The Role of TNF-α and Anti-TNF-α Agents during Preconception,Pregnancy, and Breastfeeding

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.     

Severity of delayed (“secondary”) cerebral energy failure after acute hypoxia-ischemia is related to the time integral of acute ATP depletion

The aim of this study was to reproduce the delayed (secondary) cerebral energy failure previously described in birth-asphyxiated newborn infants and to investigate relationships between primary insult severity and the extent of the delayed energy failure. Phosphorus (³¹P) magnetic resonance spectroscopy (MRS) at 7 T was used to study the brains of 12 newborn piglets during an acute, reversible, cerebral hypoxic-ischemic episode which continued until nucleotide triphosphates (NTP) were depleted. After reperfusion and reoxygenation, spectroscopy was continued for 48 h. High-energy metabolite concentrations returned to near normal levels after the insult, but later they fell as delayed energy failure developed. The time integral of NTP depletion in the primary insult correlated strongly with the minimum [phosphocreatine (PCr)]/[inorganic orthophosphate (P_i)] observed 24–48 h after the insult. (Linear regression analysis gave slope –8.04 h^–1; ordinate intercept=1.23;r=0.92;P<0.0001.) This model is currently being used to investigate the therapeutic potential of various cerebroprotective strategies including hypothermia.     

Development and Comprehensive Characteristics of Thermosensitive Liquid Suppositories of Metoprolol Based on Poly(lactide-co-glycolide) Nanoparticles

Thermosensitive liquid suppositories (LSs) carrying the model antihypertensive drug metoprolol tartrate (MT) were developed and evaluated. The fundamental purpose of this work was to produce, for the first time, liquid MT suppositories based on biodegradable nanoparticles and optimize their rheological and mechanical properties for prospective rectal administration. The nanoparticle system was based on a biodegradable copolymer synthesized by ring opening polymerization (ROP) of glycolide (GL) and L,L-lactide (LLA). Biodegradable nanoparticles loaded with the model drug were produced by the o/o method at the first stage of the investigation. Depending on the concentration of the drug in the sample, from 66 to 91% of MT was released over 12 h, according to first-order kinetics. Then, thermosensitive LSs with MT-loaded biodegradable nanoparticles were obtained by a cold method and their mechanical and rheological properties were evaluated. To adjust the thermogelling and mucoadhesive properties for rectal administration, the amounts of major formulation components such as poloxamers (P407, P188), Tween 80, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), and sodium alginate were optimized. The in vitro release results revealed that more than 80% of the MT was released after 12 h, following also first-order kinetics. It was discovered that the diffusion process was dominant. The drug release profile was mainly governed by the rheological and mechanical properties of the developed formulation. Such a novel, thermosensitive formulation might be an effective alternative to hypertension treatment, particularly for unconscious patients, patients with mental illnesses, geriatric patients, and children.     

Gene Variants Related to Cardiovascular and Pulmonary Diseases May Correlate with Severe Outcome of COVID-19

Background: Severe outcomes of COVID-19 account for up to 15% of all cases. The study aims to check if any gene variants related to cardiovascular (CVD) and pulmonary diseases (PD) are correlated with a severe outcome of COVID-19 in a Polish cohort of COVID-19 patients. Methods: In this study, a subset of 747 samples from unrelated individuals collected across Poland in 2020 and 2021 was used and whole-genome sequencing was performed. Results: The GWAS analysis of SNPs and short indels located in genes related to CVD identified one variant significant in COVID-19 severe outcome in the HADHA gene, while for the PD gene panel, we found two significant variants in the DRC1 gene. In this study, both potentially protective and risk variants were identified, of which variants in the HADHA gene deserve the most attention. Conclusions: This is the first study reporting the association between the HADHA and DRC1 genetic variants and COVID-19 severe outcome based on the cohort WGS analysis. Although all the identified variants are localised in introns, they may be correlated and therefore inherited along with other risk variants, potentially causative to severe outcome of COVID-19 but not discovered yet.     

The Use of Reverse Osmosis in the Removal of PAHs from Municipal Landfill Leachate

Polycyclic aromatic hydrocarbons (PAHs) are relatively well-known organic pollutants and due to their carcinogenic and mutagenic properties their presence in the environment still attracts a lot of attention.

According to literature reports and own research, PAHs presence in wastewaters is common. It was confirmed that PAHs are the components of municipal landfill leachate. Membrane techniques are one of the most interesting ways of removing PAHs from leachate.

The purpose of this article is to monitor PAHs concentration changes during the membrane (reverse osmosis - RO) leachate treatment processes. In the first stage of testing leachates were filtrated on the sand bed (pre-filtration). After the pre-filtration they were directed to the membrane module for the main filtration.

Sixteen PAHs listed by EPA were analyzed. The results with information on PAHs concentration in leachate samples were presented using HPLC with fluorescence detection (FLD). The changes in PAHs concentration were determined in leachate samples before and after pre-filtration as well as after RO. The decrease of PAHs concentration in the samples was observed after these processes. The total concentration of 16 PAHs in raw municipal landfill leachates amounted to 23.64–26.95 μg/L. The research confirmed the high efficiency in removal of PAHs while using a reverse osmosis (59–72%). Including the pre-filtration, the overall level of removed PAHs reached 81–86%. The average PAHs concentration after pre-filtration and RO was in the 4.46–4.99 μg/L range. The municipal landfill leachate with a high concentration of PAHs should be cleaned before it is discharged into the environment.     

Colony-blot assay with anti-p60 antibodies as a method for quick identification of Listeria in food

The present study evaluated the ability to isolate Listeria from foods, using shortened procedure of sample enrichment followed by immunomagnetic separation or filtration methods, and serological identification of isolated bacteria by colony-blot and Western blot methods with anti-p60 antibodies. By these rapid methods, identification of Listeria was achieved in much shorter time (40-48 h) than with standard cultivation and biochemical identification procedures. The rapid methods used are easy to perform and, what is most important, their specificity is very high and fulfills the expectations. The possibility to select Listeria colonies growing on non-selective media by blotting with anti-p60 antiserum seems to be particularly valuable in examination of food samples containing/not too many Listeria (1-10 CFU/25 g). However, the blot method using anti-PepD mAb specific to unique region of L. monocytogenes p60 is necessary to distinguish L. monocytogenes from other Listeria species.     

Study of the Effects of Temperature and Pressure on the Thermodynamic and Acoustic Properties of 2-Methyl-1-butanol at Temperatures from 293K to 318K and Pressures up to 100MPa

The speeds of sound in 2-methyl-1-butanol were measured at temperatures from 293K to 318K and pressures up to 101MPa. The densities were measured in the same temperature range under atmospheric pressure. The isobaric specific heat capacities were measured at atmospheric pressure and temperatures from 284K to 355K. The densities, isobaric heat capacities, isobaric thermal expansions, isentropic compressibilities, isothermal compressibilities, and internal pressures as functions of temperature and pressure were calculated using the experimental speeds of sound under elevated pressures together with the densities and heat capacities at atmospheric pressure. The effects of temperature and pressure on the isobaric thermal expansion and internal pressure of 2-methyl-1-butanol are discussed and compared with those of pentan-1-ol, 2-methyl-2-butanol, and pentan-3-ol.