Usefulness of the Sympto-Thermal Method with Standardized Cervical Mucus Assessment (InVivo Method) for Evaluating the Monthly Cycle in Women with Polycystic Ovary Syndrome (PCOS).

(1) Background: FABMs (fertility awareness-based methods) are methods that rely on the observation of clinical signs related to fertility found in women, the so-called fertility bioindicators. They can be a valuable tool for diagnosing monthly cycle disorders and infertility, for example, among patients with PCOS (polycystic ovary syndrome). Until now, it has been difficult for women with PCOS to use FABM, due to the difficulty of describing fertility bioindicators and their disorders due to the biology of the syndrome. The new InVivo sympto-thermal method with standardized cervical mucus assessment may provide a valuable diagnostic and therapeutic tool for observing the monthly cycle in this group of women. (2) Methods: The monthly cycle was evaluated in a group of 32 women of reproductive age. A total of 108 monthly cycle observation cards were analyzed: 35 monthly cycle cards were collected from 18 women with PCOS, and 73 monthly cycle cards collected from 14 healthy women. In addition, 32 pairs of macroscopic and microscopic images were evaluated: 17 pairs from the study group (four subjects) and 15 pairs from women in the control group (six subjects). (3) Results: We showed that in the group of patients with PCOS, menstruation was longer (p = 0.000814), the number of mucus peaks was statistically higher (p = 0.040747), and the interquartile range (IQR) of the duration of the follicular phase (calculated according to the BBT) was significantly higher (8 days) compared to women in the control group. We also observed that among all the women studied, the microscopic image of cervical mucus correlated with the cycle phase described in the observation card, as determined by reference to the BBT chart, provided that it showed the correct features. (4) Conclusions: Systematic maintenance of monthly cycle observation charts using the InVivo method can be an important supplement to the medical history, as it allows for a thorough assessment of, among others, the timing of monthly bleeding, cervical mucus symptoms, BBT changes, and the duration of the follicular and luteal phases among both healthy and PCOS women.

Effect of F11 Receptor/Junctional Adhesion Molecule-A-derived Peptide on Neointimal Hyperplasia in a Murine Model.

PURPOSE: To determine whether inhibition of the F11 receptor/JAM-A (F11R) using F11R-specific antagonist peptide 4D results in inhibition of smooth muscle cell (SMC) proliferation and migration in vivo, known as neointimal hyperplasia (NIH), using a mouse focal carotid artery stenosis model (FCASM). MATERIALS AND METHODS: The mouse FCASM was chosen to test the hypothesis because the dominant cell type at the site of stenosis is SMC, similar to that in vascular access stenosis. Fourteen C57BL/6 mice underwent left carotid artery (LCA) partial ligation to induce stenosis, followed by daily injection of peptide 4D in 7 mice and saline in the remaining 7 mice, and these mice were observed for 21 days and then euthanized. Bilateral carotid arteries were excised for histologic analysis of the intima and media areas. RESULTS: The mean intimal area was significantly larger in control mice compared with peptide 4D-treated mice (0.031 mm2 [SD ± 0.024] vs 0.0082 mm2 [SD ± 0.0103]; P = .011). The mean intima-to-intima + media area ratio was significantly larger in control mice compared with peptide 4D-treated mice (0.27 [SD ± 0.13] vs 0.089 [SD ± 0.081]; P = .0079). NIH was not observed in the right carotid arteries in both groups. CONCLUSIONS: Peptide 4D, an F11R antagonist, significantly inhibited NIH in C57BL/6 mice in a FCASM.

Nordic Walking training in BungyPump form improves cognitive functions and physical performance and induces changes in amino acids and kynurenine profiles in older adults.

Introduction: Although impacts of physical activity on cognitive functions have been intensively investigated, they are still far from being completely understood. The aim of this study was to evaluate the effect of 12 weeks of the Nordic Walking training with BungyPump resistance poles (NW-RSA) on the amino acid and kynurenine profiles as well as selected myokine/exerkine concentrations, which may modify the interface between physical and cognitive functions. Methods: A group of 32 older adults participated in the study. Before and after the intervention, body composition, cognitive functions, and physical performance were assessed. Blood samples were taken before and 1 h after the first and last sessions of the NW-RSA training, to determine circulating levels of exercise-induced proteins, i.e., brain-derived neurotrophic factor (BDNF), irisin, kynurenine (KYN), metabolites, and amino acids. Results: The NW-RSA training induced a significant improvement in cognitive functions and physical performance as well as a reduction in fat mass (p = 0.05). Changes were accompanied by a decline in resting serum BDNF (p = 0.02) and a slight reduction in irisin concentration (p = 0.08). Still, changes in irisin concentration immediately after the NW-RSA intervention depended on shifts in kynurenine-irisin dropped as kynurenine increased. The kynurenine-to-tryptophan and phenylalanine-to-tyrosine ratios decreased significantly, suggesting their possible involvement in the amelioration of cognitive functions. No changes of glucose homeostasis or lipid profile were found. Shifts in the concentrations of selected amino acids might have covered the increased energy demand in response to the NW-RSA training and contributed to an improvement of physical performance. Conclusion: Regular Nordic Walking training with additional resistance (BungyPump) improved cognitive functions and physical performance. These positive effects were associated with a reduced BDNF concentration and kynurenine-to-tryptophan ratio as well as changes in the amino acid profile.

Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM­A protein.

BACKGROUND: The F11R/JAM-A cell adhesion protein was examined as the therapeutic target in triple negative breast cancer (TNBC) with the use of the peptide antagonist to F11R/JAM-A, that previously inhibited the early stages of breast cancer metastasis in vitro. METHODS: The online in silico analysis was performed by TNMPlot, UALCAN, and KM plotter. The in vitro experiments were performed to verify the effect of peptide 4D (P4D) on human endothelial cell lines EA.hy926 and HMEC-1 as well as on human TNBC cell line MDA-MB-231. The cell morphology upon P4D treatment was verified by light microscopy, while the cell functions were assessed by colony forming assay, MTT cell viability assay, BrdU cell proliferation assay, and Transepithelial/Endothelial Electrical Resistance measurements. The in vivo experiments on 4T1 murine breast cancer model were followed by histopathological analysis and a series of quantitative analyses of murine tissues. RESULTS: By in silico analysis we have found the elevated gene expression in breast cancer with particular emphasis on TNBC. The elevated F11R expression in TNBC was related with poorer survival prognosis. Peptide 4D has altered the morphology and increased the permeability of endothelial monolayers. The colony formation, viability, and proliferation of MDA-MB-231 cells were decreased. P4D inhibited the metastasis in 4T1 breast cancer murine model in a statistically significant manner that was demonstrated by the resampling bootstrap technique. CONCLUSIONS: The P4D peptide antagonist to F11R/JAM-A is able to hinder the metastasis in TNBC. This assumption needs to be confirmed by additional 4T1 mouse model study performed on larger group size, before making the decision on human clinical trials.

Review of Diagnostic Modalities for Adrenal Incidentaloma.

Adrenal incidentalomas are common findings in clinical practice, with a prevalence of up to 4.2% in radiological studies. Due to the large number of focal lesions in the adrenal glands, it can be challenging to make a definitive diagnosis and determine the appropriate management. The purpose of this review is to present current diagnostic modalities used to preoperatively distinguish between adrenocortical adenoma (ACA) and adrenocortical cancer (ACC). Proper management and diagnosis are crucial in avoiding unnecessary adrenalectomies, which occur in over 40% of cases. A literature analysis was conducted to compare ACA and ACC using imaging studies, hormonal evaluation, pathological workup, and liquid biopsy. Before deciding on surgical treatment, the nature of the tumor can be accurately determined using noncontrast CT imaging combined with tumor size and metabolomics. This approach helps to narrow down the group of patients with adrenal tumors who require surgical treatment due to the suspected malignant nature of the lesion.

Immunological and Metabolic Causes of Infertility in Polycystic Ovary Syndrome.

Infertility has been recognized as a civilizational disease. One of the most common causes of infertility is polycystic ovary syndrome (PCOS). Closely interrelated immunometabolic mechanisms underlie the development of this complex syndrome and lead to infertility. The direct cause of infertility in PCOS is ovulation and implantation disorders caused by low-grade inflammation of ovarian tissue and endometrium which, in turn, result from immune and metabolic system disorders. The systemic immune response, in particular the inflammatory response, in conjunction with metabolic disorders, insulin resistance (IR), hyperadrenalism, insufficient secretion of progesterone, and oxidative stress lead not only to cardiovascular diseases, cancer, autoimmunity, and lipid metabolism disorders but also to infertility. Depending on the genetic and environmental conditions as well as certain cultural factors, some diseases may occur immediately, while others may become apparent years after an infertility diagnosis. Each of them alone can be a significant factor contributing to the development of PCOS and infertility. Further research will allow clinical management protocols to be established for PCOS patients experiencing infertility so that a targeted therapy approach can be applied to the factor underlying and driving the "vicious circle" alongside symptomatic treatment and ovulation stimulation. Hence, therapy of fertility for PCOS should be conducted by interdisciplinary teams of specialists as an in-depth understanding of the molecular relationships and clinical implications between the immunological and metabolic factors that trigger reproductive system disorders is necessary to restore the physiology and homeostasis of the body and, thus, fertility, among PCOS patients.

F11R/JAM-A: why do platelets express a molecule which is also present in tight junctions?

F11 receptor (F11R)/Junctional Adhesion Molecule -A (JAM-A) is a transmembrane protein which belongs to the immunoglobulin superfamily of cell adhesion molecules. F11R/JAM-A is present in epithelial cells, endothelial cells, leukocytes, and blood platelets. In epithelial and endothelial cells, it takes part in the formation of tight junctions. In these structures, molecules of F11R/JAM-A located on adjacent cells form homodimers and thus take part in stabilization of cellular layer integrity. In leukocytes, F11R/JAM-A was shown to play role in their transmigration through the vascular wall. Paradoxically, the function of F11R/JAM-A in blood platelets, where it was primarily discovered, is much less understood. It has been proven to regulate downstream signaling of αIIbß3 integrin and to mediate platelet adhesion under static conditions. It was also shown to contribute to transient interactions of platelets with inflamed vascular wall. The review is aimed at summarizing the current state of knowledge of the platelet pool of F11R/JAM-A. The article also presents perspectives of the future research to better understand the role of this protein in hemostasis, thrombosis, and other processes where blood platelets are involved.

The molecule of a complex name F11R/JAM-A is a protein which was primarily discovered on blood platelets. Later, the presence of the same molecule was confirmed on endothelial cells and epithelial cells. From the moment of the discovery, most of the research was focused on the role of this protein in the latter types of cells. It was found to be an important element of so-called tight junctions. These structures are crucial for maintaining of integrity and selective permeability of cellular layers composed of these types of cells. In the following years, the presence of F11R/JAM-A has also been reported on leukocytes. An important role of specific type of leukocytes is their penetration to the sites of inflammation. Interplay of F11R/JAM-A present on endothelium and that on leukocyte is involved in this process. But what about the role of this protein in blood platelets where it was originally discovered? There is limited knowledge regarding this issue. It was found to play a role in the ability of platelets to adhere to a surface under static conditions, but it is not known if the same is true under flow. Is the protein necessary for platelets to aggregate and form thrombus? Genetically engineered mice were created which lack this protein in blood platelets to answer this question. These platelets were abnormally reactive, as it transpired that the protein plays a role of a negative regulator to one of the most important mechanisms, which triggers platelet aggregation. But is this inhibitory function the only task F11R/JAM-A has to fulfil in platelets? Presented review collects all the knowledge regarding this protein in blood platelets and tries to show interesting routes which need exploration.

The role of selected adipokines in tumorigenesis and metabolic disorders in patients with adrenal tumors.

Recently, more and more attention has been directed to the role of adipose tissue and adipocytokines in the pathogenesis of metabolic and inflammatory disorders in humans. Excess fat tissue has also been associated with a higher risk of malignancies. Advances in the research on the role of adipokines in adrenal tumors may elucidate the relationship between various types of adipose tissue (visceral, subcutaneous, and periadrenal) and metabolic disorders observed in hormonally active adrenal tumors, as well as associations with adrenal cortex cancer. In patients with active or cured Cushing syndrome, increased leptin and resistin concentrations as well as release of pro-inflammatory cytokines can be associated with cardiovascular risk. Also, the renin-angiotensin-aldosterone system in patients with primary hyperaldosteronism may affect the metabolic activity of the adipose tissue. Elevated resistin concentrations in this group of patients are associated with morphological changes of the myocardium independently of the effects of the metabolic syndrome. Further, it has been suggested that hypoadiponectinemia comprises an additional factor in the pathogenesis of carbohydrate metabolism disorders and the risk of cardiovascular complications in pheochromocytoma patients. Understanding the mechanisms of action of adipokines may be important in developing prophylactic and therapeutic strategies in hormonally active and malignant tumors of the adrenal glands.

The F11 Receptor (F11R)/Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A) in cancer progression.

The F11 Receptor (F11R), also called Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is a transmembrane glycoprotein of the immunoglobulin superfamily, which is mainly located in epithelial and endothelial cell tight junctions and also expressed on circulating platelets and leukocytes. It participates in the regulation of various biological processes, as diverse as paracellular permeability, tight junction formation and maintenance, leukocyte transendothelial migration, epithelial-to-mesenchymal transition, angiogenesis, reovirus binding, and platelet activation. Dysregulation of F11R/JAM-A may result in pathological consequences and disorders in normal cell function. A growing body of evidence points to its role in carcinogenesis and invasiveness, but its tissue-specific pro- or anti-tumorigenic role remains a debated issue. The following review focuses on the F11R/JAM-A tissue-dependent manner in tumorigenesis and metastasis and also discusses the correlation between poor patient clinical outcomes and its aberrant expression. In the future, it will be required to clarify the signaling pathways that are activated or suppressed via the F11R/JAM-A protein in various cancer types to understand its multiple roles in cancer progression and further use it as a novel direct target for cancer treatment.

Safe treatment with somatostatin analogues in a woman with acromegaly whilst pregnant and lactating.

CONTEXT: Pregnancy in acromegaly is rare, there have been few case reports and series published to date. Also breastfeeding under acromegaly treatment is extremely rare. The late diagnosis of pregnancy in acromegaly will sometimes dictate the treatment and management of the patient. MATERIAL AND METHOD: We present a 32-year-old woman with acromegaly, a late diagnosed pregnancy and a completed fetal organogenesis. Due to the gestation time and bothersome headaches accompanying a pituitary macroadenoma, we decided to continue long lasting somatostatin analogues treatment but with increased injection intervals of 6 weeks. We also continued this treatment during 12 months of breastfeeding. RESULTS: Our treatment did not cause any complication of premature birth or any health problems with the newborn baby. The child has since developed normally up to the age of 5. CONCLUSION: The course of acromegaly disease and the time of pregnancy diagnosis may prompt suitable drug and treatment regimes. We administered effective and safe somatostatin analogues treatment during gestation and breastfeeding which was safe for both mother and baby.

Sclerostin and bone remodeling biomarkers responses to whole-body cryotherapy (- 110 °C) in healthy young men with different physical fitness levels.

We investigated the effects of single and repeated exposures to whole-body cryotherapy on biomarkers of bone remodeling and osteo-immune crosstalk: sclerostin, osteocalcin (OC), C-terminal cross-linked telopeptide of type I collagen (CTx-I), osteoprotegerin (OPG) and free soluble receptor activator for nuclear factor κ B ligand (sRANKL). The study included 22 healthy males, grouped in high physical fitness level (HPhL) and low physical fitness level (LPhL), all undergone 10 consecutive sessions in a cryogenic chamber (- 110 °C). We observed a significant time-effect on sclerostin (p < 0.05), OC (p < 0.01), CTx-I (p < 0.001), OC/CTx-I (p < 0.05), and significant differences in sRANKL between the groups (p < 0.05) after the 1st cryostimulation; a significant time-effect on OC (p < 0.001) and OC/CTx-I (p < 0.001) after the 10th cryostimulation, and a significant time-effect on CTx-I (p < 0.001) and OC/CTx-I (p < 0.01) after 10 sessions of WBC. In conclusion, in young men, the first exposure to extreme cold induced significant changes in serum sclerostin. The changes in sRANKL, between groups, suggest that fitness level may modify the body's response to cold. The effects of the first stimulus and the whole session are not identical, probably due to the physiological development of habituation to cold.

Short-Term Resistance Training Supported by Whole-Body Cryostimulation Induced a Decrease in Myostatin Concentration and an Increase in Isokinetic Muscle Strength.

The study aimed to determine whether combining cryostimulation with resistance training would effectively increase muscle strength, and if so, whether this adaptation would be related to changes in circulating levels of exerkines (i.e., mediators of systemic adaptation to exercise). Twenty-five students completed 12 sessions of resistance training, each followed by either cryostimulation (n = 15, 3 min exposure at -110 °C) or passive recovery (n = 10). Prior to and post this intervention, participants performed two eccentric cycling bouts (before and after training). At these points, serum concentrations of muscle damage marker (myoglobin), exerkines (interleukin 6 (IL-6), interleukin 15 (IL-15), irisin, brain-derived neurotrophic factor), hypertrophy-related factors (myostatin, insulin-like growth factor 1), and muscle strength were measured. The applied procedure reduced the physiological burden of the second eccentric cycling bout and myoglobin concentrations only in the group subject to cryostimulation. The same group also exhibited decreased levels of myostatin (from 4.7 ± 1.7 to 3.8 ± 1.8 ng·mL-1, p < 0.05). A significant and large interaction between the group × time was noted in IL-15 concentration (p = 0.01, ηp2=0.27). Training and cryostimulation induced a positive and likely significant improvement of isokinetic muscle strength. Altogether, obtained results support the claim that resistance training combined with cold exposure modified muscle strength through modulation of myostatin and IL-15 concentrations.

In vivo data: treatment with the F11R/JAM-A peptide 4D decreases mortality and reduces the generation of atherosclerotic plaques in ApoE-deficient mice.

The data in this article focus on the F11 Receptor (F11R/JAM-A; Junctional Adhesion Molecule-A; JAM-A, F11R), a cell adhesion protein constitutively expressed on the membrane surface of circulating platelets and localized within the tight junctions of healthy endothelial cells (ECs). Previous reports have shown that F11R/JAM-A plays a critical role in the adhesion of platelets to an inflamed endothelium due to its' pathological expression on the luminal surface of the cytokine-inflamed endothelium. Since platelet adhesion to an inflamed endothelium is an early step in the development of atherosclerotic plaque formation, and with time, resulting in heart attacks and stroke, we conducted a long-term, study utilizing the atherosclerosis-prone ApoE -/- mice to attempt a blockade of the formation of atherosclerotic plaques by preventing the adhesion of platelets to the inflamed vasculature in vivo. Utilizing a nonhydrolyzable peptide derived from an amino acid sequence of F11R/JAM-A, peptide 4D, we have shown in culture that the adhesion of platelets to the inflamed endothelial cells could be blocked by peptide 4D. The present data demonstrate the positive health benefits of chronic peptide 4D administration to the atherosclerosis-prone ApoE-/- mice, and provides new information for potential use of this F11R derived peptide in the prevention of atherosclerosis. The data presented in this article provide further experimental support for the study presented in Babinska et al., Atherosclerosis 284 (2019) 92-101.

Functional inhibition of F11 receptor (F11R/junctional adhesion molecule-A/JAM-A) activity by a F11R-derived peptide in breast cancer and its microenvironment.

PURPOSE: To examine the involvement of the F11R/JAM-A protein in breast cancer metastasis, we utilized the F11R/JAM-A antagonistic peptide 4D (P4D) in experiments of transendothelial migration (TEM) of breast cancer cells. METHODS: Experiments were conducted in the mouse 4T1 breast cancer model utilizing the human mammary epithelial cell and endothelial cell lines. The levels of soluble F11R/JAM-A (sJAM-A) in the murine plasmas were measured by ELISA. Levels of F11R/JAM-A mRNA and protein in cell lines were assessed by qRT-PCR and Western blot, respectively. Cell surface expression of F11R/JAM-A was demonstrated by flow cytometry. Functional tests included the TEM of breast cancer cells and adhesion of breast cancer cells to the endothelium. The endothelial permeability was studied by fluorescent tracer assay and by the Real-Time Cell Analysis (RTCA). RESULTS: The tumor inducers Tß4 and TGF-ß1 reduced the levels of sJAM-A in murine plasma, and reduced the F11R/JAM-A protein levels in the human microvascular endothelial cell line HMEC-1. The adhesion and TEM measured between breast cancer cells and inflamed or Tß4-treated endothelium were inhibited by P4D. The presence of P4D did not destabilize the pre-existing tight junctions in the endothelial monolayer. The barrier-protecting effect of P4D was stronger than that of forskolin, when a booster dose of P4D was applied to the inflamed endothelium. CONCLUSIONS: F11R/JAM-A protein can be considered as a novel target in the treatment of breast cancer metastasis. In vivo and clinical studies are needed to further investigate the effectiveness of F11R/JAM-A-derived peptide as a possible anti-metastatic drug.

Selected adipocytokines in patients with an incidentally discovered pheochromocytoma.

BACKGROUND: Adipose tissue secretes many adipokines and cytokines, which may be an additional risk factor of cardiovascular and metabolic diseases in patients with an incidentally discovered pheochromocytoma (PHEO). The aim of the study was to investigate levels of selected adipocytokines in these patients. METHODS: This prospective study included 12 patients with an incidentally discovered PHEO and 18 healthy participants. In all participants plasma/serum concentrations of triglycerides, HDL and LDL cholesterol, insulin, glucose, adipocytokines (adiponectin, leptin, resistin, TNFα, IL6, and MCP1) were determined, hormonal tests were performed in patients. RESULTS: Patients and controls did not differ significantly in terms of age, sex, and body mass index. Among incidentally discovered PHEO patients, adiponectin levels were lower, while TNFα concentrations higher than in controls. Concentrations of adiponectin correlated with 24-hour urinary excretion of normetanephrine in women. Significantly higher TNFα concentrations were found in hypertensive than in normotensive PHEO patients as well as in non-diabetic PHEO patients than controls. Further, resistin concentration was higher in PHEO patients with diabetes than in non-diabetic ones (P<0.001). Incidentally discovered PHEO tumor size correlated with leptin and IL6 levels. Adiponectin levels were higher, while TNFα and resistin lower among five patients re-examined after tumor resection. CONCLUSIONS: Among patients with an incidentally discovered pheochromocytoma, lower adiponectin, and higher resistin and TNFα levels may constitute additional factors for HT and DM. In our study, for the first time, correlations between incidentally discovered PHEO tumor size and concentrations of leptin as well as IL6 were found.

Expression of adiponectin receptors 1 and 2 and the leptin receptor in human adrenal tumors.

INTRODUCTION: The role of adipokines in neoplasms not related to obesity is unclear. The presence of adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) as well as the leptin receptor (Ob-R) has been recognized in human adrenal tumors. The authors of the present study were the first to compare the expression of these receptors in histopathologically distinct adrenal tumors. MATERIAL AND METHODS: The study encompassed tissue specimens of 128 patients with adrenal tumors (28 adrenal cortical adenomas (CA), 35 cortical nodular hyperplasia tumors (CNH), 20 cortical carcinomas (CC), 40 pheochromocytomas (PHEO), 5 malignant pheochromocytomas (PHEOM)) operated on at a single clinical center. The expression of the adiponectin receptors AdipoR1 and AdipoR2 as well as the leptin receptor Ob-R was assessed by immunohistochemistry. The results were correlated with body mass index (BMI) and gender of the patients. RESULTS: AdipoR1 expression was significantly higher in cortical cancers (p < 0.001) and pheochromocytomas (p < 0.001) as compared to benign cortical tumors. AdipoR2 expression was significantly higher in cortical carcinomas as compared to cortical adenomas and hyperplasia tumors (p = 0.01), and also significantly higher in pheochromocytomas in comparison to adrenocortical cancers (p = 0.004). Leptin receptor expression was absent or minimal in half of nodular hyperplasia tumors and adrenal cortex adenomas. This receptor's expression was significantly higher in adrenocortical cancers (p = 0.038). In pheochromocytomas this receptor was expressed more abundantly than in adrenocortical cancers (p = 0.004). CONCLUSIONS: These novel findings suggest that adiponectin and leptin receptors could play a regulatory role in human adrenal neoplasms.

A peptide antagonist of F11R/JAM-A reduces plaque formation and prolongs survival in an animal model of atherosclerosis.

BACKGROUND AND AIMS: The F11 Receptor (F11R), AKA Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is an adhesion protein constitutively expressed on the membrane surface of circulating platelets and the luminal surface of inflamed endothelial cells (EC). Platelet adhesion to an inflamed endothelium is one of the early steps of atherosclerotic plaque formation. Our previous studies, conducted with cultured EC in vitro, have demonstrated the expression of F11R/JAM-A on the luminal surface of inflamed EC, platelet adhesion to inflamed EC through F11R/JAM-A interactions, and inhibition of this interaction by the presence of F11R/JAM-A antagonistic peptide (F11Rpeptide 4D). In the present study, we examined in vivo the overall health-benefits and cardiovascular effects of long-term treatment of animals prone to atherosclerosis, ApoE-/- mice, with F11R-peptide 4D. METHODS: Twenty ApoE-/- mice were assigned to daily treatment with peptide 4D and compared to their counterparts control untreated mice. Mice were observed for wellness and survival. Plaque size in the aorta and heart was measured using histological analysis. Effects of peptide 4D (or scramble control) on platelet adhesion to inflamed endothelium were measured using intravital microscopy. RESULTS: Significant reductions in atherosclerotic plaques number and size, an overall robust health with longer survival were found in the peptide 4D treated group of ApoE-/- mice. Intravital microscopic studies conducted in exposed vessels of ApoE-/- mice demonstrated significant inhibition by peptide 4D of platelet adhesion to the cytokine-inflamed endothelium. CONCLUSIONS: Our results demonstrate that peptide 4D significantly reduces atherosclerotic plaque formation in ApoE-/- mice and inhibits platelet adhesion to the inflamed arterial endothelium.

IgG4-related disease in endocrine practice.

IgG4-related disease is a set of symptoms resulting from a chronic, usually multiple organ inflammatory condition which affects various organs. It consists of lymphoplasmacytic infiltrations with attendant fibrosis and deep vein thrombosis. Frequently observed tissue lesions are accompanied by elevated IgG4 levels in serum. The etiopathogenesis of the lesions is of multifactor character and the clinical manifestation of the disease is highly diverse. The diagnostic process is based on the patient's medical history, clinical examination and additional tests, including a histopathological examination of the infected organ's tissues. Almost forty different locations of the disease have been reported, including disorders of the endocrine system. IgG4-related endocrinopathies are quite rare. However, it is likely that the diagnosis is under-reported due to lack of awareness of this clinical entity. Despite increasing interest in the subject, there are not enough reliable studies evaluating the link between IgG4-RD and endocrine disorders.

No association between MRI changes in the lumbar spine and intensity of pain, quality of life, depressive and anxiety symptoms in patients with low back pain.

INTRODUCTION: The association between changes in magnetic resonance imaging (MRI) and clinical symptoms in patients with low back pain (LBP) is unclear. AIM: To evaluate correlations between combined MRI findings of the lumbar spine (LS) and pain intensity, depressive and anxiety symptoms and quality of life in patients with LBP. MATERIAL AND METHODS: 200 subjects (93 men and 107 women; mean age 51.42 ± 13.21 years) with LBP referred for MRI were enrolled in the study. All patients completed the Hospital Anxiety and Depression Scale (HADS), Quality of Life Scales (EQ-5D, EQ-VAS) and the Visual Analogue Scale (VAS). MRI scans were assessed according to a scoring system prepared by the authors, and the total MRI score was calculated. RESULTS: The mean total MRI score was 11.59 ± 6.73 points (range 0-50 points) and was higher in men than in women (p = 0.015). A correlation was observed between total MRI score and age (p < 0.001) and between total MRI score and BMI (p = 0.005). An association was found between total MRI score and EQ-5D (p = 0.012) and HADS-D results (p = 0.003). VAS and HADS-A results did not correlate with MRI score. When multivariate analysis was done, the total MRI score was only significantly related to age and BMI, and association between the total MRI score and EQ-5D or HADS-D results was not confirmed. Decreased quality of life was associated with increased intensity of pain and depressive and anxiety symptoms. CONCLUSIONS: Combined MRI changes in LS do not correlate with pain intensity, depressive and anxiety syndromes or quality of life in patients with LBP.