Early Low-Grade Inflammation Induced by High-Salt Diet in Sprague Dawley Rats Involves Th17/Treg Axis Dysregulation, Vascular Wall Remodeling, and a Shift in the Fatty Acid Profile.

BACKGROUND/AIMS: Unrestricted increased table salt (NaCl) intake is associated with oxidative stress and inflammation, leading to endothelial dysfunction and atherosclerosis. However, data on salt-induced immunomodulatory effects in the earliest phase of salt loading are scarce. METHODS: In the present study, an animal model of short-term salt loading was employed, including male Sprague Dawley rats consuming a high-salt diet (HSD; 4% NaCl) or standard laboratory chow (low-salt; LSD; 0.4% NaCl) during a 7-day period. The contribution of angiotensin II (ANGII) suppression was tested by adding a group of rats on a high-salt diet receiving ANGII infusions. Samples of peripheral blood/mesenteric lymph node leukocytes, brain blood vessels, and serum samples were processed for flow cytometry, quantitative real-time PCR, total proteome analysis, and multiplex immunoassay. RESULTS: Data analysis revealed the up-regulation of Il 6 gene in the microcirculation of high-salt-fed rats, accompanied by an increased serum level of TNF-alpha cytokine. The high-salt diet resulted in increased proportion of serum mono-unsaturated fatty acids and saturated fatty acids, reduced levels of linoleic (C18:2 ω-6) and α-linolenic (C18:3 ω-3) acid, and increased levels of palmitoleic acid (C16:1 ω-7). The high-salt diet had distinct, lymphoid compartment-specific effects on leukocyte subpopulations, which could be attributed to the increased expression of salt-sensitive SGK-1 kinase. Complete proteome analysis revealed high-salt-diet-induced vascular tissue remodeling and perturbations in energy metabolism. Interestingly, many of the observed effects were reversed by ANGII supplementation. CONCLUSION: Low-grade systemic inflammation induced by a HSD could be related to suppressed ANGII levels. The effects of HSD involved changes in Th17 and Treg cell distribution, vascular wall remodeling, and a shift in lipid and arachidonic acid metabolism.

Cross-cultural adaptation and reproducibility of the EPIC-Norfolk food frequency questionnaire in young people living in Croatia.

AIM: To translate and adapt the European Prospective Investigation of Cancer (EPIC)-Norfolk food frequency questionnaire (FFQ) for use in Croatia, and to assess the reliability and reproducibility of the Croatian version of the EPIC-Norfolk FFQ. METHODS: Translation and cross-cultural adaptation were performed according to published recommendations. Reliability was assessed in 140 respondents (61 men; age range 8-40 years) divided into three groups: young adults, pregnant women, and children and adolescents. Reproducibility was assessed in the group of young adults (32/61 men), who completed the questionnaire on two occasions three months apart. RESULTS: The EPIC-Norfolk FFQ showed good reliability (Cronbach alpha=0.874). Most nutrient intakes showed good reproducibility (intraclass correlation coefficient [ICC] between 0.7 and 0.9). Poor reproducibility was observed for alcohol (ICC=0.337), and moderate reproducibility was observed for beta-carotene (ICC=0.692) and total carbohydrates (ICC=0.698). Nutrient intakes measured by FFQ on two occasions did not significantly differ. CONCLUSION: The Croatian version of the EPIC-Norfolk FFQ can be a useful tool for assessing dietary intakes in young people in Croatia and possibly in neighboring countries with similar languages and dietary habits.

Penoscrotal Edema as a Rare Complication of Acute Pancreatitis: A Case Report.

Background and Objectives: Scrotal swelling or hydrocele is a rare complication of acute pancreatitis described in the literature. We present a case of penoscrotal swelling caused by the first attack of acute interstitial edematous alcohol-induced pancreatitis in a young male patient. Case report: A 22-year-old man was admitted to the emergency unit due to diarrhea and vomiting since morning which was followed by severe abdominal pain. Urgent abdominal multislice CT scan showed steatosis, pancreatic swelling and acute peripancreatic fluid collection (interstitial edematous pancreatitis). Also, scan showed fluid between small bowel loops and along the anterior renal fascia, while there was minimal amount of fluid in the Douglas space. There was no sign of penoscrotal swelling. On the second day of admission, the patient developed left scrotal swelling and mild pain without erythema. On the fourth day, a control CT scan showed progression to moderately severe pancreatitis (CT severity index 4). Dilated scrotal veins of the pampiniform venous plexus with an increased caliber of the testicular veins were present on both sides, from the scrotum to the level of the inguinal canal. Penoscrotal swelling was significantly reduced on discharge. Conclusions: Penoscrotal swelling is a rare complication or manifestation of acute inflammation of the pancreas. It is important to identify scrotal swelling caused by pancreatitis because in severe cases it can be related to possible infertility in the future.

Tff3-/- Knock-Out Mice with Altered Lipid Metabolism Exhibit a Lower Level of Inflammation following the Dietary Intake of Sodium Chloride for One Week.

A high salt intake causes hemodynamic changes and promotes immune response through cell activation and cytokine production, leading to pro-inflammatory conditions. Transgenic Tff3-/- knock-out mice (TFF3ko) (n = 20) and wild-type mice (WT) (n = 20) were each divided into the (1) low-salt (LS) group and (2) high-salt (HS) group. Ten-week-old animals were fed with standard rodent chow (0.4% NaCl) (LS) or food containing 4% NaCl (HS) for one week (7 days). Inflammatory parameters from the sera were measured by Luminex assay. The integrin expression and rates of T cell subsets of interest from the peripheral blood leukocytes (PBLs) and mesenteric lymph nodes (MLNs) were measured using flow cytometry. There was a significant increase in high-sensitivity C reactive protein (hsCRP) only in the WT mice following the HS diet, while there were no significant changes in the serum levels of IFN-γ, TNF-α, IL-2, IL-4, or IL-6 as a response to treatment in either study groups. The rates of CD4+CD25+ T cells from MLNs decreased, while CD3+γδTCR+ from peripheral blood increased following the HS diet only in TFF3ko. γδTCR expressing T cell rates decreased in WT following the HS diet. The CD49d/VLA-4 expression decreased in the peripheral blood leukocytes in both groups following the HS diet. CD11a/LFA-1 expression significantly increased only in the peripheral blood Ly6C-CD11ahigh monocytes in WT mice following salt loading. In conclusion, salt-loading in knock-out mice caused a lower level of inflammatory response compared with their control WT mice due to gene depletion.

The effect of n-3 polyunsaturated fatty acids-enriched hen eggs consumption on IgG and total plasma protein N-glycosylation in healthy individuals and cardiovascular patients.

This study determined the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs)-enriched hen eggs consumption on immunoglobulin G (IgG) and total plasma protein N-glycan profiles and inflammatory biomarkers level in healthy individuals (N = 33) and cardiovascular (CV) patients (N = 21). Subjects were divided to Control-Healthy and Control-CV subgroups [consumed three regular hens' eggs/daily (249 mg n-3 PUFAs/day)], and n-3 PUFAs-Healthy and n-3 PUFAs-CV subgroups [consumed three n-3 PUFAs-enriched hen eggs/daily (1053 mg n-3 PUFAs/day)] for 3 weeks. Serum-free fatty acids profile and high-sensitivity C-reactive protein, interleukin 6 and 10 (IL-6, IL-10) and tumor necrosis factor alpha were measured. Total plasma protein and IgG N-glycome have been profiled before and after dietary protocols. Serum n-3 PUFAs concentration significantly increased following n-3 PUFAs hen eggs consumption in both n-3 PUFAs-Healthy and n-3 PUFAs-CV. IL-10 significantly increased in both Healthy subgroups, whereas no change occurred in CV subgroups. Derived IgG N-glycan traits: bisecting N-acetylglucosamine (B) significantly decreased in n-3 PUFAs-Healthy, whereas agalactosylation (G0) and core fucosylation (CF) significantly increased in Control-Healthy. Derived total plasma protein N-glycan traits: high branching glycans, trigalactosylation, tetragalactosylation, trisialylation, tetrasialylation and antennary fucosylation significantly decreased, whereas G0, monogalactosylation (G1), neutral glycans (S0), B, CF and oligomannose structures significantly increased in n-3 PUFAs-CV. Digalactosylation significantly decreased, and G0, G1, S0, disialylation, B and CF significantly increased in Control-CV. n-3 PUFAs consumption alters IgG N-glycan traits and IL-10 in healthy individuals, and total plasma protein N-glycan traits in CV patients, by shifting them toward less inflammatory N-glycosylation profile.

Angiotensin II type 1 receptor is involved in flow-induced vasomotor responses of isolated middle cerebral arteries: role of oxidative stress.

This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague-Dawley rats. Eleven-week old, healthy male Sprague-Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilation was compared with control group. Nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) and cyclooxygenase inhibitor indomethacin (Indo) significantly reduced FID in control group. The attenuated FID in losartan group was further reduced by Indo only at Δ100 mmHg, whereas l-NAME had no effect. In losartan group, Tempol (a superoxide scavenger) restored dilatation, whereas Tempol + l-NAME together significantly reduced FID compared with restored dilatation with Tempol alone. Direct fluorescence measurements of NO and reactive oxygen species (ROS) production in MCA, in no-flow conditions revealed significantly reduced vascular NO levels with AT1R blockade compared with control group, whereas in flow condition increased the NO and ROS production in losartan group and had no effect in the control group. In losartan group, Tempol decreased ROS production in both no-flow and flow conditions. AT1R blockade elicited increased serum concentrations of ANG II, 8-iso-PGF2α, and TBARS, and decreased antioxidant enzyme activity (SOD and CAT). These results suggest that in small isolated cerebral arteries: 1) AT1 receptor maintains dilations in physiological conditions; 2) AT1R blockade leads to increased vascular and systemic oxidative stress, which underlies impaired FID.NEW & NOTEWORTHY The AT1R blockade impaired the endothelium-dependent, both flow- and acetylcholine-induced dilations of MCA by decreasing vascular NO production and increasing the level of vascular and systemic oxidative stress, whereas it mildly influenced the vascular wall inflammatory phenotype, but had no effect on the systemic inflammatory response. Our data provide functional and molecular evidence for an important role of AT1 receptor activation in physiological conditions, suggesting that AT1 receptors have multiple biological functions.

Adherence to Maastricht V/Florence consensus report for the management of Helicobacter pylori infection among primary care physicians and medical students in Croatia: A cross-sectional study.

BACKGROUND: Helicobacter pylori (H pylori) eradication is becoming increasingly difficult. The aim of our study was to determine the knowledge of current guidelines and attitude in the diagnosis and treatment of H pylori infection in primary care physicians (PCPs) and medical students in Croatia. MATERIALS AND METHODS: A study was conducted among PCPs and medical students to evaluate adherence to Maastricht V consensus guidelines. Questionnaire was distributed by e-mail to 2338 PCPs offices in Croatia and to the medical students from the University of Split School of Medicine. Responses were collected electronically from June 22 to August 22, 2020. RESULTS: Two hundred forty-nine PCPs and 169 medical students were included in the study. Bismuth or non-bismuth-based quadruple therapy as first-line treatment for H pylori was the choice of 4.8% of PCPs and 13% of students, while 66.3% PCPs and 79.9% students would choose clarithromycin-based triple therapy. Bismuth-based quadruple therapy was the most preferred second line of treatment for 45.4% of PCPs and 34.9% of students. Only 2.8% PCPs and 7.1% of students would correctly recommend first and second line of treatment for H. pylori infection. A larger proportion of students than PCPs would prefer C13-urea breath test (50.3% vs 6.4%). Only 59.0% PCPs would treat for H pylori in all patients including the asymptomatic ones. Students more frequently recognized the link between H pylori and gastric cancer compared with PCPs (92.9% vs 73.5%). CONCLUSIONS: Primary care physicians and medical students' knowledge of H pylori guidelines are insufficient in Croatia and ask for additional training.

Which factors influence liver stiffness measured by real-time two dimensional shear wave elastography in patients on maintenance hemodialysis?

AIM: To evaluate liver stiffness (LS) by real-time two-dimensional shear wave elastography (RT 2D-SWE) and to assess its correlation with the mean arterial pressure (MAP) in patients on maintenance hemodialysis (MHD). The secondary aim was to identify biological and biochemical parameters associated with elevated LS. METHODS: This study enrolled patients treated with MHD in the Split University Hospital from December 2017 through February 2018. LS was measured after a HD session using RT 2D-SWE. Mean arterial pressure was measured before RT-2D-SWE was performed. RESULTS: The study enrolled 47 patients with the mean±standard deviation age of 68.48±14.33 years. Arterial hypertension was diagnosed in 70.2% of patients. Liver stiffness >7 kPa, suggesting clinically relevant fibrosis, was found in 59.5% of patients. Arterial pressure was significantly correlated with LS (ρ=0.38, P=0.008). C-reactive protein (ρ=0.548, P=0.023), parathyroid hormone (ρ=0.507, P=0.038), and total bilirubin (ρ=0.423, P=0.020) were correlated with elevated LS. CONCLUSION: Mean arterial pressure is correlated with increased LS in patients on MHD. Our results emphasize the importance of proper regulation of arterial blood pressure and indicate that LS should always be interpreted in combination with laboratory parameters. Further prospective studies with larger series are needed.

Anti-Inflammatory Potential of n-3 Polyunsaturated Fatty Acids Enriched Hen Eggs Consumption in Improving Microvascular Endothelial Function of Healthy Individuals-Clinical Trial.

The effects of consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) enriched hen eggs on endothelium-dependent and endothelium-independent vasodilation in microcirculation, and on endothelial activation and inflammation were determined in young healthy individuals. Control group (N = 21) ate three regular hen eggs/daily (249 mg n-3 PUFAs/day), and n-3 PUFAs group (N = 19) ate three n-3 PUFAs enriched hen eggs/daily (1053 g n-3 PUFAs/day) for 3 weeks. Skin microvascular blood flow in response to iontophoresis of acetylcholine (AChID; endothelium-dependent) and sodium nitroprusside (SNPID; endothelium-independent) was assessed by laser Doppler flowmetry. Blood pressure (BP), body composition, body fluid status, serum lipid and free fatty acids profile, and inflammatory and endothelial activation markers were measured before and after respective dietary protocol. Results: Serum n-3 PUFAs concentration significantly increased, AChID significantly improved, and SNPID remained unchanged in n-3 PUFAs group, while none was changed in Control group. Interferon-γ (pro-inflammatory) significantly decreased and interleukin-10 (anti-inflammatory) significantly increased in n-3 PUFAs. BP, fat free mass, and total body water significantly decreased, while fat mass, interleukin-17A (pro-inflammatory), interleukin-10 and vascular endothelial growth factor A significantly increased in the Control group. Other measured parameters remained unchanged in both groups. Favorable anti-inflammatory properties of n-3 PUFAs consumption potentially contribute to the improvement of microvascular endothelium-dependent vasodilation in healthy individuals.

Impact of High Salt Diet on Cerebral Vascular Function and Stroke in Tff3-/-/C57BL/6N Knockout and WT (C57BL/6N) Control Mice.

High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to various physiological stimuli, some of which are mediated by arachidonic acid (AA) metabolites. Transgenic Tff3-/- gene knockout mice (Tff3-/-/C57BL/6N) have changes in lipid metabolism which may affect vascular function and outcomes of stroke. We aimed to study the effects of one week of HS diet (4% NaCl) on vascular function and stroke induced by transient occlusion of middle cerebral artery in Tff3-/- and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in Tff3-/--HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in Tff3-/- mice on both diets and WT-HS mice. HS intake and Tff3 gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of Tff3 gene deficiency on HS diet-induced changes in neuronal structural proteins and acute innate immune response proteins' expression and Tff3 depletion, but HS diet did not increase the stroke volume, which is related to proteome modification and upregulation of genes involved mainly in cellular antioxidative defense. In conclusion, Tff3 depletion seems to partially impair vascular function and worsen the outcomes of stroke, which is moderately affected by HS diet.

High salt intake shifts the mechanisms of flow-induced dilation in the middle cerebral arteries of Sprague-Dawley rats.

The goal of the present study was to examine the effect of 1 wk of high salt (HS) intake and the role of oxidative stress in changing the mechanisms of flow-induced dilation (FID) in isolated pressurized middle cerebral arteries of male Sprague-Dawley rats ( n = 15-16 rats/group). Reduced FID in the HS group was restored by intake of the superoxide scavenger tempol (HS + tempol in vivo group). The nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester, cyclooxygenase inhibitor indomethacin, and selective inhibitor of microsomal cytochrome P-450 epoxidase activity N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide significantly reduced FID in the low salt diet-fed group, whereas FID in the HS group was mediated by NO only. Cyclooxygenase-2 mRNA (but not protein) expression was decreased in the HS and HS + tempol in vivo groups. Hypoxia-inducible factor-1α and VEGF protein levels were increased in the HS group but decreased in the HS + tempol in vivo group. Assessment by direct fluorescence of middle cerebral arteries under flow revealed significantly reduced vascular NO levels and increased superoxide/reactive oxygen species levels in the HS group. These results suggest that HS intake impairs FID and changes FID mechanisms to entirely NO dependent, in contrast to the low-salt diet-fed group, where FID is NO, prostanoid, and epoxyeicosatrienoic acid dependent. These changes were accompanied by increased lipid peroxidation products in the plasma of HS diet-fed rats, increased vascular superoxide/reactive oxygen species levels, and decreased NO levels, together with increased expression of hypoxia-inducible factor-1α and VEGF. NEW & NOTEWORTHY High-salt (HS) diet changes the mechanisms of flow-induced dilation in rat middle cerebral arteries from a combination of nitric oxide-, prostanoid-, and epoxyeicosatrienoic acid-dependent mechanisms to, albeit reduced, a solely nitric oxide-dependent dilation. In vivo reactive oxygen species scavenging restores flow-induced dilation in HS diet-fed rats and ameliorates HS-induced increases in the transcription factor hypoxia-inducible factor-1α and expression of its downstream target genes.

Changes in expression of special AT-rich sequence binding protein 1 and phosphatase and tensin homologue in kidneys of diabetic rats during ageing.

Background: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM). We studied the expression of special AT-rich sequence binding protein 1 (SATB1) and phosphatase and tensin homologue (PTEN) in the kidneys of diabetic rats during ageing. Methods: Male Sprague Dawley rats were injected with 55 mg/kg streptozotocin (STZ) (DM group) or with citrate buffer (control group). Kidneys were collected after 2 weeks, 6 months and 12 months, and were analysed in three different kidney structures: glomeruli, proximal (PCT) and distal convoluted tubules (DCT). Sections were stained immunohistochemically, using SATB1 and PTEN. Results: Significant differences in marker expression were observed after 2 weeks, with higher SATB1 expression and lower PTEN expression in diabetic rats. PTEN was more highly expressed in controls after 6 and 12 months. After 12 months, there was higher SATB1 expression in diabetic rats. In the glomeruli, control rats had higher PTEN expression, whereas diabetic rats had higher SATB1 expression, after 12 months. PTEN expression increased from 2 weeks to 12 months in both the PCT and DCT of control rats. SATB1 was expressed exclusively in the PCT of diabetic rats after 2 weeks, and its expression in the DCT was higher in controls. After 6 months, both the PCT and DCT showed higher SATB1 expression in diabetic rats. Conclusions: The major changes in expression of SATB1 and PTEN occur after 2 weeks of DM onset, particularly in the PCT, implying an early onset of pathophysiological changes in diabetic kidneys, which would normally occur with ageing. These findings help to contribute to our understanding of changes associated with DN and guide towards possible appropriate treatment modalities.

Attenuated flow-induced dilatation of middle cerebral arteries is related to increased vascular oxidative stress in rats on a short-term high salt diet.

KEY POINTS: Recent studies have shown that high salt (HS) intake leads to endothelial dysfunction and impaired vascular reactivity in different vascular beds in both animal and human models, due to increased oxidative stress. The objective of this study was to assess vascular response to flow-induced dilatation (FID) and to elucidate the role of vascular oxidative stress/antioxidative capacity in middle cerebral arteries (MCAs) of HS-fed rats in vitro. The novelty of this study is in demonstrating impaired flow-induced dilatation of MCAs and down-regulation of vascular antioxidant genes with HS intake, leading to increased levels of oxidative stress in blood vessels and peripheral lymph organs, which together contribute to impaired FID. In addition, results show increased oxidative stress in leukocytes of peripheral lymph organs, suggesting the occurrence of inflammatory processes due to HS intake. Recirculation of leukocytes might additionally increase vascular oxidative stress in vivo. ABSTRACT: The aim of this study was to determine flow-induced dilatation (FID) and the role of oxidative stress/antioxidative capacity in isolated, pressurized middle cerebral arteries (MCAs) of high salt (HS)-fed rats. Healthy male Sprague-Dawley rats (11 weeks old) were fed low salt (0.4% NaCl; LS group) or high salt (4% NaCl; HS group) diets for 1 week. Reactivity of MCAs in response to stepwise increases in pressure gradient (Δ10-Δ100 mmHg) was determined in the absence or presence of the superoxide dismutase (SOD) mimetic TEMPOL and/or the nitric oxide synthases (NOS) inhibitor N(ω) -nitro-l-arginine methyl ester (l-NAME). mRNA levels of antioxidative enzymes, NAPDH-oxidase components, inducible (iNOS) and endothelial nitric oxide synthases (eNOS) were determined by quantitative real-time PCR. Blood pressure (BP), antioxidant enzymes activity, oxidative stress in peripheral leukocytes, lipid peroxidation products and the antioxidant capacity of plasma were measured for both groups. FID was reduced in the HS group compared to the LS group. The presence of TEMPOL restored dilatation in the HS group, with no effect in the LS group. Expression of glutathione peroxidase 4 (GPx4) and iNOS in the HS group was significantly decreased; oxidative stress was significantly higher in the HS group compared to the LS group. HS intake significantly induced basal reactive oxygen species production in the leukocytes of mesenteric lymph nodes and splenocytes, and intracellular production after stimulation in peripheral lymph nodes. Antioxidant enzyme activity and BP were not affected by HS diet. Low GPx4 expression, increased superoxide production in leukocytes, and decreased iNOS expression are likely to underlie increased oxidative stress and reduced nitric oxide bioavailability, leading to impairment of FID in the HS group without changes in BP values.

The role of cyclo-oxygenase-1 in high-salt diet-induced microvascular dysfunction in humans.

KEY POINTS: Recent studies have shown that some of the deleterious effects of a high-salt (HS) diet are independent of elevated blood pressure and are associated with impaired endothelial function. Increased generation of cyclo-oxygenase (COX-1 and COX-2)-derived vasoconstrictor factors and endothelial activation may contribute to impaired vascular relaxation during HS loading. The present study aimed to assess the regulation of microvascular reactivity and to clarify the role of COX-1 and COX-2 in normotensive subjects on a short-term HS diet. The present study demonstrates the important role of COX-1 derived vasoconstrictor metabolites in regulation of microvascular blood flow during a HS diet. These results help to explain how even short-term HS diets may impact upon microvascular reactivity without changes in blood pressure and suggest that a vasoconstrictor metabolite of COX-1 could play a role in this impaired tissue blood flow. ABSTRACT: The present study aimed to assess the effect of a 1-week high-salt (HS) diet on the role of cyclo-oxygenases (COX-1 and COX-2) and the vasoconstrictor prostaglandins, thromboxane A2 (TXA2 ) and prostaglandin F2α (PGF2α ), on skin microcirculatory blood flow, as well as to detect its effect on markers of endothelial activation such as soluble cell adhesion molecules. Young women (n = 54) were assigned to either the HS diet group (N = 30) (∼14 g day(-1) NaCl ) or low-salt (LS) diet group (N = 24) (<2.3 g day(-1) NaCl ) for 7 days. Post-occlusive reactive hyperaemia (PORH) in the skin microcirculation was assessed by laser Doppler flowmetry. Plasma renin activity, plasma aldosterone, plasma and 24 h urine sodium and potassium, plasma concentrations of TXB2 (stable TXA2 metabolite) and PGF2α , soluble cell adhesion molecules and blood pressure were measured before and after the diet protocols. One HS diet group subset received 100 mg of indomethacin (non-selective COX-1 and COX-2 inhibitor), and another HS group subset received 200 mg of celecoxib (selective COX-2 inhibitor) before repeating laser Doppler flowmetry measurements. Blood pressure was unchanged after the HS diet, although it significantly reduced after the LS diet. Twenty-four hour urinary sodium was increased, and plasma renin activity and plasma aldosterone levels were decreased after the HS diet. The HS diet significantly impaired PORH and increased TXA2 but did not change PGF2α levels. Indomethacin restored microcirculatory blood flow and reduced TXA2 . By contrast, celecoxib decreased TXA2 levels but had no significant effects on blood flow. Restoration of of PORH by indomethacin during a HS diet suggests an important role of COX-1 derived vasoconstrictor metabolites in the regulation of microvascular blood flow during HS intake.

[LOW SPECIFICITY OF PLATELET TO SPLEEN RATIO FOR NONINVASIVE PREDIC- TION AND CHARACTERIZATION OF ESOPHAGEAL VARICES IN PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS]. / OMJER BROJA TROMBOCITA I VELICINE SLEZENE IMA NISKU SPECIFICNOST U NEINVAZIVNOJ PREDIKCIJI I KARAKTERIZACIJI VARIKOZITETA JEDNJAKA KOD BOLESNIKA S ALKOHOLNOM CIROZOM JETRE.

Diagnosis of esophageal varices (EV) is based upon endoscopic examination, which is a rather unpleasant method that carries a certain risk of complications. For that reason, efforts have been made to develop noninvasive methods for characterization of EV. The aim of this study was to explore the value of platelet count to spleen size ratio (PSR) for noninvasive prediction and characterization of EV in patients with alcoholic liver cirrhosis (ALC). One hundred and seventeen patients (20 females and 97 males, mean age 60.7) with ALC were included in our research. All patients underwent endoscopic examination upon which the EV were classified as small (< 5 mm), large (> 5 mm), or absent. Spleen size (bipolar diameter in mm) was assessed by ultrasound. Platelet count to spleen diameter ratio was calculated and the values obtained were compared to the presence, size and risk of bleeding from EV as defined by endoscopy. No significant difference in PSR could be found between patients without and with EV (1.341 ± 0.725 vs. 1.053 ± 0.636, respectively; p = 0.06). The PSR was significantly different between the patients with small and large EV (1.103 ± 0.689 vs. 0.876 ± 0.314; p < 0.05) with a cut-off value of 1.141 (sensitivity 94.7%, specificity 38.2%, AUROC = 0.656; p = 0.042). The value of PSR below 1.182 pointed to patients at risk from variceal bleeding with 91.7% sensitivity and 38.5% specificity (AUROC = 0.625, p = 0.035). Based on our results, it is not possible to recommend the use of PSR as the exclusive noninvasive indicator for the presence, size and bleeding risk from EV due to its low specificity for these categories in patients with ALC.

The Influence of Wound Closure Techniques after Surgical Decompression in Patients with Carpal Tunnel Syndrome on Sleep Disturbance and Life Quality: A Prospective Comparison of Surgical Techniques.

BACKGROUND: The compression of the median nerve within the carpal tunnel is the cause of carpal tunnel syndrome (CTS). Surgical decompression is successful in improving sleep and quality of life, but the effect of tissue adhesives as a material for wound closure has not been investigated. The objective of the study was to evaluate sleep disorders and health-related life quality by comparing two methods for wound closure after carpal surgery in participants who were randomized to receive tissue adhesives or transcutaneous sutures. METHODS: The subjects, aged 61.56 ± 12.03 years, were randomized to receive either tissue adhesives (n = 50) or suture-based wound closure (n = 50) using the Glubran Tiss 2® skin adhesive after subcutaneous running sutures. The outcomes were assessed during the 12-month postoperative follow-up. The Pittsburgh Sleep Quality Index (PQSI) and Insomnia Severity Scale (ISI) were used for the sleep disturbance assessment, and for the health-related quality of life assessment, the total SF-36 (36-Item Short Form Survey) was used. RESULTS: The PQSI, ISI, and SF-36 were not statistically different between groups during the follow-up, except in the ISI score two weeks after surgery (9.40 ± 1.18 in the tissue adhesive group vs. 9.96 ± 1.09 in the suture-based group, p = 0.008). The PQSI, ISI, and SF-36 scores for all the subjects and groups were persistently improved at all the follow-up intervals after surgery. The total SF-36 score increased 12 months after surgery (49.84 ± 5.85 vs. 82.46 ± 5.68, p < 0.001). CONCLUSIONS: Cyanoacrylate-based adhesion material can be used for wound closure after open CTS decompression as a standard transcutaneous suture, and both techniques equally lead to improved sleep and life quality. The possible advantages of tissue adhesives include a faster reduction in the ISI.

The Influence of the Tissue Adhesive Material as a Surgical Wound-Closure Technique Following Carpal Tunnel Decompression on Neurological and Functional Outcomes: A Single-Center Randomized Controlled Trial.

Background Carpal tunnel syndrome (CTS) is caused by compression of the median nerve in the carpal tunnel. The effect of tissue adhesives as a material for wound closure following CTS decompression has been insufficiently investigated. This study aimed to evaluate outcomes by comparing two modalities of wound closure following carpal surgery in patients randomly assigned to either tissue adhesives or sutures. Methodology This randomized, prospective study was conducted in April 2022 at the University Hospital of Split in Croatia. Patients aged 61.56 ± 12.03 years were randomized to either tissue adhesive Glubran Tiss 2®-based (n = 50) or suture-based (n = 50) wound-closure techniques. The following outcomes were assessed before surgery and six months postoperatively: hand strength, electroneurographic characteristics of the median nerve, and the Boston Carpal Tunnel Questionnaire. Results Significant differences between glue-based and suture-based wound-closure techniques were found in the six-month postoperative hand grip strength (25.06 ± 6.69 vs. 21.41 ± 5.62 kg; p = 0.002), postoperative sensory amplitude (10.08 ± 5.50 vs. 7.54 ± 5.41 mV; p = 0.012), and postoperative sensory velocity (42.22 ± 11.04 vs. 35.23 ± 16.40 m/s; p = 0.008). In the glue-based group, significantly more patients achieved a postoperative sensory velocity greater than 45 m/s (47.9% vs. 22.0%; p= 0.006), postoperative distal sensory latency less than 3.5 ms (89.6% vs. 84.0%; p = 0.304), and postoperative motor latency of less than 4.2 ms (60.42% vs. 38.00%; p = 0.022). Conclusions This trial demonstrated that cyanoacrylate-based adhesion material for wound closure after open CTS decompression compared with sutures showed a significant six-month postoperative increment in hand grip strength and median nerve sensory conduction.

Enhancing Endothelial Function with Nutrient-Enriched Table Hen Eggs: A Randomized Study in Patients Recovering from Acute Coronary Syndrome.

Purpose: This study investigated the effect of consumption of table eggs enriched with n-3 polyunsaturated fatty acids (n-3 PUFA), lutein, vitamin E and selenium on microvascular function, oxidative stress and inflammatory mediators in patients after acute coronary syndrome (ACS). Patients and Methods: In a prospective, randomized, interventional, double-blind clinical trial, ACS patients were assigned to either the Nutri4 (N=15, mean age: 57.2 ± 9.2 years), or the Control group (N=13; mean age 56.8 ± 9.6 years). The Nutri4 group consumed three enriched hen eggs daily for three weeks, providing approximately 1.785 mg of vitamin E, 0.330 mg of lutein, 0.054 mg of selenium and 438 mg of n-3 PUFAs. Biochemical parameters, including serum lipids, liver enzymes, nutrient concentrations, serum antioxidant enzyme activity (catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD)), and markers of oxidative stress (thiobarbituric acid reactive substances (TBARS) and ferric reducing ability (FRAP)), were assessed before and after the dietary interventions. Additionally, arterial blood pressure, heart rate, body composition, fluid status, anthropometric measurements, and skin microvascular blood flow responses to various stimuli (postocclusive reactive hyperemia (PORH), acetylcholine- (Ach ID), and sodium nitroprusside- (SNP ID)) were measured using laser Doppler flowmetry (LDF) throughout the study. Results: The intake of Nutri4 eggs led to a significant reduction in LDL cholesterol levels, while the levels of total cholesterol remained within the established reference values. Consuming Nutri4 eggs resulted in a 12.7% increase in serum vitamin E levels, an 8.6% increase in selenium levels, and demonstrated a favorable impact on microvascular reactivity, as evidenced by markedly improved PORH and ACh ID. Nutri4 eggs exerted a significant influence on the activity of GPx and SOD, with no observed changes in TBARS or FRAP values. Conclusion: The consumption of Nutri4 eggs positively influenced microvascular function in individuals with ACS, without eliciting adverse effects on oxidative stress.

Emergency Air Transport of Patients with Acute Chest Pain in the Adriatic Islands of Croatia: A Four-Year Analysis.

BACKGROUND: An efficient first-aid system usually supports ground services with a helicopter emergency medical service (HEMS). An HEMS is important for patients with acute chest pain on remote islands. The current study sought to identify the characteristics of HEMS in acute chest pain cases on the Croatian Adriatic islands over a four-year period. METHODS: We conducted a four-year observational study to investigate HEMS from Adriatic islands. The study population consisted of all patients with acute coronary syndrome or pulmonary embolisms who were urgently transferred by HEMS to the University Hospital in Split 1 June 2018-1 June 2022. RESULTS: During the observation period, 222 adult patients (67 females, or 30.2%) were urgently transferred. The mean age was 71.81 ± 13.42 years. The most common diagnosis was ST-elevated myocardial infarction (113, 50.9%). Most of the HEMS cases were from Hvar (91, 41.0%). The mean call-to-flight time was 19.10 ± 10.94 min, and the total time from call to hospital was 68.50 ± 22.29 min. The total time from call to hospital was significantly correlated with call-to-flight time (r = 0.761, P < 0.001). Of the 222 participants, 5 (2.25%) were transported for more than 120 min, and 35 (15.8%) were transported for more than 90 min. CONCLUSION: This study provided a detailed insight into HEMS in the area of the Croatian Adriatic islands. The average time from the call to the helicopter taking off was 19.10 min. An increase in dispatching time has a significant impact on the prolongation of the total time for the hospital admission. Shortening the response time is critical to reducing hospital arrival time.