Cyclic nucleotides in tissues during long-term hypokinesia

Male Wistar rates were kept hypokinetic by placing them in small containers for 22 days. Blood plasma cAMP content was subsequently found increased, and cGMP content decreased, in the experimental animals. Liver and thymus cAMP content was similar in the control and experimental animals. There was a 20 and 38% decrease of cAMP content in the kidneys and spleen, respectively. Hypokinesia's reduction of cyclic nucleotides seems to inhibit RNA and protein synthesis

Experiment K-6-16. Morphological examination of rat testes. The effect of Cosmos 1887 flight on spermatogonial population and testosterone level in rat testes

Testes from rats flown on Cosmos 1887 for twelve and a half days were compared to basal control, synchronous control and vivarium maintained rats. When the mean weights of flight testes, normalized for weight/100 gms, were compared to the vivarium controls they were 6.7 percent lighter. Although the flight testes were lighter than the synchronous, the difference is not significant. Counts of spermatogonial cells from 5 animals in each group revealed a 4 percent decrease in flight compared to vivarium controls. In both cases the t-Test significance was less than 0.02. The serum testosterone levels of all animals (flight, synchronous and vivarium) were significantly below the basal controls

Changes of the body functions during long-term hypokinesia

Prolonged hypokinesis (100-170 days) studied in 2000 rats kept in cages limiting their mobility provoked considerable changes in the gaseous and energetic metabolism: an elevation of the total gaseous metabolism and of the rate of O2 requirement by the muscles (in the late periods of hypokinesis) and a change in the intensity of tissue respiration of the liver and myocardium. There also proved to be a reduction in the level of phosphorylation and separation of oxidative phosphorylation in the myocardium, liver, and partially in the skeletal muscle. Prolonged hypokinesia led to changes in tissue metabolism: a disturbance of development of the animals, a marked delay and an increase in the weight of the organism and the muscular system, and disturbances of the mineral and protein metabolism. Prolonged hypokinesis also lead to exhaustion of the hypothalamus-hypophysis-adrenal cortex system

Клиническое наблюдение успешной фотодинамической терапии пациентки с тяжелой дисплазией вульвы

A case of successful photodynamic therapy (PDT) of the patient with grade 3 vulvar dysplasia. One course of treatment with photolon was performed. The photosensitizer was administered intravenously as 30 min infusion in dose of 1.0 mg/kg body weight. The PDT session was performed 3h after infusion of photolon, the light dose was 350 J/cm2. The treatment was well tolerated. Due to PDT a complete tumor regression was achieved. The patient received a strict follow-up schedule, for 8 months after PDT no recurrence was observed. Описан клинический случай успешного применения фотодинамической терапии (ФДТ) для лечения больной с дисплазией III ст. вульвы. Проведен 1 курс лечения с препаратом фотолон. Фотосенсибилизатор вводили внутривенно посредством 30-минутной инфузии в дозе 1,0 мг/кг массы тела. Сеанс ФДТ проводили через 3 ч после введения фотолона, плотность энергии лазерного облучения – 350 Дж/см2. Лечение пациентка перенесла удовлетворительно. В результате ФДТ получена полная регрессия опухоли. После лечения больная находилась под строгим динамическим наблюдением, в течение 8 месяцев с момента проведения ФДТ – без рецидива заболевания.

Фотодинамическая терапия в клинической практике

The review is on opportunities and possibilities of application of photodynamic therapy in clinical practice. The advantages of this method are the targeting of effect on tumor foci and high efficiency along with low systemic toxicity. The results of the set of recent Russian and foreign clinical trials are represented in the review. The method is successfully used in clinical practice with both radical (for early vulvar, cervical cancer and pre-cancer, central early lung cancer, esophageal and gastric cancer, bladder cancer and other types of malignant tumors), and palliative care (including tumor pleuritis, gastrointestinal tumors and others). Photodynamic therapy delivers results which are not available for other methods of cancer therapy. Thus, photodynamic therapy allows to avoid gross scars (that is very important, for example, in gynecology for treatment of patients of reproductive age with cervical and vulvar cancer), delivers good cosmetic effect for skin tumors, allows minimal trauma for intact tissue surrounding tumor. Photodynamic therapy is also used in other fields of medicine, such as otorhinolaryngology, dermatology, ophthalmology, orthopaedics, for treatment of papilloma virus infection and purulent wounds as antibacterial therapy.Обзор посвящен перспективам и возможности применения фотодинамической терапии в клинической практике. Преимуществами данного метода являются направленность воздействия на опухолевые очаги и высокая эффективность при низкой системной токсичности. В обзоре приведены результаты ряда отечественных и зарубежных клинических исследований последних лет. Показано, что метод успешно применяется в клинической онкологии как с радикальной целью (при ранних стадиях рака и предраке вульвы, шейки матки, раннем центральном раке легких, раке пищевода и желудка, раке мочевого пузыря и других), так и с паллиативной целью (в том числе, при опухолевых плевритах, опухолях желудочно-кишечного тракта и других). Фотодинамическая терапия позволяет достичь результатов, недоступных при использовании других методов противоопухолевой терапии. Так, проведение фотодинамической терапии позволяет избежать появления грубых рубцов (что очень важно, например, в гинекологии при лечении пациенток раком шейки матки и вульвы репродуктивного возраста), достичь хорошего косметического эффекта при локализации опухоли на коже, минимально травмировать окружающие опухоль здоровые ткани. Фотодинамическая терапия также применяется и в других отраслях медицины, таких как оториноларингология, дерматология, офтальмология, ортопедия, в лечении папилломавирусной инфекции, а также в лечении гнойных ран в качестве антибактериальной терапии

Результаты III фазы клинических исследований препарата радахлорин для фотодинамической терапии предрака и начального рака шейки матки

The results of clinical study for efficacy of photodynamic therapy (PDT) with radachlorine in patients with pre-cancer and cancer of cervix are represented. The study enrolled 30 patients including 4 patients with cervical erosion, 5 patients with cervical intraepithelial neoplasia II, 13 patients with cervical intraepithelial neoplasia III, 4 patients with carcinoma in situ and 4 patients with cervical cancer stage Ia. Radachlorine was administrated as single 30 minute intravenous injection at dose of 1,0 mg/kg of body weight 3 h before irradiation (wavelength of 662 nm, light dose of 300–350 J/cm2). The results of treatment in 26 (86,7%) patients was assessed as complete tumor regression and in 4 (13,3%) patients — as partial regression. In cervical erosion, intraepithelial neoplasia II and carcinoma in situ groups total regression was in all cases. In the cervical intraepithelial neoplasia III group total regression after first course of PDT was achieved in 77% of patients, in cervical cancer stage Ia group – in 75% of patients. From 3 to 6 months after first course of treatment all patients with partial tumor regression underwent the second course of PDT with complete regression. There were no side-effects due to radachorine or PDT in the course of treatment and during follow-up. Thus, PDT with Russian photosensitizer radachlorine showed high efficiency for treatment of pre-cancer and cancer of cervix. Приведены результаты клинического исследования эффективности фотодинамической терапии (ФДТ) с препаратом радахлорин у пациенток с предопухолевой и опухолевой патологией шейки матки. В исследование включено 30 пациенток, в том числе с эрозией шейки матки – 4 пациентки, с дисплазией II ст. – 5 пациенток, с дисплазией III ст. – 13 пациенток, с carcinoma in situ – 4 пациентки и с диагнозом рак шейки матки Ia ст. – 4 пациентки. Радахлорин вводили однократно внутривенно посредством 30-минутной инфузии в дозе 1,0 мг/кг массы тела за 3 ч до проведения облучения (длина волны 662 нм, плотность энергии 300–350 Дж/см2). Результат лечения у 26 (86,7%) пациенток оценен, как полная регрессия опухоли, у 4 (13,3%) – как частичная регрессия. В группах с клиническим диагнозом эрозия шейки матки, дисплазия II ст. и carcinoma in situ полная регрессия отмечена во всех наблюдениях. В группах с дисплазией III ст. полная регрессия после первого курса ФДТ достигнута у 77% пациенток, с диагнозом рак шейки матки Ia ст. – у 75% больных. У всех больных с частичной регрессией был проведен второй курс ФДТ в срок от 3 до 6 мес после первого курса, после чего была зарегистрирована полная регрессия. В процессе лечения и при последующем наблюдении не было зарегистрировано каких-либо нежелательных реакций, связанных с применением радахлорина или проведением ФДТ. Таким образом, ФДТ с отечественным фотосенсибилизатором радахлорин показала высокую эффективность в лечении предопухолевой и опухолевой патологии шейки матки.

Фотодинамическая терапия больных с внутрикожными метастазами меланомы

Results of treating 114 skin metastases of melanoma in 21 patients are represented. Melanoma progression with cutaneous metastases after previous treatment was diagnosed in all patients. The method of prolonged photodynamic therapy developed by authors with fotosens administrated intravenously at dose of 0.4 mg/kg of body weight was used in the study. First session of tumor irradiation was performed 2 h after injection of photosensitizer. Patients underwent superfi cial or contact irradiation depending on topography and type of growth of metastatic foci. Course of treatment accounted for 7–10 sessions of photodynamic therapy with 24 h interval, light dose delivered to tumor for one session – 350 J/cm2. Signifi cant clinical effect (complete and partial tumor regression) was obtained in 89% of cases for developed method. Представлены результаты лечения 114 метастатических очагов меланомы в кожу у 21 пациента. У всех больных было диагностировано прогрессирование меланомы с метастазированием в кожу после предшествующего противоопухолевого лечения. В исследовании использована разработанная авторами методика пролонгированной фотодинамической терапии с препаратом фотосенс, который вводили внутривенно в дозе 0,4 мг/кг массы тела больного. Первый сеанс облучения опухолевых очагов проводили через 2 ч после введения фотосенсибилизатора. Пациентам выполняли поверхностное или контактное облучение в зависимости от топографии и характера роста метастатического узла. Курс лечения – 7–10 сеансов фотодинамической терапии с интервалом в 24 ч, плотность энергии лазерного излучения, подводимой к опухоли за один сеанс – 350 Дж/см2. При применении разработанной методики получен объективный клинический эффект (полная и частичная регрессия опухоли) в 89% наблюдений.

Morphophysiological alterations caused by insertional mutagenesis of contactin 5 (Cntn5) gene in transgenic mice

Transgenesis has become a routine for modern biological studies. The most popular method for producing transgenic animals–pronuclear microinjection–frequently leads to host gene disruption due to a random transgene integration. In this paper, we report our analysis of morphophysiological parameters of the transgenic mouse line GM9, in which a transgene designed for milk-specific expression of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene was integrated into the intron of the Contactin 5 gene (Cntn5). We studied Cntn5 expression with RT-PCR and discovered that its expression in the brain, the primary organ of Cntn5 activity, was unperturbed. However, transgenic animals had less Cntn5 transcripts in other tissues such as the kidney and heart. In addition, we observed a decreased amount of splice variants of Cntn5 exons that flank the transgene integration site. These data suggest that the transgene integration event might affect proper Cntn5 splicing in some tissues. Publications exist that imply that some polymorphisms in the Cntn5 gene are associated with obesity and arterial hypertension in humans. We evaluated core parameters of lipid metabolism and heart activity in mice homozygous and heterozygous for Cntn5 mutation using wild- type animals as control. Our results uncovered that homozygous mutant mice have lower body weight than controls and that it is caused by slower accumulation of fat tissue. Cntn5 mutants also exhibit abnormalities in blood circulation: homozygous Cntn5 mutants are characterized by a higher blood pressure and heart beat rate, as well as faster blood flow in the tail vessels. Heterozygous animals showed intermediate results for all of these parameters

Флюоресцентная диагностика предопухолевой и опухолевой патологии эндометрия

The technique of fluorescence hysteroscopy with Alasens includes visual assessment of fluorescence of Alasens-induced protoporphyrin IX and local fluorescence spectroscopy. The technique allows to improve the efficacy of early diagnosis for endometrial pathology including early endometrial cancer, to assess definitely an extent of pre-tumor and tumor process. The sensitivity of fluorescence hysteroscopy accounts for 100%, the specificity – 98%. Технология флюоресцентной гистероскопии с препаратом аласенс включает визуальную оценку флюоресценции аласенс-индуцированного протопорфирина IX и локальную флюоресцентную спектроскопию. Технология позволяет повысить эффективность ранней диагностики патологии эндометрия, в том числе ранних форм рака эндометрия, достоверно оценить распространенность предопухолевого и опухолевого процесса. Чувствительность флюоресцентной гистероскопии составляет 100%, специфичность 98%.

Reproductive parameters and the use of MOET in transgenic founder goat carrying the human granulocyte colony-stimulating factor (hG-CSF) gene.

Abstract: This study aimed to monitor estrous cycle parameters of a human granulocyte colony-stimulating factor (hG-CSF)-transgenic founder female goat and to perform superovulation and embryo recovery (surgical or transcervical method) for further transfer to recipients to quickly obtain offspring. Two experiments were performed using a transgenic (TF) and a non-transgenic (NTF) female. In experiment 1, three estrous cycles were monitored for the following parameters: estrus behavior, progesterone concentration and ovarian activity. In experiment 2, two superovulation/embryo recovery sessions were performed and the recovered embryos were transferred to previously prepared recipients. Data were compared by either t test or Fisher's exact test. The mean interval between natural estrus was 20.7 ± 0.6 and 19.7 ± 0.6 (P > 0.05) days for the TF and NTF, respectively. Progesterone concentrations and ovarian activity were normal and similar between goats. The ovulation rate was similar between TF and NTF (12.0 ± 1.4 vs. 18.0 ± 4.2 CL; P > 0.05). No significant differences in embryo recovery rate (P > 0.05) were observed between the surgical and transcervical methods for TF (69.2 vs. 72.7%) or NTF (100.0 vs. 86.7%). Sixteen embryos from the TF were transferred to recipients, and eight kids were born. Among these kids, the transgene was identified in three (two males and one female), resulting in a transgenesis rate of 37.5%. In summary, the TF is a true founder, since she proved fertility and capacity of transmitting the hG-CSF transgene to progeny, suggesting that the analyzed reproductive traits were not compromised by the presence of the transgene