Maternal obesity results in a number of obstetrical and fetal complications with both immediate and long-term consequences. The increased prevalence of obesity has resulted in increasing numbers of ...women of reproductive age in this high-risk group. Since many of these obese women have been subjected to hypercaloric diets from early childhood we have developed a rodent model of life-long maternal obesity to more clearly understand the mechanisms that contribute to adverse pregnancy outcomes in obese women. Female Sprague Dawley rats were fed a control diet (CON--16% of calories from fat) or high fat diet (HF--45% of calories from fat) from 3 to 19 weeks of age. Prior to pregnancy HF-fed dams exhibited significant increases in body fat, serum leptin and triglycerides. A subset of dams was sacrificed at gestational day 15 to evaluate fetal and placental development. The remaining animals were allowed to deliver normally. HF-fed dams exhibited a more than 3-fold increase in fetal death and decreased neonatal survival. These outcomes were associated with altered vascular development in the placenta, as well as increased hypoxia in the labyrinth. We propose that the altered placental vasculature may result in reduced oxygenation of the fetal tissues contributing to premature demise and poor neonatal survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Biofilms formed by
Proteus mirabilis
strains are a serious medical problem, especially in the case of urinary tract infections. Early stages of biofilm formation, such as reversible and irreversible ...adhesion, are essential for bacteria to form biofilm and avoid eradication by antibiotic therapy. Adhesion to solid surfaces is a complex process where numerous factors play a role, where hydrophobic and electrostatic interactions with solid surface seem to be substantial. Cell surface hydrophobicity and electrokinetic potential of bacterial cells depend on their surface composition and structure, where lipopolysaccharide, in Gram-negative bacteria, is prevailing. Our studies focused on clinical and laboratory
P. mirabilis
strains, where laboratory strains have determined LPS structures. Adherence and biofilm formation tests revealed significant differences between strains adhered in early stages of biofilm formation. Amounts of formed biofilm were expressed by the absorption of crystal violet. Higher biofilm amounts were formed by the strains with more negative values of zeta potential. In contrast, high cell surface hydrophobicity correlated with low biofilm amount.
Bacterial drug resistance and uropathogenic tract infections are among the most important issues of current medicine. Uropathogenic
Escherichia coli
strains are the primary factor of this issue. This ...article is the continuation of the previous study, where we used Kohonen relations to predict the direction of drug resistance. The characterized collection of uropathogenic
E. coli
strains was used for microbiological (the disc diffusion method for antimicrobial susceptibility testing), chemical (ATR/FT-IR) and mathematical (artificial neural networks, Ward’s hierarchical clustering method, the analysis of distributions of inhibition zone diameters for antibiotics, Cohen’s kappa measure of agreement) analysis. This study presents other potential tools for the epidemiological differentiation of
E. coli
strains. It is noteworthy that ATR/FT-IR technique has turned out to be useful for the quick and simple identification of MDR strains. Also, diameter zones of resistance of this
E. coli
population were compared to the population of
E. coli
strains published by EUCAST. We observed the bacterial behaviors toward particular antibiotics in comparison to EUCAST bacterial collections. Additionally, we used Cohen’s kappa to show which antibiotics from the same class are closely related to each other and which are not. The presented associations between antibiotics may be helpful in selecting the proper therapy directions. Here we present an adaptation of interdisciplinary studies of drug resistance of
E. coli
strains for epidemiological and clinical investigations. The obtained results may be some indication in deciding on antibiotic therapy.
In reference to gene annotation, more than half of the tRNA species synthesized by Mycobacterium tuberculosis require the enzymatic addition of the cytosine-cytosine-adenine (CCA) tail, which is ...indispensable for amino acid charging and tRNA functionality. It makes the mycobacterial CCA-adding enzyme essential for survival of the bacterium and a potential target for novel pipelines in drug discovery avenues. Here, we described the rv3907c gene product, originally annotated as poly(A)polymerase (rv3907c, PcnA) as a functional CCA-adding enzyme (CCA
) essential for viability of M. tuberculosis. The depletion of the enzyme affected tRNAs maturation, inhibited bacilli growth, and resulted in abundant accumulation of polyadenylated RNAs. We determined the enzymatic activities displayed by the mycobacterial CCA
in vitro and studied the effects of inhibiting of its transcription in bacterial cells. We are the first to properly confirm the existence of RNA polyadenylation in mycobacteria, a previously controversial phenomenon, which we found promoted upon CCA-adding enzyme downexpression.
Acute pulmonary embolism (PE) is associated with a serious mortality rate. Thus, the rapid diagnosis and identification of patients at high risk of death is pivotal. The search for echocardiographic ...parameters for this purpose continues. Recent publications reveal correlations between myocardial longitudinal strain (LS) and body surface area (BSA). The aim of the study was to evaluate the usefulness of indexing the right ventricular (RV) speckle tracking LS to BSA in detecting PE and stratifying the risk of 30-day all-cause mortality.
the prospective cross-sectional observational study group consisted of 167 consecutive patients (76 men, 45.5%) aged 69.5 ± 15.3 years, and they were referred for computed tomography pulmonary angiography. Patients underwent a transthoracic echocardiographic examination within 24 h of admission to the hospital ward. RVLS and their derivatives indexed to BSA were included in the analysis.
PE was confirmed in 88 patients, while 79 patients had no radiological features of PE. The only echocardiographic parameters that differed between subgroups were pulmonary flow acceleration (Act), McConnell's sign, LS of the middle segment of the RV free wall, and its derivative indexed to BSA. During the 30-day follow-up of a subgroup of subjects with PE, 12 patients died. The mortality predictors with increasing prediction value included a RV free wall mid-segment LS (cut-off value: -21%, Area Under the Curve-AUC 0.6,
= 0.02) and its derivative indexed to BSA (-14 %/m
, AUC 0.62,
= 0.003), body mass index (24.7 kg/m
, AUC 0.63,
= 0.002), D-dimer serum concentration (3559 pg/mL, AUC 0.66,
< 0.001), Act (67 ms, AUC 0.67,
< 0.001), septal basal LS (-15%, AUC 0.68,
= 0.02), RV free wall basal segment LS (-14%, AUC 0.7,
= 0.015), age (66 years, AUC 0.74,
= 0.004), NT-proBNP (1120 pg/mL, AUC 0.75,
= 0.01), troponin T (66 ng/mL, AUC 0.78,
= 0.005), and the complex score of the Pulmonary Embolism Severity Index (AUC 0.88,
< 0.001).
indexing of RVLS to BSA does not improve its prognostic value in patients with acute PE.
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are widely available drugs with anti‐inflammatory and analgesic properties. Their mechanism of action is associated with the enzymes of the arachidonic ...acid cycle (cyclooxygenases: COX‐1 and COX‐2). The cyclooxygenase pathway results in the formation of prostanoids (prostaglandins PGs, prostacyclins, and thromboxanes). It affects various structures of the human body, including the kidneys. Medical literature associates the usage of NSAIDs with acute kidney injury (AKI), tubulointerstitial nephritis (TIN), as well as nephrotic syndrome and chronic kidney disease (CKD). AKI associated with the chronic consumption of NSAIDs is mainly attributed to pharmacological polytherapy and the presence of cardiovascular or hepatic comorbidities. The pathomechanism of AKI and CKD is associated with inhibition of the biosynthesis of prostanoids involved in the maintenance of renal blood flow, especially PGE2 and PGI2. It is suggested that both COX isoforms play opposing roles in renal function, with natriuresis increased by COX‐1 inhibition followed by a drop in a blood pressure, whereas COX‐2 inhibition increases blood pressure and promotes sodium retention. TIN after NSAID use is potentially associated with glomerular basement membrane damage, reduction in pore size, and podocyte density. Therefore, nephrotic proteinuria and impairment of renal function may occur. The following article analyzes the association of NSAIDs with kidney disease based on available medical literature.
The NSAIDs are one of the most frequently used drugs worldwide available over the counter. Medical literature associates the usage of NSAIDs with acute kidney injury (AKI), tubulointerstitial nephritis, as well as nephrotic syndrome and chronic kidney disease.
Abstract
Triacylglycerol is a key lipid compound involved in maintaining homeostasis of both membrane lipids and free fatty acids (FFA) in plant cells under adverse environmental conditions. However, ...its role in the process of lipid remodeling has not been fully recognized, especially in monocots, including grass species. For our study, two closely related introgression forms of Lolium multiflorum (Italian ryegrass) and Festuca arundinacea (tall fescue), distinct in their level of drought tolerance, were selected as plant models to study rearrangements in plant lipidome under water deficit and further re-watering. The low drought tolerant (LDT) form revealed an elevated level of cellular membrane damage accompanied by an increased content of polyunsaturated FFA and triacylglycerol under water deficit, compared with the high drought tolerant (HDT) form. However, the LDT introgression form demonstrated also the ability to regenerate its membranes after stress cessation. The obtained results clearly indicated that accumulation of triacylglycerol under advanced drought in the LDT form could serve as a cellular protective mechanism against overaccumulation of toxic polyunsaturated FFA and other lipid intermediates. Furthermore, accumulation of triacylglycerol under drought conditions could serve also as storage of substrates required for further regeneration of membranes after stress cessation. The rearrangements in triacylglycerol metabolism were supported by the upregulation of several genes, involved in a biosynthesis of triacylglycerol. With respect to this process, diacylglycerol O-acyltransferase DGAT2 seems to play the most important role in the analyzed grasses.
Recent studies have shown that methylation changes identified in blood cells of COVID-19 patients have a potential to be used as biomarkers of SARS-CoV-2 infection outcomes. However, different ...studies have reported different subsets of epigenetic lesions that stratify patients according to the severity of infection symptoms, and more importantly, the significance of those epigenetic changes in the pathology of the infection is still not clear. We used methylomics and transcriptomics data from the largest so far cohort of COVID-19 patients from four geographically distant populations, to identify casual interactions of blood cells’ methylome in pathology of the COVID-19 disease. We identified a subset of methylation changes that is uniformly present in all COVID-19 patients regardless of symptoms. Those changes are not present in patients suffering from upper respiratory tract infections with symptoms similar to COVID-19. Most importantly, the identified epigenetic changes affect the expression of genes involved in interferon response pathways and the expression of those genes differs between patients admitted to intensive care units and only hospitalized. In conclusion, the DNA methylation changes involved in pathophysiology of SARS-CoV-2 infection, which are specific to COVID-19 patients, can not only be utilized as biomarkers in the disease management but also present a potential treatment target.
Display omitted
•We identified a subset of genome-wide methylation changes, uniformly present in all COVID-19 patients regardless of symptoms.•A subset of those changes is specific only to COVID-19 patients.•Identified methylation changes are associated with the expression of genes involved in interferon alfa and gamma response.•A subset of those genes is deferentially expressed between patients admitted to intensive care unit and only hospitalized.
Air plasma spraying (APS) is a common method of producing hydroxyapatite (HA) coatings for alloprosthetic implants. Modification of HA spraying potentially may diminish the risk of inflammation and ...local infection during bone implantation. Titanium implants were HA coated with different deposition process parameters. HA powder was deposited using APS with axial powder injection at three different distances (100, 120, and 140 mm). The surface morphology of each implant was examined and the direct contact cytotoxicity of each HA coating was evaluated according to norm ISO 10993 5:2009. The response of monocytes to HA was assessed via the activation of transcription nuclear factor. All coatings had a lamellar structure. HA sprayed at a distance of 120 mm showed the highest roughness and little phase change. The analysis of the results of the conducted research showed that plasma-spraying distance during the HA coating process had a negligible impact on biocompatibility. The results obtained for a distance of 120 mm showed a slight increase in the biological properties tested. Moreover, HA coatings sprayed at different distances were not cytotoxic and did not stimulate the NF-kB. Bare titanium was less susceptible to colonization by Staphylococcus aureus than HA-coated surfaces. HA constitutes a potentially good, low-cost, non-cytotoxic material for joint prostheses.
PDF
