Oxazoline scaffold in synthesis of benzosiloxaboroles and related ring-expanded heterocycles: diverse reactivity,structural peculiarities and antimicrobial activity

Two isomeric benzosiloxaborole derivatives 3a and 5a bearing fluorine and 4,4-dimethyl-2-oxazolin-2-yl substituents attached to the aromatic rings were obtained. Both compounds were prone to hydrolytic cleavage of the oxazoline ring after initial protonation or methylation of the nitrogen atom. The derivative 3c featuring N-methylammoniumalkyl ester functionality was successfully subjected to N-sulfonylation and N-acylation reactions to give respective derivatives which demonstrates its potential for modular synthesis of structurally extended benzosiloxaboroles. Compound 5c bearing N-ammoniumalkyl ester underwent conversion to a unique macrocyclic dimer due to siloxaborole ring opening. Furthermore, an unexpected 4-electron reduction of the oxazoline ring occurred during an attempted synthesis of 5a. The reaction gave rise to an unprecedented 7-membered heterocyclic system 4a comprising a relatively stable B–O–B–O–Si linkage and stabilized by an intramolecular N–B coordination. It could be cleaved to derivative 4c bearing BOH and SiMe₂OH groups which acts as a pseudo-diol as demonstrated by formation of an adduct with Tavaborole. Apart from the multinuclear NMR spectroscopy characterization, crystal structures of the obtained products were determined in many cases by X-ray diffraction. Investigation of biological activity of the obtained compounds revealed that derivatives 3e and 3f with pendant N-methyl arylsulfonamide groups exhibit high activity against Gram-positive cocci such as methicillin-sensitive Staphylococcus aureus ATCC 6538P, methicillin-resistant S. aureus (MRSA) ATCC 43300 as well as the MRSA clinical strains, with MIC values in the range of 3.12–6.25 mg L⁻¹. These two compounds also showed activity against Enterococcus faecalis ATCC 29212 and Enterococcus faecium ATCC 6057 (with MICs of 25–50 mg L⁻¹). The results of the antimicrobial activity and cytotoxicity studies indicate that 3e and 3f can be considered as potential antibacterial agents, especially against S. aureus MRSA.

Transformations of oxazoline–benzosiloxaborole conjugates gave rise to novel boracyclic systems as well as functionalized derivatives featuring antibacterial activity.     

CA 125 regression after two cycles of neoadjuvant chemotherapy as prognostic factor in patients with advanced ovarian cancer and primary peritoneal serous cancer who underwent interval surgical cytoreduction

OBJECTIVES: The aim of our study was to assess the prognostic role of CA 125 regression during neoadjuvant chemotherapy (NAC) in patients with ovarian cancer (OC) or primary peritoneal serous carcinoma (PPSC) that underwent interval debulking surgery (IOC). MATERIAL AND METHODS: Thirty one patients with advanced OC or PPSC (FIGO stage IIIC and IV) who underwent initial exploratory surgery, followed by NAC containing platinum analogs, have been analyzed, retrospectively. We have used a regression coefficient (RCA 125), which was calculated as following: log10 (CA 125 level measured after two cycles of NAC/baseline CA 125) for statistical analysis. The median value of RCA 125 reached -0.788 and has been used to dichotomize. Optimal IOC has been performed in 67.74% (21/31) patients, suboptimal in 25.81% (8/31) patients and 6.45% (2/31) of patients did not undergo IOC due to the progression of the disease. RESULTS: We have noted significant correspondence between time to progression and RCA 125 in univariate analysis, which we have also confirmed in multivariate analysis (HR 0.27; 95% CI, 0.15-0.96; p = 0.0178). Similarly, we have observed significant relationship between overall survival, RCA 125 and extension IOC in univariate analysis. Multivariate analysis confirmed that RCA 125 was independent prognostic factor, HR-0.18 (95% CI, 0.07-0.56; p = 0.004). In case of patients with high RCA 125, a greater rate of optimal debulking cytoreduction (p = 0.0278, U = 50.0) has been observed. CONCLUSIONS: RCA 125 after two courses of NAC appears to be an important prognostic factor in patients with OC or PPSC, who underwent IOC High RCA 125 during NAC seems to be a good predictive factor in order to achieve optimal IOC.     

Differential flow cytometric detection of intracellular cytokines in peripheral and peritoneal mononuclear cells of women with endometriosis

OBJECTIVE: The pathogenesis of endometriosis is related to functional changes in CD3+ and CD14+ cells observed both at the local and systemic level. Here we investigated whether, and if so, how the body compartment influences cytokine expression in stimulated peritoneal and peripheral CD3+ and CD14+ cells of women with endometriosis. STUDY DESIGN: Isolated peripheral blood (PB) and peritoneal fluid (PF) mononuclear cells from women with endometriosis were cultured under non-adherent conditions and stimulated with PMA and ionomycin for 6h to induce intracellular cytokine synthesis of TNF-alpha, IFN-gamma, and IL-8 by CD3+ cells or with LPS for 9h to produce TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 by CD14+ cells. RESULTS: The percentages of positive CD3+ cells stained for TNF-alpha and IFN-gamma were significantly higher and those stained for IL-8 were significantly lower in PF compared with PB, this being independent of the stage of endometriosis. In contrast, the percentages of CD14+ cells producing TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 were significantly higher in PB than PF of women with endometriosis. CONCLUSIONS: Monocytes/macrophages and lymphocytes derived from the peripheral and peritoneal compartments of women with endometriosis differentially respond to stimulated cytokine synthesis induction. However, it is difficult to state whether the observed phenomenon is more related to body compartment influence per se or to the presence of endometriosis.     

A case of mediastinal teratoma as a cause of nonimmune hydrops fetalis, and literature review

This article reviews the current literature of mediastinal tumors as the cause of nonimmune hydrops fetalis (NIHF), the outcomes of reported cases, and a general overview of NIHF including diagnosis, workup, and a management algorithm, with particular attention made to intrathoracic lesions and gestation age. We present a unique case report of a premature neonate who initially presented with NIHF at birth and was subsequently diagnosed with a germ cell mediastinal teratoma as the etiology of NIHF. The patient survived for 50 days while having undergone surgical resection and chemotherapy during the hospital course. The patient represents the first reported case of a mediastinal tumor as the etiology of NIHF in the neonatal period and only one of three cases that have been reported to survive in the neonatal period. Survival is dependent on the thoracic lesion's size, location, resectability, impact on the growth and development of other vital organs, and in the case of tumors, malignant potential. Though the combination of mediastinal teratoma and NIHF is rare, it should be included in the diagnostic evaluation of a newborn with NIHF.     

Leptin, leptin gene, leptin gene receptor polymorphisms and pregnancy

The article presents information about leptin as the major metabolic hormone. The structure, localization of the hormone and its receptor have been described focusing on maturation and fertility processes. Several polymorphisms of leptin gene and its receptor have been described as potential developmental factors of pregnancy complications such as diabetes mellitus or pregnancy induced hypertension.     

The insertion/deletion polymorphism (I/D) of the ACE gene in pregnant women with excessive weight gain

INTRODUCTION: The body mass gain is conditioned by lifestyle, as well as many environmental and genetic factors. Recent studies suggest that renin-angiotensin system (RAS) plays a fundamental role in process of growth and differentiation of adipocytes through the acting of angiotensin II and seems to be a significant factor in excessive weight gain development. The purpose of this study was to determine the frequency and significance of insertion/deletion polymorphism (I/D) of the ACE gene in pregnant women with excessive weight gain. MATERIALS AND METHODS: The examined group consisted of 212 pregnant women, including 107 women with normal (DeltaBMI< or =5) and 105 women with excessive weight gain (DeltaBMI>5). Genomic DNA was extracted from venous blood. The I/D polymorphism of ACE gene was determined by polymerase chain reaction (PCR). RESULTS: During the course of the study we did not observe the statistically significant higher frequency of ACE genotypes in any of the two investigated groups of women with normal and excessive weight gain. Nevertheless, an overrepresentation of II genotype frequency in group with excessive weight gain has been observed (33.3 vs 21.5%, p=ns). The same findings were visible as far as the frequency of I allele in group with excessive weight gain was concerned (55.2 vs 45.8%, p=ns). The frequency of observed genotypes was in agreement with Hardy-Weinberg equilibrium. CONCLUSIONS: Although overrepresentation of II genotype and I allele in the group of pregnant women with excessive weight gain (DeltaBMI>5) has been observed, a close correlation between II genotype and higher risk of overweight could be not indicated (due to the lack of significant difference). The results should be confirmed in a more numerous group of pregnant women. At this stage the results of the study did not suggested the presence of association of I/D polymorphism of ACE gene with weight gain in investigated group of pregnant women.     

The safety and tolerance of isoflavones (Soyfem) administration in postmenopausal women

INTRODUCTION: In recent years, considerable attention has been paid to isoflavones and their proprieties to alleviate the climacteric symptoms. The goal of this study was to evaluate the efficacy of standardized isoflavones extract (Soyfem) in moderate and medium-severe climacteric syndrome. MATERIAL AND METHODS: 555 postmenopausal women were recruited for the study. Out of this group, 169 women completed the study (12-month observation period). The patients were classified according to the intensity of climacteric symptoms (< or =34 points in Kupperman index). 1 or 2 tablets of Soyfem were administered twice a day,. RESULTS: A regular decrease of Kupperman index value and improvement of life quality were observed in the group of 169 postmenopausal women. We have noted a decrease in the intensity and number of hot flushes, diaphoresis (p < 0.05), diminished sleep disturbances (p < 0.05), decreased headache, dizziness, and arthrosis pain. The diminished intensity of tiredness, palpitation and breathlessness have been also observed (p < 0.05). 80% of all investigated women noted the regression of paresthesis, 20% indicated the decreased number of paresthesis (p < 0.05). Influence of Soyfem on the variability and moderation of depressive mood (p < 0.05) have been also positive evaluated by patients. CONCLUSIONS: Administration of Soyfem in the dosage 52 to 104 mg/24 hours (2 times daily 1 or 2 tablets) is a safe and effective therapy in the postmenopausal women with moderate and medium-severe climacteric syndrome evaluated according to the Kupperman index. Administration of Soyfem is connected with a good compliance and correlated with well-being in the investigated women allowing a long-term administration.     

Analysis of Dietary Habits and Nutritional Status of Children with Down Syndrome in the Context of Lipid and Oxidative Stress Parameters

Introduction: The risk of obesity in children with Down syndrome is high. Undoubtedly, proper nutrition plays an important role in the prevention of excess body weight and is associated with a reduction of metabolic complications. The aim of the study was to assess the problem of disturbances in the nutritional status and eating habits of children with DS. Methods: A total of 39 patients were included in the study. The nutritional status was assessed by anthropometric tests and Dual X-ray Absorptiometry. Eating habits were assessed using the Child Eating Behavior Questionnaire and the Food Frequency Questionnaire. Blood samples were taken to determine the oxidative stress and lipid parameters. Results: Obesity was recognized in 15% of subjects and 23% were overweight. Children that were overweight were characterized by higher levels of triglycerides, atherogenic index of plasma, and apoA2 and apoE levels. Fat mass, fat mass/height² index, and visceral fat mass correlated with thiobarbituric acid reactive substances and advanced oxidative protein product level. The analysis of the Child Eating Behavior Questionnaire showed that children struggling with being overweight were more interested in food compared to those with normal body weight. A positive correlation was identified between waist circumference and food interest categories. Insufficient consumption of dairy products, vegetables, whole grain products, as well as fruits, seeds, nuts, and fatty fish was noted. Patients were less likely to consume products that are a good source of mono- and polyunsaturated fatty acids. Conclusions: In children with Down syndrome and obesity, disturbances in lipid and oxidative stress parameters are observed. Abnormal eating habits in all children with Down syndrome regardless of their nutritional status were noted. Proper nutritional education, nutritional control, and management of metabolic problems are essential in this group of patients.     

Computational and Experimental Studies of Selected Types of Biomass Combustion in a Domestic Boiler

The paper analyzes the suitability of four types of biomass pellets as a fuel for heating purposes. Three types of waste biomass (sunflower husks, rapeseed cake, and corn straw) and one type of biomass grown for energy purposes (willow) were selected. After appropriate preparation, the selected starting materials were subjected to the pelletization process. Selected physical and chemical properties of the studied biomass pellets were determined. All four types of the analyzed pellets met the EN-ISO-17225-2:2014 standard in terms of bulk density, dimensions, as well as nitrogen and moisture content. The highest calorific value was pellets made of sunflower husk (17.27 MJ/m³) and willow (16.81 MJ/m³), while the calorific value of pellets made of corn straw and rapeseed cake did not exceed 16.5 MJ/m³ and did not meet the standard. In addition, the ash content for these two types of pellets was well above the standard. A 10 kW domestic biomass boiler was employed for burning the tested pellets. The consumption of analyzed fuels during boiler operation was determined. The concentration of CO, CO₂, and NO_x in exhaust gases was also examined. The obtained experimental results were compared with the numerical calculations with the use of ANSYS Chemkin-Pro using two mechanisms. The highest concentrations of CO₂ and CO were observed during the combustion of sunflower and willow husk pellets, which probably resulted from the highest carbon content and, thus, the highest calorific value when compared to cake and straw pellets. For all analyzed pellets, the value of NO and NO₂ concentration was similar and did not exceed 368 ppm and 18 ppm, respectively. The results closest to the experiment were obtained for calculations using the mechanism developed by Glarborg et al. The research carried out in the article shows that out of the four analyzed types of pellets, only sunflower and willow husk pellets can be burned in a domestic boiler adapted to burning wood pellets, which is a cheap alternative to wood pellets.