Sex-specific differences in telomere length of patients with primary knee osteoarthritis.

Accelerated telomere shortening is associated with age-related diseases, including osteoarthritis (OA). We aimed to determine the relative telomere length (TL) in leukocytes and cartilage of patients with primary knee OA and to investigate factors that may affect TL in OA. Relative TL measurements were performed using qPCR in leukocytes of 612 individuals (310 patients with primary knee OA undergoing total knee arthroplasty (TKA) and 302 unaffected controls). We also analysed cartilage in 57 of the 310 OA patients, measuring relative TL in severely affected and less affected (control) cartilage collected from the same knee. Cartilage TLs were compared to leukocyte TLs in all 57 patients. A significant sex-by-disease-status interaction was found in regard to relative TL. Controlling for age, the average difference of leukocyte TL between female OA patients versus female controls was 0.217 units greater than that between male OA patients versus male controls (95% CI; [0.014, 0.421]). Relative TL comparison of severely and less affected cartilage samples from the same joint showed attrition of telomeres corresponding to disease severity (0.345 mean TL difference with 95% CI of [0.151, 0.539]) in the joint. We also noted that both severely and less affected cartilage had shorter telomeres than leukocytes collected from the same patient. Severe and moderate pain in OA patients was associated with shorter TL in leukocytes, but there was no association with depression or smoking in leukocytes and cartilage. Our study indicates that sex is an important factor in OA contributing to leukocyte and cartilage TL and that pain in OA shows an inverse association only with leukocyte TL.

Decreased toll-like receptor 4 and CD11b/CD18 expression on peripheral monocytes of hypertensive patients correlates with a lesser extent of endothelial damage: a preliminary study.

BACKGROUND: Low-grade chronic inflammation is recognized to contribute to the physiopathology of arterial hypertension. Therefore, this study aimed to assess the pro-inflammatory phenotype of peripheral monocytes of hypertensive patients by analyzing Toll-like receptor 4 (TLR4) and CD11b/CD18 surface expression. In the second part, the influence of phenotypic alterations of monocytes on the endothelial status reflected by circulating endothelial cells (CECs) was evaluated. PATIENTS: The study included 60 patients with arterial hypertension, who were divided into two subgroups based on the disease severity according to the applicable criteria. The mild hypertension and resistant hypertension groups included 30 patients each. The control group consisted of 33 normotensive volunteers matched for age and sex. RESULTS: Both in the entire group of patients and individual subgroups, reduced surface expression of TLR4 and CD11b/CD18 was found compared to normotensive volunteers. A reduced percentage of monocytes with the CD14 + TLR4 + immunophenotype was correlated with a lower MFI level of CD18 and CD11b in the entire group of patients and after division only in the mild hypertension group. Reduced surface expression of TLR4 in hypertensive patients correlated with a lower number of CECs. This relationship was not observed in the resistant hypertension group; instead, an independent effect of reduced CD11b/CD18 expression on the reduction of CEC number was demonstrated. CONCLUSION: Our preliminary study showed for the first time that hypertension of varying severity is accompanied by phenotypic changes in monocytes, manifested by reduced surface expression of both TLR4 and CD11b/CD18. These phenotypic changes were associated with a reduced degree of endothelial injury. Our study opens a new, unexplored area of research on the protective features of peripheral monocytes in hypertension.

The Diagnostic Value of Trace Metal Concentrations in Hair in Carotid Artery Disease.

Several studies showed the role of trace elements in the increase in human susceptibility to cardiovascular diseases. Carotid artery stenosis is a leading cause of ischemic neurological events. We aimed to analyze the potential role of trace elements in hair as biomarkers of atherosclerotic carotid artery disease. Materials and Methods: Fifty-seven (n = 31 (54%) men and n = 26 (46%) women) individuals with a mean age of 67.7 ± 7.7 years who were white, European, non-Hispanic, and non-Latino were diagnosed and treated in hypertensiology/internal medicine and surgical departments over three consecutive months. Of these patients, forty were diagnosed with advanced carotid artery disease, and seventeen comprised a group of healthy controls. Inflammatory and oncological diseases were exclusion criteria. Hair samples were collected, and 14 trace elements were analyzed. Clinical and laboratory data were compared and revealed differences in the co-existence of diabetes (p = 0.036) and smoking history (p = 0.041). In the multivariable analysis, zinc, chrome, and copper revealed predictive value for the occurrence of carotid artery disease, and their combined receiver operating curve showed area under the curve of 0.935, with a sensitivity of 95% and a specificity of 82.4%. Conclusion: Our report shows the significance of trace elements analyses in patients with advanced carotid artery disease. We revealed that zinc, copper, and chrome concentrations are of particular importance in differentiating atherosclerotic disease and may serve as biomarkers of carotid atherosclerosis. Hair samples represent an easily obtained and beneficial biomatrix for the assessment of biomarkers.

Visual outcomes in carotid stenosis patients treated using endarterectomy.

IntroductionCarotid arthrosclerosis can be a cause of visual impairment. It has been observed that carotid endarterectomy has a positive effect on ophthalmic parameters. The aim of this study was to evaluate the impact of endarterectomy on the optic nerve function.Materials and methods54 asymptomatic patients (19 women and 35 men - 108 eyes) with unilateral carotid stenosis >70% of internal carotid artery, were recruited to the study. All of them were qualified for the endarterectomy procedure. The whole study group underwent Doppler ultrasonography of internal carotid arteries and ophthalmic examination before the surgery, with 22 of them (11 women and 11 men) were examined after the endarterectomy. The ophthalmic examination included; distant best-corrected visual acuity, measurement of the intraocular pressure, electrophysiology (pattern visual evoked potentials), perimetry, and optical coherent tomography (the retinal nerve fiber layer thickness).DiscussionCarotid arteries supply brain and face with blood. Extensive research has observed a concomitant improvement in eyesight after enduring carotid endarterectomy in patients with artery stenosis. This effect was associated with a better blood flow in the ophthalmic artery and its branches, the central retinal artery and the ciliary artery; the major blood supply of the eye.ResultsThe present study proved that carotid endarterectomy has a positive impact on the function of the optic nerve. The visual field parameters and amplitude of pattern visual evoked potentials significantly improved. Preoperative and postoperative values of intraocular pressure and the retinal nerve fiber layer thickness remained stable.

The Potential Role of Circulating Endothelial Cells and Endothelial Progenitor Cells in the Prediction of Left Ventricular Hypertrophy in Hypertensive Patients.

BACKGROUND: The main aim of present study is to evaluate the potential role of circulating endothelial cells (CECs) and endothelial progenitor cells (CEPCs) - representing specific markers of endothelial damage, in the prediction of left ventricular hypertrophy (LVH) in hypertensive patients categorized into two groups; mild (MH) and resistant hypertension (RH). MATERIALS AND METHODS: Thirty patients with MH and 28 subjects with RH were involved in the study. In both groups, patients were divided into an LVH and non-LVH group. The control group included 33 age and sex-matched normotensive volunteers. Physical examination, laboratory tests and echocardiography were conducted. RESULTS: In both the MH and RH group, patients with as well as without LVH demonstrated a higher number of CECs and a lower ratio of CEPCs/CECs as compared to the healthy control. Multiple linear regression analysis showed a positive association of CEPCs with left ventricular mass (LVM) and left ventricular mass index (LVMI), independently of other confounders. CONCLUSION: Our results suggest that endothelial injury observed as an elevated CECs number and its impaired regeneration, reflected by a lowered CEPCs/CECs ratio, precede LVH occurrence and may play a significant role in LVH development regardless of the clinical severity of hypertension. Moreover, independent correlation of CEPCs with echocardiographic (ECG) incidences of LVH suggests their potential use as a screening biomarker to stratify the risk of LVH development.

Association between Advanced Glycation End Products, Soluble RAGE Receptor, and Endothelium Dysfunction, Evaluated by Circulating Endothelial Cells and Endothelial Progenitor Cells in Patients with Mild and Resistant Hypertension.

The aim of the present study was to evaluate advanced glycation end products (AGEs) and soluble form of receptor RAGE (sRAGE) concentrations as well as the AGEs/sRAGE ratio in mild (MH) and resistant (RH) hypertensive patients in comparison with normotensive individuals. We also evaluated the association between AGEs, sRAGE as well as AGEs/sRAGE ratio and circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs). The MH group consisted of 30 patients, whereas 30 patients were classified for the RH group. The control group (C) included 25 normotensive volunteers. AGEs and sRAGE were measured using enzyme-linked-immunosorbent assay (ELISA). The multicolor flow cytometry was used for analysis of CECs and CEPCs. Significantly higher levels of AGEs in RH cohort were observed as compared to C cohort. Furthermore, significantly lower sRAGE levels as well as a higher AGEs/sRAGE ratio were observed between MH and RH cohorts. Significant correlations were found in the MH cohort for sRAGE and CECs, and CEPCs. The elevation of AGEs levels suggests that oxidative modification of proteins occurs in hypertension pathogenesis. The decrease in sRAGE levels and elevation of the AGEs/sRAGE ratio in MH and RH groups may suggest that hypertensive patients are less protected against the side effects of AGEs as a consequence of an insufficient competitive role of sRAGE against the AGEs-RAGE axis. Finally, it may be concluded that the level of AGEs may be an independent predictor of the condition and function of the endothelium. Furthermore, sRAGE may be classified as a potential biomarker of inflammation and endothelium dysfunction.

Obesity and the Risk of Gastrointestinal Cancers.

Obesity is a risk factor for all major gastrointestinal cancers. With the rapid increase in the prevalence of obesity worldwide, this link could lead to an elevated burden of cancers of the digestive system. Currently, three main mechanisms explaining the link between excess adiposity and gastrointestinal cancer risk are being considered, including altered insulin signaling, obesity-associated chronic low-grade inflammation, and altered sex hormone metabolism, although new potential mechanisms emerge. This review is aimed to present our current knowledge on biological mechanisms involved in adiposity-related gastrointestinal carcinogenesis supported by results collected in epidemiological studies.

The endothelial status reflected by circulating endothelial cells, circulating endothelial progenitor cells and soluble thrombomodulin in patients with mild and resistant hypertension.

BACKGROUND: The aim of the present study was to evaluate endothelial status by measuring the concentration of novel markers of endothelial dysfunction (ED): a number of circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs) and their ratio (CEPCs/CECs) as well as a traditional parameter - soluble thrombomodulin (sTM) in patients with resistant (RH) and mild hypertension (MH). MATERIALS AND METHODS: Thirty patients with MH and thirty subjects with RH were involved in the study. The control group included thirty-three age and sex-matched normotensive volunteers. We used multicolor flow cytometry for CECs and CEPCs analysis and the commercial human sTM ELISA kit to measure plasma sTM concentration. RESULTS: An elevated CECs number and a decreased CEPCs/CECs ratio was found in MH as well as in RH patients in comparison with normotensive volunteers. CECs correlated positively with an increased triglycerides in MH patients and an elevated LDL-cholesterol and hsCRP in RH group. Positive correlation between CEPCs and LDL-cholesterol level was observed in both types of hypertension. CONCLUSIONS: The results of the present study suggest that an endothelial alteration accompanies hypertension. The number of CECs reflecting the extent of endothelial damage does not appear to be related to the severity of disease. The drastically decreased ratio between CEPCs and CECs observed in both groups of patients suggests an inadequate process of endothelial regeneration. Among analyzed factors inflammation and lipid abnormalities may have significant contribution in endothelial pathology in hypertension.

Comprehensive review on how platinum- and taxane-based chemotherapy of ovarian cancer affects biology of normal cells.

One of the most neglected aspects of chemotherapy are changes, and possible consequences of these changes, that occur in normal somatic cells. In this review, we summarize effects of selected drugs used to treat ovarian cancer (platin derivatives-cisplatin and carboplatin; and taxanes-paclitaxel and docetaxel) on cellular metabolism, acquisition of reactive stroma features, cellular senescence, inflammatory reactions, apoptosis, autophagy, mitophagy, oxidative stress, DNA damage, and angiogenesis in various types of normal cells, including fibroblasts, epithelial cells, endothelial cells, and neurons. The activity of these drugs against the normal cells is presented from a broader perspective of their desirable anti-tumoral effects.

Obesity and inflammation.

The prevalence of obesity has recently increased dramatically and has contributed to the increasing prevalence of various pathological conditions, including type 2 diabetes mellitus, nonalcoholic fatty liver disease, asthma, various types of cancer, cardiovascular and neurodegenerative diseases, and others. Accumulating evidence points to localized inflammation in adipose tissue, which, in turn, promotes systemic low-grade inflammation as a primary force contributing to the development of these pathologies. A better understanding of the underlying mechanisms behind obesity-induced adipose tissue inflammation is required to develop effective therapeutic or prophylactic strategies. This review is aimed to present the current knowledge of adipose tissue inflammation associated with obesity.

Does the timing of aspirin administration influence its antiplatelet effect - review of literature on chronotherapy.

This publication is a summary of the multidirectional effects of aspirin and its role in modern medicine. The history of aspirin, or acetylsalicylic acid (ASA), and its use dates back to ancient times, although the substance in its pure form has been produced and sold since 1899. Initially it was used for its antipyretic, analgesic, and anti-inflammatory effects. Over the years many other benefits associated with the administration of ASA have been revealed. The mechanism of aspirin's action was discovered thanks to the British pharmacologist and Nobel Prize winner Sir John Vane. Understanding the effects of acetylsalicylic acid, associated with the inhibition of cyclooxygenase and proinflammatory thromboxane A2 and with increased concentration of vasoprotective, antithrombotic prostacyclin, gave rise to the era of using small "cardiac" doses of ASA in cardiovascular diseases. In addition to the well-researched antiplatelet effect, other properties of ASA have been discovered, such as the non-COX-1 dependent improvement of endothelial function or the hypotensive effect after evening administration. According to the currently available knowledge, it is possible to speak of a pleiotropic effect of ASA and its use in the prevention of cardiovascular diseases, taking into account its anti-aggregation effect, circadian rhythms, and the principles of chronotherapy.

Antiplatelet treatment in the primary prophylaxis of cardiovascular disease in patients with arterial hypertension.

The benefits of using acetylsalicylic acid (ASA) in the primary prophylaxis of cardiovascular diseases may only slightly exceed the risk of serious bleeding. This warrants the search for alternative, safer preparations with antiaggregatory properties, which could be used in patients burdened with cardiovascular risk factors. Antiaggregatory compounds identified in water-soluble tomato extract include nucleosides, flavonoids, and phenolic acids. The action of standardized tomato extract is multidirectional, reversible, and weaker in comparison to ASA. The European Food Safety Authority (EFSA) has approved this preparation as a dietary agent with antiaggregatory properties. The use of standardized tomato extract appears beneficial in arterial hypertension patients with low or moderate cardiovascular risk and in patients in whom good pressure control cannot be achieved.

The influence of adding tomato extract and acetylsalicylic acid to hypotensive therapy on the daily blood pressure profiles of patients with arterial hypertension and high cardiovascular risk.

INTRODUCTION: Arterial hypertension (HT) is one of the most common diseases around the world and constitutes a significant medical, social, and economic problem. Lifestyle changes, including adequate fruit and vegetable consumption, play an important role in controlling blood pressure (BP) and other cardiovascular risk factors. AIM: To compare the influence of adding acetylsalicylic acid (ASA) or standardized tomato extract (STE) to standard hypotensive therapy on the values of arterial pressure and the daily blood pressure profiles of patients with hypertension and high cardiovascular risk. MATERIAL AND METHODS: The study included 65 patients with arterial hypertension and high cardiovascular risk. High-risk patients with primary hypertension were randomly allocated in a blinded fashion to one of two groups (ASA or STE). In each case, two visits were made: the first - before the treatment, and the second - after 4 weeks of treatment. During each visit, the patients underwent a clinical measurement of arterial pressure and an ambulatory blood pressure measurement (ABPM). Blood platelet aggregation was assessed using the VerifyNow analyzer. RESULTS: After 4 weeks of treatment, the blood pressure values during the day (p < 0.001), during the night (p < 0.05), and in 24-h BP profiles (p < 0.01) obtained with ABPM were significantly lower in the STE group in comparison to the ASA group. The addition of STE to standard hypotensive treatment resulted in a favorable increase in the nocturnal fall of diastolic blood pressure (DBP) (by 6.5%) and mean arterial pressure (MAP) (by 3.3%). CONCLUSIONS: The use of STE is significant in HT patients with high total cardiovascular risk; it is associated with better BP control and improvements in the daily BP profile.

Changes in flow-mediated dilatation in patients with femoropopliteal occlusion receiving conservative and invasive treatment.

BACKGROUND: Although the beneficial effect of revascularisation on reduction of local clinical ischaemic symptoms has been well established, its effect on systemic vascular endothelial function has not been fully explained yet. AIM: To determine changes in endothelium-dependent flow-mediated dilatation in patients with unilateral femoropopliteal occlusion receiving medical and surgical treatment. METHODS: Seventy-nine patients with symptomatic atherosclerotic ischaemia of lower extremities, treated with endovascular procedures, with femoropopliteal graft, or receiving conservative treatment (21-day controlled treadmill training) were enrolled in the study. Ankle brachial pressure index (ABPI), skin blood flow on the feet, and flow-mediated dilatation (FMD) of brachial arteries were measured in each patient at baseline and after 90 days of follow-up. RESULTS: The ABPI, vasomotion in the myogenic frequency band, and FMD increased significantly in surgical patients. In patients after femoropopliteal bypass a significant increase of vasomotion in the endothelial frequency band was also observed. In patients receiving conservative treatment (treadmill training), vasomotion in the myogenic frequency band increased whereas the FMD remained unchanged. CONCLUSIONS: It seems that surgical treatment may contribute to reducing the risk of cardiovascular complications in patients with advanced peripheral artery disease, as a result of improving the systemic vascular endothelial function. Limiting treatment to just treadmill training increases pain-free walking distance but does not improve systemic vascular endothelial function.

Sulodexide reduces the inflammatory reaction and senescence of endothelial cells in conditions involving chronic venous disease.

BACKGROUND: According to previous studies, sulodexide suppresses intravascular inflammation when used in patients with chronic venous disease (CVD). In the current study, we tested the effect of prolonged in vitro exposure of human venous endothelial cells to the serum from patients with CVD, examining the function of these cells and how it is modified when these cells are simultaneously exposed to sulodexide. METHODS: Human umbilical venous cells (HUVEC) were cultured in standard medium (control), in medium supplemented with 5% serum pooled from CVD patients (CVD-serum) or in medium from CVD patients who were treated with sulodexide (CVD-serum-SUL). The synthesis of interleukin-6 (IL-6), monocyte chemoattractant protein -1(MCP-1) and soluble intercellular adhesion molecule - 1 (s-ICAM-1) were studied at the beginning of incubation and were measured after 9 and 15 days of exposure to the studied media. The concentration of IL-6 after cell stimulation by interleukin -1 (IL-1) was also measured. In a subsequent part of the experiment, the effect of the studied sera on the in vitro replicative ageing of HUVEC was evaluated. A total of 15 passages of the cell culture were performed and both the PDT (population doubling time) and the cell hypertrophy were assessed. RESULTS: The concentrations of Il-6, MCP-1, and ICAM-1 gradually increased in the supernatants containing 5% CVD serum compared with the control medium. In the supernatants obtained after cell incubation with serum from sulodexide treated patients, the increase in concentrations of IL-6, MCP-1 and ICAM-1 was significantly less than the control. Release of IL-6 after stimulation with IL-1 (100 pg/mL) was the highest in the CVD-serum group: 3540±670 pg/105 cells vs. 1850±540 pg/105 cells in the control (P<0.01 vs. CVD-serum) and 2320 ±430 pg/105 cells in CVD-serum-SUL (P<0.02 vs. CVD-serum). PDT was significantly longer in the cells incubated with CVD serum compared with the control group, and PDT was reduced when serum from sulodexide treated patients was used. The cells became senescent in the presence of CVD serum, but the cells obtained from patients at the end of 8 weeks of treatment with sulodexide showed a much weaker inflammatory phenotype than the CVD group. CONCLUSIONS: Chronic in vitro exposure of HUVEC to medium supplemented with CVD patient serum induces an inflammatory phenotype. Sulodexide treatment significantly reduces that effect and slows HUVEC senescence in the milieu of CVD serum.