Some Dietary Phenolic Compounds Can Activate Thyroid Peroxidase and Inhibit Lipoxygenase-Preliminary Study in the Model Systems.

The presented research concerns the triple activity of trans-cinnamic (tCA), ferulic (FA) and syringic acids (SA). They act as thyroid peroxidase (TPO) activators, lipoxygenase (LOX) inhibitors and show antiradical activity. All compounds showed a dose-dependent TPO activatory effect, thus the AC50 value (the concentration resulting in 50% activation) was determined. The tested compounds can be ranked as follows: tCA > FA > SA with AC50 = 0.10, 0.39, 0.69 mM, respectively. Strong synergism was found between FA and SA. The activatory effects of all tested compounds may result from interaction with the TPO allosteric site. It was proposed that conformational change resulting from activator binding to TPO allosteric pocket results from the flexibility of a nearby loop formed by residues Val352-Tyr363. All compounds act as uncompetitive LOX inhibitors. The most effective were tCA and SA, whereas the weakest was FA (IC50 = 0.009 mM and IC50 0.027 mM, respectively). In all cases, an interaction between the inhibitors carboxylic groups and side-chain atoms of Arg102 and Arg139 in an allosteric pocket of LOX was suggested. FA/tCA and FA/SA acted synergistically, whereas tCA/SA demonstrated antagonism. The highest antiradical activity was found in the case of SA (IC50 = 0.22 mM). FA/tCA and tCA/SA acted synergistically, whereas antagonism was found for the SA/FA mixture.

Volatile anesthetics reduce biochemical markers of brain injury and brain magnesium disorders in patients undergoing coronary artery bypass graft surgery.

OBJECTIVES: Neuropsychological disorders are some of the most common complications of coronary artery bypass graft (CABG) surgery. The early diagnosis of postoperative brain damage is difficult and mainly based on the observation of specific brain injury markers. The aim of this study was to analyze the effects of volatile anesthesia (VA) on plasma total and ionized arteriovenous magnesium concentrations in the brain circulation (a-vtMg and a-viMg), plasma matrix metalloproteinase-9 (MMP-9), and glial fibrillary acidic protein (GFAP) in adult patients undergoing CABG surgery. DESIGN: An observational study. SETTING: The Department of Cardiac Surgery in a Medical University Hospital. PATIENTS AND METHODS: Studied parameters were measured during surgery and in the early postoperative period. Patients were assigned to 3 groups: group O, patients who did not receive VA; group ISO, patients who received isoflurane; and group SEV, patients who received sevoflurane. RESULTS: Ninety-two patients were examined. CABG surgery increased MMP-9 and GFAP. The highest MMP-9, GFAP, and the most dramatic disorders in a-vtMg and a-viMg were noted in group O. CONCLUSIONS: Cardiac surgery increased plasma MMP-9 and GFAP concentrations. Changes in MMP-9, GFAP, and arteriovenous tMg and iMg were significantly higher in group O. Volatile anesthetics, such as ISO or SEV, reduced plasma MMP-9, GFAP concentrations, and disturbances in a-vtMg and a-viMg.

Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells.

BACKGROUND: Kynurenic acid (KYNA), a tryptophan metabolite, was found in human saliva, gastric juice, bile, pancreatic juice and mucus of rat small intestine. METHODS: KYNA content in mucus aspirated from human caecum or colon ascendens and KYNA production in colon epithelial and cancer cells were determined using HPLC. Moreover, biological properties of KYNA and kynurenine aminotransferases (KATs) expression in colon epithelial and colon cancer cells were studied. RESULTS: Considerably higher KYNA concentration was detected in samples from patients diagnosed with colon carcinoma (269.40 ± 107.00 pmol/ml, N = 4), Adenoma tubulovillosum (200.50 ± 36.72, N = 10) or Adenoma tubulare (243.50 ± 38.09, N = 9) than in control group (82.22 ± 7.61 pmol/ml, N = 30). Moreover, colon epithelium CCD 841 CoTr cells actively synthesized KYNA in a concentration- and time-dependent manner. This process was decreased by aminooxyacetic acid and L-glutamate in opposite to 4-aminopyridine treatment. Interestingly, KYNA production in colon cancer cells (HT-29 1.39 ± 0.27, LS-180 1.18 ± 0.15 and Caco-2 4.21 ± 0.30 pmol/1 x 10(5) cells/2 h) was considerably higher in comparison to normal colon epithelial cells (0.70 ± 0.07 pmol/1 x 10(5) cells/2 h). However, KATs I and II were expressed at similar level in both colon epithelium and cancer cells. Furthermore, KYNA exerted an antiproliferative effect at higher micro- and millimolar concentrations against colon cancer cells with the IC(50) of 0.9, 0.2 and 1.2 mM for HT-29, LS-180 and Caco-2 cells, respectively. CONCLUSION: Summarizing, this is the first report presenting KYNA synthesis and KAT expression in colon derived normal and cancer cells.

Interobserver and interdisciplinary reproducibility of 3D endovaginal ultrasound assessment of pelvic floor anatomy.

INTRODUCTION AND HYPOTHESIS: the study aims were to evaluate (1) the interobserver and (2) the interdisciplinary repeatability of levator hiatus, urethral thickness, and anorectal angle measurements using three-dimensional endovaginal ultrasound (3D-EVUS). METHODS: twenty-seven nulliparous asymptomatic females were imaged with 3D-EVUS. Analyses were conducted off-line from stored 3D volumes by six readers (two radiologists, two urogynecologists, and two colorectal surgeons) using a standardized technique. Reproducibility was determined using the interclass correlation coefficients (ICC). RESULTS: the overall interobserver repeatability for levator hiatus dimensions was good to excellent (ICC, 0.655-0.889), for urethral thickness was good (ICC, 0.624), and for anorectal angle was moderate (ICC, 0472). The interdisciplinary repeatability for levator hiatus indices was good to excellent (ICC, 0.639-0.915), for urethral thickness was moderate to good (ICC, 0.565-0.671), and for anorectal angle was fair to moderate (ICC, 0.204-0.434). CONCLUSIONS: 3D-EVUS yields reproducible measurements of levator hiatus dimensions and urethral thickness in asymptomatic nulliparous women.

Additional secure circular suture during sphincteroplasty - preliminary results on the efficacy of fecal incontinence surgery in urogynecological patients.

OBJECTIVES: The paper is a ten case series study presenting women with complex pelvic floor disorders involving fecal incontinence (FI) with stress urinary incontinence or pelvic organ prolapse. Our study aimed at ascertaining whether FI-induced sphincteroplasty with an additional secure circular suture around the external anal sphincter muscle (EAS) may improve long term success rates. MATERIALS AND METHODS: Twelve patients had scheduled urogynecological surgery and overlapping sphincteroplasty with the placement of an additional circular suture around the EAS. Of these, the status of ten women was established by way of the Cleveland Clinic Fecal Incontinence Score/Wexner Score before and about 70 months after surgery. RESULTS: Statistical analysis of fecal incontinence score showed that patients were not completely cured from FI, but were significantly better (p = 0.011). CONCLUSIONS: A circular secure suture around the external anal sphincter in FI patients may help to improve anal sphincter function.

Plasma magnesium concentration in patients undergoing coronary artery bypass grafting.

[b]Introduction[/b]. Magnesium (Mg) plays a crucial role in cell physiology and its deficiency may cause many disorders which often require intensive treatment. The aim of this study was to analyse some factors affecting preoperative plasma Mg concentration in patients undergoing coronary artery bypass grafting (CABG). [b]Materials and method[/b]. Adult patients scheduled for elective CABG with cardio-pulmonary bypass (CPB) under general anaesthesia were studied. Plasma Mg concentration was analysed before surgery in accordance with age, domicile, profession, tobacco smoking and preoperative Mg supplementation. Blood samples were obtained from the radial artery just before the administration of anaesthesia. [b]Results. [/b]150 patients were studied. Mean preoperative plasma Mg concentration was 0.93 ± 0.17 mmol/L; mean concentration in patients - 1.02 ± 0.16; preoperative Mg supplementation was significantly higher than in patients without such supplementation. Moreover, intellectual workers supplemented Mg more frequently and had higher plasma Mg concentration than physical workers. Plasma Mg concentration decreases in elderly patients. Patients living in cities, on average, had the highest plasma Mg concentration. Smokers had significantly lower plasma Mg concentration than non-smokers. [b]Conclusions. [/b]1. Preoperative magnesium supplementation increases its plasma concentration. 2. Intellectual workers frequently supplement magnesium. 3. Smoking cigarettes decreases plasma magnesium concentration.

Intra-abdominal pressure correlates with extracellular water content.

BACKGROUND: Secondary increase in intra-abdominal pressure (IAP) may result from extra-abdominal pathology, such as massive fluid resuscitation, capillary leak or sepsis. All these conditions increase the extravascular water content. The aim of this study was to analyze the relationship between IAP and body water volume. MATERIAL AND METHODS: Adult patients treated for sepsis or septic shock with acute kidney injury (AKI) and patients undergoing elective pharyngolaryngeal or orthopedic surgery were enrolled. IAP was measured in the urinary bladder. Total body water (TBW), extracellular water content (ECW) and volume excess (VE) were measured by whole body bioimpedance. Among critically ill patients, all parameters were analyzed over three consecutive days, and parameters were evaluated perioperatively in surgical patients. RESULTS: One hundred twenty patients were studied. Taken together, the correlations between IAP and VE, TBW, and ECW were measured at 408 time points. In all participants, IAP strongly correlated with ECW and VE. In critically ill patients, IAP correlated with ECW and VE. In surgical patients, IAP correlated with ECW and TBW. IAP strongly correlated with ECW and VE in the mixed population. IAP also correlated with VE in critically ill patients. ROC curve analysis showed that ECW and VE might be discriminative parameters of risk for increased IAP. CONCLUSION: IAP strongly correlates with ECW.

Changes in plasma kynurenic acid concentration in septic shock patients undergoing continuous veno-venous haemofiltration.

Kynurenic acid (KYNA) is one of the end products of tryptophan metabolism. The aim of this study was to analyse plasma KYNA concentration in septic shock patients (SSP) with acute kidney injury (AKI) undergoing continuous veno-venous haemofiltration (CVVH). Changes in KYNA content were compared to alterations in the levels of procalcitonin (PCT), C-reactive protein and lactate. Adult SSP with AKI were examined. Measurements were conducted at seven time points: before beginning CVVH and at 6, 12, 24, 48, 72 and 96 h after the beginning of CVVH. Based on clinical outcomes, the data were analysed separately for survivors and non-survivors. Twenty-seven patients were studied. CVVH was associated with reduced plasma KYNA concentration only in survivors. Plasma KYNA concentration correlated with the levels of lactate and PCT only in survivors. (1) CVVH reduced plasma KYNA concentration only in survivors; (2) lack of this reduction may predict fatal outcomes in SSP.

Total antioxidant status value and superoxide dismutase activity in human colorectal cancer tissue depending on the stage of the disease: a pilot study.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors in developed countries. Oxidative stress can cause damage to colonocytes by inducing cell cytokine synthesis and triggering the process of carcinogenesis. OBJECTIVES: The aim of the study was to analyze relationships between: 1] total antioxidant status (TAS) value in CRC tissue and healthy colon tissue; 2] superoxide dismutase (SOD) activity in CRC tissue and healthy colon tissue; 3] TAS value in CRC tissue and the stage of colorectal cancer; and 4] SOD activity in CRC tissue and the stage of colorectal cancer. MATERIAL AND METHODS: Adult patients undergoing colonic surgery for CRC were studied. The patients were divided into four groups according to the TNM Classification of Malignant Tumors. Spectrophotometric methods were used to measure TAS values and SOD activity, using diagnostic kits produced by Randox Laboratories. RESULTS: The mean TAS value in CRC tissue was 0.0073 ± 0.0038 mmol/g of tissue, which was not significantly different from the mean value in healthy tissue (0.0067 ± 0.0035 mmol/g of tissue). SOD activity was 170 ± 32 U/g of tissue and was significantly higher in CRC than in healthy tissue (107 ± 25 U/g of tissue). In stages I, II and III of CRC, SOD activity as well as TAS value were increased in tumor tissue as compared to healthy tissue. Both SOD activity and TAS value markedly decreased in stage IV in contrast to the other stages of the disease. CONCLUSIONS: The study results suggest that TAS and SOD monitoring could be valuable during the treatment of CRC.

Varices of the descending duodenum explored during emergency gastro-duodenal resection for upper gastrointestinal haemorrhage. Case report.

Upper gastrointestinal haemorrhage is a major medical emergency and accounts for approximately 7,000 admissions to hospitals in Scotland each year. Over the last 10 years there has been a number of improvements in diagnosis and conservative management of the condition, which significantly reduced the ratio of life-threatening cases requiring an emergency surgery. Despite these achievements surgical intervention or, if accessible, endovascular procedures must be undertaken as emergency actions, should conservative management fail. Vascular malformations of the duodenum are less frequent causes of upper GI bleeding. Duodenal varices found endoscopically occur in 0.4% of patients with portal hypertension (PHT) and are believed to be caused mainly by liver cirrhosis, idiopathic PHT, extrahepatic PHT, or previous surgical trauma. The duodenal bulb is their most common site, followed by the second portion of the duodenum. Forty per cent of patients with PHT have duodenal varices at angiography; however, their penetration unusually affects submucosa, hence no symptoms develop. Isolated bleeding duodenal varices are scarcely reported in literature, although present a significant surgical problem: massive haemorrhage combined with failure to identify them as a source has led to catastrophic outcomes with mortality rate of 40%. The case hereby presented is unique in several aspects. Duodenal varices were explored on emergency laparotomy rather than on prior endoscopies, which, performed by the same well-established endoscopists, were twice negative. This corresponds to the study by Cottam et al. stating that duodenal varices may not penetrate the submucosa, hence haemorrhages of their origin may even be more difficult to diagnose on endocsopy. Secondly, the haemorrhage here reported was undoubtedly a life-threatening condition that required a multidisciplinary team to be managed successfully. Along with Shirashi et al. we confirm that surgical ligation followed by the excision of duodenal / small intestinal varices may be an effective method of their management--both cases have been free of recurrence at 15 months postoperatively. In contrast to the study by Hashizume et al. the duodenal varices here presented were not associated with portal hypertension (PTH). Finally, duodenal varices located in the posterolateral aspect of the descending duodenum are less common as the majority of cases reported so far were of duodenal bulb location.

Brain damage in cardiac surgery patients.

Neuropsychological disorders and brain injury are still a serious problem in cardiac surgery patients. Owing to multifactorial mechanism of brain injury during extracorporeal circulation, the effective and safe protection is extremely difficult. Despite several studies, the ideal neuroprotective treatment has not been found. Based on literature we analysed the main mechanisms of brain injury and new methods of brain protection.

Increase in intra-abdominal pressure raises brain venous pressure, leads to brain ischaemia and decreases brain magnesium content.

BACKGROUND: Intra-abdominal hypertension (IAH) may increase brain venous pressure, which may lead to brain injury. The aim of the present study was to analyse the effect of IAH on brain venous pressure and brain total and ionised magnesium (tMg and iMg), calcium (Ca) and zinc (Zn) contents in rats. MATERIAL AND METHODS: Forty four adult Wistar rats were examined. Animals were divided into two groups: control, and IAH: rats with intra-abdominal pressure (IAP) elevated to 25 mmHg. IAP was measured directly in the abdominal cavity. After retrograde cannulation of the jugular vein, the jugular venous pressure (JVP) was measured as the brain venous pressure. JVP and IAP were noted after induction of anaesthesia, immediately following induction of IAH and 90 min after induction of IAH. In all rats, brains were removed for biochemical and histological analysis. RESULTS: Biochemical analysis was performed in 30 rats, histological visualisation in 14. IAP elevated to 25 mmHg increased JVP in the IAH group. After 90 min, JVP decreased; however, its value was still higher compared with pre-IAH. In the IAH group, tMg and iMg were significantly lower than in the control group. Moreover, Ca and Zn levels were higher in the IAH group compared with the control group. The histological examination showed changes indicative of ischaemic neuronal cell stress. CONCLUSIONS: Firstly, increase in IAP elevates JVP. Secondly, raised JVP decreases tMg and iMg. Thirdly, raised JVP increases the Ca and Zn content in the rat brain. Fourthly, IAH leads to changed characteristics of brain ischaemia.

Changes in intra-abdominal, iliac venous and central venous pressures in patients undergoing abdominal surgery due to large tumors of the colon--a pilot study.

Changes in intra-abdominal pressure during bowel tumor surgery have not been documented. The purpose of the present study was to analyze changes in intra-abdominal pressure (IAP), central venous pressure (CVP) and iliac venous pressure (IVP) in patients undergoing laparotomy due to large tumor of the bowel. Twenty-one adult patients undergoing elective abdominal surgery were examined. Intra-abdominal pressure, CVP and IVP were measured during anesthesia, surgery and early postoperative period. The mean IAP before anesthesia was 12.76 +/- 1.09 mm Hg and mean bowel tumor volume 1550 +/- 227.48 mL. Anesthesia induction decreased IAP to 10.52 +/- 1.32 mm Hg and excision of intra-peritoneal tumors to 5.24 +/- 1.51 mm Hg (49.7%). Ten minutes after anesthesia, IAP increased to 7.47 +/- 1.2 mm Hg and one hour after surgery decreased to 6.19 +/- 1.43 mm Hg. There was a strong overall correlation between IAP and CVP (P = 0.0000; r = 0.7779), as well as between IAP and IVP (P = 0.0000; r = 0.8635). Moreover, IAP correlated with IVP immediately after anesthesia and one hour after anesthesia. In conclusion, induction of anesthesia decreased IAP; excision of large bowel tumors decreased IAP; and IAP strongly correlated with CVP and IVP.

Plasma matrix metalloproteinase 9 correlates with disorders of brain magnesium homeostasis in patients undergoing coronary artery bypass surgery.

BACKGROUND: Changes in plasma matrix metalloproteinase 9 (MMP-9) concentrations and parallel changes in brain magnesium homeostasis have not been examined in cardiac surgery patients. The purpose of the present study was to analyse these relationships in patients undergoing coronary artery bypass surgery (CABG) with extracorporeal circulation (ECC). Additionally, the effect of volatile anaesthetics was considered. PATIENTS AND METHODS: Adult patients undergoing CABG with ECC under general anaesthesia were studied. Plasma MMP-9 and total (tMg) and ionized (iMg) magnesium concentrations were measured during surgery and during the early postoperative period. The plasma arteriovenous (a-v) tMg and iMg differences in the brain circulation were considered to be markers for brain magnesium homeostasis. The Mini-Mental State Examination test and computer tomography were used to diagnose postoperative neuropsychological disorders (PNPDs). RESULTS: In total, 92 patients were examined. PNPDs were noted in 17 cases. Cardiac surgery resulted in increased plasma levels of MMP-9. The highest MMP-9 concentrations were observed in patients with PNPDs. MMP-9 concentrations strongly correlated with a-v tMg and a-v iMg differences. Compared with arterial measurements, venous tMg and iMg concentrations were higher during and immediately after surgery and lower during the early postoperative period. The most severe differences in a-v tMg and iMg were noted in patients with PNPDs. CONCLUSION: 1. Cardiac surgery resulted in an increase in plasma MMP-9 concentrations. 2. This increase in MMP-9 was significantly greater in patients with PNPDs. 3. The plasma MMP-9 concentration was correlated with disorders of brain Mg homeostasis.