Consensus statements for the establishment of medical intensive care in low-resource settings: international study using modified Delphi methodology.

BACKGROUND: The inadequacy of intensive care medicine in low-resource settings (LRS) has become significantly more visible after the COVID-19 pandemic. Recommendations for establishing medical critical care are scarce and rarely include expert clinicians from LRS. METHODS: In December 2023, the National Association of Intensivists from Bosnia and Herzegovina organized a hybrid international conference on the topic of organizational structure of medical critical care in LRS. The conference proceedings and literature review informed expert statements across several domains. Following the conference, the statements were distributed via an online survey to conference participants and their wider professional network using a modified Delphi methodology. An agreement of ≥ 80% was required to reach a consensus on a statement. RESULTS: Out of the 48 invited clinicians, 43 agreed to participate. The study participants came from 20 countries and included clinician representatives from different base specialties and health authorities. After the two rounds, consensus was reached for 13 out of 16 statements across 3 domains: organizational structure, staffing, and education. The participants favored multispecialty medical intensive care units run by a medical team with formal intensive care training. Recognition and support by health care authorities was deemed critical and the panel underscored the important roles of professional organizations, clinician educators trained in high-income countries, and novel technologies such as tele-medicine and tele-education. CONCLUSION: Delphi process identified a set of consensus-based statements on how to create a sustainable patient-centered medical intensive care in LRS.

Do dynamic changes in haematological and biochemical parameters predict mortality in critically ill COVID-19 patients?

BACKGROUND: Critically ill COVID-19 patients are usually subjected to clinical, laboratory, and radiological diagnostic procedures resulting in numerous findings. Utilizing these findings as indicators for disease progression or outcome prediction is particularly intriguing. OBJECTIVES: Exploring the significance of dynamic changes in haematological and biochemical parameters in predicting the mortality of critically ill COVID-19 patients. METHODS: The present study was a prospective and observational study involving mechanically ventilated 75 critically ill adult COVID-19 patients with hypoxemic respiratory failure. The collected data included baseline patient characteristics, treatment options, outcome, and laboratory findings at admission and 7 days after. The dynamics of the obtained findings were compared between survivors and non-survivors. RESULTS: The 28-day survival rate was 61.3%. In the group of non-survivors significant dynamic changes were found for C-reactive protein (p= 0.001), interleukin-6 (p< 0.001), lymphocyte (p= 0.003), neutrophil-lymphocyte ratio (p= 0.003), platelets (p< 0.001), haemoglobin (p< 0.001), iron (p= 0.012), and total iron-binding capacity (p< 0.001). Statistically significant changes over time were found for ferritin (p= 0.010), D-dimer (p< 0.001), hs-troponin T (p< 0.002), lactate dehydrogenase (p= 0.001), glucose (p= 0.023), unsaturated iron-binding capacity (p= 0.008), and vitamin D (p< 0.001). CONCLUSION: The dynamic changes in inflammatory, haematological and biochemical parameters can predict disease severity, and outcome.

The Evolution and Challenges of Academic Family Medicine: Insights from the Banja Luka Declaration.

Academic medicine encompasses education, research and clinical practice, and plays a crucial role in advancing medical science and training physicians. However, the field faces a crisis, with fewer graduates pursuing academic careers. Family medicine emerged as an academic discipline in the second half of the 20th century, contributing significantly to science and primary healthcare. Despite its recognised status, the World Health Organization has yet to formally define it as an academic discipline. Nevertheless, the discipline must continually update its academic dimension in order to address future challenges. The international conference in Banja Luka, attended by deans or representatives of Medical Faculties in Southeast Europe, emphasized family medicine's role in primary healthcare and academic medicine, adopting the Banja Luka Declaration to promote family medicine as an independent academic discipline. The conference aims to inspire global support for family medicine as an academic discipline.

NLRP3 Inflammasome and Gut Dysbiosis Linking Diabetes Mellitus and Inflammatory Bowel Disease.

Diabetes mellitus and inflammatory bowel disease are chronic conditions with significant overlap in their pathophysiology, primarily driven by chronic inflammation. Both diseases are characterized by an aberrant immune response and disrupted homeostasis in various tissues. However, it remains unclear which disease develops first, and which one contributes to the other. Diabetes mellitus increases the risk of inflammatory bowel disease and inflammatory bowel disease may increase the risk of developing diabetes. This review focuses on comprehensively discussing the factors commonly contributing to the pathogenesis of diabetes mellitus and inflammatory bowel disease to draw a relationship between them and the possibility of targeting common factors to attenuate the incidence of one if the other is present. A key player in the intersection of diabetes mellitus and inflammatory bowel disease is the NLRP3 inflammasome, which regulates the production of pro-inflammatory cytokines leading to prolonged inflammation and tissue damage. Additionally, toll-like receptors via sensing microbial components contribute to diabetes mellitus and inflammatory bowel disease by initiating inflammatory responses. Gut dysbiosis, a common link in both diseases, further intensifies inflammation and metabolic dysfunction. Alterations in gut microbiota composition affect intestinal permeability and immune modulation, perpetuating a vicious cycle of inflammation and disease progression by changing protein expression. The overlap in the underlying inflammatory mechanisms has led to the potential of targeting mediators of chronic inflammation using anti-inflammatory drugs and biologics that benefit both conditions or attenuate the incidence of one in the presence of the other.

Galectin 3 rs4644 gene polymorphism is associated with metabolic traits in Serbian adolescent population.

Background: Among many genes which have been analyzed to understand obesity and related metabolic traits among children and adolescents, not many studies are conducted on LGALS3 gene, especially in population of children. A positive correlation of circulating galectin 3 serum levels with impaired blood glucose, high blood pressure and higher values of serum lipids and was found in general population. The aim was to investigate possible association of rs4644 with body mass index, glycaemia, and lipid profile in Serbian adolescents. Methods: The study included 72 boys and 79 girls, 14-15 years of age. Among boys 51 (67.1%) had normal values of BMI, 11 (14.5%) were overweight, and 14 (18.4%) were obese. Among girls, 53 (63.9%) had normal BMI, 16 (19.3%) were overweight, and 14 (16.9%) were obese. Diabetes type 1 or 2, genetic syndromes, generalized inflammation, cardiovascular and malignant diseases were criteria for exclusion. Genotyping was performed by Real time PCR.

Clinical and epidemiological risk factors associated with hospitalization and mortality rate of COVID-19 patients in Banja Luka County: A retrospective observational cohort study on 40,000 patients.

Context: Since beginning of the coronavirus disease (COVID-19) it became clear that severe forms of this infection have primarily affected patients with chronic conditions. Aims: The aim of the study was to explore clinical and epidemiological characteristics associated with COVID 19 outcomes. Settings and Design: The retrospective observational study included 40,692 citizens of Banja Luka County, Bosnia and Herzegovina, who were confirmed as reverse transcriptase polymerase chain reaction (RT-PCR) positive on COVID-19 at a primary healthcare centre from March 2020 to September 2022. Methods and Materials: Epidemiological data were obtained from Web-Medic medical records of patients. The COVID-19 data were obtained from COVID-19 data sheets comprised of patients' RT-PCR testing forms, surveillance forms for severe acute respiratory syndrome coronavirus-2 status, and a map of their positive and isolated contacts. Statistical Analysis Used: Differences regarding the distributions of patients between groups were analysed using the Pearson chi-square test and Mantel-Haenszel chi-square test for trends, while differences in mean values were compared using an independent sample t-test. Results: The average age of hospitalised patients was significantly higher compared to the age of non-hospitalised patients (P < 0.001). The average age of patients with lethal outcomes was nearly twice as high in comparison to patients with non-lethal outcomes (P < 0.001). Male patients had a higher hospitalization and mortality rate (P < 0.001). The highest hospitalization rate was in patients with chronic renal failure (CRF), diabetes and cardiovascular diseases (CVDs), while the death rate was the highest among patients with CRF and hearth comorbidities. Patients with fatigue and appetite loss had a higher percentage of lethal outcomes. Vaccinated patients had a significantly lower rate of lethal outcome. Conclusions: Clinical symptoms, signs and outcomes, are posing as predictive parameters for further management of COVID-19. Vaccination has an important role in the clinical outcomes of COVID-19.

Design of Novel TRPA1 Agonists Based on Structure of Natural Vasodilator Carvacrol-In Vitro and In Silico Studies.

Considering the escalating global prevalence and the huge therapeutic demand for the treatment of hypertension, there is a persistent need to identify novel target sites for vasodilator action. This study aimed to investigate the role of TRPA1 channels in carvacrol-induced vasodilation and to design novel compounds based on carvacrol structure with improved activities. In an isolated tissue bath experiment, it was shown that 1 µM of the selective TRPA1 antagonist A967079 significantly (p < 0.001) reduced vasodilation induced by 3 mM of carvacrol. A reliable 3D-QSAR model with good statistical parameters was created (R2 = 0.83; Q2 = 0.59 and Rpred2 = 0.84) using 29 TRPA1 agonists. Obtained results from this model were used for the design of novel TRPA1 activators, and to predict their activity against TRPA1. Predicted pEC50 activities of these molecules range between 4.996 to 5.235 compared to experimental pEC50 of 4.77 for carvacrol. Molecular docking studies showed that designed molecules interact with similar amino acid residues of the TRPA1 channel as carvacrol, with eight compounds showing lower binding energies. In conclusion, carvacrol-induced vasodilation is partly mediated by the activation of TRPA1 channels. Combining different in silico approaches pointed out that the molecule D27 (2-[2-(hydroxymethyl)-4-methylphenyl]acetamide) is the best candidate for further synthesis and experimental evaluation in in vitro conditions.

Comparative Effects of Target-Controlled Infusion of Propofol Versus Spinal and Thiopental-Sevoflurane Anesthesia on Lipid Peroxidation in Elective Cesarean Section: A Prospective, Open-Label Study.

BACKGROUND: During pregnancy, physiological changes can increase oxidative stress (OS) in both mothers and fetuses. The use of anesthesia for cesarean sections (CSs) could exacerbate this stress due to its impact on the ischemia-reperfusion effect. Our study aimed to explore the effects of target-controlled infusion of propofol on OS during CSs, and to compare these effects with those of spinal and thiopental-sevoflurane anesthesia. METHODS: The study included ninety parturients undergoing elective CS, allocated into three groups: Group S (spinal) (n = 30), Group P (propofol) (n = 30), and Group TS (thiopental-sevoflurane) (n = 30). Venous blood samples were taken from mothers at three time points, before, during, and after surgery, and one sample was taken from the umbilical vein after delivery. Blood samples were analyzed with the thiobarbituric acid reactive substances (TBARS) assay and blood gas analysis. A statistical comparison between groups was obtained by one-way analysis of variance (ANOVA) and the Wilcoxon test where appropriate. RESULTS: Levels of TBARS after the induction of anesthesia were lower in all groups compared to values preoperatively. In Group P, TBARS levels started to decrease in the first five minutes after the induction (1.90 ± 0.47; P < 0.001) and had significantly lower values compared to Group S (2.22 ± 0.21) and Group TS (2.40 ± 0.20). Two hours after surgery, TBARS values were the lowest in Group P (1.76 ± 0.15, P<0.001), compared to Group S (2.18 ± 0.24) and Group TS (2.41 ± 0.21). TBARS value in umbilical venous blood was significantly lower in Group P (1.56 ± 0.16, P < 0.001) compared to Group S (2.18 ± 0.17) and Group TS (2.09 ± 0.09). Umbilical cord venous blood gas values (pH, PCO2, HCO3, lactates, and base excess (BE)) were not different between the groups, except for PO2, which was significantly lower in Group S (20.5 ± 5.0; P < 0.001) compared to Group P (36.5 ± 19.2) and Group TS (33.5 ± 10.1). CONCLUSION: Target-controlled infusion of propofol anesthesia could be advantageous for parturients with compromised oxidative status, especially those undergoing emergency CSs when general anesthesia is required.

Formulation and Evaluation of Polysaccharide Microparticles for the Controlled Release of Propranolol Hydrochloride.

Propranolol hydrochloride, a non-cardio-selective beta blocker, is used to treat several conditions in children, including hypertension, arrhythmias, hyperthyroidism, hemangiomas, etc. Commercial liquid formulations are available in Europe and the US, but they have disadvantages, such as limited stability, bitter taste, and the need for multiple daily doses due to the drug's short half-life. Considering these limitations, controlled-release solid formulations, such as microparticles, may offer a better solution for pediatric administration. The main objective of this study was to formulate an encapsulation system for propranolol hydrochloride, based on sodium alginate and other polysaccharide polymers, to control and prolong its release. Microparticles were prepared using the ionotropic gelation method, which involves instilling a polymer solution into a solution of gelling ions via the extrusion technique. Physicochemical characterization was conducted by assessing the entrapment efficiency, drug loading, swelling index, microparticle size, rheological properties, and surface tension. In order to improve the characteristics of the tested microparticles, selected formulations were coated with chitosan. Further experimental work included differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) analysis, and SEM imaging. This in vitro release study showed that chitosan-coated microparticles demonstrate favorable properties, suggesting a novel approach to formulating pediatric dosage forms, although further optimization is necessary.

Intensive Intervention on Smoking Cessation in Patients Undergoing Elective Surgery: The Role of Family Physicians.

Background and Objectives: The aim of this study was to determine the role of physicians in the intensive intervention and education regarding the smoking cessation of patients undergoing elective surgery under general anaesthesia. Materials and Methods: A randomised prospective study was conducted in family physicians' clinics in which smokers of both sexes, aged 21-65 years, without cognitive impairments, and who were not addicted to psychoactive substances voluntarily participated. Four weeks preoperatively, 120 smokers were randomised into two equal groups; the intervention group (IG) underwent an intervention for the purpose of smoking cessation and the control group (CG) underwent no intervention. Biochemical tests were performed in order to determine the smoking status of the participants in the phase of randomisation, one week preoperatively, as well as 40, 120, and 180 days and 12 months postoperatively. The examinees of the IG talked to the physician five times and received 140 telephone messages, leaflets, and motivational letters along with the pharmacotherapy, while the participants in the CG received little or no advice on smoking cessation. Results: The results of this study confirmed a significant influence of the intervention and education on the smoking abstinence in the IG compared to the CG (p < 0.001). The smokers in the IG had 7.31 (95% CI: 2.32-23.04) times greater odds of abstinence upon the 12-month follow-up than the smokers in the CG. The smokers in the IG who did not stop smoking had a lower degree of dependence and smoked fewer cigarettes (p < 0.0001) compared to those in the CG, as well as a multiple times higher prevalence of short- and long-term abstinence. Conclusions: It can be concluded that the intensive intervention and education can motivate patients preparing for elective surgery to stop smoking in the short- and long term.

Biocompatibility of nano/micro-sized pyrophyllite particles by pulmo, liver, kidney and gastric mucosis cells.

Pyrophyllite is the least studied natural clay in terms of its potential in biomedical applications, although there are many deposits of this aluminosilicate around the world. Genotoxicity study was performed in vitro for this mineral. Subsequently, Wister rats were exposed to the pyrophyllite micronized to below 100 µm. After the exposure period, histology of the lung, liver, kidney and gastric tissues were performed, followed by the stereological and hematological analysis. The physicochemical analyses revealed typical XRD characteristics of pyrophyllite clay with particle-size distribution ranging 50 nm-100 µm with stable mineral composition and unique buffering property to pH around 8. The results showed that there were no cytotoxic effects on to THP-1 cells, or genotoxicity of pyrophyllite measured by the Comet assay. In vivo studies are accompanied by the thorough physicochemical characterization of the micronized pyrophyllite. Histology of the lung tissue proved presence of an inflammatory reaction. On the other hand, gastric tissue has shown the selective accumulation of nanoparticles in enterocytes of the stomach only, as supported by ultrastructural analysis. Liver and kidney tissues have shown tolerability for pyrophyllite particles. The results give directions for further comprehensive studies of potential biomedical applications of the pyrophyllite.

Liraglutide Protects Cardiomyocytes against Isoprenaline-Induced Apoptosis in Experimental Takotsubo Syndrome.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, characterized by an increased concentration of catecholamines, free radicals, and inflammatory cytokines, endothelial dysfunction, and increased apoptotic activity. High doses of isoprenaline are used in animal models to induce Takotsubo (TT)-like myocardial injury. The aim of the study was to investigate the antiapoptotic effects of liraglutide in experimental TTS and its role in the NF-κB pathway. Wistar rats were pretreated with liraglutide for 10 days, and on days 9 and 10, TT-like myocardial injury was induced with isoprenaline. After the sacrifice on day 11, hearts were isolated for histopathological and immunohistochemical analysis. Liraglutide reduced isoprenaline-induced cardiomyocyte apoptosis by decreasing cleaved caspase-3 (CC3), BCL-2-associated X protein (BAX), and NF-κB and increasing B-cell lymphoma/leukemia-2 (BCL-2). An increase in NF-κB in isoprenaline-treated rats was in positive correlation with proapoptotic markers (BAX and CC3) and in negative correlation with antiapoptotic marker BCL-2. Liraglutide increased BCL-2 and decreased NF-κB, BAX, and CC3, preserving the same correlations of NF-κB to apoptotic markers. It is concluded that liraglutide protects cardiomyocytes against isoprenaline-induced apoptosis in experimental TT-like myocardial injury through downregulation of the NF-κB pathway.

Comparative Efficacy of High-Dose Dexamethasone Versus Methylprednisolone in Coronavirus Disease 2019 (COVID-19)-Associated Acute Respiratory Distress Syndrome.

OBJECTIVE: This retrospective (matched paired) clinical trial aimed to compare the efficacy of dexamethasone vs. methylprednisolone at equipotent (high) doses in patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS). METHODS: A total of 347 patients with moderate and severe COVID-19-associated ARDS were administered either a high (equipotent) dose of dexamethasone (32 mg) or methylprednisolone (180 mg) for a duration of up to 10 days. All participants received the standard of care for critically ill COVID-19 patients. RESULTS: The primary outcomes included length of stay in the ICU, ICU mortality, and discharge from the hospital. Based on the obtained results, a tendency towards more favorable clinical outcomes concerning the length of stay in the ICU (in the group of patients treated with non-invasive mechanical ventilation (NIV), p<0.05), ICU mortality, and discharge from the hospital (in the group of patients who were intubated, p<0.05) in patients receiving the high dose of dexamethasone compared to those receiving methylprednisolone was observed. CONCLUSION: It appears that severe cases of COVID-19, especially intubated ones, treated with high doses of dexamethasone have a more favorable clinical outcome than the use of equipotent doses of methylprednisolone. However, larger multicenter studies are needed to validate our observations.

Beneficial Effects of Ursodeoxycholic Acid on Metabolic Parameters and Oxidative Stress in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind, Placebo-Controlled Clinical Study.

Background: Oxidative stress and inflammation are closely related pathophysiological processes, both occurring in type 2 diabetes mellitus (T2DM). In addition to the standard treatment of T2DM, a potential strategy has been focused on the use of bile acids (BAs) as an additional treatment. Ursodeoxycholic acid (UDCA), as the first BA used in humans, improves glucose and lipid metabolism and attenuates oxidative stress. The aim of this study was to evaluate the potential metabolic, anti-inflammatory, and antioxidative effects of UDCA in patients with T2DM. Methods: This prospective, double-blind, placebo-controlled clinical study included 60 patients with T2DM, randomly allocated to receive UDCA or placebo. Subjects were treated with 500 mg tablets of UDCA or placebo administered three times per day (total dose of 1500 mg/day) for eight weeks. Two study visits, at the beginning (F0) and at the end (F1) of the study, included the interview, anthropometric and clinical measurements, and biochemical analyses. Results: UDCA treatment showed a significant reduction in body mass index (p = 0.024) and in diastolic blood pressure (p = 0.033), compared to placebo. In addition, there was a statistically significant difference in waist circumference in the UDCA group before and after treatment (p < 0.05). Although no statistical significance was observed at the two-month follow-up assessment, an average decrease in glucose levels in the UDCA group was observed. After two months of the intervention period, a significant decrease in the activity of liver enzymes was noticed. Furthermore, a significant reduction in prooxidative parameters (TBARS, NO2-, H2O2) and significant elevation in antioxidative parameters such as SOD and GSH were found (p < 0.001). Conclusions: The eight-week UDCA administration showed beneficial effects on metabolic and oxidative stress parameters in patients with T2DM. Thus, UDCA could attenuate the progression and complications of diabetes and should be considered as an adjuvant to other diabetes treatment modalities. This trial is registered with NCT05416580.

Effect of folic acid on isoprenaline-induced myocardial injury in rats.

Background: Isoprenaline (ISO), a synthetic catecholamine and a ß-adrenoceptor agonist, is widely used to develop an experimental model of myocardial injury (MI) in rats. The leading hypothesis for ISO-induced MI in rats is that it results from catecholamine overstimulation, oxidative stress, inflammatory responses, and development of cardiomyopathy during ISO administration. Folic acid (FA) reduces oxidative stress, improves endothelial function and prevents apoptosis, thereby contributing to cardiovascular protection. This study aimed to investigate the potentially protective effect of FA pretreatment on ISO-induced MI in rats. Methods: For 7 days, adult male Wistar albino rats were pretreated with 5 mg/kg/day of FA. On the sixth and seventh days, MI in rats was induced by administering 85 mg/kg/day of ISO. Prooxidant markers in plasma samples, antioxidant capacity in erythrocyte lysates, cardiac damage markers, lipid profile, electrocardiography (ECG) and histopathological analysis were evaluated. Results: FA pretreatment significantly alleviated changes induced by ISO; it decreased the homocysteine and high-sensitivity troponin I level. FA moderately decreased the reactive oxygen species (ROS) levels (superoxide anion radical, hydrogen peroxide and thiobarbituric acid reactive substances) and improved the antioxidant activities of catalase, superoxide dismutase and reduced glutathione. ISO reduced the nitrite level and FA significantly alleviated this change. Conclusion: It can be concluded that FA, as a mild antioxidant, could be an appropriate cardioprotective substance in the rat model of ISO-induced MI.

Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta.

Hypotensive influences of benzodiazepines and other GABAA receptor ligands, recognized in clinical practice, seem to stem from the existence of "vascular" GABAA receptors in peripheral blood vessels, besides any mechanisms in the central and peripheral nervous systems. We aimed to further elucidate the vasodilatatory effects of ligands acting through GABAA receptors. Using immunohistochemistry, the rat aortic smooth muscle layer was found to express GABAA γ2 and α1-5 subunit proteins. To confirm the role of "vascular" GABAA receptors, we investigated the vascular effects of standard benzodiazepines, midazolam, and flumazenil, as well as the novel compound MP-III-058. Using two-electrode voltage clamp electrophysiology and radioligand binding assays, MP-III-058 was found to have modest binding but substantial functional selectivity for α5ß3γ2 over other αxß3γ2 GABAA receptors. Tissue bath assays revealed comparable vasodilatory effects of MP-III-058 and midazolam, both of which at 100 µmol/L concentrations had efficacy similar to prazosin. Flumazenil exhibited weak vasoactivity per se, but significantly prevented the relaxant effects of midazolam and MP-III-058. These studies indicate the existence of functional GABAA receptors in the rat aorta, where ligands exert vasodilatory effects by positive modulation of the benzodiazepine binding site, suggesting the potential for further quest for leads with optimized pharmacokinetic properties as prospective adjuvant vasodilators.

Analysis of redox status and HDL subclasses in patients with lymphoma and the associations with FDG-PET/CT findings.

Newer research points to alterations in the plasma redox status and the HDL subclass distributions in cancer. We aimed to assess the redox status and the HDL subclass distributions, lipids, and inflammatory markers in lymphoma patients in order to determine whether they were correlated with changes in FDG-PET/CT scans. At the beginning of this study, redox status, HDL subclasses, lipids, and inflammation biomarkers were determined in 58 patients with lymphoma (Hodgkin lymphoma, n=11 and non-Hodgkin lymphoma, n=47), and these same measurements were reassessed during their ensuing treatment (in 25 patients). Initially, the total oxidation status (TOS), the prooxidant-antioxidant balance (PAB), the OS index (OSI), the total protein sulfhydryl groups (SH-groups), and the advanced oxidation protein products (AOPP) were significantly higher in lymphoma patients as compared to healthy subjects, but the total antioxidant status (TAS) was significantly reduced. The PAB had a strong correlation with the CRP and interleukin-6 (rho=0.726, p<0.001; rho=0.386, p=0.003). The correlations between these parameters and the maximum standardized uptake values (SUVmax) were: PAB, rho=0.335 and p=0.010; SH-groups, rho=0.265 and p=0.044; CRP, rho=0.391 and p=0.002; HDL3b, rho=0.283 and p=0.031; HDL2b, rho= -0.294 and p=0.025; and HDL size, rho= -0.295 and p=0.024. The reductions in SUVmax between two follow-up points were associated with increases in the OSI, TOS, and SH-groups, as well as a reduction in the PAB and TAS. In conclusion, the redox parameters in patients with lymphoma were consistent with FDG-PET/CT findings. Targeting the redox status parameters and the HDL subclasses could be potential strategies in the molecular fight against lymphoma.

Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions.

Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms involved are poorly understood. The aim of this study was to test the effect of pomegranate peel extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva (n = 3 of each) were established. The lines were treated with two non-toxic concentrations of PoPEX (low-10; high-40 µg/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four genes in GMSCs involved in different functions were examined using real-time polymerase chain reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of IL-6, MCP-1, GRO-α, RANTES, IP-10, HIF-1α, SDF-1, and HGF but increased the expression of IL-8, TLR3, TGF-ß, TGF-ß/LAP ratio, IDO-1, and IGFB4 genes in H-GMSCs. PoPEx increased IL-6, RANTES, MMP3, and BMP2 but inhibited TLR2 and GRO-α gene expression in P-GMSCs. LPS upregulated genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (MMP3, IGFBP4, HGF), and immunomodulation (IP-10, RANTES, IDO-1, TLR3, COX-2), more strongly in P-GMSCs. PoPEx also potentiated most genes' expression in LPS-stimulated P-GMSCs, including upregulation of osteoblastic genes (RUNX2, BMP2, COL1A1, and OPG), simultaneously inhibiting cell proliferation. In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more pronounced in inflammation-simulating conditions.

Methodological challenges in using human umbilical artery as a model for in vitro studies.

NEW FINDINGS: What is the central question of this study? What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries? What is the main finding and its importance? The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries. ABSTRACT: Human umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre-eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L-type voltage-operated calcium channels and different types of potassium channels (KATP , BKCa and KV ) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin-induced contraction and a decrease in minoxidil-induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that KATP and KV channels participate in the minoxidil-induced relaxation, while L-type voltage-dependent Ca2+  channels play an important role in the serotonin-induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine-induced pre-eclampsia model.