Treatment of overactive bladder symptoms in women with Diunorm®: preliminary results report

Introduction. Overactive bladder (OAB) with or without urgent incontinence tends to progress with age and occurs in both men and women. However, the frequency of occurrence in the female population averages about 25%.Purpose of the study. To assess the effectiveness and safety of the drug Diunorm® (in caps.) in the prevention and treatment of OAB in women.Materials and methods. The statistical analysis includes the results of a survey of 28 women with symptoms of OAB, whose average age was 35.3 years. The drug Diunorm® was used for treatment in dosage 400 mg QD for 90 days. Patients completed the Overactive Bladder Awareness Tool and a urination diary. Additionally, urinalysis, bacteriological examination of urine, uroflowmetry, bladder ultrasound and cystoscopy were performed.Results. All women throughout the study had negative urine cultures and no pyuria in urinalysis, which excluded an infectious etiology of urinary dysfunction. During therapy, a statistically significant decrease in irritative symptoms was recorded according to the Overactive Bladder Awareness Tool questionnaire. The sum of points after 1 and 3 mo decreased by 3.0 and 4.3 points, respectively (p < 0.05). Positive dynamics in terms of the points' sum was noted in 75%, in relation to nocturia in 82% of patients (p < 0.01). The average urination rate increased from 13.3 ± 0.7 ml/s to 15.1 ± 0.7 ml/s and 15.4 ± 0.5 ml/s after 1.5 and 3 months, respectively (p < 0,0001). A similar trend was observed for maximum urine flow and residual urine volume. The maximum urine flow when taking Diunorm® increased from 15.9 ± 0.6 ml/s to 17.4 ± 0.5 ml/s and 18.1 ± 0.4 ml/s (p < 0.001). Residual urine volume decreased throughout the study. When included in the study, after 1,5 and 3 mo, this indicator was 19.9 ± 1.4; 12.2 ± 1.6 and 6.4 ± 1.1 ml, respectively (p < 0.001).Conclusion. Diunorm® can become a worthy alternative to traditional first-line OAB therapy. Comparative studies are required to obtain a high-level evidence base

Combination therapy for benign prostate hyperplasia-related urinary symptoms

Introduction. Non-neurogenic lower urinary tract symptoms (LUTS) are a serious polyetiologic problem in the male population. The side effects of the medication agents used to treat LUTS significantly reduce treatment compliance. According to the literature data, the frequency of refusal for the proposed treatment during the year varies from 20 to 80%. Several studies have shown the benefits of herbal medicine for LUTS concerning the fewer side effects and increased adherence to treatment. However, to obtain a high-level recommendation base, clinical trials are required.Purpose of the study. To evaluate the effectiveness of Gardaprost® in LUTS combination therapy.Materials and methods. The study included 57 men aged 60 – 70 years with diagnosed medium- or large-volume benign prostatic hyperplasia (BPH) and moderate-to-severe LUTS according to I-PSS, morphologically excluded prostate cancer, without urinary infection signs. The patients were randomized into two follow-up groups. Tamsulosin 0.4 mg q.d. was prescribed to patients in the control group. Patients of the main group received Gardaprost® 0.4 mg q.d. in addition to Tamsulosin. The follow-up period in both groups was one-year. The statistical analysis includes data from 56 men. To evaluate therapy at the screening visit and on days 180 and 360, I-PSS, urination diary, IIEF-5, urinalysis, prostate-specific antigen, uroflowmetry, ultrasound were analyzed. Paired t-test and one-way ANOVA test were used to determine intergroup differences in normally distributed variables. For variables with a distribution other than normal, Friedman's two-way ANOVA for related samples was used. Events with a probability greater than 95% were considered statistically significant.Results. At the time of inclusion in the study, the groups were comparable concerning the control parameters. In the main group, there was a more pronounced positive dynamics in the I-PSS score, maximum urine flow rate, and post-void residual urine volume, which corresponded to 7.9 ± 2.1 points, 18.0 ± 7.3 ml/sec, 23.6 ± 13.6 ml vs 19.7 ± 7.2 points, 10 ± 3.5 ml/sec, 65.9 ± 33.2 ml in the main and control groups, respectively (p < 0.001). Additionally, in the main observation group, a decrease in prostate volume was recorded by 18.8% (p < 0.001) was recorded.Conclusion. We have obtained encouraging long-term results from the use of Gardaprost® in combination therapy of moderate-to-severe LUTS caused by medium- and large-volume BPH

Фотодинамическая терапия экспериментальных опухолей различных морфологических типов с липосомальным борированным хлорином е6

The article summarizes the results of studies of the effectiveness of photodynamic therapy using a new domestic photosensitizer liposomal borated chlorin e6 (LBC) after its parenteral administration (intraperitoneal and intravenous). Antitumor efficacy was evaluated in rats with M-1 sarcoma and PC-1 alveolar liver cancer and mice with B16 melanoma and Ehrlich’s carcinoma, which were transplanted subcutaneously into the thigh area of the animals. The aim of the study was to determine the optimal regimes of photodynamic therapy that would allow achieving the maximum antitumor effect up to 21 days after the photodynamic therapy. The therapy was carried out under the control of the accumulation of the photosensitizer in the tumor and surrounding tissues of the thigh by selecting the doses of the drug and the parameters of laser radiation (energy density and power density). The effectiveness of therapy was assessed by the inhibition of tumor growth, by the percentage of animals with complete tumor regression, by the absolute growth rate in animals with continued tumor growth compared to controls. The results of our studies have shown that the domestic photosensitizer liposomal borated chlorin e6 has high antitumor activity in vivo. In an experimental study of the photosensitizer under certain PDT modes, the maximum antitumor effect (complete tumor regression in 100% of animals) was obtained up to 21 days after PDT in all tumor models used.Обобщены результаты исследований эффективности фотодинамической терапии (ФДТ) с использованием нового отечественного фотосенсибилизатора липосомального борированного хлорина е6 после его парентерального введения (внутрибрюшинное и внутривенное). Противоопухолевую эффективность препарата оценивали на моделях перевивных опухолей: саркома М–1 и альвеолярный рак печени РС–1 у крыс, меланома В16 и карцинома Эрлиха у мышей. Опухоли перевивали подкожно в область бедра животных. Цель исследования состояла в определении оптимальных режимов ФДТ, позволяющих добиться максимального противоопухолевого эффекта до 21 сут после проведения ФДТ. Терапию проводили под контролем накопления фотосенсибилизатора в опухолевой и окружающих тканях бедра, осуществляя подбор доз препарата и параметров лазерного излучения (плотность энергии и плотность мощности). Эффективность терапии оценивали по следующим параметрам: торможение роста опухоли, процент животных с полной регрессией опухоли, коэффициент абсолютного прироста опухоли у животных с продолженным ростом. Результаты исследований показали, что отечественный фотосенсибилизатор липосомальный борированный хлорин е6 обладает высокой противоопухолевой активностью in vivo. При экспериментальном исследовании фотосенсибилизатора при определенных режимах ФДТ получен максимальный противоопухолевый эффект (полная регрессия опухоли у 100% животных) до 21 сут после проведения ФДТ на всех использованных опухолевых моделях

Chromium spinel in Late Quaternary volcanic rocks from Kamchatka: Implications for spatial compositional variability of subarc mantle and its oxidation state

Highlights • First comprehensive dataset of spinel inclusions in high-Mg olivine from Kamchatka • Oxidation state of parental magmas of Kamchatka ranging from ΔQFM+0.7 to +3.7 • ΔQFM correlates with Ba/La and La/Nb for back-arc magmas of Kamchatka • Decoupling of Cr# and TiO2 in primitive Cr-Spinel suggests slab melt contribution Abstract The Kamchatka volcanic arc (Russia) is one of well-studied but complex tectonic margins on Earth, with an extensive geologic history stretching as far back as the Late Cretaceous. Unlike many other subduction zones, primitive basalts with Mg# > 65 are abundant in Kamchatka, thereby allowing characterization of the mantle source through compositional analyses of near-liquidus minerals in the rocks. In this paper, we present a comprehensive dataset on the composition of Cr-spinel inclusions in olivine for all main Late Quaternary volcanic zones in Kamchatka, comprising of analyses of 1604 spinel inclusions and their host-olivine from 104 samples representing 30 volcanoes and volcanic fields. The studied rocks are basalts, basaltic andesites and high-Mg andesites, which cover the whole compositional range the Late Quaternary primitive volcanic rocks in Kamchatka. The composition of spinel shows large variability. Spinel inclusions with the lowest Cr# and Fe3+/Fe2+ ratios were found in basalts from Sredinny Range and Northern Kamchatka, whereas the most Cr-rich and oxidized spinel inclusions occur in basalts and high-Mg andesites from the Central Kamchatka Depression. Intermediate Cr-spinel compositions characterize the Eastern Volcanic Belt of Kamchatka. The compositions of olivine-spinel pairs were used to quantify the oxidation state of parental Kamchatka magmas and the degree of partial mantle melting. The redox conditions recorded in spinel compositions range from ΔQFM = +0.7 to +3.7. ΔQFM for samples from the Sredinny Range and Northern Kamchatka correlates with a number of proxies of the involvement of slab-derived components incorporated in the composition of their host-rocks (e.g., La/Nb and Ba/La), which suggests a coupling between the mantle oxidation and metasomatism by slab-derived fluids or melts. These correlations were not observed for frontal Kamchatka volcanoes with the highest estimated ΔQFM, which possibly indicates a buffering of the mantle oxidation state by sulfur. The estimated degrees of partial mantle melting range from 8 to >20% for Kamchatka volcanoes. Spinel from the Central Kamchatka Depression has the highest Cr# and could crystallize from magmas generated from the most depleted sources. In contrast to the Eastern Volcanic Belt, spinel Cr# and the inferred degrees of melting in the Central Kamchatka Depression do not correlate with spinel TiO2 content. The apparent decoupling between the proxies of mantle depletion in the CKD spinel is interpreted to reflect refertilization of the CKD mantle by oxidized Ti-rich slab- or mantle lithosphere-derived melts near the northern edge of the subducting Pacific Plate. This study demonstrates that the composition of Cr-spinel in volcanic rocks in combination with bulk-rock compositions can be a powerful tool to map regional variations of the mantle source depletion, oxidation state, and involvement of various slab derived components in island-arc magmatism

The Origin and Evolution of the Parental Magmas of Frontal Volcanoes in Kamchatka: Evidence from Magmatic Inclusions in Olivine from Zhupanovsky Volcano

The paper presents data on naturally quenched melt inclusions in olivine (Fo 69–84) from Late Pleistocene pyroclastic rocks of Zhupanovsky volcano in the frontal zone of the Eastern Volcanic Belt of Kamchatka. The composition of the melt inclusions provides insight into the latest crystallization stages (~70% crystallization) of the parental melt (~46.4wt%SiO2, ~2.5wt%H2O, ~0.3wt%S), which proceeded at decompression and started at a depth of approximately 10 km from the surface. The crystallization temperature was estimated at 1100 ± 20°C at an oxygen fugacity of ΔFMQ = 0.9–1.7. The melts evolved due to the simultaneous crystallization of olivine, plagioclase, pyroxene, chromite, and magnetite (Ol : Pl : Cpx : (Crt–Mt) ~ 13 : 54 : 24 : 4) along the tholeiite evolutionary trend and became progressively enriched in FeO, SiO2, Na2O, and K2O and depleted in MgO, CaO, and Al2O3. Melt crystallization was associated with the segregation of fluid rich in S-bearing compounds and, to a lesser extent, in H2O and Cl. The primary melt of Zhupanovsky volcano (whose composition was estimated from data on the most primitive melt inclusions) had a composition of low-Si (~45wt%SiO2) picrobasalt (~14wt%MgO), as is typical of parental melts in Kamchatka and other island arcs, and was different from MORB. This primary melt could be derived by ~8% melting of mantle peridotite of composition close to the MORB source, under pressures of 1.5 ± 0.2 GPa and temperatures 20–30°C lower than the solidus temperature of “dry” peridotite (1230–1240°C). Melting was induced by the interaction of the hot peridotite with a hydrous component that was brought to the mantle from the subducted slab and was also responsible for the enrichment of the Zhupanovsky magmas in LREE, LILE, B, Cl, Th, U, and Pb. The hydrous component in the magma source of Zhupanovsky volcano was produced by the partial slab melting under water-saturated conditions at temperatures of 760–810°C and pressures of ~3.5 GPa. As the depth of the subducted slab beneath Kamchatkan volcanoes varies from 100 to 125 km, the composition of the hydrous component drastically changes from relatively low-temperature H2O-rich fluid to higher temperature H2O-bearing melt. The geothermal gradient at the surface of the slab within the depth range of 100–125 km beneath Kamchatka was estimated at 4°C/km