Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model.

The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions.

Lipid raft disruption as an opportunity for peripheral analgesia.

Chronic pain conditions are unmet medical needs, since the available drugs, opioids, non-steroidal anti-inflammatory/analgesic drugs and adjuvant analgesics do not provide satisfactory therapeutic effect in a great proportion of patients. Therefore, there is an urgent need to find novel targets and novel therapeutic approaches that differ from classical pharmacological receptor antagonism. Most ion channels and receptors involved in pain sensation and processing such as Transient Receptor Potential ion channels, opioid receptors, P2X purinoreceptors and neurokinin 1 receptor are located in the lipid raft regions of the plasma membrane. Targeting the membrane lipid composition and structure by sphingolipid or cholesterol depletion might open future perspectives for the therapy of chronic inflammatory, neuropathic or cancer pain, most importantly acting at the periphery.

Stable carbon and nitrogen isotopes identify nuanced dietary changes from the Bronze and Iron Ages on the Great Hungarian Plain.

The Great Hungarian Plain (GHP) served as a geographic funnel for population mobility throughout prehistory. Genomic and isotopic research demonstrates non-linear genetic turnover and technological shifts between the Copper and Iron Ages of the GHP, which influenced the dietary strategies of numerous cultures that intermixed and overlapped through time. Given the complexities of these prehistoric cultural and demographic processes, this study aims to identify and elucidate diachronic and culture-specific dietary signatures. We report on stable carbon and nitrogen isotope ratios from 74 individuals from nineteen sites in the GHP dating to a ~ 3000-year time span between the Early Bronze and Early Iron Ages. The samples broadly indicate a terrestrial C3 diet with nuanced differences amongst populations and through time, suggesting exogenous influences that manifested in subsistence strategies. Slightly elevated δ15N values for Bronze Age samples imply higher reliance on protein than in the Iron Age. Interestingly, the Füzesabony have carbon values typical of C4 vegetation indicating millet consumption, or that of a grain with comparable δ13C ratios, which corroborates evidence from outside the GHP for its early cultivation during the Middle Bronze Age. Finally, our results also suggest locally diverse subsistence economies for GHP Scythians.

Newly Diagnosed Chronic Lymphocytic Leukemia During Symptomatic COVID-19: Two Cases.

Patients suffering from malignant diseases have a high risk of developing severe or critical forms of COVID-19 (Coronavirus Disease 2019). Chronic lymphocytic leukaemia (CLL) is characterized by dysregulated adaptive and innate immune responses, because both T and B cells, the function of phagocytes and the activity of the complement system may be affected. Severe SARS-CoV-2 infection also influences the immunological functions mainly via causing the depletion of CD4+ and CD8+ T cells. We present the cases of two patients, whose de novo CLL were observed during severe COVID-19 pneumonia. A 43-year-old man with IDDM (Insulin dependent diabetes mellitus) was sent to hospital in February 2021. He had a bilateral severe COVID-19 pneumonia. There was a suspected sign of malignancy on a thoracic vertebra in his chest CT, and haematological consultation was requested. In parallel, a 53-year-old man was hospitalized in March of 2021 because of severe COVID-19 pneumonia. CLL was suspected based on his haematology test results (WBC: 123 G/L, lymphocytes: 91%, haemoglobin: 107 g/L). Flow cytometric analysis revealed CLL in both cases. Based on the result of the molecular genetic tests, the first patient had a good prognosis in Rai 0 stage, while the other patient suffered from Rai I stage with a worse prognosis. Both patients recovered from bilateral COVID-19 pneumonia without the need for intensive care unit treatment. The follow-up of these CLL patients that manifested during symptomatic COVID-19 disease further enriched our knowledge on such clinical conditions where the immune system is dysfunctional due to different simultaneous causes.

An integrative skeletal and paleogenomic analysis of stature variation suggests relatively reduced health for early European farmers.

Human culture, biology, and health were shaped dramatically by the onset of agriculture ∼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared "predicted" genetic contributions to height from paleogenomic data and "achieved" adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (∼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

Nucleophosmin1 and isocitrate dehydrogenase 1 and 2 as measurable residual disease markers in acute myeloid leukemia.

Monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML) plays an important role in predicting relapse and outcome. The applicability of the leukemia-initiating nucleophosmin1 (NPM1) gene mutations in MRD detection is well-established, while that of isocitrate dehydrogenase1/2 (IDH1/2) mutations are matter of debate. The aim of this study was to investigate the stability of NPM1 and IDH1/2 mutations at diagnosis and relapse retrospectively in 916 adult AML patients. The prognostic value of MRD was evaluated by droplet digital PCR on the DNA level in a selected subgroup of patients in remission. NPM1 re-emerged at relapse in 91% (72/79), while IDH1/2 in 87% (20/23) of mutation-positive cases at diagnosis. NPM1 mutation did not develop at relapse, on the contrary novel IDH1/2 mutations occurred in 3% (3/93) of previously mutation-negative cases. NPM1 MRD-positivity after induction (n = 116) proved to be an independent, adverse risk factor (MRDpos 24-month OS: 39.3±6.2% versus MRDneg: 58.5±7.5%, p = 0.029; HR: 2.16; 95%CI: 1.25-3.74, p = 0.006). In the favorable subgroup of mutated NPM1 without fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) or with low allelic ratio, NPM1 MRD provides a valuable prognostic biomarker (NPM1 MRDpos versus MRDneg 24-month OS: 42.9±6.7% versus 66.7±8.6%; p = 0.01). IDH1/2 MRD-positivity after induction (n = 62) was also associated with poor survival (MRDpos 24-month OS: 41.3±9.2% versus MRDneg: 62.5±9.0%, p = 0.003; HR 2.81 95%CI 1.09-7.23, p = 0.032). While NPM1 variant allele frequency decreased below 2.5% in remission in all patients, IDH1/2 mutations (typically IDH2 R140Q) persisted in 24% of cases. Our results support that NPM1 MRD even at DNA level is a reliable prognostic factor, while IDH1/2 mutations may represent pre-leukemic, founder or subclonal drivers.

Integrating buccal and occlusal dental microwear with isotope analyses for a complete paleodietary reconstruction of Holocene populations from Hungary.

Dietary reconstruction is used to make inferences about the subsistence strategies of ancient human populations, but it may also serve as a proxy to characterise their diverse cultural and technological manifestations. Dental microwear and stable isotope analyses have been shown to be successful techniques for paleodietary reconstruction of ancient populations but, despite yielding complementary dietary information, these techniques have rarely been combined within the same study. Here we present for the first time a comprehensive approach to interpreting ancient lifeways through the results of buccal and occlusal microwear, and δ13C and δ15N isotope analyses applied to the same individuals of prehistoric populations of Hungary from the Middle Neolithic to the Late Bronze Age periods. This study aimed to (a) assess if the combination of techniques yields a more precise assessment of past dietary and subsistence practices, and (b) contribute to our understanding of the dietary patterns of the prehistoric Hungarian populations. Overall, no correlations between microwear and δ13C and δ15N isotope variables were observed, except for a relationship between nitrogen and the vertical and horizontal index. However, we found that diachronic differences are influenced by the variation within the period. Particularly, we found differences in microwear and isotope variables between Middle Neolithic sites, indicating that there were different dietary practices among those populations. Additionally, microwear results suggest no changes in the abrasiveness of the diet, neither food processing methods, despite higher C4 plant resource consumption shown by carbon isotopic signal. Thus, we demonstrate that the integration of dental microwear and carbon and nitrogen stable isotope methodologies can provide complementary information for making inferences about paleodietary habits.

A minimally destructive protocol for DNA extraction from ancient teeth.

Ancient DNA sampling methods-although optimized for efficient DNA extraction-are destructive, relying on drilling or cutting and powdering (parts of) bones and teeth. As the field of ancient DNA has grown, so have concerns about the impact of destructive sampling of the skeletal remains from which ancient DNA is obtained. Due to a particularly high concentration of endogenous DNA, the cementum of tooth roots is often targeted for ancient DNA sampling, but destructive sampling methods of the cementum often result in the loss of at least one entire root. Here, we present a minimally destructive method for extracting ancient DNA from dental cementum present on the surface of tooth roots. This method does not require destructive drilling or grinding, and, following extraction, the tooth remains safe to handle and suitable for most morphological studies, as well as other biochemical studies, such as radiocarbon dating. We extracted and sequenced ancient DNA from 30 teeth (and nine corresponding petrous bones) using this minimally destructive extraction method in addition to a typical tooth sampling method. We find that the minimally destructive method can provide ancient DNA that is of comparable quality to extracts produced from teeth that have undergone destructive sampling processes. Further, we find that a rigorous cleaning of the tooth surface combining diluted bleach and UV light irradiation seems sufficient to minimize external contaminants usually removed through the physical removal of a superficial layer when sampling through regular powdering methods.

A transdisciplinary and community-driven database to unravel subduction zone initiation.

Subduction zones are pivotal for the recycling of Earth's outer layer into its interior. However, the conditions under which new subduction zones initiate are enigmatic. Here, we constructed a transdisciplinary database featuring detailed analysis of more than a dozen documented subduction zone initiation events from the last hundred million years. Our initial findings reveal that horizontally forced subduction zone initiation is dominant over the last 100 Ma, and that most initiation events are proximal to pre-existing subduction zones. The SZI Database is expandable to facilitate access to the most current understanding of subduction zone initiation as research progresses, providing a community platform that establishes a common language to sharpen discussion across the Earth Science community.

Peripheral blood stem cell mobilization and engraftment after autologous stem cell transplantation with biosimilar rhG-CSF.

INTRODUCTION: Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen(®)], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio(®), Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary. METHODS: In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 × 5 µg) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required. RESULTS: In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU(®), Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8-11 days) and 10 (8-12) days, respectively. Median time to platelet engraftment was 10.5 days (7-19 days). In Study 2, the patients' median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9-27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 × 10(6)/kg (2.22-57.07 × 10(6)/kg). The median yield of CD34+ cells per leukapheresis product was 2.47 × 10(6)/kg. In total, 58 leukaphereses were performed in 40 successfully harvested patients. CONCLUSIONS: In line with previous studies with originator rhG-CSF, the findings of this study indicate that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+ cells. In conclusion, the authors have demonstrated that the use of biosimilar rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment after AHSCT.

Role of nitric oxide in the central interferon-alpha-induced inhibition of gastric acid secretion in rats.

Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000, 10000, 100 000 IU, s.c.) and intracisternal (10, 100, 1000 IU, i.c.) injections of IFN-α dose-dependently inhibited GAS induced by pylorus ligation in male SD rats in 2 hrs (370±40, 233±39, 208±50 micromol vs control 415±59 micromol and 481±50, 249±75, 141±25 micromol vs control 485±65 micromol, respectively). Central doses inducing same level inhibition were 100 times lower. NOS inhibitor L-NAME (3 mg/kg, i.v.) blocked the inhibitory effect of i.c. ED(50) dose 100 IU IFN-α (507±75 micromol/2 hrs), while L-arginine, the substrate of nitric oxide synthase (NOS) prevented L-NAME action (266±82 micromol/2 hrs). D-arginine failed to prevent L-NAME action on IFN-α-induced inhibition of GAS. Aminoguanidine, a selective inhibitor of inducible NOS (iNOS) failed to block IFN-α induced inhibition of GAS. Results suggest that IFN-α inhibits GAS centrally through nitric oxide pathways probably mediated by continuous isoform of NOS that can be important in regulation of GAS in healthy or pathological conditions.

Changes in NADPH oxidase mRNA level can be detected in blood at inhaled corticosteroid treated asthmatic children.

AIM: Oxidative stress, observed in the asthmatic airways, is not localized only to the bronchial system. It would be a great advantage to monitor the oxidative stress markers from blood especially in childhood asthma following the inflammation. Our aim was to measure the levels of antioxidants and the oxidatively damaged biomolecules. We were also interested in the gene expression alterations of the free radical source gp91(phox) subunit (CYBB) of the NADPH oxidase system, and the antioxidant heme oxygenase-1 (HMOX-1) isoenzyme in the blood. Our findings were also examined in the context of medical treatment. MAIN METHODS: Oxidative stress parameters via photometric methods, CYBB and HMOX-1 expressions via real-time PCR were measured in 58 asthmatic and 30 healthy children. KEY FINDINGS: Higher blood thiobarbituric acid reactive substances (TBARS) (p<0.03) and carbonylated protein (p<0.05) levels were found in the asthmatic children than in the controls. The relative expression of CYBB was significantly lower (p<0.05) in patients treated with a low daily dose of inhaled corticosteroid (ICS), than in asthmatics not receiving ICS therapy. Higher ICS doses alone or combined with long acting ß2-receptor agonists did not influence the expression significantly. No similar tendency was found as regards to HMOX-1 expression. SIGNIFICANCE: Elevated levels of damaged lipid (TBARS) and protein (carbonylated) products corroborate the presence of oxidative stress in the blood during bronchial asthma and suggest the presence of chronic oxidative overload. Our findings also suggest that ICS treatment can influence the relative CYBB mRNA expression in circulating leukocytes in a dose dependent manner.

Measurement of gastric-to-end-tidal carbon dioxide difference in neonates requiring intensive care.

OBJECTIVE: Gastric-arterial partial CO(2) pressure gap (P(g-)(a)CO(2) gap) measured by gastric tonometry may detect the disturbance of splanchnic perfusion. As in the neonatal age it is very difficult to follow up the circulatory condition with frequent acid-base examinations, we wanted to compare the P(g-)(a)CO(2) gap with an alternative gap of P(g)CO(2) - end-tidal carbon dioxide (P(g)(-)(ET)CO(2) gap). METHODS: A prospective study was performed on ventilated neonates requiring intensive therapy (n = 44, weight: 1813 ± 977 g). P(ET)CO(2) and P(g)CO(2) were measured with a side stream capnograph. We applied a newly developed gastric tonometric probe. Patients were divided into two groups: Group 1 of patients in stable condition (n = 35) and Group 2 of patients with severe condition (i.e. Clinical Risk Index for Babies [CRIB] score higher than 10; n = 9). For main statistical analysis a mixed model repeated measurements ANOVA, Bland-Altman analysis were applied. RESULTS: P(g)(-)(ET)CO(2) gap was higher than P(g-)(a)CO(2) gap (11.40 ± 7.79 versus 3.63 ± 7.98 mmHg, p < 0.01). Both gaps were higher in Group 2 (8.71 ± 10.89 and 18.27 ± 10.49 versus 2.53 ± 6.78 and 9.92 ± 6.22 mmHg, p < 0.01 and p < 0.05). Bland-Altman analysis of the two gaps showed an acceptable correspondence. CONCLUSIONS: P(g)(-)(ET)CO(2) gap may be used as a method for continuous estimation of splanchnic perfusion and a prognostic index also in critically ill neonates. However, the P(g-)(a)CO(2) gap should not be abandoned.

Intraoperative gastric tonometric examinations in children and infants with a new probe, combined with measurement of the endtidal PCO2.

BACKGROUND: Important progress relating to the early prediction of postoperative complications was recently achieved through the combined use of endtidal PCO(2) (P(ET)CO(2)) and gastric tonometry. The aim of this article was to present results obtained with a new tonometric instrument, proving its feasibility and extending its use to the control of anesthetized infants and children. METHODS: The new tonometric probe, which is balloon free, consists basically of silicone rubber tubing. The room air initially inside the tubes of the probe equilibrates with the PCO(2) of the body cavity throughout its full length. The PCO(2) content of the gastric cavity (P(g)CO(2)) and simultaneously P(ET)CO(2) were measured with a microcapnograph. A total of 108 measurements were performed intraoperatively on 25 infants and young children operated on at the Surgical Unit of the Department of Pediatrics. The patients were divided into elective surgery cases <2 years of age, group I; elective surgery cases >2 years of age, group II; and acute surgery cases, independently of age, group III. To examine the degree of agreement between the measurements, Pearson's correlation coefficients were determined and Bland-Altman analysis was performed. A mixed model repeated measurements anova was used to compare the differences between the groups. RESULTS: P(ET)CO(2) and P(g)CO(2) for groups I and II were nearly identical, and statistically not significantly different (mean difference 0.10 mmHg and 0.85 mmHg, P = 0.96 and 0.45, respectively), whereas the corresponding data for group III differed significantly from those for groups I and II (P = 0.03 and 0.001, respectively). On Bland-Altman analysis, the bias value for groups proved to be statistically significantly different (P = 0.001). CONCLUSIONS: The tested new probe worked very well in small children. The clinical implications of the large gaps found between P(ET)CO(2) and P(g)CO(2) values in acutely ill children and children undergoing elective operations must be investigated further.

Effect of laparoscopic fundoplication on hypertensive lower esophageal sphincter associated with gastroesophageal reflux.

For hypertensive lower esophageal sphincter with dysphagia and chest pain, a laparoscopic cardiomyotomy is recommended. Recently, the role of gastroesophageal reflux in this abnormality has been recognized. A prospective study on six patients with manometrically proven hypertensive lower esophageal sphincter was performed. Laparoscopic floppy Nissen fundoplication was performed in all cases. The first follow up was performed 6 weeks after the operation. The mean follow up time was 56 months (range 50-61). Before the operation, all patients had abnormal esophageal acid exposure. Mean DeMeester score was 41.7 (range 16.7-86). Average LES pressure before the operation was 50.5 mmHg (range 35.6-81.3). Six weeks after operation, all patients were symptom free. DeMeester score returned to a normal level of 2.9. Furthermore, a marked decrease in the lower esophageal sphincter pressure (24.7 mmHg) was detected. At late follow up, all patients were symptom-free, and only two patients agreed to undergo functional testing. The mean DeMeester score of this two patients was 1.2. The pressure remained at normal value (15.7 mmHg). In our study, an antireflux operation normalized lower esophageal sphincter pressure suggesting that abnormal esophageal acid exposure may be an etiologic factor in the development of hypertensive lower esophageal sphincter.

[Family study in Peutz-Jeghers syndrome]. / A Peutz-Jeghers-szindrómáról családvizsgálatok kapcsán.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant hereditary disease characterized by mucocutaneous pigmentation, gastrointestinal hamartomatous polyposis and an increased risk for the development of gastrointestinal and extra-gastrointestinal malignancies. AIM AND METHODS: Five generations of two PJS families (21-21 patients) were analyzed to summarize the clinical appearance of the disorder by interview, physical examination, laboratory and imaging studies. RESULTS: Phenotypic variability was observed in PJS both in and between families. In family "A" 13 people were diagnosed as being affected, all of them had melanin spots at birth and the first presenting clinical symptom was colicky abdominal pain (median age 12 years, range: 2-35) resulting in 14 laparotomies in 9 of the affected persons. 4/13 patients died from small-bowel ileus (median age 7 years, range 2-31), 2/13 from GI cancer (median age 54 years). In family "B" 7 patients were documented as being affected. The first features were also abdominal cramps (at age 22). The main causes of death were gynaecological (1/5) and GI malignancies (4/5) at advanced age, no one died in ileus. CONCLUSIONS: The results based on the analysis of the two families suggest that PJS is not a benign disease. It is difficult to predict the outcome of the disorder regarding the variable expression and incomplete penetrance. Therefore we emphasize the importance of checking the pedigree, finding out the leading symptom in the family; hemoccult test and routine lab studies should be carried out at every affected individual. If clinical signs and symptoms are present we recommend to perform the complete diagnostic protocol and a yearly follow-up by a gastroenterologist familiar with PJS focusing on the leading symptoms.

[Investigation of visceral hyperesthesia in irritable bowel syndrome]. / A visceralis hyperaesthesia vizsgálata irritabilis bél szindrómcában.

BACKGROUND: It has been well established that visceral hyperesthesia plays a role in the development of irritable bowel syndrome (IBS). AIMS: 1. to detect the possible changes of visceral perception in different subtypes of IBS patients, 2. to analyze the difference of visceral hyperaesthesia in different subtypes of IBS, 3. to examine whether distension protocols (e.g. phasic or ramp distension) has any influence on sensory thresholds, 4. to analyze the differences of perception thresholds produced by phasic or ramp distension in different subtypes of IBS. METHODS: 10 patients having colorectal polypectomy (control group) and 40 IBS patients were studied. The diagnosis was based on the Rome-II criteria. Diarrhoea-predominant, alternating and constipation-predominant subtypes were determined by the Talley bowel habit questionnaire. Sensory thresholds were detected by semi random ascending phasic and ramp rectosigmoid distension. Rectal dynamic compliance was calculated by using the dV/dP ratio. RESULTS: 1. The pain thresholds determined by phasic distension were significantly lower in all subtypes of IBS. 2. Increased thresholds for pain were found in almost half of constipation-predominant IBS patient determined by ramp distension. Thus two distinct subgroups could be found based on the findings of ramp distension: a normosensitive and a hyposensitive group. 3. Rectal dynamic compliance was significantly higher both in the constipation-predominant and alternating subtype of IBS patients. CONCLUSION: Visceral hyperesthesia can be detected in all types of IBS. Tolerance to physiologic stimuli could be observed in constipating IBS patients that is not related to the increase of rectal compliance.