. Up-to-date methods of combined spectral analysis allow fulfilling the intraoperative quantitative evaluation of the protoporphyrin IX content, as well as the scattering and absorption properties of a tissue. This paper presents a new method of the simultaneous analysis of hemoglobin concentration in oxygenated and reduced forms, tumor marker concentration (5-ALA-induced PP IX) and a new way to analyze the changes in the scattering properties of the tissues. The method is implemented by splitting the visible spectrum into intervals where hemoglobin and protoporphyrin IX have the characteristic peaks of absorption and fluorescence. The present method shows the dependence of the fluorescence index from the tumor grade. Combined spectroscopy (optical biopsy) can detect the differences between the subtypes of gliomas that are similar in the protoporphyrin IX fluorescence index. This method complements and enhances the diagnostic capabilities of spectroscopy, which is particularly important in the non-fluorescent glioma surgery.

[Intraoperative fluorescent visualization and laser spectrosopy in intrinsic brain tumor surgery].

Absence of well-defined borders of the glial tumor due to their infiltrative growth is one of the main issues in neurosurgery. A number of methods for intraoperative visualization are available today. The fluorescent metabolic navigation with 5-aminolevulinic acid (5-ALA) combined with quantitative laser spectroscopy is one of the latest technique. In our series of 99 consecutive patients with brain gliomas (WHO Grade I-IV) we found that visible fluorescence was observed in 68% of cases. Additional use of the laser spectroscopy could increase method sensitivity up to 74% due to accumulation of the protoporphyrine IX in nonfluorescense tumors. It was shown that there are some differences in quantitative fluorescence not only within same tumor (glioblastoma) but also in-between low- and high-grade gliomas. Intraoperative fluorescence and laser spectroscopy are effective and very helpful methods of intraoperative imaging in of intrinsic brain tumor surgery.

[First experience of photodynamic diagnosis and laser spectroalanysis in surgery of intracranial meningiomas].

Photodynamic diagnosis (PDD) has been actively implemented into neurooncological practice, especially in cerebral gliomas surgery. This paper describes our first experience of PDD combined with laser spectroanalysis in intracranial meningiomas. The study included 21 patients (8 male and 13 female patients, mean age was 58 years, range--between 37 and 74 years) with intracranial meningiomas operated with PDD in Burdenko Neurosurgical Institute between 2008 and 2011. In 14 cases laser spectroanalysis was used. Tumor fluorescence was present in all but one cases (95%). Spectroanalysis demonstrated that peaks of fluorescence varied between 5 and 46 (mean level was 18.5). These data correlated with visual impression of fluorescence and confirmed that meningioma is a tumor with bright fluorescence. Radical removal (Simpson grade I-II) was achieved in 10 cases, subtotal resection was performed in the rest of the patients. Application of PDD and laser spectroanalysis allows gaining complete information about accumulation of photosensibilizer in the tissue. To our opinion, these methods may be the most useful for determination of the borders of dural and bony invasion which directly affects the surgical tactics and degree of radical removal. Further studies are needed to evaluate the influence of PDD and laser spectroanalysis on long-term surgical outcomes.

[Genetic control of metabolism of mutagenic purine base analogs 6-hydroxylaminopurine and 2-amino-6-hydroxylaminopurine in yeast Saccharomyces cerevisiae].

The influence of inactivation of genes, which control biosynthesis of inosine monophosphate (IMP) de novo and the purine utilization and interconversion pathway, on sensitivity of yeast Saccharomyces cerevisiae cells to the mutagenic and toxic action of 6-hydroxylaminopurine (HAP) and 2-amino-6-hydroxylaminopurine (AHA) was studied. It was shown that the manifestation of HAP and AHA mutagenic properties involves the action of enzyme adenine phosphoribosyltransferase encoded in yeast by APT1 gene. A blockade of each stage of IMP biosynthesis, with the exception of the block mediated by inactivation of genes ADE16 and ADE17 leading to the accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), was shown to enhance yeast cell sensitivity to the HAP mutagenic effect; however, it does not affect the sensitivity to AHA. A blockade of conversion of IMP into adenosine monophosphate (AMP) causes hypersensitivity of yeast cells to the mutagenic action of HAP and to the toxic effect of HAP, AHA, and hypoxanthine. It is fully probable that this enhancement of sensitivity to HAP and AHA is conditioned by changes in the pool of purines. This indicates that genes ADE12, ADE13, AAH1, and HAM1 controlling processes of purine utilization and interconversion in yeast make the greatest contribution to the system of protection against the toxic and mutagenic action of the examined analogs. Possible mechanisms of HAP detoxication in bacteria, yeast, and humans are considered.

The effect of high pressure-low temperature treatment on physicochemical properties in milk.

This study was carried out to investigate the effect of high pressure-low temperature (HPLT) treatment on physicochemical properties and nutrients in milk. The milk was treated at 200 MPa and -4 degrees C for 10, 20, and 30 min. Protease and lipase activities of HPLT-treated milk were highly inactivated compared with that of raw milk. Among time treatments, the 30-min treatment showed the lowest activities compared with others. Absorbance of thiobarbituric acid increased with time in HLPT-treated milks; however, no difference was observed between the raw milk and milk treated for 10 min. The concentrations of short-chain fatty acids except C(4) in HPLT-treated milks increased with time. The total free amino acids in HPLT-treated milks were greater than that of the raw milk for the 30-min treatment. L-Ascorbic acid, niacin, and riboflavin in HPLT-treated milks were significantly lower compared with concentrations in raw milk. For color, the L-value of HPLT-treated milks was significantly lower than that of the raw milk; however, there was no difference in the a-value for 10 min and in the b-value at 20 min between the raw milk and the HPLT-treated milks.

[Experimental rationale for a transscleral approach to thermotherapy for intraocular tumors, by using a photosensitizer].

The authors present the results of an experimental study of the pattern of distribution of laser radiation at a wavelength of 810 nm in the normal and Photosens-photosensitized eye tissues and analyze the distribution of a temperature at the sclera/choroidea/ tumor border during transscleral radiation delivery. To further the goal, the authors have resorted to computer mathematical simulation. In convergent-beam radiation supply, the proportion of a scattered radiation component has been ascertained to be lower in the surface scleral layer than that in the layers adjacent to the choroidea and the base of a tumor. On entering the sclera, a splash of light decreases and power density and radiation-induced heating of the deeply located tissues increase. Thus, the major hyperthermic effects show themselves in the tumor rather than on the sclera.

[Analysis of changes in the accumulation of the photosensitizer Photosens, its elimination kinetics and distribution in the tissues of the eye and eyelids in health and in some tumorous processes].

The authors analyze and present the results of spectroscopic studies into changes in the accumulation of the photosensitizer Photosens, its elimination kinetics and distribution in the tissues of the eye and eyelids, as well as in the tumors that have developed at these sites. The findings allowed the authors to estimate the duration of the agent's persistence in the eye tissues and the time interval associated with the high risk for phototoxic eyelid skin and conjunctival reactions and to determine a possibility of and conditions for photodynamic therapy, as well as the length of hospital stay when the latter was performed.

[Feasibilities of photodynamic therapy in the treatment of corneal mycotic lesions: an experimental study].

The paper presents the results of studying the photofungicidal activity of a photosens (octacationic phthalocyanine) in the in vitro and in vivo systems. Cultured Candida guilliermondii were employed in in vitro investigations. The single combined action of octacationic phthalocyanine at a concentration of up to 1 microM and laser irradiation at a wavelength of 675 nm were established to allow the high activation (up to 100%) of yeast fungi to be achieved in the in vitro system. In vivo investigations were performed on 14 rabbits (28 eyes) with induced keratomycosis. In the first series, fluorescent diagnosis of photosens accumulation in the pathological corneal areas was made in 9 (18 eyes). Based on the data obtained in the second series of experiments, the authors examined the feasibilities of photodynamic therapy for corneal mycotic lesions with the above photosensitizer in 5 rabbits (10 eyes).

[Photodynamic therapy in treatment of chorioid neovascularization].

The authors studied the effectiveness of photodynamic therapy (PDT) with Photosence, a Russian photosensitizer, in treatment of chorioid neovascularization (CNV) in cases of age-related macular degeneration (ARMD) and pathological myopia (PM). The subjects were 73 patients with CNV suffering from ARMD and PM. The efficiency of PDT and complex conservative therapy was compared using vision acuity measurement, retinal morphometry, and fluorescent eye ground angiography (FEGA), performed before treatment, immediately after treatment, and 1, 3, 6, and 12 months later. The study showed that PDT in patients with CNV, ARMD and PM was more efficient than pharmacotherapy. Vision acuity improved or stabilized, and the parameters of retinal morphometry and FEGA improved as well. The results of the study evidence high efficiency of PDT with Photosence in treatment of CNV with ARMD and PM.

[Photodynamic therapy for subretinal neovascular membranes. Communication 2. Results of treatment for complicated myopia].

The efficiency of photodynamic therapy (PDT) versus drug therapy was evaluated in patients with subretinal neovascular membranes (SNM) in complicated myopia (CM). Photosens (aluminum phthalocyanine) was intravenously injected in a dose of 0.05 mg/kg. The irradiation conditions were as follows: a session was carried out, using a laser at a wavelength of 675 nm, in an exposure light dose of 120 J/cm2. The number of sessions ranged from 3 to 5 a week, depending on the clinical picture of SNM. The total light dose was not greater than 500 J/cm2. Twelve months after drug therapy and a course of PDT, reduced visual acuity was observed in 50% and only 20.8% of cases, respectively. Stabilization or increase of visual functions occurred in the remaining patients receiving a course of PDT.

[Role of fluorescence diagnosis using Photosens in patients with subretinal neovascular membrane].

The paper shows the capacity of fluorescence diagnosis (FD) in patients with subretinal neovascular membranes. Photosens was used as a photosensitizer (PS) (NIOPIK) in FD. The agent was intravenously injected in a dose of 0.05 mg/kg. To study the kinetics of tissue PS distribution, the authors employed a procedure of local fluorescence spectroscopy using a LESA-01-Biospek spectrometer, which was improved when applying the procedure for visual assessment of a visual fluorescence image. It was ascertained that the results of photodynamic therapy (PDT) should be compulsorily taken into account in processing its parameters. In some cases, PDT may be recommended on days 3, 5, and 7 after administration of an agent. By taking into account the pharmacodynamics of Photosens, 0.5 mg/kg, all patients should keep the light regime for 3 months.

[Photodynamic therapy for subretinal neovascular membranes. Communication 1. Results of treatment for age-related macular degeneration].

The purpose of the study was to assess the results of photodynamic therapy (PDT) for subretinal neovascular membranes (SNM) in age-related macular degeneration (ARMD), by using the Russian drug Photosens. According to the treatment performed, all the patients were divided into 2 groups: 1) 18 patients with the neovascular form of ARMD who received a course of PDT; 2) 14 patients with the same form who had drug therapy. Photosens (aluminum phthalocyanine) was intravenously injected in a dose of 0.05 mg/kg. The irradiation conditions were as follows: a session was carried out, using a laser at a wavelength of 675 nm, in an exposure light dose of 120 J/cm2. The number of sessions ranged from 3 to 5 a week, depending on the clinical picture of SNM. The total light dose was not greater than 500 J/ cm2. PDT showed a higher efficiency, as compared to drug therapy. PDT using Photosens increases and stabilizes visual acuity in 50% of cases, improves retinal functional activity (an increase in the mean value of a b-wave amplitude), and causes positive changes in the morphometric values of the mean neuroepithelial thickness above SNM and in the foveola.

Variability in temperature distribution and cooking properties of ground pork patties containing different fat level and with/without salt cooked by microwave energy.

This study was carried out to evaluate the cooking effects of fat level (10% and 20%) with and without NaCl (1.5%) on the microwave cooking pattern and properties of ground pork patties. Each patty was cooked from a thawed state to 76.7°C in a microwave oven with full power (900W). Cooking rate in patties produced without salt was not affected by fat level, but the addition of salt in pork patties decreased cooking rate, regardless of fat levels. The temperatures at the edges of the patties increased faster than those at the center or the mid-way positions. In the patties with NaCl, the temperature of the center position was higher than that of the mid-way position. Patties containing salt within the same fat level had higher moisture content and lower fat content than those without salt, although no significant differences in compositional properties were observed between the center, midway, or edge positions. Total cooking loss, drip loss, and reduction in diameter and thickness were higher in patties with 20% fat compared to those with 10% fat, but the addition of salt resulted in reduction, regardless of fat level. Also, the addition of salt increased the redness and reduced yellowness of the cooked products.

[Experimental assessment of the capacities of use of photosense. Communication 1. Fluorescence diagnosis of epibulbar and choroid tumors].

Whether Photosense (PS) may be used in the fluorescence diagnosis (FD) of experimental epibulbar and choroid tumors is discussed. The fluorescent ability of Photosense in FD permits detection of advanced malignancies. The kinetics of concentration of PS and the selectivity of its accumulation in malignant versus normal tissues were investigated. PS is shown to be an effective photosensitizer in the FD and, possibly, photodynamic therapy of tumors.

[The first results of phase IIA of clinical studies of photodynamic therapy for subretinal neovascular membranes with photosense].

The subretinal neovascular membrane (SNM) is a common complication of diseases, such as senile macular degeneration, myopia, pseudohistoplasmic syndrome, and many others. There is no algorithm of treatment for this pathology in today's ophthalmological care; however, many authors have arrived at the conclusion that photodynamic therapy (PDT) plays a major role in solving this difficult problem. Fifteen (18 eyes) patients, including 8 (8 eyes) patients diagnosed as having senile macular degeneration and SNM and 7 (10 eyes) patients diagnosed as having complicated high-grade myopia, and 3 were diagnosed as having bilateral SNM. The Russian agent Photosense, 0.05 mg/kg, was used as a photosensitizer. PDT was performed on day 3 after administration of the agent according to the peak of accumulation and the maximum laser concentration gradient at a wavelength of 675 nm and a light dose of 120 J/cm2. Good functional and angiographic results may be observed after the first 3 months of a prospective controlled open-labeled study of the efficiency of PDT with Photosense; however, longer follow-ups and larger groups of patients are required to make a final assessment of this treatment.

[Experimental assessment of the capacities of use of photosense. Communication 2. Photodynamic therapy for epibulbar and choroid tumors].

The study was undertaken to evaluate the efficiency of photodynamic therapy of pigmented choroid and epibulbar melanoma, by using the agent Photosense. Pigmented choroid and epibulbar melanoma were identified in 50 rabbit eyes. After intravenous injection of Photosense, 0.7 mg/kg, the tumors were irradiated at 675 nm with an argon-pumped dye laser at 150 J/cm2. Photodynamic therapy with Photosense may be effective in treating pigmented choroid and epibulbar melanomas.

[Photodynamic approaches to elimination and prevention of atherosclerotic changes in the vessels]. / Fotodinamicheskie podkhody k ustraneniiu i predotvrashcheniiu arteroskleroticheskikh izmenenii v sosudakh

Photodynamic therapy (PDT) is a method based on a selective accumulation of a photo-sensitive dye in the target cells with their subsequent destruction with the aid of a low-intensity laser radiation of a certain wavelength. It is widely used today in clinical practice, mostly in oncology. This review elucidates possibilities of using the PDT in prophylactics and treatment of cardiovascular pathological conditions, atherosclerosis in particular. Data are cited indicating a successful application of the PDT for preventing the intima hyperplasia following and angioplasty. A possibility of using the PDT for treatment and prophylactics of atherosclerotic alterations in the vessels with due consideration of specifics of formation and cullular composition of the atherosclerotic lesions.