Preoperative differentiation between responders and non-responders to ventriculoperitoneal (VP) shunting in the treatment of normal pressure hydrocephalus (NPH) remains a significant challenge. Identifying biomarkers in presurgical assessment represents a promising approach to reducing the need for invasive cerebrospinal fluid CSF testing. In this prospective observational study, thirty adult patients were classified into Group A (responders to VP shunting) and Group B (non-responders) based on their responsiveness to invasive CSF testing. The overall clinical condition and Idiopathic NPH (iNPH) scale were assessed at baseline. Additionally, biomarker levels were compared between the two groups. Elevated levels of Neurofilament Light Chain (NfL) and Neurofilament Heavy Chain (NfH) in CSF and a reduced level of beta-amyloid Aβ42 were observed. No significant differences in biomarker levels were found between groups. Individual biomarkers demonstrated only poor predictive value (AUC = 0.37-0.53). Clinical factors were stronger predictors (AUC = 0.642-0.669), with no improvement when combined with all examined biomarkers (AUC = 0.428-0.431). No single biomarker reliably predicted confirmed postoperative shunt responsiveness among patients who underwent VP shunt placement and demonstrated clinical improvement. Clinical factors were stronger predictors, suggesting that patient history and clinical assessment (e.g., the iNPH scale) provide more reliable diagnostic information. Notably, combining biomarkers with clinical factors did not improve predictive accuracy.
- MeSH
- amyloidní beta-protein mozkomíšní mok MeSH
- biologické markery * mozkomíšní mok MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurofilamentové proteiny mozkomíšní mok MeSH
- normotenzní hydrocefalus * chirurgie mozkomíšní mok diagnóza MeSH
- peptidové fragmenty mozkomíšní mok MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ventrikuloperitoneální zkrat * metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BackgroundThe ischemia-reperfusion injury (IRI) is unavoidable in vascular surgery. Damage to the microcirculation and endothelial glycocalyx might set up a shock with loss of circulatory coherence and organ failure. Sulodexide may help to protect endothelial glycocalyx and alleviate the ischemia-reperfusion injury.MethodsTwenty female piglets underwent surgery with a 30-min-long suprarenal aortic clamp, followed by two hours of reperfusion. Ten piglets received sulodexide before the clamp, and 10 received normal saline. Blood and urine samples were taken at baseline and in 20-min intervals until the 120th minute to analyze the serum syndecan-1, E-selectin, and thrombomodulin. Albumin and glycosaminoglycans were examined in the urine. The kidney biopsies before and after the protocol were examined by light microscopy with hematoxylin-eosin staining. The sublingual microcirculation was recorded by side-stream dark field imaging at the time as blood and urine.ResultsBased on the 2-way ANOVA testing, there was no statistically significant difference in the parameters of sublingual microcirculation. Serum markers of endothelial cell activation and damage (E-selectin and thrombomodulin) did not show any statistically significant difference either. Syndecan-1, a marker of glycocalyx damage, showed statistically significantly higher values based on the 2-way ANOVA testing (p < 0.0001) with the highest difference in the 80th minute: 7.8 (3.9-44) ng/mL in the control group and 1.8 (0.67-2.8) ng/mL in the sulodexide group. In the urine, the albuminuria was higher in the control group, although not statistically significant. Glycosaminoglycans were statistically significantly higher in the sulodexide group based on the mixed-effect analysis due to the intervention itself. Histological analysis of the renal biopsies showed necrosis in both groups after reperfusion.ConclusionAdministering sulodexide significantly reduced the level of endothelial markers of IRI. The study results support further research into using preemptive administration of sulodexide to modulate IRI in clinical medicine.
- MeSH
- E-selektin krev MeSH
- glykokalyx MeSH
- glykosaminoglykany * farmakologie terapeutické užití MeSH
- ledviny patologie krevní zásobení MeSH
- mikrocirkulace účinky léků MeSH
- modely nemocí na zvířatech MeSH
- prasata MeSH
- reperfuzní poškození * prevence a kontrola MeSH
- syndekan-1 krev MeSH
- trombomodulin krev MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BackgroundSulodexide is a glycosaminoglycan-based drug prescribed to patients with angiopathy. We performed a pilot study to investigate whether sulodexide positively modulates the endothelial glycocalyx (EG) layer and the microcirculation in a porcine model of EG enzymatic damage. The EG is a sugar-based endothelial lining that is involved in the physiology of the capillary wall and the pathogenesis of many diseases.MethodsEG damage was induced in eight piglets by hyaluronidase III and heparanase I given intravenously. Four animals received sulodexide 600 IU intravenously before the enzymes and four animals after the enzymes were administered. Four animals constituted a control group. Sublingual microcirculation by side-stream dark field imaging and plasmatic concentration of syndecan-1 by ELISA were measured at baseline, 20 min after intervention, and at the 40th, and 60th minute onwards. The statistics were performed with a one-way ANOVA test with Turkey's correction for multiple comparisons testing. Timepoint comparison was performed by Student t-test or Mann-Whitney test.ResultsAt baseline, there were no statistically significant differences between the animal groups. After the intervention, the levels of syndecan-1 were significantly lower in the control group. While there were no differences between the two intervention groups. The sublingual microcirculation analysis showed that the DeBacker score was significantly higher in the control group. At 60 min, there was also a statistically significant difference in DeBacker score between the groups (8.1 ± 1.6 mm-1 in the group with enzymes given first and 11 ± 0.92 mm-1 in the group with sulodexide given first, p = 0.03). The analysis of the proportion of perused vessels did not show any statistically significant differences.ConclusionThe results of the study demonstrated a working model of EG damage but no specific action of sulodexide on EG modulation. In the sublingual microcirculation analysis, the sulodexide reduced the fall in absolute tissue perfusion in 60 min.
- MeSH
- cévní endotel * účinky léků MeSH
- glykokalyx * účinky léků metabolismus MeSH
- glykosaminoglykany * farmakologie MeSH
- hyaluronoglukosaminidasa MeSH
- mikrocirkulace účinky léků MeSH
- modely nemocí na zvířatech MeSH
- pilotní projekty MeSH
- prasata MeSH
- syndekan-1 krev MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The process of kidney transplantation remains the optimal treatment for end-stage renal disease, offering improved quality of life and increased survival rates compared to long-term dialysis. However, despite advances in surgical techniques, immunosuppression regimens, and post-operative care, there are still significant challenges in predicting the organ's status and long-term outcomes of transplantation. Among the many factors that influence graft survival, the quality of the donated organ plays a fundamental role. There is an ongoing need for accurate and reliable biomarkers. Syndecan-1 is found in the endothelial glycocalyx and shed at a higher rate into the blood during systemic pathological conditions. The aim of this study is to evaluate the potential of serum syndecan-1 levels as a biomarker for assessing donor kidney quality and to investigate its correlation with donor characteristics and short-term outcomes in kidney recipients. MATERIAL AND METHODS: We investigated serum syndecan-1 levels in 80 deceased donors and correlated them with donor characteristics and short-term outcomes (defined as delayed graft function - defined as the need for dialysis within the first week post-transplantation and renal function at 3 months post-transplantation - assessed using serum creatinine levels) in 104 corresponding kidney recipients. This single-center retrospective observational cohort study was conducted from April to December 2021. RESULTS: The donor pool consisted of 65% males with a median age of 53 years. Of these, 45 donors (56%) were classified as extended criteria donors. Higher syndecan-1 levels correlated with the last creatinine levels before organ procurement (R = 0.32, p = 0.01) and were marginally higher in donors with acute kidney injury (p = 0.07). However, syndecan-1 levels were not associated with short-term outcomes in kidney recipients (renal function at 3 months). CONCLUSIONS: The data suggests syndecan-1 could be a potential biomarker for assessing donor kidney quality, although its implications on recipient outcomes require further study. This pilot investigation underscores the importance of syndecan-1 in evaluating organ quality but highlights the necessity for more extensive research to validate these findings and explore their implications in transplant success.
- MeSH
- biologické markery * krev MeSH
- chronické selhání ledvin chirurgie krev terapie MeSH
- dárci tkání * MeSH
- dospělí MeSH
- ledviny patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- opožděný nástup funkce štěpu krev MeSH
- přežívání štěpu MeSH
- retrospektivní studie MeSH
- syndekan-1 * krev MeSH
- transplantace ledvin * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space. OBJECTIVE: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats. METHODS: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blue + hyaluronidase, or (3) Evans blue + hyaluronidase + 20% human albumin via the tail vein. Spectrophotometric analysis was performed 2 h later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle. RESULTS: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (P < 0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (P < 0.011). CONCLUSION: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.
- MeSH
- albuminy * metabolismus MeSH
- cévní endotel účinky léků metabolismus MeSH
- Evansova modř MeSH
- glykokalyx * metabolismus účinky léků MeSH
- hyaluronoglukosaminidasa farmakologie MeSH
- kapilární permeabilita * účinky léků MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Indoxyl sulfát (IS) vzniká v organismu degradací z aminokyseliny tryptofanu obsaženého ve stravě. Ten se dostává jako součást reziduálního proteinu do tlustého střeva, kde je účinkem gastrointestinálních bakterií přeměněn na indol a následně vstřebán do krevního oběhu. V játrech poté dochází k enzymatické hydroxylaci a konverzi indolu na IS. Fyziologicky je IS vylučován močí – tubulární sekrecí a jeho sérová koncentrace je < 5,4 μmol/L. Jako uremický toxin, který je z 90 % vázaný na proteiny, je velmi těžko odstranitelný dialyzačními technikami. U pacientů s poškozenou funkcí ledvin dochází k akumulaci IS, což negativně ovlivňuje celý organismus, např. způsobuje progresi kardiovaskulárních onemocnění a stimuluje oxidační stres. Cílem studie bylo potvrdit spojitost mezi koncentrací IS a rychlostí katabolismu proteinů za využití predialyzační a postdialyzační koncentrace močoviny, a tudíž možnost ovlivnit koncentraci IS vhodnou dietou. Typ studie: Monocentrická prospektivní otevřená kohortní studie byla provedena na 108 pacientech podstupujících dialyzační léčbu na Nefrologické klinice Fakultní nemocnice Hradec Králové. Výsledky: Byl potvrzen pozitivní vliv reziduální diurézy na snížení hladin IS (p=0,005), u anurických pacientů je koncentrace IS 160,4 μmol/L (122,6; 200,5), zatímco u oligourických pacientů 124,6 μmol/L (98,7; 168,1). Dále byla nalezena korelace mezi rostoucím příjmem bílkovin ve stravě a vzrůstající koncentrací IS (p=0,040). Závěr: Vhodná personalizovaná úprava složení diety při zachování potřebného příjmu proteinů by mohla vést ke snížení sérové koncentrace IS u těchto pacientů.
Indoxyl sulfate (IS) is produced in the body by degradation from the amino acid tryptophan contained in the diet. It reaches the large intestine as part of the residual protein, where it is converted into indole by the action of gastrointestinal bacteria and subsequently absorbed into the bloodstream. Enzymatic hydroxylation and conversion of indole to IS then occurs in the liver. Physiologically, IS is excreted in the urine - tubular secretion, and its serum concentration is <5.4 μmol/L. As a uremic toxin that is 90% protein bound, it is very difficult to remove by dialysis techniques. IS accumulates in patients with impaired kidney function, which negatively affects the entire organism, e.g. causes progression of cardiovascular diseases and stimulates oxidative stress. The aim of the study was to confirm the connection between the concentration of IS and the speed of protein catabolism using the predialysis and postdialysis concentration of urea and, therefore, the possibility of influencing the concentration of IS with a suitable diet. Type of study: A monocentric prospective open cohort study was conducted on 108 patients undergoing dialysis treatment at the Nephrology Clinic of the Hradec Králové University Hospital. Results: A positive effect of residual diuresis on the reduction of IS levels was confirmed (p=0.005), in anuric patients the concentration of IS is 160.4 μmol/L (122.6; 200.5), while in oligouric patients it is 124.6 μmol/L (98.7; 168.1). Furthermore, a correlation was found between increasing protein intake in the diet and increasing IS rate (p=0.040). Conclusion: An appropriate personalized adjustment of the diet composition while maintaining the necessary protein intake would lead to a decrease in the serum concentration of IS in these patients.
INTRODUCTION: High indoxyl sulfate (IS) concentration is a serious problem for patients with CKD increasing the risk of cardiovascular diseases and CKD progression. Thus, the methods of decreasing the toxin concentrations are highly desired. The study aimed to discover the role of selected intestine-related factors on IS concentration. METHODS: We evaluated the impact of ABCG2 and ABCC2 polymorphisms influencing activity and protein intake by normalized protein catabolic rate. Additionally, we examined the relation of IS and uric acid (UA) that can share common elimination transporters. A monocentric, prospective, open cohort pilot study was performed on 108 patients undergoing dialysis treatment. RESULTS: The positive effect of residual diuresis on the reduction of IS levels was confirmed (p = 0.005). Also, an increase in IS depending on the dietary protein intake was confirmed (p = 0.040). No significant correlation between ABC gene polymorphisms was observed either, suggesting the negligible role of ABCG2 and ABCC2 in the elimination of IS in small bowel. The significant difference was observed for UA where ABCG2 421C>A (rs72552713) gene polymorphism was higher (505.3 μmol/L) in comparison with a wild-type genotype (360.5 μmol/L). CONCLUSION: No evidence of bowel elimination pathway via ABCC2 and ABCG2 transporters was found in renal replacement therapy patients.
Objective: The implementation of nutritional support is a basic need of patients in palliative oncological care. This pilot study optimized the use of sipping to improve the nutritional status of cancer patients in palliative care. Materials and Method: The pilot study included 63 patients, 61.3 years of age on average (range: 32-82 years of age). The patients were assigned to either group A (no nutritional support n = 39 patients) or group B (sipping as nutritional support n = 24 patients). The patients were evaluated through by noninvasive methods: body weight, waist and arm circumference, and triceps skinfold, bioimpedance analysis, and dynamometry. Quality of life was assessed through modified questionnaires. Results: In contrast with group A, group B did not have a significant weight loss, that is, A: 81.9 ± 15.8-80.5 ± 15.8 kg (P = .028) and B: 73.9 ± 14.9-73 ± 16 kg. Body mass index A: 29 ± 5-28.5 ± 5 kg/m2 (P = .007) and B: 25.3 ± 4.7-25 ± 4.9 kg/m2 (P = .614). Waist circumference A: 93.5 ± 15.1-92.5 ± 14.8 cm (P = .008) and B: 80.1 ± 13.2-80.6 ± 12.3 cm (P = .234). Triceps skinfold A: 12.3 ± 7.2-11 ± 6.7 mm (P = .001) and B: 8.2 ± 6.1-7.9 ± 5.7 mm (P = .207). Fat free mass A: 54.8 ± 11.5-52.8 ± 11.6 kg (P = .018) and B: 54.7 ± 10.9-52.8 ± 11.5 kg (P = .207). Significantly lower dynamometer values were recorded in both groups; A: 25.6 ± 10.4-23.1 ± 10.3 kg (P = .010) and B: 27.4 ± 9.9-24.3 ± 9.1 kg (P = .009). In contrast to group B, the patients in group A showed slight variations in their health status, thus decreasing their scores into the significance limit (P = .072). Conclusion: Our results suggest that providing nutritional support in the form of sipping (∼12 g proteins, 300 kcal) on a daily basis prevents the loss of active tissue mass in palliative oncology patients. Based on these results, we recommend the inclusion of this simple nutritional support to prevent malnutrition in cancer patients in palliative care. The clinical study was registered by the internal ethics committee under the heading of its approval - Institutional Ethics Committee of the Hradec Králové Faculty Hospital, number 201311S2OP.
- MeSH
- dospělí MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory * terapie MeSH
- nutriční stav MeSH
- paliativní péče * MeSH
- pilotní projekty MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
