Effects of Long-Term High-Fat Diet and Its Reversal on Lipids and Lipoproteins Composition in Thoracic Duct Lymph in Pigs.

BACKGROUND This study was carried out to evaluate the effects of a long-term high-fat diet on lipids and lipoproteins composition in thoracic duct lymph in pigs. MATERIAL AND METHODS We examined lymph taken from the thoracic duct from 24 female white sharp-ear pigs, divided into 3 experimental groups fed different diets for 12 months: (a) the control group, fed the standard balanced diet; (b) the HFD group, fed an unbalanced, high-fat diet, and (c) the reversal diet group (RD), fed an unbalanced, high-fat diet for 9 months and then a standard balanced diet for 3 months. RESULTS Lymph analysis after 12 months of fixed diets revealed significantly higher concentration of proteins in the HFD group in comparison to the control and RD groups. Examination of lymph lipoproteins fractions showed that the high-fat diet in the HFD group in comparison to control group caused an increase in cholesterol, phospholipids, and proteins content within HDL and chylomicrons. There were also more proteins within HDL in the HFD group in comparison to the RD group and more triglycerides within chylomicrons in the HFD group in comparison to the control group. CONCLUSIONS A long-term high-fat diet resulted in changed structure of HDL and chylomicrons in the thoracic duct lymph. Alterations in HDL composition suggest that a high-fat diet enhances reverses cholesterol transport. Changes in chylomicrons structure show the adaptation to more intense transport of dietary fat from the intestine to the liver under the influence of a high-fat diet. Reversal to a standard balanced diet had the opposite effects.

Assessment of nutritional status on the basis of the mini nutritional assessment (MNA) questionnaire in patients on the internal medicine ward

Background: The inadequate nutritional status of hospitalized patients leading to the malnutrition is one of the crucial clinical problems. Objective: The aim of the study was to assess nutritional status of patients on the basis of the mini nutritional assessment (MNA) questionnaire. Material and Methods: The study group included 120 patients staying on the internal medicine ward. The average age for female and male was 65±9.7 and 63±8.4 years, respectively. To assess malnutrition the anthropometric measurements and the MNA questionnaire was conducted. Results: The average MIS (Malnutrition Indicator Score) value in female and male was 25.0 ± 3.0. Among 29% of women and 18.2% of men the risk of malnutrition occurrence was noted. The incorrect values of BMI (body mass index) were observed more frequently in male compared to female (84.0% vs. 67.0%). Incorrect values of the MAC (mid arm circumference) and CC (calf circumference) were found respectively in 6.6 % and 10.5% of female and in 2.3% of male. 55.3% of women and 75% of men declared taking more than 3 prescription drugs a day. In women were observed a significantly higher deficiency of dairy products, meat, fish, or poultry as well as meals containing legume plants or eggs per week compared to men (21.0% vs. 4.5%). An insufficient daily intake of vegetables was declared by 20.4% of men and 15.8% of women. Conclusions: The occurrence of malnutrition or its risk was observed in about a quarter of studied hospitalized patients. The malnutrition was worsened by a reported loss of appetite, a significant number of drugs being taken, and inadequate nutrition among the patients.

A novel mass spectrometry-based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l-arginine and l-citrulline optimized for LC-MS-TOF and LC-MS/MS.

Nitric oxide (NO) is a regulatory molecule involved in many biological processes. NO is produced by nitric oxide synthase by conversion of l-arginine to l-citrulline. l-Arginine methylated derivatives, asymmetric and symmetric dimethylarginines (asymmetric dimethylarginine, ADMA, and symmetric dimethylarginine, SDMA), regulate l-arginine availability and the activity of nitric oxide synthase. As such, they have been frequently investigated as potential biomarkers in pathologies associated with dysfunctions in NO synthesis. Here, we present a new multistep analytical methodology based on liquid chromatography combined with mass spectrometry for the accurate identification of l-arginine, l-citrulline, ADMA and SDMA. Compounds are measured as stable 2,3,4,5,6-pentafluorobenzoyl chloride derivatives, which allows for simultaneous analysis of all compounds through chromatographic separation of ADMA and SDMA using a reverse-phase column. Serum aliquots (100 µL) were spiked with isotope-labeled internal standards and sodium carbonate buffer. The derivatization process was carried out at 25°C for 10 minu using pentafluorobenzoyl chloride as derivatization reagent. Calibration demonstrated good linearity (R2 = 0.9966-0.9986) for all derivatized compounds. Good accuracy (94.67-99.91%) and precision (1.92-11.8%) were observed for the quality control samples. The applicability of the method was evaluated in a cohort of angiological patients and healthy volunteers. The method discerned significantly lower l-arginine and l-citrulline in angiologic patients. This robust and fast LC-ESI-MS method may be a useful tool in quantitative analysis of l-arginine, ADMA, SDMA and l-citrulline.

Frequency of the use of biological treatment of patients with rheumatoid arthritis and ankylosing spondylitis in Lower Silesia.

BACKGROUND: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic connective tissue diseases. Inadequate treatment of RA and AS results in health failure, disability and premature death. In recent years, development of immunology and genetic engineering techniques has started a new generation of drugs in the treatment of RA and AS, called biologic response modifiers or biologics. It is a very effective therapy of serious RA and AS. In many cases, they represent the only way to improve the quality of life, slowing or even arresting the development of these diseases. According to national statistics, the percentage of patients with rheumatic diseases treated with biologic treatment in Poland is less than 1.5%, and it is much lower than in Western European countries (20%). PURPOSE: The aim of the study was to evaluate the use of biological treatment in Lower Silesia in patients with RA and AS in the years 2006-2015, based on data obtained from the Lower Silesian Branch of the Polish National Health Fund. RESULTS AND CONCLUSIONS: In the last 10 years the frequency of biological treatment of RA or AS in Lower Silesia was estimated as 2.06% of patients (in 2011) to 6.03% of patients (during the first 8 months of 2015). Biological treatment is more often used in Lower Silesia in comparison to national statistics and ranks at a similar level as in other countries of Central and Eastern Europe.

Disability and emotional symptoms in women with lipedema: A comparison with overweight/obese women.

BACKGROUND: Lipedema is characterized by the painful abnormal deposition of adipose tissue in the lower limbs and is often misdiagnosed as obesity. Considering the numerous bothersome physical symptoms of lipedema, women with lipedema may have greater disability and emotional problems than women with lifestyle-induced obesity. OBJECTIVES: Our study aims to assess disability, anxiety and depression symptoms in women with lipedema compared to women with overweight/obesity. MATERIAL AND METHODS: Women with lipedema (n = 45, with a mean age of 41 years) and women who are overweight/obese (n = 43, with a mean age of 44.95 years) were asked to complete the following questionnaires: The World Health Organization Disability Assessment Schedule (WHO-DAS II), Beck's Depression Inventory - II (BDI-II), and The Hospital Anxiety and Depression Scale (HADS). RESULTS: Despite the higher BMI in the overweight/obesity group, the group with lipedema was more disabled in numerous domains of the WHO-DAS II questionnaire, including Life activities - domestic, work and school responsibilities and Participation in society When the influence of BMI was adjusted, a difference in the domain of Mobility was also present. The study groups did not differ in anxiety and depression symptoms. CONCLUSIONS: We showed that behavioral impairment was the main factor affecting functioning in women with lipedema. Emotional symptoms did not differentiate the study groups. Leg volumes and adipose tissue pain intensity were associated with greater disability in women with lipedema, and should be considered in managing women with this condition and in future research estimating the effectiveness of lipedema treatment.

Association between skin lymphangiogenesis parameters and arterial hypertension status in patients: An observational study.

BACKGROUND: Recent studies have indicated that the skin lymphatic system and interstitium may play a role in the pathophysiology of arterial hypertension (AH). OBJECTIVES: We aimed to determine whether the set of pathway parameters described previously in rodents would allow for the distinction between hypertensive and normotensive patients. MATERIAL AND METHODS: Molecular and histopathological parameters from the skin and blood of patients with AH (AH group, n = 53), resistant AH (RAH group, n = 32) and control (C group, n = 45) were used, and a statistical multivariate bootstrap methodology combining partial least squares-discriminant analysis (PLS-DA) and selectivity ratio (SR) were applied. RESULTS: The C vs RAH model presented the best prediction performance (AUC test = 0.90) and had a sensitivity and specificity of 73.68% and 83.33%, respectively. However, the parameters selected for the C vs AH group model were the most important for the pathway described in the rodent model, i.e., greater density of the skin lymphatic vessels (D2-40 expression) and greater number of macrophages (CD68 expression), higher expression of the messenger ribonucleic acid (mRNA) of nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGFC) and podoplanin (PDPN) in the skin, greater concentration of hyaluronic acid (HA) in the skin, and lower serum concentration of VEGF-C. CONCLUSIONS: Our study suggests that the NFAT5/VEGF-C/lymphangiogenesis pathway, previously described in rodent studies, may also be present in human HA. Further experiments are needed to confirm our findings.

[Lymphatic endothelium]. / Sródblonek naczyn limfatycznych.

Compared to the knowledge about the structure and function of endothelial cells of blood vessels, which was heavily developed over the past few decades, advance in the knowledge of lymphatic endothelial cells (LECs) for many years has been impossible, because of the lack of specific methods that allow histological visualization of lymphatic vessels in the tissues. The last years have brought significant progress in this field. Identification of specific markers of LECs and the development of new experimental animal models have allowed to recognize a number of antigens and growth factors of LECs and to isolate pure LECs populations. Studies indicate heterogeneity and plasticity of LECs and their active participation in the extracellular homeostasis, lipid transport, immune response and in the pathophysiology of acute and chronic inflammatory diseases, graft rejection and cancer. The article presents the current knowledge on the importance and regulation of LECs, both in health and disease.

The Lymphatic System In The Brain Clearance Mechanisms - New Therapeutic Perspectives For Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Pathological deposits of neurotoxic proteins within the brain, such as amyloid-ß and hyperphosphorylated tau tangles, are the prominent features in AD. According to recent studies, the newly discovered brain lymphatic system was demonstrated to be crucial in the clearance of metabolic macromolecules from the brain. Meningeal lymphatic vessels located in the dura mater drain the fluid, macromolecules, and immune cells from cerebrospinal fluid (CSF) and transport them, as lymph, to the deep cervical lymph nodes. The lymphatic system provides the perivascular exchange of CSF with interstitial fluid (ISF) and ensures the homeostasis of neuronal interstitial space. In this review, we aim to summarize recent findings on the role of the lymphatic system in AD pathophysiology and discuss possible therapeutic perspectives, targeting the lymphatic clearance mechanisms within the brain.

The Effect of a Low-Carbohydrate High-Fat Diet on Laboratory Parameters in Women with Lipedema in Comparison to Overweight/Obese Women.

The aim of this study was to evaluate alterations in blood parameters after a low-carbohydrate high-fat (LCHF) diet in women with lipedema in comparison to overweight or obese women. A total of 115 women were classified into two groups: the lipedema group and the overweight/obesity group. Both study groups followed the caloric-restricted LCHF diet for 7 months. A total of 48 women completed the study. A reduction in body weight was observed in both study groups. A significant decrease in triglycerides and an increase in HDL-C concentrations were observed in both study groups. Despite the increase in the concentration of LDL-C observed in the lipedema group, changes in LDL-C differed between individual patients. Improvements in liver parameters, glucose tolerance, and a decrease in fasting insulin levels were observed, although they were less pronounced in the lipedema group than in the overweight/obesity group. Kidney and thyroid functions were similar before and after the LCHF diet in both groups. The LCHF diet may be a valuable nutritional strategy for lipedema and overweight/obese women, with a beneficial effect on weight, glucose profile, liver function, the concentration of triglycerides, and HDL-C and with no effect on kidney and thyroid function.

Lymphoscintigraphic alterations in lower limbs in women with lipedema in comparison to women with overweight/obesity.

Introduction: Lipedema is a bilateral enlargement of the legs due to abnormal depositions of subcutaneous fat. Recent studies using lymphoscintigraphy documented that lipedema associates with lymphatic alterations. It is still not known, whether non-lipedema obesity also leads to similar lymphoscintigraphic changes within lower legs. Clinically, both, lipedema and obesity may progress to secondary lymphedema. The aim of the study was to evaluate lymphoscintigraphy of lower limbs in women with lipedema in comparison to overweight/obese women. Methods: 51 women (in the mean age of 43.3 ± 13.56) with the diagnosis of lipedema and 31 women (in the mean age of 44.7 ± 13.48) with overweight/obesity were enrolled into the study. Women in both study groups had no clinical signs of lymphedema. The groups were matched by mean volume of their legs, calculated using the formula for a truncated cone. Lymphoscintigraphy was evaluated in every women qualitatively. Body composition parameters were assessed using bioelectric impedance analysis (BIA). Results: Lymphoscintigraphic alterations within lower extremities were similar in both, lipedema and overweight/obese groups and were present in majority of women in both study groups. The most common lymphoscintigraphic alteration in both groups were additional lymphatic vessels (in the lipedema group observed in 76.5% of patients and in the overweight/obesity group - in 93.5%). Visualization of popliteal lymph nodes and dermal backflow were observed respectively in 33% and in 5.9% in the group with lipedema and in 45.2% and in 9.7% in the overweight/obesity group. There were significant relationships between severity of lymphoscintigraphic alterations and weight, lean body mass (LBM), total body water (TBW), volume of both legs and thigh circumference in the lipedema group. Such relationships were absent in the overweight/obesity group. Discussion: Our study indicates that lymphatic alterations are present before development to clinically visible secondary lymphedema in both conditions, lipedema and overweight/obesity. In majority of women from both study groups they indicate rather an overload of the lymphatic system than insufficiency. Lymphoscintigraphic alterations are similar in both groups, therefore, lymphoscintigraphy is not a diagnostic tool that might distinguish lipedema from overweight/obesity.

The Benefits of Low-Carbohydrate, High-Fat (LCHF) Diet on Body Composition, Leg Volume, and Pain in Women with Lipedema.

This study aimed to assess the potential benefits of a low-carbohydrate, high-fat (LCHF) diet on body composition, leg volume, and pain reduction in women with lipedema compared to overweight or women with obesity. The study included 113 female participants, 56 with lipedema and 57 with overweight/obesity (BMI >25 kg/m2) without lipedema. All subjects were prescribed a low-carbohydrate, high-fat (LCHF) diet with anti-inflammatory properties to adhere to for a duration of 7 months. Measurements of anthropometry, body weight, composition, and pain (VAS) were conducted at the study's commencement and conclusion. 52 participants completed the study. Both groups experienced a similar weight reduction, amounting to 12.9% compared to the baseline (-10.8 kg vs. -11.9 kg; p = 0.14, for lipedema and women with overweight/obesity, respectively). The most reduction was in body fat mass. Improvements in various parameters were observed, except for ankle circumferences, which decreased more in the lipedema group. Lipedema participants showed significantly reduced pain levels following the LCHF diet (4.6 ± 2.6 vs 3.0 ± 2.3; p < 0.001). The LCHF diet holds promise for weight loss, body fat reduction, leg volume management, and pain alleviation in women with lipedema. These findings provide valuable insights into potential therapeutic strategies for lipedema management.

Sodium accumulation in the skin is associated with higher density of skin lymphatic vessels in patients with arterial hypertension.

PURPOSE: Recent studies, conducted mainly on the rodent model, have demonstrated that regulatory pathway in the skin provided by glycosaminoglycans, nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGF-C) and process of lymphangiogenesis may play an important role in extrarenal regulation of sodium (Na+) balance, body water volume, and blood pressure. We aimed to investigate the concentrations and relations among the main factors of this pathway in human skin to confirm that this regulatory axis also exists in humans. PATIENTS AND METHODS: Skin specimens from patients diagnosed with arterial hypertension and from control group were histologically and molecularly examined. RESULTS: The primary hypertensive and control groups did not differ in Na+ â€‹concentrations in the skin. However, the patients with hypertension and higher skin Na+ concentration had significantly greater density of skin lymphatic vessels. Higher skin Na+concentration was associated with higher skin water content. In turn, skin water content correlated with factors associated with lymphangiogenesis, i.e. NFAT5, VEGF-C, and podoplanin (PDPN) mRNA expression in the skin. The strong mutual pairwise correlations of the expressions of NFAT5, VEGF-C, vascular endothelial growth factor D (VEGF-D) and PDPN mRNA were noted in the skin in all of the studied groups. CONCLUSIONS: Our study confirms that skin interstitium and the lymphatic system may be important players in the pathophysiology of arterial hypertension in humans. Based on the results of our study and existing literature in this field, we propose the hypothetical model which might explain the phenomenon of salt-sensitivity.

Left ventricular myocardial strain assessed by cardiac magnetic resonance feature tracking in patients with rheumatoid arthritis.

PURPOSE: The aim of the study was to assess a relationship between the occurrence of rheumatoid arthritis (RA) and its selected clinical parameters, and left ventricular myocardial strain. MATERIAL AND METHODS: Fifty-six subjects were qualified for the study: 30 RA patients and 26 subjects without rheumatoid diseases. The study design included taking medical history, assessment of the disease activity using selected scales of activity, collecting samples of venous blood to assess selected laboratory parameters and the assessment of cardiac magnetic resonance (CMR). Using the feature tracking method, the following parameters of the left ventricular myocardial strain were assessed: longitudinal strain (LS), radial strain (RS) and circumferential strain (CS). RESULTS: Regarding global values, peak LS and peak CS were statistically significantly lower in RA patients than in the control group. In the whole study group, the factors independently related to low global LS peaks were as follows: occurrence of RA, occurrence of arterial hypertension, increased activity of antibodies against cyclic citrullinated peptide and increased concentration of neutrophil gelatinase-associated lipocalin. The occurrence of RA, occurrence of diabetes, tobacco smoking, higher activity of antibodies against cyclic citrullinated peptide and current use of methotrexate are the risk factors for low peak of global CS. The current use of steroids constitutes a protecting factor against low global CS peaks. CONCLUSION: In subjects with no clinically manifested cardiac damage, RA is associated with a deteriorated left ventricular systolic function assessed by left ventricular myocardial strain measured by CMR feature tracking.

Selected clinical parameters and changes in cardiac morphology and function assessed by magnetic resonance imaging in patients with rheumatoid arthritis and ankylosing spondylitis without clinically apparent heart disease.

BACKGROUND: The aim of the study was to assess the relationship between the occurrence of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and the cardiac magnetic resonance (CMR) changes in people without clinically overt heart disease. METHODS: The study group consisted of 74 people (48.81 ± 11.35 years): 29 patients with RA, 23 patients with AS and 22 people from control group. Blood samples were taken to assess laboratory parameters, disease activity was determined using activity scales, and CMR was performed. RESULTS: It was shown that the factors independently related to higher left ventricular mass index are AS occurrence, human B27 leukocyte antigen occurrence, higher neutrophil gelatinase-associated lipocalin concentration (NGAL) and higher body mass index (BMI). The lower right ventricular ejection fraction is result of an independent effect of RA, AS and higher NGAL. RA presence, methotrexate use, higher rheumatoid factor titer, higher NGAL, older age and higher BMI should be considered independent risk factors for greater left ventricular myocardium water content. RA occurrence, AS occurrence, type 2 diabetes occurrence and a higher C-reactive protein concentration can be independently associated with a higher probability of non-ischemic left ventricular myocardium injury. Larger pericardial fluid volume is result of an independent effect of higher NGAL, higher anti-cyclic citrullinated peptide antibodies titer and higher DAS28 disease activity index. Use of steroids is protective factor against larger volume of pericardial fluid. CONCLUSIONS: RA and AS in people without clinically apparent heart disease are associated with the occurrence of adverse changes in CMR. Key Points •RA and AS in people without clinically apparent heart disease are associated with the occurrence of adverse changes in CMR.. •The independent risk factors for higher LVEF are AS occurrence, human B27 leukocyte antigen occurrence, higher NGAL concentration and higher BMI.. •RA presence, methotrexate use, higher RF, higher NGAL, older age and higher BMI are independent risk factors for higher LV T2 ratio.. •RA occurrence, AS occurrence, type 2 diabetes occurrence and a higher CRP are independently associated with a higher risk of non-ischemic LV myocardium injury..

Metabolomic profiling reveals plasma GlycA and GlycB as a potential biomarkers for treatment efficiency in rheumatoid arthritis.

In this pilot study, we carried out metabolic profiling of patients with rheumatoid arthritis (RA) starting therapy with biological disease-modifying antirheumatic drugs (bDMARDs). The main aim of the study was to assess the occurring metabolic changes associated with therapy success and metabolic pathways involved. In particular, the potential of the metabolomics profiles was evaluated as therapeutically valuable prognostic indicators of the effectiveness of bDMARD treatment to identify responders versus non-responders prior to implementing treatment. Plasma metabolomic profiles of twenty-five patients with RA prior bDMARD treatment and after three months of therapy were obtained by 1H NMR, liquid chromatography - mass spectrometry, and gas chromatography - mass spectrometry and evaluated by statistical and multivariate analyses. In the group of responders, significant differences in their metabolic patterns were seen after three months of the bDMARD therapy compared with profiles prior to treatment. We identified 24 metabolites that differed significantly between these two-time points mainly belonging to amino acid metabolism, peptides, lipids, cofactors, and vitamins and xenobiotics. Eleven metabolites differentiated responders versus non-responders before treatment. Additionally, N-acetylglucosamine and N-acetylgalactosamine (GlycA) and N-acetylneuraminic acid (GlycB) persisted significant in comparison responders to non-responders after three months of therapy. Moreover, those two metabolites indicated prediction of response potential by results of receiver-operating characteristic (ROC) curve analysis. The applied analysis provides novel insights into the metabolic pathways involved in RA patient's response to bDMARD and therapy effectiveness. GlycA and GlycB are promising biomarkers to identify responding patients prior onset of bDMARD therapy.

Physical and psychological impairments of women with upper limb lymphedema following breast cancer treatment.

OBJECTIVE: The aim of the study was to identify factors associated with worse physical and emotional functioning of breast cancer survivors with upper extremity lymphedema. METHODS: 1250 sets of questionnaires consisting of WHO-DAS II, EORTC QLQ-C30, EORTC QLQ-BR23 and GHQ-30 were mailed to women who underwent a breast cancer surgery at the Lower Silesian Oncology Center in Poland between January 1998 and December 2005. RESULTS AND CONCLUSIONS: The response rate was 33.47%. 117 women were included into a lymphedema group and 211 into a group without this complication. Women with lymphedema were more disabled (overall disability (DAS) score 39.78 versus 34.67; p<0.001), reported symptoms from the upper extremity (shoulder or arm pain and difficulties in arm movement) and from the operated breast (pain and swelling) 2-3 times more often, experienced poorer quality of life (global quality of life (QOL) score 0.50 versus 0.57; p=0.005) and higher psychological distress (GHQ score 10.61 versus 8.01; p=0.007) in comparison to breast cancer survivors without lymphedema. The factors associated with higher DAS score, higher GHQ score and lower QOL score in women with lymphedema were as following: pain in the upper limb (mainly shoulder and arm), pain in operated breast, difficulties with arm movement, localization of lymphedema within the hand or in operated breast, a history of dermatolymphangitis and of receiving chemotherapy. Severity of lymphedema, younger age, BMI and localization of lymphedema within the dominant limb were not considerably related to worse outcomes in these women.

[Factorial structure of the general health questionnaire (GHQ-30)]. / Struktura czynnikowa Kwestionariusza Ogólnego Zdrowia (GHQ-30).

UNLABELLED: The General Health Questionnaire (GHQ) was designed by Goldberg in the 1970's as a screening instrument to provide information on the mental wellbeing. Although it is widely used as a unidimensional instrument, factor analyses tend to suggest that it contains more than one dimension. AIM: The purpose of this paper is to review the factor-analytic research that has been carried out with regard to the 30-item General Health Questionnaire (GHQ-30) and to present the results of the analysis of our research. MATERIAL AND METHODS: A total of 623 patients suffering from neurotic disorders and somatic illnesses were included into the study, 130 men and 493 women at the age ranged from 17 to 85 years old. A total score was calculated with Likert's method. The principal factor analysis with orthogonal varimax normalised rotation was used. Results. The GHQ-30 was found to have high internal consistency as a scale and high item-total correlations for most of the items. The factorial analysis showed that three factors labelled as the followed can be abstracted from the scale: depression and anxiety, interpersonal relations, general functioning. These factors jointly account for 58% of the variance. CONCLUSIONS: Results showed both multifactorial (at the level of a lower order) and unifactorial (at the level of an upper order) structure of the GHQ-30.

Metabolomics of Interstitial Fluid, Plasma and Urine in Patients with Arterial Hypertension: New Insights into the Underlying Mechanisms.

There is growing evidence that lymphatic system plays a pivotal role in the pathogenesis of hypertension. Here, for the first time, the metabolome of interstitial fluid is analyzed in patients with arterial hypertension. Due to ethical issues to obtain human interstitial fluid samples, this study included only oncological patients after axillary lymph node dissection (ALND). These patients were matched into hypertensive (n = 29) and normotensive (n = 35) groups with similar oncological status. Simultaneous evaluation of interstitial fluid, plasma, and urine was obtained by combining high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy with chemometric analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) provided a clear differentiation between the hypertension and normotensive group, with the discrimination visible in each biofluid. In interstitial fluid nine potential metabolomic biomarkers for hypertension could be identified (creatinine, proline, pyroglutamine, glycine, alanine, 1-methylhistidine, the lysyl group of albumin, threonine, lipids), seven distinct markers in plasma (creatinine, mannose, isobutyrate, glycine, alanine, lactate, acetate, ornithine), and seven respectively in urine (methylmalonate, citrulline, phenylacetylglycine, fumarate, citrate, 1-methylnicotinamide, trans-aconitate). Biomarkers in plasma and urine allowed for the identification of specific biochemical pathways involved in hypertension, as previously suggested. Analysis of the interstitial fluid metabolome provided additional biomarkers compared to plasma or urine. Those biomarkers reflected primarily alterations in the metabolism of lipids and amino acids, and indicated increased levels of oxidative stress/inflammation in patients with hypertension.

[Reverse cholesterol transport processes and their role in artherosclerosis regression]. / Procesy transportu zwrotnego cholesterolu i ich rola w regresji miazdzycy.

Atherosclerosis represents dynamic process with periodic tendency to reverse. Although animal experiments and human studies have provided considerable evidence of atherosclerosis regression, our understanding of this phenomenon remains still incomplete. Atherosclerosis regression depends on removal of cholesterol deposits from atherosclerotic plague in the process of reverse cholesterol transport and possibly other mechanisms including migration of macrophages and foam cells, inhibition of inflammation and endothelial regeneration. Our paper reviews available data on the process of atherosclerosis regression with special attention to the reverse cholesterol transport.

Influence of miR-7a and miR-24-3p on the SOX18 transcript in lung adenocarcinoma.

The molecular pathogenesis of the development of non-small cell lung carcinomas (NSCLCs) is extremely complex. Understanding the molecular basis of the development of this malignant tumor may enable the use of targeted therapy, which may result in a better treatment outome for these patients. Adenocarcinoma (AC) is the most common NSCLC subtype, equally common among smokers and non-smokers, and its pathogenesis remains unknown. The SOX18 protein is an important protein that plays a role in the development of blood and lymphatic vessels during the process of embryogenesis. Recent studies have also shown that the SOX18 protein may play a significant role in tumors, including lung cancers. In the present study, we analyzed the expression of the SOX18 protein and the mRNA level in postoperative samples of AC and non-malignant lung tissues (NMLTs), and a disparity in both levels was observed. Based on our previous observations that miR-7a and miR-24-3p are able to modulate SOX18 expression in NSCLC, the main aim of this study was to verify the miRNA modulation of the SOX18 transcript with the use of the MirTrap System in established lung cancer cell lines NCI-H1703, NCI-H522 and A549. The SOX18 mRNA expression level was significantly lower in AC than that noted in the NMLTs (P<0.0001). However, the protein levels were higher in AC cases compared to levels noted in the NMLTs (P<0.0001). Additionally, correlations between the RQ values of SOX18 in NMLT and AC cases (r=0.8195, P=0.0001), and between miR-7a and miR24-3p in AC cases (r=0.4344, P=0.0016), were noted. In conclusion, we confirmed that miR-7a and miR-24-3p are more highly expressed in NMLTs than in the AC samples, and that they modulate the SOX18 transcript in NSCLC cells.