Nanоbiocomposite based on dihydroquercetin and arabinogalactan in the form of a gel for external use as a means for the treatment of chronic venous insufficiency in an experiment

Background. Due to the high prevalence of chronic venous insufficiency among the population, with a decrease in the quality of life of patients and their early disability, there is a need to develop modern effective and safe means for the prevention and treatment of this pathology. We have developed the optimal composition and technology of a gel for external use based on a nanobiocomposite of dihydroquercetin and arabinogalactan, which has a venoprotective effect. The article presents data on the results of a preclinical study of the safety and specific activity of the gel.The aim. To study the specific activity (decongestant, antitranssudative action) and safety of a gel for external use based on nanobiocomposite of dihydroquercetin and arabinogalactan used for the treatment of chronic venous insufficiency in the framework of preclinical studies.Materials and methods. The object of the study was a gel for external use based on dihydroquercetin and arabinogalactan nanobiocomposite. The study was conducted on 32 white male rats of the same age, for 15 days. The study of the pharmacological activity of a gel based on a nanobiocomposite of dihydroquercetin and arabinogalactan, was carried out on a model of acute venous stagnation in the tail of a rat (edema of non-inflammatory genesis), the dynamics of tail volume growth in the experimental and control group of animals was evaluated. The irritant effect of the gel on the skin of animals was also determined, the permeability of the capillaries of the skin was determined.Results. When studying the pharmacological activity of the gel on a model of acute venous stagnation in the tail, it was shown that a soft dosage form for external use developed on the basis of nanobiocomposite of dihydroquercetin and arabinogalactan has decongestant and antitranssudative activity. The presence of a locally irritating effect in the gel under study has not been established in the framework of the experiment.Conclusion. In the course of preclinical study of the gel of the nanobiocomposite dihydroquercetin and arabinogalactan on laboratory animals, its antitranssudative activity and safety have been proven

Associative connection of infectious and inflammatory diseases in pregnancy and severe preeclampsia

Materials and methods. This retrospective case-control study enrolled 50 women with severe preeclampsia and 50 control women with spontaneous singleton pregnancy. Median age of women ranged from 20 to 35 years. All women did not have a history of hypertension, autoimmune, metabolic, renal, or cardiac diseases, and preeclampsia before this pregnancy. We have analyzed χ2, odds ratio (OR) and its 95% confidence intervals (95% Cl). Results. We found significant association between maternal systemic infectious and severe preeclampsia (OR = 49.6; 95% Cl 13.05-188.64). The risk of severe preeclampsia were significantly lower in patients with local infections of the lower genital tract (OR = 4.5; 95% Cl 1.49-6.71). Asymptomatic bacteriuria is associated with the highest risk of severe preeclampsia (OR = 17.0; 95% Cl 4.66-61.81). Acute gravidarum pyelonephritis showed lower association with severe preeclampsia (OR = 5.4; 95% Cl 1.69-10.54). We did not observe increased risk of severe preeclampsia with acute respiratory infections (OR = 2.0; 95% Cl 0.71-4.69). Acute non-specific bacterial vaginitis and acute candidiasis vulvovaginitis were found to be risk factors of severe preeclampsia (OR = 6.7; 95% Cl 1.90-11.02 and OR = 4.3; 95% Cl 1.45-9.99 respectively). Cytomegalovirus infection (2 %), toxoplasmosis (2 %), Chlamydia trachomatis cervicitis (4 %), acute Trichomonas colpitis (2 %) and bacterial vaginosis (4 %) were found only in patients with severe preeclampsia. Conclusion. Our data support that acute maternal infection is associated with an increased risk of severe preeclampsia in healthy women with singleton pregnancy. Systemic inflammatory response might be the main potential mechanisms related to infections and enhanced development of severe preeclampsia. Further research is required to elucidate the underlying mechanism of this association

Studying of the Polylactide or Polyglycylidactide Surface Layer Biodegradation in Neutral Media for the Subsequent Layered Composite Creation

  The processes of biodegradation in phosphate buffer with pH 7.4 and 0.9 wt.% NaCl of polymer polylactide or polyglycylidactide films for the subsequent creation of a layered composite with a biodegradable layer on the basis of a nickel-free shape memory alloy TiNbTaZr were studied. The structure of the samples was determined by SEM and an optical microscope. For polylactide films the rate of biodegradation did not depend on the mass of the film. A gradual decrease in the rate of biodegradation at any mass with a similar dependence on time is noted. With an increase in the mass of films based on poly(glycolide-lactide) the rate of biodegradation increased. And even at the initial stage the dissolution rate is 2-3 times higher than in pure polylactide. On day 180, complete dissolution of the polyglycolidelactide was observed (even a precipitate was not observed) and completely entire polylactide films, however, lost  their transparency, was noted

Трудности диагностики и лечения при пневмотораксе и гигантских буллах

Spontaneous pneumothorax is the most common acute chest disease. Often, giant bullae give the impression of the presence of air in the pleural cavity. Inadequate differential diagnosis leads to vain drainage of the pleural cavity, damage to the lung with its collapse and pneumothorax.The aim. Analyze diagnostic and tactical mistakes in patients with pulmonary emphysema, which manifests with giant bullae, and outline the ways to prevent complications.Methods. The analysis of the treatment of 1,636 patients with pulmonary emphysema and its complications undergoing treatment in the thoracic surgical department of the Samara Regional Clinical Hospital named after V.D.Seredavin in the period from 2001 to 2018 is presented.Results. Giant bulla were diagnosed in 35 (2.1%) patients, 16 of them were hospitalized ungently. In 6 patients, the diagnosis of a giant bulla of the lung was correct, and the patients were referred to the thoracic surgical department. In 10 patients, a giant bulla of the lung was regarded as pneumothorax, and pleural drainage was performed before referral to the thoracic surgical department.Conclusion. The correct interpretation of the radiological data and comparison with the clinical picture allows avoiding diagnostic errors and the associated danger and complications.Спонтанный пневмоторакс является самым частым острым заболеванием органов грудной клетки. Нередко гигантские буллы создают впечатление о наличии воздуха в плевральной полости. Неадекватная дифференциальная диагностика приводит к напрасному дренированию плевральной полости, повреждению легкого с его спадением и возникновением пневмоторакса.Целью исследования явился анализ диагностических и тактических ошибок у пациентов с буллезной эмфиземой легких, представленной гигантскими буллами, и обозначение путей профилактики осложнений.Материалы и методы. Проведен анализ лечения пациентов (n = 1 636) с эмфиземой легких и ее осложнениями, госпитализированных в хирургическое торакальное отделение Государственного бюджетного учреждения здравоохранения «Самарская областная клиническая больница имени В.Д.Середавина» Министерства здравоохранения Самарской области (2001–2018).Результаты. Гигантские буллы диагностированы у 35 (2,1%) пациентов, 16 из которых госпитализированы в экстренном порядке. Верный диагноз гигантская булла легкого установлен в 6 случаях, больные направлены в хирургическое торакальное отделение. В 10 случаях гигантская булла легкого расценена как пневмоторакс и до поступления в хирургическое торакальное отделение больным проведено дренирование плевральной полости.Заключение. Верная интерпретация рентгенологических данных и сопоставление с клинической картиной позволяет избежать диагностических ошибок и связанных с этим дальнейших опасностей и осложнений

Новая мутация в гене TYMP: клинико-морфологическая характеристика пациента с синдромом MNGIE

Mitochondrial neurogastrointestinal encephalomyopathy is an extremely rare (1–9:1 000 000, Orphanet, 2021) multisystem genetic disease caused by mutations in the TYMP gene encoding the enzyme thymidine phosphorylase.The article presents the data of a thirteen‑year survey on 40‑year‑old patient D. with clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy syndrome associated with the previously undescribed missense mutation c.1301G>T (p.Gly434Val) of the TYMP gene. Detailed clinical picture (gastrointestinal dysfunction, cachexia, blepharoptosis, ophthalmoparesis, peripheral polyneuropathy and leukoaraiosis), electroneuromyography data (demyelination with secondary axonopathy), high blood serum level of dihydrothymine together with normal levels of thymidine and deoxyuridine made it possible to verify the diagnosis. Histopathological examination revealed atrophy of the longitudinal (outer) muscle layer of the small and large intestines and a significant decrease in the number of CD117+ cells (telocytes), signs of damage to the striated skeletal muscles of a mixed nature with a predominance of the myogenic pattern, as well the destruction of the myelin sheaths of peripheral nerves. Histochemical examination did not reveal “ragged red fibers” characteristic of mitochondrial pathology. Transmission electron microscopy demonstrated the presence of megalomitochondria in the myocardium.Синдром митохондриальной нейрогастроинтестинальной энцефаломиопатии – редкое (1–9:1000000, Orphanet, 2021) генетическое мультисистемное заболевание, обусловленное мутациями в ядерном гене TYMP, кодирующем фермент тимидинфосфорилазу.Представлены данные 13‑летнего наблюдения пациентки Д., 40 лет, с синдромом митохондриальной нейрогастроинтестинальной энцефаломиопатии, связанным с ранее не описанной миссенс‑заменой c.1301G>T (p.Gly434Val) в гене TYMP. Диагноз синдрома митохондриальной нейрогастроинтестинальной энцефаломиопатии был поставлен на основании клинических проявлений (дисфункция желудочно‑кишечного тракта, кахексия, блефароптоз, офтальмопарез, периферическая полинейропатия и лейкоэнцефалопатия), результатов электронейромиографии (демиелинизация с вторичной аксонопатией), а также повышения уровня дигидротимина в сыворотке крови при нормальных уровнях тимидина и дезоксиуридина. Патогистологическое исследование выявило атрофию продольного (наружного) мышечного слоя тонкой и толстой кишок и значимое уменьшение количества CD117+‑клеток (телоцитов), поражение скелетных мышц смешанного характера с преобладанием миогенного паттерна, а также деструкцию миелиновых оболочек периферических нервов. Исследование S100‑положительных вегетативных образований кишечной стенки не выявило патологических изменений. При гистохимическом исследовании не были обнаружены «рваные красные волокна», характерные для митохондриопатий. Трансмиссионная электронная микроскопия продемонстрировала наличие полиморфизма митохондрий кардиомиоцитов и мегаломитохондрий лейомиоцитов кишечника

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Tracking down carbon inputs underground from an arid zone Australian calcrete.

Freshwater ecosystems play a key role in shaping the global carbon cycle and maintaining the ecological balance that sustains biodiversity worldwide. Surficial water bodies are often interconnected with groundwater, forming a physical continuum, and their interaction has been reported as a crucial driver for organic matter (OM) inputs in groundwater systems. However, despite the growing concerns related to increasing anthropogenic pressure and effects of global change to groundwater environments, our understanding of the dynamics regulating subterranean carbon flows is still sparse. We traced carbon composition and transformations in an arid zone calcrete aquifer using a novel multidisciplinary approach that combined isotopic analyses of dissolved organic carbon (DOC) and inorganic carbon (DIC) (δ13CDOC, δ13CDIC, 14CDOC and 14CDIC) with fluorescence spectroscopy (Chromophoric Dissolved OM (CDOM) characterisation) and metabarcoding analyses (taxonomic and functional genomics on bacterial 16S rRNA). To compare dynamics linked to potential aquifer recharge processes, water samples were collected from two boreholes under contrasting rainfall: low rainfall ((LR), dry season) and high rainfall ((HR), wet season). Our isotopic results indicate limited changes and dominance of modern terrestrial carbon in the upper part (northeast) of the bore field, but correlation between HR and increased old and 13C-enriched DOC in the lower area (southwest). CDOM results show a shift from terrestrially to microbially derived compounds after rainfall in the same lower field bore, which was also sampled for microbial genetics. Functional genomic results showed increased genes coding for degradative pathways-dominated by those related to aromatic compound metabolisms-during HR. Our results indicate that rainfall leads to different responses in different parts of the bore field, with an increase in old carbon sources and microbial processing in the lower part of the field. We hypothesise that this may be due to increasing salinity, either due to mobilisation of Cl- from the soil, or infiltration from the downstream salt lake during HR. This study is the first to use a multi-technique assessment using stable and radioactive isotopes together with functional genomics to probe the principal organic biogeochemical pathways regulating an arid zone calcrete system. Further investigations involving extensive sampling from diverse groundwater ecosystems will allow better understanding of the microbiological pathways sustaining the ecological functioning of subterranean biota

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years