Imre Szabó

Upregulation of the transient receptor potential ankyrin 1 ion channel in the inflamed human and mouse colon and its protective roles.

Transient Receptor Potential Ankyrin 1 (TRPA1) channels are localized on sensory nerves and several non-neural cells, but data on their functional significance are contradictory. We analysed the presence and alterations of TRPA1 in comparison with TRP Vanilloid 1 (TRPV1) at mRNA and protein levels in human and mouse intact and inflamed colons. The role of TRPA1 in a colitis model was investigated using gene-deficient mice. TRPA1 and TRPV1 expressions were investigated in human colon biopsies of healthy subjects and patients with inflammatory bowel diseases (IBD: ulcerative colitis, Crohns disease) with quantitative PCR and immunohistochemistry. Mouse colitis was induced by oral 2% dextran-sulphate (DSS) for 10 days. For investigating the functions of TRPA1, Disease Activity Index (weight loss, stool consistency, blood content) was determined in C57BL/6-based Trpa1-deficient (knockout: KO) and wildtype (WT) mice. Sensory neuropeptides, their receptors, and inflammatory cytokines/chemokines were determined with qPCR or Luminex. In human and mouse colons TRPA1 and TRPV1 are located on epithelial cells, macrophages, enteric ganglia. Significant upregulation of TRPA1 mRNA was detected in inflamed samples. In Trpa1 KO mice, Disease Activity Index was significantly higher compared to WTs. It could be explained by the greater levels of substance P, neurokinins A and B, neurokinin 1 receptor, pituitary adenylate-cyclase activating polypeptide, vasoactive intestinal polypeptide, and also interleukin-1beta, macrophage chemoattractant protein-1, monokine induced by gamma interferon-1, tumor necrosis factor-alpha and B-lymphocyte chemoattractant in the distal colon. TRPA1 is upregulated in colitis and its activation exerts protective roles by decreasing the expressions of several proinflammatory neuropeptides, cytokines and chemokines.

A combined treatment for advanced oral cavity cancers

Effects of preoperative chemotherapy with three courses of a combination of bleomycin, vincristine, mitolactol, prednisone, and methotrexate, with a leucovorin rescue, followed by surgery were studied in 43 patients with advanced squamous cell carcinoma of the oral region. Before chemotherapy 34 patients (79%) had Stage III or IV carcinomas whereas nine patients had Stage II lesions. The clinical response was very encouraging: 20 patients (46%) achieved a clinical complete response and 23 patients (54%) were judged as partial responders. Side effects of this chemotherapy were minimal and reversible. Between 15 and 22 days after the last course of chemotherapy patients went to surgery. Wound healing complications did not occur. The surgical specimens were tested microscopically. The microphotographs showed small tumor rests with giant cells bordered by fibrous scar tissue and separated from the healthy tissues. With a median follow‐up of 36 months (range, 21–58 months) 74% of patients are alive and 70% remain disease‐free. Eleven patients died but only five (11%) because of the failure of the therapy. This combined therapy appears both safe and promising treatment for advanced squamous cell carcinomas of the oral cavity. A further follow‐up study needed to confirm the promising 5‐year results.

SEX DIFFERENCES ON THE HAND MENTAL ROTATION TASK FOR 9-YR.-OLD CHILDREN AND YOUNG ADULTS

The Hand Mental Rotation task is assumed to activate an egocentric spatial reference frame to realize mental rotation. This study presents significant sex differences in hand mental rotation performances between men and women (n = 23 and 25, respectively; age: 20.7 yr.). Differences in hand mental rotation in school girls and boys (ns = 48 and 41, respectively; age: 9 yr) were not significant. Our results suggest that the change in sex differences in egocentric mental rotation may occur with developmental change. This requires further testing with a larger sample so testing can occur at several ages between 9 and 20.7 years.

Neuronal activity in rat medial prefrontal cortex during sucrose solution intake

The rats prefrontal cortex plays a role in integration of feeding-related information. In this study, we investigated the neuronal activity changes of medial prefrontal cortex during licking of sucrose solution by freely moving rats. We found two different types of excitatory and two different types of inhibitory single neuron responses time locked to the beginning of the licking clusters. Changes in firing rates occurred either within 2 s before the first lick of the licking cluster or during the licking cluster. These observations suggest that neuronal responses in the medial prefrontal cortex may represent anticipation and consummation of liquid food reward.

Decrease in serum levels of vitamin A and zeaxanthin in patients with colorectal polyp

OBJECTIVE Several retrospective and prospective epidemiological investigations have demonstrated that a diet rich in carotenoids could prevent the development of pre-cancerous and neoplastic lesions of the digestive tract. The aim of this examination was to analyse the correlation between colorectal polyps with different histological classifications and serum carotenoid levels. DESIGN AND METHODS A 10 ml blood sample was taken from all of the patients after the colonoscopic diagnosis. The serum levels of vitamin A, lutein, zeaxanthin, alpha- and beta-cryptoxanthin, alpha- and beta-carotene were measured in patients with adenomatous colorectal polyp (n = 59, 35 males, 24 females) by high-pressure liquid chromatography (HPLC) and compared with those in healthy subjects (n = 20, 10 males, 10 females). The patients were separated into four groups depending on their histological findings. RESULTS The serum levels of vitamin A and zeaxanthin were significantly lower in all patients with polyps (vitamin A: 0.913 +/- 0.112 micromol/l, zeaxanthin: 0.071 +/- 0.012 micromol/l) than in the control healthy group (vitamin A: 2.036 +/- 0.354 micromol/l, zeaxanthin: 0.138 +/- 0.048 micromol/l). The lowest levels were found in patients with focal adenocarcinoma in the polyp. There were no significant differences in the serum levels of other carotenoids. The serum levels of cholesterol, haemoglobin, total protein and albumin were normal in these patients. CONCLUSIONS There are close and inverse correlations between the serum level of carotenoids and colorectal polyps with different histological grades. The low mean carotenoid levels in patients with adenocarcinoma in the polyp indicate that deficiency of carotenoids may be an important factor in the development of colorectal cancer.

Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies

Background Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. Objectives We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). Methods A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. Statistical methods Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (χ2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. Results The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. Conclusions This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These data suggest that a low-FODMAP diet with dietitian control can be a candidate for first-line therapeutic modality in IBS. Because of a lack of data, well-planned randomized controlled studies are needed to ascertain the correlation between improvement of separate key IBS symptoms and the effect of a low-FODMAP diet.

Small doses of capsaicin given intragastrically inhibit gastric basal acid secretion in healthy human subjects.

Although the direct inhibitory effect of small dose of capsaicin on gastric secretory responses was proved in animal observations, the role of capsaicin-sensitive afferent nerves (CSAN) and the effect of capsaicin applied in small and high doses on gastric secretion in human has not been clarified yet. In this study we investigated the influence of different small doses (100-800 microg) of capsaicin given intragastrically through an orogastric tube on gastric basal secretory responses in 10 healthy human subjects. Gastric basal secretory responses (volume, H+-concentration, H+-output) were measured from the suctions of gastric juice for a 1-h period. It has been found that: a) capsaicin dose-dependently inhibited the volume and H+-output of gastric juice; b) ID50 was found to be about 400 microg for capsaicin on gastric acid secretion; c) the time interval for capsaicin-induced gastric inhibition existed for about 1 h indifferently from the higher dose (800 microg) of capsaicin given after. It has been concluded that the capsaicin (given in small doses) inhibits the gastric basal acid output via stimulation of the inhibition of capsaicin sensitive afferent nerves.

Gastrin and pentagastrin enhance the tumour proliferation of human stable cultured gastric adenocarcinoma cells.

The effect of gastrin on stimulating tumour proliferation has been evaluated on human pancreas cancer cells in culture and in tumours transplanted to nude mice. The presence of CCK-B/gastrin-like receptor responsible for that effect of gastrin has been proved in colonic (WiDr, HT-29, YAMC) and pancreatic (PANC-1, BON) cell lines. The aim of our study was to examine the stimulating effect of gastrin and pentagastrin on the growth of human gastric adenocarcinoma cell line. The human gastric adenocarcinoma cell line (AGS, CRL-1739) was purchased from ATCC (Rockville, MA, USA). Gastrin-17 was purchased from Sigma-Aldrich (Budapest, Hungary), pentagastrin was from Zeneca Limited (Macclasfield, UK). The cells were incubated in DMEM containing 10% FCS on 96-well culturing plate with 10(4) cells/well starting cell number at 37 degrees C with 5% CO2. The proliferation rates were detected: by the measurements of the metabolically active cells with Owens reagent and the determination of protein content, and by cell counting in a haemocytometer at several incubation times. As a result, we detected similar proliferation rates using gastrin-17 or pentagastrin in the incubation medium. The stimulating effect of gastrin/pentagastrin on cell line proliferation was in correlation with its concentration. Our results proved that pentagastrin is a 10 times less effective stimulator of proliferation of gastric cancer than gastrin-17, and that AGS human adenocarcinoma cell line might be CCK receptor positive.

Prospective, Multicentre, Nationwide Clinical Data from 600 Cases of Acute Pancreatitis

Objective The aim of this study was to analyse the clinical characteristics of acute pancreatitis (AP) in a prospectively collected, large, multicentre cohort and to validate the major recommendations in the IAP/APA evidence-based guidelines for the management of AP. Design Eighty-six different clinical parameters were collected using an electronic clinical research form designed by the Hungarian Pancreatic Study Group. Patients 600 adult patients diagnosed with AP were prospectively enrolled from 17 Hungarian centres over a two-year period from 1 January 2013. Main Results With respect to aetiology, biliary and alcoholic pancreatitis represented the two most common forms of AP. The prevalence of biliary AP was higher in women, whereas alcoholic AP was more common in men. Hyperlipidaemia was a risk factor for severity, lack of serum enzyme elevation posed a risk for severe AP, and lack of abdominal pain at admission demonstrated a risk for mortality. Abdominal tenderness developed in all the patients with severe AP, while lack of abdominal tenderness was a favourable sign for mortality. Importantly, lung injury at admission was associated with mortality. With regard to laboratory parameters, white blood cell count and CRP were the two most sensitive indicators for severe AP. The most common local complication was peripancreatic fluid, whereas the most common distant organ failure in severe AP was lung injury. Deviation from the recommendations in the IAP/APA evidence-based guidelines on fluid replacement, enteral nutrition and timing of interventions increased severity and mortality. Conclusions Analysis of a large, nationwide, prospective cohort of AP cases allowed for the identification of important determinants of severity and mortality. Evidence-based guidelines should be observed rigorously to improve outcomes in AP.

Capsaicin and capsiate could be appropriate agents for treatment of obesity: A meta-analysis of human studies

ABSTRACT Consumption of capsaicin or its nonpungent analogues, capsinoids has been reported to affect energy expenditure and fat oxidation, although available data are still controversial. The aim of the present study was to conduct a meta-analysis regarding the effects of these substances on energy expenditure and respiratory quotient, with special emphasis on the role of body mass index (BMI) of the participants. Medical databases were systematically searched for papers. Of the 627 trials identified, 9 provided results suitable to be included in analysis. Data analysis showed that after ingestion of capsaicin or capsinoids the energy expenditure increased (245 kJ/day, 58.56 kcal/day, p = 0.030) and the respiratory quotient decreased (by 0.216; p = 0.031) indicating a rise in fat oxidation. Studies with mean BMI of the participants below 25 kg/m2 failed to report any effect of capsaicin or capsinoids on the energy expenditure (p = 0.718) or on the respiratory quotient (p = 0.444), but studies with mean BMI exceeding 25 kg/m2 demonstrated an increase in energy expenditure (292 kJ/day, 69.79 kcal/day, p = 0.023) and a marked decrease in respiratory quotient (−0.257, p = 0.036). Our data clearly suggest that capsaicin or capsiate could be a new therapeutic approach in obesity promoting a negative energy balance and increased fat oxidation.