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Biomedical subjects

G Eibl

Publications and source records attributed to G Eibl.

At least 19 recordsLinked to original sources

Evaluation of antimitotic activity of Rotula aquatica (Lour): a traditional herb used in treatment of cancer.

Rotula aquatica was extensively used by vaidyas (Ayurvedic practioners) in holistic treatment of cancer. In the present study, an attempt has been made to evaluate the antimitotic activity of R. aquatica. Preliminary antimitotic screening was done using Allium cepa root tip assay. The mitotic index of the root tips markedly decreased with increasing concentration of the aqueous extract. The different fractions obtained by successive extraction of R. aquatica using solvents of increasing polarity were also evaluated for their antimitotic activity. Tannins were isolated which showed a better activity than the non-tannin fraction. Experiments were also carried out with incorporation of folic acid in the aqueous extract. Folic acid inhibited the antimitotic activity of aqueous extract of R. aquatica in a dose dependent manner. The results obtained were compared with methotrexate--a known drug available in market as anti-cancer agent. The studies were extended to human cells using 3 pancreatic cancer cell lines, viz: HPAF-II, BxPC-3, and CAPAN-2. Extract of R. aquatica was found to be extremely effective in the prevention of cell proliferation of the pancreatic cancer cell lines. The phytochemical evaluation revealed presence of polyphenols (tannins) and steroids. A HPTLC fingerprinting was developed and studied. Two compounds were isolated and subjected to spectral studies like UV, IR and mass spectrums. The empirical formula was derived by considering this data with elemental analysis of the compounds.

Allium↗

Physical and physiological factors associated with success in professional alpine skiing.

Scientific data on the physiological profile of world class skiers are sparse. During the last decade the Austria Ski Team was the most successful in the world. It was the objective of this study to describe the physical and physiological characteristics of World Cup (WC) skiers. Twenty female and 28 male members of the Austrian WC Ski Team were examined pre- and post-seasonally from 1997 to 2000. Physical parameters such as age, height, body mass, body mass index, percent body fat and thigh circumference were recorded from each athlete. The physiological variables investigated consisted in the aerobic power and in the muscle strength of the lower limbs. Racing performance was defined by the WC ranking position. The athlete's aerobic performance capacity was assessed by maximal exercise testing on a bicycle ergometer, and the isokinetic muscle strength of the knee extensor and flexor muscles by the use of a computer-interfaced dynamometer. From 1997 to 2000 about half (48 %; n = 106) of all alpine WC racing events (n = 221) were won by the athletes investigated. The typical world class skier is in the mid-twenties (25.2 y [female]; 27.6 y [male]). The mean values for height were 1.66 m (female) vs. 1.81 m (male), for body mass 65.1 kg (female) vs. 87 kg (male) and for the percentage of body fat 24.5 % (female) vs. 15.8 % (male). The maximum power output was 4.3 +/- 0.4 (female ) and 4.7 +/- 0.4 W/kg (male), the corresponding values for VO(2)max were 55 +/- 3.5 (female) and 60 +/- 4.7 ml/kg/min (male). The maximal values for peak torque and work for knee extension amounted to 206 +/- 21 (female) and 334 +/- 43 Nm (male), and 2690 +/- 364 (female) and 4414 +/- 629 J (male), respectively. In both sexes there were neither significant laterality nor dysbalance. The hamstring/quadriceps ratios were between 0.57 - 0.60. Among all physical and physiological variables, only the aerobic power in males was found to be strongly correlated (r = 0.947; p = 0.001 for W (max); r = 0.964; p < 0.001 for VO(2)max) to racing performance. The study proves the practical experience that success in professional alpine skiing is not related to single physiological variables. Two main factors, however, are crucial, i. e. high levels of aerobic power and muscle strength.

Adult↗

Asymmetric termination of secondarily generalized tonic-clonic seizures in temporal lobe epilepsy.

In patients with secondarily generalized tonic-clonic seizures (sGTCS) an asymmetric termination of the clonic phase can be observed. The authors systematically analyzed this phenomenon in patients with temporal lobe epilepsy (TLE). Thirty-nine sGTCS from 29 patients with TLE who underwent successful epilepsy surgery were analyzed, in addition to a prospectively collected group of 28 patients with TLE who had 35 sGTCS. The clonic phase of sGTCS did not end synchronously in 65.7% of all patients and in 59.4% of all seizures. In 79.3% to 80% this was ipsilateral to the hemisphere of seizure onset, and there was excellent interobserver agreement.

Adult↗

Persistent multiple organ microcirculatory disorders in severe acute pancreatitis: experimental findings and clinical implications.

This study characterizes microcirculatory changes (capillary blood flow, capillary permeability, and leukocyte rolling) in the pancreas, colon, liver, and lungs at different stages of severe acute pancreatitis (AP) in a well-established rat model using intravital microscopy and computerized image analysis. The results demonstrate that microcirculatory disorders in severe AP are not confined to the pancreas but can also be found in the colon, liver, and lungs; that they extend beyond the early stage of AP and persist for 48 hr (and longer); and that they not only affect capillary blood flow but also involve prolonged changes of capillary permeability and leukocyte endothelial interaction. These findings may explain previous observations that therapeutic strategies aimed at enhancing microcirculation improve outcome in AP even if therapy is delayed and pancreatic necrosis can no longer be influenced. Since these systemic microcirculatory disturbances may contribute to AP-associated multiple organ dysfunction syndrome, further studies are warranted to evaluate whether improvement of microcirculation stabilizes organ function in AP and how long this may be effective after disease onset.

Acute Disease↗

Short-term effects of prolonged strenuous endurance exercise on the level of haematocrit in amateur cyclists.

Knowledge is sparse about the extent of potential dehydration due to prolonged strenuous cycling and its haematological acute effects on the haematocrit (Hct) in study populations credibly not taking any kind of doping. With increasing training load levels of Hct and haemoglobin (Hb) decrease in both amateurs and professionals as a long-term consequence due to expanded plasma volume (PV). On a short-term basis, however, counteracting dehydration potentially brought about by endurance exercise may cause a rise in Hct bringing competitive cyclists into conflict with the current condition regulations and Hct cut-off of 50 % set by the International Cycling Union (UCI) in its fight against erythropoietin (rhEPO) doping. On the other hand adequate and sufficient fluid substitution being substantial for a successful endurance performance should prevent any pronounced Hct rises. To study the haematological acute effects of prolonged strenuous cycling we measured Hct, Hb, red blood cell (RBC) count and plasma protein in a reliably 'clean' population of 38 well-trained male amateur cyclists before, immediately after and one day after an extraordinary ultramarathon. The pre-race levels of Hct, Hb and RBC count were placed in the lower range of normal distribution and well below the Hct cut-off limit of the UCI. Immediately post-exercise the mean levels of Hct, Hb, RBC count and protein remained unchanged. One day after race, however, all four parameters significantly dropped by 3 %, 6.7 %, 6.5 %, 9.9 % respectively (p < 0.001), indicating marked post-exercise PV expansion. The calculated percentage increase in PV was 11.9 %. No evidence for coexisting exercise-induced haemolysis was found. Our study shows that in "clean, rhEPO-free" amateur cyclists who involve in strenuous marathon cycling the haematological short-term effects of extraordinary marathon cycling consist in considerable PV expansion making Hct values fall on the following day. The findings - gained from amateurs though - suggest that despite all its disadvantages the UCI Hct cut-off represents an appropriate means to discourage from excessive rhEPO doping at least as long as the available direct methods for detecting this kind of misuse are not yet applied by the international sports federations.

Adult↗

Exercise intensity of cycle-touring events.

The aim of the study was to analyze the exercise intensity of recreational cyclists participating in a cycling-touring event. In 14 male healthy recreational cyclists heart rate (HR) monitoring was performed during the Otztal Radmarathon 1999 (distance: 230 km; altitude difference: 5500 m) in order to evaluate the HR response and to estimate the cardiopulmonary strains for the less-trained athlete confronted with such a marathon. Four different exercise intensities were defined as percentages of maximal HR (HR(max)) as follows: recovery HR (HR(re)) < 70 % of HR max; moderate aerobic HR (HR(ma)) = 70 - 80 %; intense aerobic HR (HR(ia)) = 80 - 90 %; and anaerobic HR (HR(an)) > 90 %. All athletes finished the competition successfully. The mean racing time was 10 h 14 min, the average speed 22.5 km/h. The mean HR(max) was 188 bpm, the average value of the measured HRs (HR(average)) was 145 bpm resulting in a mean HR(average)/HR(max) ratio of 0.77. Athletes spent 18.5 % (1 h 54 min) of total race time within HR(re), 28 % (2 h 52 min) within HR(ma), 39.5 % (4 h 02 min) within HR(ia), and 14 % (1 h 26 min) within HR(an). The vast majority of exercise was done under "aerobic conditions" (HR(re) + HR(ma) + HR(ia) = 86 % or 8 h 48 min) - confirming the knowledge that the aerobic energy supply is crucial for the performance of long-term exercise. The large amount of high exercise intensities (HR(ia) + HR(an) = 53.5 % or 5 h 30 min), however, features the intense cardiopulmonary strains evoked by such competitions. The HR response was related to the course profile with HRs significantly declining in all subjects to an extent of 10 % during the course of race. Our findings show that the exercise intensity borne by recreational cyclists during a cycle-touring event is high and very similar to that of professionals. With respect to the high cardiovascular strains a thorough medical screening is advisable for any participant of such an event combining both high volume and high intensity loads.

Adult↗

[The evaluation of the second-look operation of patients with ovarian carcinoma and tubal carcinoma by means of a retrospective comparison study].

INTRODUCTION: This investigation is a retrospective analysis to evaluate the influence of second-look surgery on the relapse-free and overall survival of patients with ovarian and tubal carcinomas. METHOD: For 208 patients with and without second-look operation out of 469 of the total collective, a matched analysis and a Cox regression model were established in the framework of a multivariate analysis. RESULTS: Second-look surgery in patients with ovarian cancer had no significant influence on the relapse-free and overall survival. The 10-year survival was equal in both groups: CONCLUSION: Second-look surgery cannot be justified on the basis of clinically noninvasive methods such as radiological findings with additional use of tumor markers. It should only be done in control clinical trials to evaluate new means of treatment.

Aged↗

Peroxisome proliferator-activated receptor gamma induces pancreatic cancer cell apoptosis.

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) decreases the growth of certain cancer cells. In the present study, we found that six different human pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-2, HPAF-II, MIA PaCa-2, and PANC-1) expressed PPAR-gamma m-RNA and synthesized the protein. The endogenous and exogenous PPAR-gamma ligands 15-deoxy-d12,14-prostaglandin J(2) (15-PGJ(2)) and ciglitazone decreased cell number, cell viability, and increased floating/attached ratio, in a time- and dose-dependent fashion. 15-PGJ(2) increased intracellular nucleosome concentration after 6 h, but did not increase caspase-3 activity even after 96 h. Combined treatment with both 15-PGJ(2) and the caspase-3 inhibitor DEVD-CHO had no effect on cell viability, but the general caspase inhibitor ZVAD-FMK reduced 15-PGJ(2)-induced apoptosis. We concluded that the six human pancreatic cancer cells tested all expressed PPAR-gamma receptor, and treatment with PPAR-gamma agonists decreased cell viability and growth in a time- and dose-dependent manner. These effects were partially mediated by induction of caspase-3 independent apoptosis.

Apoptosis↗

High expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood acute lymphoblastic leukaemia.

Childhood acute lymphoblastic leukaemia (ALL) is a malignancy with the potential to infiltrate the liver, spleen, lymph nodes and brain. Such extramedullary presentation is important for understanding the biology of childhood ALL and also for developing new prognostic parameters. A potential mechanism in the trafficking of leukaemia cells is the interaction of the chemokine receptor CXCR4, which is expressed on ALL cells, and its ligand stromal cell-derived factor-1 (SDF-1), produced by stromal cells in bone marrow and extramedullary organs. Functionality of CXCR4 was demonstrated by a high correlation between cell surface density of CXCR4 and transendothelial migration of leukaemia blasts towards a gradient of SDF-1 (r = 0.73, P = 0.001). Inhibition of SDF-1-induced migration by an anti-CXCR4 monoclonal antibody (78.33 +/- 23.86% inhibition) evidenced the specificity of CXCR4 to SDF-1. In order to evaluate clinical significance of CXCR4 expression, lymphoblasts from the bone marrow of 73 patients with and without extramedullary organ infiltration were compared. Multiparameter flow cytometry revealed that lymphoblasts from patients with high extramedullary organ infiltration, defined as ultrasonographically measured enlargement of liver or spleen, expressed the CXCR4 receptor at higher fluorescence intensity (median 66.12 +/- 66.17) than patients without extramedullary organ infiltration (median 17.56 +/- 19.29; P < 0.001). Consequently, high expression of CXCR4 was strongly predictive for extramedullary organ involvement, independently of the peripheral lymphoblast count. Highest CXCR4 expression was seen in mature B ALL (median 102.74 +/- 92.13; P < 0.003), a disease characterized by a high incidence of extramedullary bulky disease. As high expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood ALL, we suggest that CXCR4 and its ligand play an essential role in extramedullary invasion.

Antibodies, Monoclonal↗

Inappropriate detection of supraventricular arrhythmias by implantable dual chamber defibrillators: a comparison of four different algorithms.

Inappropriate therapy of supraventricular tachyarrhythmias by an ICD is still a common problem. Dual chamber (DDD) ICDs provide additional atrial sensing and should result in higher specificity for detection of supraventricular tachyarrhythmias. However, a direct comparison of different dual chamber algorithms has not been reported. The detection algorithms of four different DDD ICDs were tested: Phylax AV, Defender IV, Ventak AV III DR, and Gem DR 7271. Based on arrhythmias recorded from patients undergoing invasive electrophysiological studies and in many cases of catheter ablation at our institution, a library consisting of 71 supraventricular and 15 ventricular tachyarrhythmias was created. The library consists of episodes of atrial fibrillation, atrial flutter with different AV conduction, typical and atypical AV nodal reentrant tachycardia, AV reentrant tachycardia, sinus tachycardia, and ventricular tachycardia with and without ventriculoatrial conduction. Atrial fibrillation was appropriately classified by all four algorithms. However, the specificity for detection of other supraventricular tachyarrhythmias achieved by the Biotronik (12%) and the Guidant (11%) devices was significantly lower compared to the specificity of the ELA (28%) and the Medtronic DDD ICD (20%). This is due to the fact that the Biotronik and the Guidant algorithm classified all supraventricular tachyarrhythmias resulting in a stable ventricular rate as ventricular tachycardia, whereas the ELA and Medtronic algorithms performed a more detailed analysis by assessment of PR association, atrial onset, or timing of the atrial event relative to the ventricular event, respectively. Atrial fibrillation, the most common supraventricular tachyarrhythmia in patients with ICD, was detected by all devices.

Algorithms↗

Prolonged iron depletion after allogeneic 2-unit RBC apheresis.

BACKGROUND: Allogeneic 2-unit RBC apheresis is a safe procedure offering many advantages for donors and blood banks. A controlled study was performed to determine whether the recommended minimum interval of 4 months between 2-unit RBC apheresis donations is appropriate in terms of the recovery of RBCs and the regeneration of iron stores. STUDY DESIGN AND METHODS: Twenty male subjects each donated 2 units of RBCs by apheresis. The RBC count, reticulocyte count, EPO, and measures of iron status were analyzed before and during the 4 months after donation. RESULTS: A significant decrease in Hb (15.89 +/- 0.82 [mean +/- SD] vs. 14.08 +/- 0.97 mg/dL, baseline vs. Day 7; p<0.001) was equalized within 2 months. In contrast, ferritin values declined significantly from 54.2 +/- 33.7 to 23.42 +/- 21.94 microg per L (predonation vs. Day 30) and remained significantly below predonation values, but within the normal range, until the end of the study period. CONCLUSION: A donation interval of 4 months is appropriate in terms of RBC recovery, but may not be appropriate in terms of iron store regeneration. The tendency to shorten the donation interval should be reconsidered in light of the measurements of iron storage. The use of ferritin levels is recommended as a preselection criterion for allogeneic 2-unit RBC apheresis.

Adult↗

[Influence of reflex zone therapy of the feet on intestinal blood flow measured by color Doppler sonography].

OBJECTIVE: An influence on organ-associated blood flow is considered as a possible mechanism of action of reflex zone massage of the feet (FRZM) therapy. In the present study we investigated whether changes in intestinal blood flow can be achieved by FRZM. MATERIAL AND METHODS: 32 healthy adults (19 women and 13 men) were randomly assigned to the treatment or the placebo group. Subjects of the treatment group received foot massage on the zones assigned to the intestines and those of the placebo group received massage on zones unrelated to the intestines. Before, during and after FRZM, the blood flow velocity, the peak systolic and the end diastolic velocities in the superior mesenteric artery as well as the resistive index as a parameter of vascular resistance were calculated. RESULTS: During FRZM, in the subjects of the treatment group there was a significant reduction in the resistive index (p = 0.021), suggesting an increase in the blood flow in the superior mesenteric artery and the subordinate vascular system. In contrast, there were no significant changes in the resistive index in the subjects of the placebo group. CONCLUSION: The reduction in the resistive index observed in the treatment group supports the assumption that FRZM improves blood flow in the organs considered to be associated with the specific foot zones, at least during the therapy process.

Adult↗

Experimental models of acute pancreatitis: are they suitable for evaluating therapy?

Since randomized controlled studies of severe acute human pancreatitis can be performed only with restrictions, at least some aspects of innovative therapy concepts should first be clarified in animal experiments. In vitro trials are inadequate for this purpose since they cannot simulate the complex course of severe acute pancreatitis. Animal test results can be transferred to clinical practice if the results are based on trials with established models, standardized methods, and a study design imitating the clinical situation. This contribution discusses the demands on such an animal model of acute pancreatitis and a corresponding study protocol and presents models and protocols which meet these requirements. Concrete examples are presented to show that animal experiments are of great value under these conditions, especially in acute necrotizing pancreatitis. Further standardization of models, protocols, and monitoring should further improve future animal therapy studies at least to the extent that it is possible to select particularly promising substances, which should then be tested in randomized controlled trials.

Acute Disease↗

Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates.

BACKGROUND: We previously demonstrated that therapy with a new endothelin A receptor antagonist (ET-RA) significantly reduced mortality rates in severe acute pancreatitis (AP) in the rat without attenuating local signs of disease severity (intrapancreatic protease activation, acinar cell necrosis). This raised the question as to why ET-RA was so effective. The purpose of this study was to assess the effect of ET-RA on microcirculation (particularly capillary permeability) within and outside of the pancreas on intravascular fluid loss and extravascular fluid sequestration and on distant organ function. METHODS: Severe AP was induced in rats by standardized intraductal bile acid infusion and cerulein hyper-stimulation. Starting 6 hours (n = 24 rats) and 12 hours (n = 30 rats) after the onset of AP, animals randomly received either the ET-RA (LU-135252) or saline solution with fluid resuscitation (6 mL/kg/h Ringer's lactate). At 24 hours, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Further monitoring included cardiorespiratory and renal parameters, hematocrit levels and quantification of ascites and pleural effusions, and acinar cell necrosis at autopsy. Groups of sham-operated healthy animals (n = 6 animals each) that had been treated according to the same protocol served as control animals. RESULTS: ET-RA treatment that was started 6 hours after AP-induction significantly decreased hematocrit levels (38% +/- 1% vs 45% +/- 2% with saline solution treatment), reduced ascites and pleural effusions (6.7 +/- 1.3 mL vs 11.9 +/- 1.3 mL), and improved urine production (4.8 +/- 0.5 mL vs 2.9 +/- 0.6 mL) and respiratory parameters. Moreover, all microcirculatory parameters were improved; in particular, capillary permeability was stabilized (158% +/- 9% vs 248% +/- 8% in the colon). These beneficial effects were also seen when therapy was delayed until 12 hours after AP induction. Pancreatic necrosis was not significantly reduced. The overall mortality rate was 12% in ET-RA-treated animals and 42% in saline solution-treated control animals (P <.05). In healthy animals ET-RA did not significantly alter the target parameters, except for a reduction of capillary permeability in the pancreas. CONCLUSIONS: Improved microcirculation and stabilized capillary permeability in ET-RA-treated animals together with reduced intravascular fluid loss and extravascular fluid sequestration and improved renal and pulmonary function (1) may explain improved survival in this model, (2) support the hypothesis that systemic disease sequelae significantly contribute to outcome in AP, and (3) suggest that ET-RA may be a promising therapeutic tool in AP because it counteracts microcirculatory disorders that contribute to pancreatitis-associated organ dysfunction even when therapy is delayed to a point at which pancreatic injury may no longer be influenced.

Acute Disease↗

Effect of endothelin and endothelin receptor blockade on capillary permeability in experimental pancreatitis.

BACKGROUND: Capillary leakage with fluid loss into the third space contributes to many of the early systemic complications in severe acute pancreatitis. There has been increasing interest in endothelin as one of the factors affecting capillary permeability. AIM: To elucidate further the role of endothelin in the development of capillary leakage in acute pancreatitis by investigating the effect of exogenous endothelin administration and endothelin receptor blockade in sham operated animals and two models of acute pancreatitis. METHODS: Determination of capillary permeability in the pancreas and colonic mucosa by quantifying extravasation of fluorescein labelled dextran using a novel computer assisted video image analysis system. RESULTS: Pancreatic and colonic capillary permeability increased stepwise from mild to severe acute pancreatitis. Endothelin increased pancreatic and colonic capillary permeability in healthy animals and animals with mild acute pancreatitis but had no additional adverse effect in severe acute pancreatitis. Endothelin receptor blockade decreased pancreatic capillary permeability in sham operated rats but had no effect on the colon. In mild and severe acute pancreatitis, endothelin receptor blockade stabilised increased capillary permeability in both the pancreas and colon. CONCLUSIONS: Endothelin plays an important role in mediating capillary permeability in the pancreas. In severe pancreatitis, it increases capillary permeability even outside the pancreas, thereby contributing to capillary leakage. Endothelin receptor blockade significantly reduces capillary permeability in acute pancreatitis both in and outside the pancreas, suggesting a therapeutic approach to counteract capillary leakage in severe acute pancreatitis.

Animals↗

Effect of fluid resuscitation with and without endothelin A receptor blockade on hemoconcentration and organ function in experimental pancreatitis.

BACKGROUND: Intravascular fluid loss contributes to pancreatitis-associated multiple organ dysfunction and is thus a major target for therapy in this life-threatening disease. AIM: To evaluate intravascular fluid loss and extravascular fluid sequestration together with cardiorespiratory and renal function in a well-established rat model of severe acute pancreatitis (AP) and to investigate the effect of fluid resuscitation with and without endothelin receptor A blockade on these parameters. METHOD: Induction of AP in rats by a standardized bile salt infusion into the pancreatic duct and intravenous cerulein hyperstimulation. Six hours after AP induction, animals were randomized into 4 groups to receive (1) no therapy; (2) 4 ml/kg/h Ringer's lactate (RL) i.v.; (3) 8 ml/kg/h RL i.v., or (4) 4 ml/kg/h RL plus an endothelin receptor antagonist. Target parameters measured before and after AP induction and during the 24-hour observation period included: mean arterial blood pressure, heart rate, hematocrit, arterial blood gases, urine production, ascites and pleural effusions. RESULTS: After 6 h, all animals presented with severe hemoconcentration (hematocrit >57%) and oliguria (<0.5 ml/6 h). Cardiorespiratory parameters were within the normal range. Up to 12 h after AP induction, animals without therapy had an increased hematocrit and oliguria and developed metabolic acidosis. Animals receiving fluid resuscitation had a significant drop in hematocrit and maintained compensated blood gas values. A significant increase in urine production was only observed in animals given 8 mg/kg/h RL. Between 12 and 24 h, urine production significantly increased with fluid resuscitation and respiratory parameters stabilized except for animals treated with 8 ml/kg/h RL which developed arterial hypoxia and hypercapnia. CONCLUSIONS: Intravascular fluid loss and extravascular fluid sequestration together with decreased urine production characterize the early phase of this model of severe AP. Massive fluid resuscitation necessary for increasing urine output may lead to respiratory distress. Reduction of intravascular fluid loss by endothelin receptor blockade is associated with improved renal and respiratory function.

Acute Disease↗

Does glutamine reduce bacterial translocation? A study in two animal models with impaired gut barrier.

Failure of intestinal barrier function and subsequent translocation of bacteria from the gut are believed to play a decisive role in the development of systemic septic complications, for example, following major trauma or major abdominal surgery. This study evaluated: (a) the effect of glutamine on colonic microcirculation and electrophysiological parameters reflecting gut barrier function, (b) the translocation of live bacteria to extraintestinal organs, and (c) disease outcome in two animal models with impaired gut barrier function. Severe acute pancreatitis or colitis was induced in rats randomized for therapy with or without glutamine (0.5 g/kg daily). After 48 h one animal group was prepared for intravital microscopy of colonic capillary blood flow and electrophysiological measurement of gut permeability; another was killed after 96 h for histological and microbiological examination. In animals with pancreatitis, glutamine (Gln) supplementation significantly improved gut permeability, i.e., Gln increased colonic transmucosal resistance from 67+/-7 to 92+/-3 Omega/cm(2) and decreased mannitol flux through the epithelium by 53%. Capillary blood flow in the colonic mucosa was improved by 25%. The prevalence of pancreatic infections was reduced from 86% in animals on standard parenteral nutrition to 33% in animals given the Gln-enriched diet (P<0.05); mortality decreased by 32%. In colitis, Gln had no significant effect on these parameters except for improving colonic capillary blood flow in colon segments not adjacent to the major injury site. Glutamine supplementation improves colonic capillary blood flow, stabilizes gut permeability, and reduces secondary pancreatic infections and mortality in severe rodent pancreatitis, but it is not helpful in colitis. This confirms previous reports that glutamine stabilizes gut barrier function only in certain diseases. Our experimental data strongly suggest that acute pancreatitis (rather than colitis) is one of the diseases with gut barrier dysfunction in which glutamine substitution may be helpful to reduce bacterial translocation and should therefore be tested in a controlled clinical trial.

Animals↗