Hypotensive drugs mitigate the high-sodium diet-induced pro-inflammatory activation of mouse macrophages in vivo.

Nowadays, there is an increasing emphasis on the need to alleviate the chronic inflammatory response to effectively treat hypertension. However, there are still gaps in our understanding on how to achieve this. Therefore, research on interaction of antihypertensive drugs with the immune system is extremely interesting, since their therapeutic effect could partly result from amelioration of hypertension-related inflammation, in which macrophages seem to play a pivotal role. Thus, current comprehensive studies have investigated the impact of repeatedly administered hypotensive drugs (captopril, olmesartan, propranolol, carvedilol, amlodipine, verapamil) on macrophage functions in the innate and adaptive immunity, as well as if drug-induced effects are affected by a high-sodium diet (HSD), one of the key environmental risk factors of hypertension. Although the assayed medications increased the generation of reactive oxygen and nitrogen intermediates by macrophages from standard fed donors, they reversed HSD-induced enhancing effects on macrophage oxidative burst and secretion of pro-inflammatory cytokines. On the other hand, some drugs increased macrophage phagocytic activity and the expression of surface markers involved in antigen presentation, which translated into enhanced macrophage ability to activate B cells for antibody production. Moreover, the assayed medications augmented macrophage function and the effector phase of contact hypersensitivity reaction, but suppressed the sensitization phase of cell-mediated hypersensitivity under HSD conditions. Our current findings contribute to the recognition of mechanisms, by which excessive sodium intake affects macrophage immune activity in hypertensive individuals, and provide evidence that the assayed medications mitigate most of the HSD-induced adverse effects, suggesting their additional protective therapeutic activity.

Unattended automatic blood pressure measurements vs conventional office readings in predicting hypertension-mediated organ damage.

INTRODUCTION: Hypertension is a leading cardiovascular risk factor. Accurate blood pressure (BP) measurement is pivotal in hypertension diagnosis and management. Conventional office blood pressure measurements (OBPMs) are error­prone, exacerbated by the white­coat effect. Unattended automated office blood pressure measurement (UAOBPM) is emerging as an alternative, mitigating the white­coat effect. However, its ability to predict hypertension­mediated organ damage (HMOD) remains disputable. OBJECTIVES: This study compares UAOBPM with OBPM in terms of their association with various types of HMOD, including left ventricular hypertrophy, left atrial enlargement, left ventricular systolic and diastolic dysfunction, intima­media complex thickening, microalbuminuria, and abnormal pulse wave velocity. PATIENTS AND METHODS: A total of 219 hypertensive patients were recruited, interviewed, and examined. Subsequently, BP measurements were conducted in a randomized manner: 1) UAOBPM, after 5 minutes of solitary rest in an examination room, BP was automatically measured 3 times at 1­minute intervals; 2) OBPM, after 5 minutes of rest, a physician performed 3 consecutive BP measurements at 1­minute intervals. Subsequent evaluations aimed to detect HMOD and included echocardiography, carotid artery ultrasound, pulse wave velocity assessment, and laboratory tests. RESULTS: UAOBP values were lower than the OBP ones (mean [SD], 124.7 [14.4] vs 128.2 [14.2] mm Hg; P <0.001 for systolic BP, and 73.3 [10.2] vs 75.2 [10.6] mm Hg; P <0.001 for diastolic BP). Correlation and receiver operating characteristic curve analyses revealed no superiority of either method in predicting HMOD. CONCLUSIONS: The UAOBPM did not prove superior to OBPM in predicting HMOD. Further research is warranted to determine the role of UAOBPM in clinical practice.

Overreactive macrophages in SARS-CoV-2 infection: The effects of ACEI.

Among various factors influencing the course of SARS-CoV-2 infection in humans, macrophage overactivation is considered the main cause of the cytokine storm that leads to severe complications of COVID-19. Moreover, the increased expression of angiotensin converting enzyme 2 (ACE2), an obligatory entry receptor of the coronavirus, caused by treatment with ACE inhibitors (ACEI) lowered overall confidence in the safety of these drugs. However, analysis of the course of coronavirus infection in patients treated with ACEI does not support these concerns. Instead, the beneficial effect of ACEI on macrophages has increasingly been emphasized. This includes their anti-inflammatory activation and the consequent reduction in the risk of severe disease and life-threatening complications. Herein, we summarize the current knowledge and understanding of the dual role of macrophages in SARS-CoV-2 infection, with a special focus on the postulated mechanisms underlying the beneficial effects of macrophage targeting by ACEI. These seem to involve the stimulation of macrophage angiotensin II type 2 and Mas receptors by angiotensin 1-7, intensively produced due to the up-regulation of ACE2 expression on macrophages, as well as the direct inhibition of macrophage hyper-responsiveness by ACEI. The impact of ACEI on macrophages may also lead to the activation of an effective antiviral response due to the increased expression of ACE2.

Does the incidence of infectious endocarditis show seasonal patterns? - a single center retrospective study.

I n t r o d u c t i o n: Seasonal variation has been observed for bacterial and viral infections (e.g., COVID-19 [1]), but also for numerous cardiac problems. However, little information is available on the seasonality of infectious endocarditis (IE), a rare disease that is usually linked to a bacterial origin. Data from the Polish population are lacking. Materials and M e t h o d s: Our retrospective study focused on the identification of patients with IE, who were hospitalized at the University Hospital in Krakow between 2005-2022. For this purpose, we searched the medical records system using the ICD-10 code. We decided to divide our patients into four groups (winter, spring, summer, autumn), based on the date of admission to the hospital. Comparison of the distribution of IE incidents by season was performed with the ch2 test. R e s u l t s: One hundred and ten patients were included in the study (median age 62.5 years (range 20-94), 72 men (65.45%)). The left native valve IE was diagnosed in 49% of the patients, the prosthetic valve IE in 16%, the right valve IE in 27% and the implantable cardiac electronic devices IE in 12% of the subjects. The outcomes comprised of cardiac surgery (n = 53), embolism (n = 16), death (n = 15) and metastatic infections (n = 5). No differences in the incidence of IE by season were observed. C o n c l u s i o n s: In the preliminary observation of IE cases of patients admitted to the University Hospital in Krakow, Poland no seasonal pattern of IE was detected. Therefore, IE should be taken into account in the differential diagnosis at any time of the year.

The immunomodulatory effects of antihypertensive therapy: A review.

Hypertension remains the leading preventable risk factor for stroke and coronary artery disease, significantly contributing to all-cause global mortality and predisposing patients to renal and heart failure, as well as peripheral vascular disease. Due to the widespread usage of antihypertensive drugs, global mean blood pressure has remained unchanged or even slightly decreased over the past four decades. However, considering the broad spectrum of mechanisms involved in the action of antihypertensive drugs and the prevalence of their target receptors on immune cells, possible immunomodulatory effects which may exert beneficial effects of lowering blood pressure but also potentially alter immune function should be considered. In this review, we attempt to assess the consequences to immune system function of administering the five most commonly prescribed groups of antihypertensive drugs and to explain the mechanisms behind those interactions. Finally, we show potential gaps in our understanding of the effects of antihypertensive drugs on patient health. With regard to the widespread use of these drugs in the adult population worldwide, the discussed results may be of vital importance to evidence-based decision-making in daily clinical practice.

Usefulness of bee bread and capped brood for the assessment of monocyclic aromatic hydrocarbon levels in the environment.

Monitoring airborne pollutants, like aromatic hydrocarbons, are raising more and more concerns recently. Various sampling techniques and methods are known to collect, measure, and analyse environmental pollution levels based on honey bee bodies or bee product samples. Although honey bees are studied in detail and sampling methods are becoming more and more sophisticated biological samples may significantly differ in pollutant accumulation, showing a wide range of pollution levels even in the same site and environment. We have compared the pollution levels of honey bee capped brood and bee bread (pollen collected by honey bees and deposited in the hive) originating from four sites during two years of study and twelve honey bee families near various pollution sources emitting monocyclic aromatic hydrocarbons (BTEX) to the environment. Our result showed, that the environmental monitoring of BTEX can be based on sampling honey bees, and bee bread in particular. However, we found a significant difference in the uptake of these pollutants regarding sample type. Pollen collected as a food source revealed consistently higher levels of BTEX than bee brood, as well as some other differences in pollution levels between samples and between seasons, as opposed to capped brood. Based on our results, we suggest that for measuring and monitoring of BTEX pollution in the environment the use of bee bread is a valuable source of information.

Spontaneous laterality in mouse Crl:CD1.

Lateralization developed very early in evolution and it is a characteristic of a wide range of representatives from the animal kingdom. The aim of the present study was to examine the spontaneous laterality in mice (Mus musculus) with the T-maze test. We wanted to check if this kind of functional asymmetry occurs at a population level, and also if there are gender differences in this regard. The study involved 40 mice Crl:CD1. The research procedure was simple: mice had to choose one arm of the T-shaped apparatus to find the exit. The animals performed the 10 trails one after another. We took into account only the animals' fist reactions while preparing results. Most of the animals (68%) chose the right arm of the maze. The lateralization was stronger among females--75% of them had preferences for the right side. The majority of animals, which preferred the right side, were from the food deprivation group. However, the results did not unequivocally resolve whether mice evince the functional asymmetry at the population level, or whether there are gender differences in this area. Further research with a larger group and multiple observations for each animal are required to answer these questions.

Interactions of pentacyclic triterpene acids with cardiolipins and related phosphatidylglycerols in model systems.

Pentacyclic triterpene acids (PTAs): betulinic (BAc), oleanolic (Ola) and ursolic (Urs) are potent pharmaceuticals applied in the therapy of cancer and bacterial infections. The mechanism of PTA action is multifactor, but the important step is their interaction with the lipids of mitochondrial and bacterial membranes. In our studies we applied the Langmuir monolayer technique to investigate the interactions between PTAs and cardiolipins (CLs) and phosphatidylglycerols (PGs). We applied two different mammalian mitochondrial CLs and one species extracted from the membrane of Escherichia coli. For comparison we performed the same experiments on the systems containing PTAs and 3 PGs strictly correlated structurally to the applied CLs. Our studies proved that PTAs can disturb the organization of CL-rich domains and affect the bacterial membrane fluidity by the interactions with phosphatidylglycerols, so anionic phospholipids are the targets of their membrane action. The thermodynamic interpretation of the results indicated that Urs has the highest membrane disorganizing potential among the 3 studied PTAs. The studies performed on model systems proved also that BAc can discriminate over structurally similar animal cardiolipin species, interacts specifically with BHCL - the main mammalian CL and can disturb its organization in the membrane. In contrast, Ola and Urs are much active as far as the interaction with bacterial CLs and PGs is concerned.

Langmuir monolayer studies of the interaction of monoamphiphilic pentacyclic triterpenes with anionic mitochondrial and bacterial membrane phospholipids - searching for the most active terpene.

The interactions of three representative monoamphiphilic pentacyclic triterpenes (PTs) with cardiolipins (CL) and phosphatidylglycerols (PG) extracted from mitochondrial and bacterial membranes were comparatively characterized in binary Langmuir monolayers. The studied terpenes: lupeol, α- and ß-amyrin are isomeric compounds known from their broad biological activity. Anticancer and antimicrobial activity of PTs is often correlated with their propensity of being incorporated into mitochondrial and bacterial membranes and their specific interactions with cardiolipins. In our studies on 18 model systems surface pressure (π)-mean molecular area (A) isotherms were registered at five different component proportions in each system. Thermodynamic analysis complemented by in situ Brewster angle microscopy visualization of the investigated mixed films enabled the thorough characterization of the studied systems. It turned out that the investigated terpenes interact more favorably with PG molecules as compared to CLs. For most of the system containing CLs the values of ΔG(exc) were positive which was interpreted as the ability of the terpenes to disintegrate the membranes rich in CLs. Our results confirmed also that in the light of thermodynamic criterion α-amyrin exhibited the highest potential to disintegrate the CL containing domains in mitochondrial and bacterial membranes. The probable origin of the observed specific interactions between α-amyrin and investigated phospholipids could be explained based on the phenomenon of chiral discrimination. The obtained results were also widely discussed in reference to the biological activity of the studied compounds.

Size exclusion chromatography and viscometry in paper degradation studies. New Mark-Houwink coefficients for cellulose in cupri-ethylenediamine.

The paper deals with the application of size exclusion chromatography (SEC) for the studies of paper degradation phenomena. The goal is to solve some of the technical problems connected with the calibration of multi-detector SEC system and to find the correlation between SEC and viscometric results of degree of polymerization of cellulose. The results gathered for the paper samples degraded by acidic air pollutant (NO(2)) are used as an example of SEC-MALLS application. From the correlation between intrinsic viscosities and absolute value of molecular masses obtained with SEC/MALLS (Multi Angle Laser Light Scattering) technique, Mark-Houwink coefficients for cellulose in cupri-ethylenediamine solution were determined. Thus obtained coefficients were used for the determination of viscometric degree of polymerization (molecular mass) of the aged samples. An excellent correlation was found between the chromatographic values of molecular masses obtained with SEC-UV/VIS detection and the viscometric ones utilizing the improved values of Mark-Houwink coefficients.