Correlation of synovial caspase-3 concentration and the photodynamic effectiveness in osteoarthritis treatment.

BACKGROUND: The present study focuses on investigation of Intra-articular PDT mechanisms for OA treatment. Also, a search for determination of the most effective dose of chlorin e6 (Ce6) for anti-inflammatory PDT of OA was carried out. METHODS: The study was carried out on laboratory animals (11 Chinchilla rabbits, 1 year, 2.5 kg) with a gonarthritis model of post-traumatic OA. According to the instructions for using Photoditazin (Ce6 based PS) for PDT of human oncological and non-oncological diseases, the recommended dose is 0.7-1.2 mg/kg. For studies on rabbits, taking into account the conversion coefficient (3.2), the PS doses of 2.4, 3.2 and 6.4 mg/kg were selected. Fluorescence spectra were measured intra-articular before and after PDT using spectrometer with fiber-optic probe. The intrajoint PDT was carried out using a laser (662 ± 10 nm) and a fiber-optic catheter with a cylindrical diffuser inside a sapphire needle for a uniform distribution of the laser radiation. The immunohistochemical study was carried out by staining the samples with caspase-3. RESULTS: Histological and immunohistochemical analysis showed that the best PS dose for intravenous administration for PDT of rabbit gonarthritis is 3.2 mg/kg. The PS concentration directly in the synovial tissue was 0.5 mg/kg, and this was enough to achieve the most positive results to reduce the caspase-3 level. CONCLUSION: The caspase-3 level correlates well with other signs of inflammation in the synovial membrane (edema, etc.). Therefore, to assess the PDT effectiveness in the treatment of gonarthritis accompanied by synovitis, it is sufficient to analyze only for caspase-3. The efficacy of PDT with Ce6 showed that 3.2 mg/kg PS dose (1 mg/kg for a human) is the most effective.

Combined treatment of nonresectable cholangiocarcinoma complicated by obstructive jaundice.

BACKGROUND: The five-year survival rate for successful surgical treatment of cholangiocellular cancer is only 20-40%, and in the case of an unresectable tumor, the life expectancy does not usually exceed 6 months. Survival decreases with the presence of jaundice, due to the spread of the tumor process along the bile ducts, leading to their obstruction. We report outcomes of patients with nonresectable bile duct carcinoma complicated by obstructive jaundice treated with Photodynamic Therapy (PDT). METHODS: Combined diagnosis and treatment included percutaneous cholangiostomy, intraductal video fluorescence diagnostics, photodynamic therapy, and bile duct stenting. All patients were treated at the Sechenov University Oncology Center in Moscow. The results of treatment of 33 patients have been presented. The intraductal diagnosis of malignant bile duct lesions was performed after cholangiostomy using the endovideofluorescence module for minimally invasive surgery and endoscopy. With the use of this method, it is the first time in Russia that it has become possible to obtain a videofluorescent image of the tumor and to determine the high level of photosensitizer accumulation in all cholangiocarcinoma patients. The preparations Photolon, Radachlorin, and Photosens were employed as photosensitizers (PS). Intraductal photodynamic therapy was used to achieve the antitumor effect. Laser power density was about 200 mW/cm2. RESULTS: We present initial results, improved the diagnostic possibilities in this difficult localization of carcinoma, and demonstrated the feasibility of prolongation of life without significant deterioration of its quality. The average survival time in the treatment group is 9.5 months. CONCLUSION: The treatment of patients with nonresectable cholangiocarcinoma with Photodynamic Therapy should be an available option. In this context, the additional use of intraductal endovideofluorescence diagnostics is a highly specific technique that allows reliable detection of the photosensitizer accumulation predominantly by the tumor tissue and appears promising. As shown by our experience, flourescent localization followed by Photodynamic Therapy, enabled us to improve diagnostic techniques and treat the tumor with improved outcome.

[Analysis of photosensitizer gel penetration through the teeth structure]. / Analiz glubiny proniknoveniia gelia fotosensibilizatora v strukturu tkanei zubov.

As a result of the studies carried out on 20 extracted frontal teeth it was reliably shown that after 10 minutes the concentration of the photosensitizer in enamel at full depth reached values sufficient for performing photodynamic teeth whitening. At the same time, the penetration of the photosensitizer into the deep layers of dentin was not detected which allows to carry out the photodynamic bleaching procedure only within the enamel and enamel-dentine boundary, thus not affecting the pulp of the tooth.

EPR hyperthermia of S. cerevisiae using superparamagnetic Fe3O4 nanoparticles.

Presently we communicate a newly developed method of resonant radiofrequency heating, applicable in hyperthermal therapy. This method uses electron paramagnetic resonance (EPR) to transform the electromagnetic field energy into heat. We report the growth dynamics of the S. cerevisiae yeast cells exposed to EPR heating with superparamagnetic magnetite (Fe3O4) nanoparticles, with only 4% of yeast cells surviving hyperthermia. Given that EPR functions independently of type of the biologic species exposed, and produces spatially localized heating in conjunction with MRI hardware, it may be used in hyperthermal therapy of cancer and other diseases.

Gonarthritis photodynamic therapy with chlorin e6 derivatives.

BACKGROUND: The new methods of osteoarthritis treatment are in constant demand due to the complexity of the early diagnosis and therapy. Specific features of Сhlorin e6 derivative (Ce6) accumulation in knee joint tissues and the efficiency of photodynamic therapy (PDT) of gonarthritis were studied. METHODS: The experimental research was conducted on the model of posttraumatic gonarthritis on rabbits. The analysis of dynamics of change of Ce6 concentration in tissues of a knee joint was carried out by the method of fluorescent diagnostics. The intra-joint PDT was carried out using 662nm laser with energy density of 120-150J/cm(2) and a sapphire diffuser. An analysis of slices was conducted to confirm the anti-inflammatory effect through apoptosis. RESULTS: The method of fluorescent spectroscopy revealed that the highest amount of Ce6 was accumulated in the synovial membrane of a damaged knee joint 2.5h after its intravenous introduction. On 14th day after gonarthritis modeling but before PDT the synovial membrane showed signs of synovitis. On 21st day after PDT the synovial membrane possessed noticeable villous structure, and no cells of inflammatory nature were observed. CONCLUSION: Fluorescent diagnostics in knee joint tissues can be used in clinical practice of gonarthritis before, during and after PDT for monitoring the Ce6 accumulation and for treatment control. Optimal radiation energy density was determined to be 150J/cm(2). In the studied time intervals (5-25min) no dependency of PDT effect on irradiation time at the same energy density was observed. The analysis of results of clinical and morphological research shows that PDT is a low-invasive method of gonarthritis treatment with a high degree of efficiency and selectivity.

[Efficacy of cytoflavin in therapy of encephalophathy in patients with neuroinfection].

The use of cytoflavin solution in complex therapy of patients with neuroinfection was studied. It showed a favourable effect on the disease clinical process, evident from less pronounced intoxication and meningeal signs by the 11th day of the treatment and improvement of the liquorological picture. The cytoflavin efficacy was also confirmed by normalization of the brain bioelectric activity evident from the electroencephalograms and by reduction of the level of antioxidants, such as metalloproteids and superoxidodismutase, that was in favour of the drug antiinflammatory and antioxidant effects. The use of cytoflavin tablets during in early convalescence period promoted earlier recovery of the intellectual and mnestic reactions. On the whole, the use of cytoflavin promoted favourable process and outcomes of neuroinfections and could be recommended for the use during the acute state and re habilitation of the patients.

[Effect of intensive motor activity in different periods of time on the human functional state and efficiency].

Effects of heavy physical work on gas-energy exchange, cardiac activity, thermal condition, nervous system and the subjective status were evaluated in 43 athletes in the morning, afternoon and evening. It was shown that same muscular work done at the ambient temperature of 17 +/- 1 degrees C, relative humidity of 65 +/- 3% and air flow of 0.3 +/- 0.1 m/s requires a significantly higher straining of the body functions in the evening hours (after 06.00 p.m.).

[Errors in diagnosis and surgical strategy in ruptures of the diaphragm].

The present-day diagnosing and treatment of ruptures of the diaphragm is a most difficult part of polytrauma surgery. From 1989 to 2006 in the surgical clinic of the Vladivostok medical university there were 36 patients with ruptures of the diaphragm. An analysis of case histories helped to formulate the main causes of difficulties of the diagnosis of this pathology, all necessary diagnostic measures and rational surgical strategy were established. It allowed to obtain favorable results in 72% of cases.

[Endoscopic dissection of perforating veins: surgical and pharamacoeconomic aspects].

Analysed herein are the outcomes of endoscopic dissection of perforating veins (EDPV) in a total of 113 patients presenting with chronic venous insufficiency (CVI). Of these, 71 patients suffered from varicose disease (VD) and 42 subjects had postthrombophlebic disease (PTPD). 54.9 % of the patients were in CEAP class C5-6. All of them underwent EDPV combined with simultaneous phlebectomy or crossectomy. The control group consisted of 26 patients who endured the classic operation by the Linton technique. All those engaged underwent ultrasonograp-hic angioscanning, with part of them being subjected to distal phlebography. Postoperative complications were observed in 2.65 % of the Study Group patients subjected to the EDPV procedure combined with phlebectomy, and in 34.5 % of those who had endured the Linton's operation. Both subjective and clinical assessment of surgical outcomes made it possible to define the obtained results as good in 82.3% of cases, as fair in 14.16%, and in four patients with PTPD, the results were defined as poor. The hospital stay following surgery in the Study Group patients amounted to 7.3+/-0.54 bed days, while in those of the Comparison Group it was 21.2+/-0.74 bed days. The obtained findings make it possible to conclude that the scope of surgical interventions in patients presenting with CEAP class C4-6 CVIs should in the majority of cases amount to simultaneous EDPV and radical venectomy. Such policy reduces the duration of the hospital stay 2.7-fold, with a 1.76-fold decrease in the treatment costs.

[Acute chlamydial lesions of the nervous system: etiology, diagnosis, clinical aspects]. / Ostrye khlamidiinye porazheniia nervnoi sistemy: étiologiia, diagnostika, klinika.

The examination of 180 patients with acute neuroinfection (105 males, 75 females at the age from 18 to 45 years) has detected C. trachomatis in 23.8%, C. Pneumoniae in 66.6%, C. psittaci in 9.5% patients. Acute and chlamydial lesions of the central nervous system were characterized by all forms of neuroinfection: serous and purulent meningitides, meningoencephalitides. Development of acute neuroinfection is accompanied by sluggish chlamydial infection of the viscera.

[Application of different kinds of internal biliary duct drainage in emergency surgery]. / Primenenie razlichnykh vidov vnutrennego drenirovaniia zhelchnykh protokov v neotlozhnoi khirurgii.

The immediate and late results of treatment of 139 patients, operated on with formation of biliodigestive anastomosis, were analyzed. Six (4.32%) patients died. Of 39 patients, to whom choledochoduodenostomy was performed, in 18--good late follow-up result was noted and the fair one--in 21. Of 23 patients, in whom choledochojejunostomy in Roux-en-Y fashion was performed, good result was noted in 4, fair--in 18 and poor--in 1.

[Special surgery of blood vessels injuries in abdominal trauma]. / Chastnye voprosy khirurgii sosudistykh povrezhdenií pri travme zhivota.

The analysis of the results of treatment of 41 victims with large vessels injuries in abdominal trauma was carried out. According to their location, all the injured vessels were divided in 5 groups: 1) on median line above the mesocolon (9 cases); 2) on median line under the mesocolon (14 cases); 3) in superior lateral part of the abdominal cavity (2); 4) in interior-lateral part of abdominal cavity (8); 5) in the region of hepato-duodenal ligament and retrohepatic area (13). Combined vascular injuries were observed in 5 patients. Basic aspects of diagnosis, surgical policy and treatment are discussed, 14 patients died.

[Experimental bases of the use of pharmacologic agents aimed at higher heat resistance of humans as means of individual protection]. / Eksperimental'noe obosnovanie primeneniia farmakologicheskikh preparatov dlia povysheniia teplovoi ustoichivosti cheloveka v izoliruiushchikh sredstvakh individual'noi zashchity.

A group of volunteers was exposed to action of heating microclimate (ambient temperature 30 +/- 1 degrees C, relative humidity 35 +/- 5%) and other critical occupation factors (physical loading, personal protective equipment). They received simultaneously one of the medicines: placebo, bemethyl (0.5 g), phenibut (0.25 g), obsidan (0.08 g), or phenibut (0.25 g) combined with obsidan (0.08 g). Combined phenibut (0.25 g) with obsidan (0.08 g) were proved to be the most effective method to increase stability of the human body against studying critical occupational factors.

[The enhancement of human thermal resistance by the single use of bemitil and fenibut]. / O povyshenii teplovoi ustoichivosti cheloveka pri odnokratnom primenenii bemitila i fenibuta.

The authors studied the effect of single intake of bymetil (0.5 g) and phenibut (0.25 g) on the thermal state, gas-energy exchange, blood oxygenation, working capacity, and the subjective status of man in intensive physical exertion in isolating means of individual protection. The drugs under study increased thermal resistance, promoted normal supply of the organism with oxygen, and provided the maintenance of man's high working capacity under conditions which lead to his overheating. The best protective effects was produced in this case with phenibut.