Aprotinin is a potent multi-target drug for the combination therapy of moderate COVID-19 cases

Objectives. COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) and Avifavir or Hydroxychloroquine (HCQ) combinations for the therapy of COVID-19. Methods. Three prospective single-center (cohorts 1 – 3) studies included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2 and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU 4 times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). Results. In the cohorts 1 – 3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of combination therapy in the cohort 3 was the most prominent and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0 – 4.0), normalization of CRP concentration was 3.5 days (IQR 3 – 5), of D-dimer concentration - 5 days (IQR 4 – 5); body temperature - 1 day (IQR 1 – 3), improvement in clinical status or discharge from the hospital - 5 days (IQR 5 – 5), and improvement in lung lesions of patients on 14 day - 100%. Conclusions. The administration of Aprotinin combinations prevented the transfer of moderate COVID-19 patients to the ICU for mechanical ventilation (ALV) or non-invasive ventilation (NIV) and by shortening of their hospital stay

Aprotinin - a New Drug Candidate for The Prevention of SARS-CoV-2 (COVID-19)

The efficacy of Aprotinin as prophylactic treatment of Covid-19 was studied in the hamster model of SARS-CoV-2 and in the health care personnel working with Covid-19 patients in hospital. High efficacy of Aprotinin in pre- and post-exposure prophylaxis of SARS-CoV-2 was demonstrated

The Efficacy of Aprotinin Combinations with Selected Antiviral Drugs in Mouse Models of Influenza Pneumonia and Coronavirus Infection Caused by SARS-CoV-2

The efficacy of aprotinin combinations with selected antiviral-drugs treatment of influenza virus and coronavirus (SARS-CoV-2) infection was studied in mice models of influenza pneumonia and COVID-19. The high efficacy of the combinations in reducing virus titer in lungs and body weight loss and in increasing the survival rate were demonstrated. This preclinical study can be considered a confirmatory step before introducing the combinations into clinical assessment

Organic matter accumulation by alkaline-constructed soils in heavily metal-polluted area of Subarctic zone

Purpose: The research aimed to investigate properties and functions of soils constructed from alkaline mining wastes of different origin to remediate the industrial barren resulted from long-term emissions of the copper-nickel factory in the Subarctic region (Kola Peninsula, Russia). Conventional indicators of the remediation effectiveness (pH and metal content in geochemical fractions) were related to the indicators of soil functions such as biomass production, accumulation of organic carbon, microbial activity, and soil respiration. Materials and methods: The experimental area included two sites with polluted and degraded Podzol and Histosol soils located in 1.5 and 0.7 km from the nonferrous (Cu-Ni) smelter, respectively. At the sites, artificial soil constructions were made from mining wastes or quarry sand covered by the vermiculite layer with lawn grasses planted on top. Plant biomass was collected every year starting from the experiment set-up. In 5 to 8 years, soil samples were collected on the layer basis, and chemical, biological, and morphological properties were analyzed. Sequential fractionation of metals was conducted using a modified Tessier’s scheme. The microbial biomass and its respiration activity were determined. Micromorphological studies were conducted using an optical microscope. Soil respiration was measured on-site by IRGA with simultaneous observations of soil moisture and temperature. Results: The plant growth and residues' deposition at both experimental sites triggered carbon accumulation and resulted in 2–3 times higher content of organic carbon in the upper constructed soil layer compared to the initial content in mining wastes. Carbon accumulation was a key driver for the development of soil microbial communities and had a positive effect on the metal immobilization. This effect was strengthened by high pH inherited from the alkaline wastes and resulted in the performance of constructed soils as geochemical barriers. In their upper layers, where the root biomass was the highest, about 30–60% of Cu and Ni were bound by organic matter. In the underlying polluted soil, the most toxic water-soluble metal fraction was completely neutralized; and the metal concentrations in exchangeable fraction decreased by a factor of four improving the habitat conditions of the microbiome. Organic matter accumulation by clay material with the formation of organo-mineral films was found in the vermiculite-lizardite variant. Conclusion: Soil constructions made from alkaline mining wastes in the Subarctic supported the development of plant and microbial communities, organic matter accumulation, and metal immobilization. This technology allows protecting the environment from further pollution under the continuous emissions of the copper-nickel factory

QUANTITATIVE STRUCTURE-METABOLISM RELATIONSHIP MODELING OF METABOLIC N-DEALKYLATION REACTION RATES

It is widely recognized that preclinical drug discovery can be improved via the parallel assessment of bioactivity, absorption, distribution, metabolism, excretion, and toxicity properties of molecules. High-throughput computational methods may enable such assessment at the earliest, least expensive discovery stages, such as during screening compound libraries and the hit-to-lead process. As an attempt to predict drug metabolism and toxicity, we have developed an approach for evaluation of the rate of N-dealkylation mediated by two of the most important human cytochrome P450s (P450), namely CYP3A4 and CYP2D6. We have taken a novel approach by using descriptors generated for the whole molecule, the reaction centroid, and the leaving group, and then applying neural network computations and sensitivity analysis to Quantitative structure-metabolism relationship (QSMR) models allow the estimation of complex metabolism-related phenomena from relatively simple calculated molecular properties or descriptors. Such models can be used for the design of structural analogs of bioactive compounds with improved pharmacokinetic properties (Bouska et al.

Balakin DMSO Solubility et al. of Organic Compounds for Bioscreening In Silico Estimation of DMSO Solubility of Organic Compounds for Bioscreening

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Options for individualizing therapy for postoperative central diabetes insipidus

Postoperative diabetes insipidus is a common life-threatening morbidity after pituitary surgery. More frequent neurosurgeon interventions make drugs’ adjustment very important for higher life quality in the case of postoperative complications. We present the case of personalized adjustment of drug dosage to treat postoperative diabetes insipidus in patient undergoing reccurent transnasal adenomectomy

Central diabetes insipidus after transnasal adenomectomy:trends in development and recovery, clinical and laboratory characteristics

Background: Currently, there is an increase in the incidence of chiasmosellar neoplasms and respective neurosurgical interventions. The postoperative period may be complicated by vasopressin synthesis and secretion disorders. Both the development and abortion of the fluid and electrolyte disorders can be delayed. Due to a tendency for an earlier discharge of the patients, a proportion of the disorders remain unaddressed. There is no data on the evolution and time to regress of transient abnormalities in the published studies with a long-term postoperative follow-up. Aim: To assess the incidence, evolution and regression trends, clinical and laboratory characteristic of postoperative central diabetes insipidus (CDI). Materials and methods: The single center retrospective comparative study included 150 patients who had undergone transnasal adenomectomy for Cushing’s disease, acromegaly, prolactinomas, and hormonally inactive pituitary adenomas. Clinical and laboratory assessments were performed pre- and postoperatively. In the event of CDI, treatment with desmopressin was administered. Ninety six (96) patients aged 20 to 65 years (median age 43 [35; 54] years) were followed for at least 60 months after the procedure. Results: Median time to the onset of permanent CDI (pCDI) was Day 5 [1; 9.5] after surgery, that of transient CDI (tCDI) Day 1 [1; 4.5] with its remission by Day 30 [1.5; 199]. The maximally delayed onset was on Day 86 for the pCDI and Day 61 for tCDI; that to the remission of tCDI, 738 days. At discharge from the hospital, postoperative CDI was present in 34/150 patients (23%; 95% CI 17–30), and in 25/150 of the patients (16%; 95% CI 12–24) the disorder resolved. At 5 to 7 years after surgery, the prevalence of pCDI was 16% (95% CI 10–24), that of tCDI 35% (95% CI 27–45), 49% (95% CI 39–59) of the patients had no abnormalities (respective absolute patient numbers being 15, 34, and 47 of 96 followed for at least 60 months). At Days 1 to 7 after surgery, the patients with pCDI and tCDI had more frequent complaints of dry mouth and thirst than those without the disorder. These complaints were verified by higher 24-hour fluid intake and diuresis at the day of surgery and Days 5 to 7 thereafter, compared to those in the patients without the disorders. At Days 5–7 after surgery, urine sodium and urine specific gravity were significantly lower, as was urine osmolality at all postoperative stages, compared to those in the patients without the disorders. Conclusion: Within 2 years after transnasal adenomectomy, the incidence of postoperative CDI is gradually decreasing (from 23% to 16%). Due to potentially delayed manifestation of water and electrolyte imbalance, it is recommended that these parameters should be monitored at least for 2,5 months after the discharge from hospital. Due to potentially delayed remission (12 months and more), follow-up and monitoring for 1.5 years is reasonable, with periodic assessment of sodium levels, fluid intake and excretion, and attempts to withdraw desmopressin