Quantitative determination of mogroside V in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

Mogroside V is the most abundant (approximately 0.50%) cucurbitane-type triterpene glycoside in Siraitia grosvenorii and exhibits significant antitussive, expectorant, anti-carcinogenic, and anti-inflammatory effects. A sensitive, robust and selective liquid chromatography tandem with mass spectrometry (LC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of mogroside V in rat plasma. Samples were prepared through an one-step deproteinization procedure with 250 µL of methanol to a 75-µL plasma sample. Plasma samples were effectively separated on a Shiseido Capcell Pak UG120 C18 column (2.0 × 50mm, 3.0µm) using a mobile phase consisting of methanol: water (60:40, v/v) with an isocratic elution program. The running time for each sample was 7.0 min and the elution times of mogroside V and IS were 2.0 and 4.8 min, respectively. The detection relied on a triple-quadrupole tandem with mass spectrometer equipped with negative-ion electrospray ionization interface by selected-reaction monitoring (SRM) of the transitions at m/z 1285.6 → 1123.7 for mogroside V and m/z 1089.6 → 649.6 for IS. The calibration curve was linear over the range of 96.0-96000ng/mL with a limit of quantitation (LOQ) of 96.0ng/mL. Intra-day and inter-day precisions were both <10.1%. Mean recovery and matrix effect of mogroside V in plasma were in the range of 91.3-95.7% and 98.2-105.0%, respectively. This method was successfully applied in the pharmacokinetic study of mogroside V after intravenous or intraperitoneal administration of 1.12mg/kg mogroside V in rats.

Evaluation of nasal mucociliary clearance using saccharin test in smokers: A prospective study.

BACKGROUND AND AIM: Nasal mucociliary clearance time (NMCT) can be measured with the saccharine clearance test which is an inexpensive and easy method. The aim of the present study was to compare and evaluate NMCT using the saccharine clearance test in smokers and non-smokers. MATERIALS AND METHODS: Eighty-five patients whose ages ranged from 18 to 65 years were included in the study. Fifty of the patients were smokers (Group 1) while 35 were healthy, non-smoking volunteers (Group 2). Saccharin clearance test was used to evaluate NMCT in both groups. The results obtained were compared and the statistical analyses were performed using the Statistical Package for Social Sciences (SPSS). RESULTS: NMCT was statistically significantly higher in Group 1 as compared to Group 2 (P < .001, Mann-Whitney U test). However, in cumulative smoking duration (pack-year), Fagerström test values and gender categories, there was no statistically significant difference in the average NMCT values of the two groups (P = .943 vs P = .812 respectively), P = .45). CONCLUSION: Mucociliary activity, the primary defence mechanism of the respiratory epithelium, is significantly depressed in smokers. Our findings showed that the said depression is not associated with the number of cigarettes smoked, duration of smoking or nicotine dependence.

Torsemide Fast Dissolving Tablets: Development, Optimization Using Box-Bhenken Design and Response Surface Methodology, In Vitro Characterization, and Pharmacokinetic Assessment.

The present study planed to develop new fast dissolving tablets (FDTs) of torsemide. Solid dispersions (SDs) of torsemide and sorbitol (3:1) or polyvinylpyrrolidone (PVP) k25 were prepared. The prepared SDs were evaluated for in-vitro dissolution. Fourier transform infrared spectroscopy and differential scanning calorimetry for SDs revealed no drug/excipient interactions and transformation of torsemide to the amorphous form. Torsemide/sorbitol SD was selected for formulation of torsemide FDTs by direct compression method. Box-Bhenken factorial design was employed to design 15 formulations using croscarmellose sodium and crospovidone at different concentrations. The response surface methodology was used to analyze the effect of changing these concentrations (independent variables) on disintegration time (Y1), percentage friability (Y2), and amount torsemide released at 10 min. The physical mixtures of torsemide and the used excipients were evaluated for angle of repose, Hausner's ratio, and Carr's index. The prepared FDTs tablets were evaluated for wetting and disintegration time, weight variation, drug content, percentage friability, thickness, hardness, and in vitro release. Based on the in-vitro results and factorial design characterization, F10 and F7 were selected for bioavailability studies following administration to Albino New Zealand rabbits. They showed significantly higher C max and (AUC0-12) and shorter T max than those obtained after administration of the corresponding ordinary commercial Torseretic ® tablets. Stability study was conducted for F10 that showed good stability upon storage at 30°C/75% RH and 40°C/75% RH for 3 months.

Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale.

Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels.

Dexamethasone reverses the effects of high glucose on human retinal endothelial cell permeability and proliferation in vitro.

Diabetic macular oedema (DMO), a leading cause of preventable visual loss in the working population, is caused by an increase in microvascular endothelial cell permeability, and its prevalence is on the increase in parallel with the rising worldwide prevalence of diabetes. It is known that retinal vascular leakage in DMO is contributed to by VEGF upregulation as well as non-VEGF dependent inflammatory pathways, and the potential use of anti-inflammatory agents such as the glucocorticoids, including dexamethasone are being extensively studied. However, the mechanisms of action of dexamethasone in DMO reduction are not fully understood. Using human primary retinal endothelial cells (REC) the in vitro effect of dexamethasone in modulating the proliferation, permeability and gene expression of key tight and adheren junction components, and the expression of angiopoietins (Ang) 1 and 2 in high (25 mM) glucose conditions were investigated. High glucose decreased REC proliferation, an effect that was reversed by dexamethasone. High glucose conditions significantly increased REC permeability and decreased claudin-5, occludin and JAM-A gene expression; dexamethasone was effective in partially reversing these changes, restoring EC permeability to the normal or near normal state. High glucose levels resulted in reduction of Ang1 secretion, although Ang2 levels were consistently high. DEX increased Ang1 and decreased Ang2, indicating that the balance of Ang1/Ang2 may be important in determining functional changes in REC under high glucose conditions.

Occurrence of artificial sweeteners in human liver and paired blood and urine samples from adults in Tianjin, China and their implications for human exposure.

In this study, acesulfame (ACE), saccharin (SAC) and cyclamate (CYC) were found in all paired urine and blood samples collected from healthy adults, with mean values of 4070, 918 and 628 ng mL(-1), respectively, in urine and 9.03, 20.4 and 0.72 ng mL(-1), respectively, in blood. SAC (mean: 84.4 ng g(-1)) and CYC (4.29 ng g(-1)) were detectable in all liver samples collected from liver cancer patients, while ACE was less frequently detected. Aspartame (ASP) was not found in any analyzed human sample, which can be explained by the fact that this chemical metabolized rapidly in the human body. Among all adults, significantly positive correlations between SAC and CYC levels were observed (p < 0.001), regardless of human matrices. Nevertheless, no significant correlations between concentrations of SAC (or CYC) and ACE were found in any of the human matrices. Our results suggest that human exposure to SAC and CYC is related, whereas ACE originates from a discrete source. Females (or young adults) were exposed to higher levels of SAC and CYC than males (or elderly). The mean renal clearance of SAC was 730 mL per day per kg in adults, which was significantly (p < 0.001) lower than those for CYC (10 800 mL per day per kg) and ACE (10 300 mL per day per kg). The average total daily intake of SAC and ACE was 9.27 and 33.8 µg per kg bw per day, respectively.

Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors.

G protein-coupled receptors mediate responses to a myriad of ligands, some of which regulate adipocyte differentiation and metabolism. The sweet taste receptors T1R2 and T1R3 are G protein-coupled receptors that function as carbohydrate sensors in taste buds, gut, and pancreas. Here we report that sweet taste receptors T1R2 and T1R3 are expressed throughout adipogenesis and in adipose tissues. Treatment of mouse and human precursor cells with artificial sweeteners, saccharin and acesulfame potassium, enhanced adipogenesis. Saccharin treatment of 3T3-L1 cells and primary mesenchymal stem cells rapidly stimulated phosphorylation of Akt and downstream targets with functions in adipogenesis such as cAMP-response element-binding protein and FOXO1; however, increased expression of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α was not observed until relatively late in differentiation. Saccharin-stimulated Akt phosphorylation at Thr-308 occurred within 5 min, was phosphatidylinositol 3-kinase-dependent, and occurred in the presence of high concentrations of insulin and dexamethasone; phosphorylation of Ser-473 occurred more gradually. Surprisingly, neither saccharin-stimulated adipogenesis nor Thr-308 phosphorylation was dependent on expression of T1R2 and/or T1R3, although Ser-473 phosphorylation was impaired in T1R2/T1R3 double knock-out precursors. In mature adipocytes, artificial sweetener treatment suppressed lipolysis even in the presence of forskolin, and lipolytic responses were correlated with phosphorylation of hormone-sensitive lipase. Suppression of lipolysis by saccharin in adipocytes was also independent of T1R2 and T1R3. These results suggest that some artificial sweeteners have previously uncharacterized metabolic effects on adipocyte differentiation and metabolism and that effects of artificial sweeteners on adipose tissue biology may be largely independent of the classical sweet taste receptors, T1R2 and T1R3.

Effects of cigarette smoking intensity on the mucociliary clearance of active smokers.

BACKGROUND: Smoking impairs mucociliary clearance and increases respiratory infection frequency and severity in subjects with and without smoking-related chronic lung diseases. OBJECTIVE: This study evaluated the effects of smoking intensity on mucociliary clearance in active smokers. METHODS: Seventy-five active smokers were grouped into light (1-10 cigarettes/day; n = 14), moderate (11-20 cigarettes/day; n = 34) and heavy smokers (≥21 cigarettes/day; n = 27) before starting a smoking cessation programme. Smoking behaviour, nicotine dependence, pulmonary function, carbon monoxide in exhaled air (exCO), carboxyhaemoglobin (COHb) and mucociliary clearance measured by the saccharin transit time (STT) test were all evaluated. An age-matched non-smoker group (n = 24) was assessed using the same tests. RESULTS: Moderate (49 ± 7 years) and heavy smokers (46 ± 8 years) had higher STT (p = 0.0001), exCO (p < 0.0001) and COHb (p < 0.0001) levels compared with light smokers (51 ± 15 years) and non-smokers (50 ± 11 years). A positive correlation was observed between STT and exCO (r = 0.4; p < 0.0001), STT and cigarettes/day (r = 0.3, p = 0.02) and exCO and cigarettes/day (r = 0.3, p < 0.01). CONCLUSION: Smoking impairs mucociliary clearance and is associated with cigarette smoking intensity.

Effect of the artificial sweetener, acesulfame potassium, a sweet taste receptor agonist, on glucose uptake in small intestinal cell lines.

INTRODUCTION: Sweet taste receptors may enhance glucose absorption. AIM: This study aimed to explore the cell biology of sweet taste receptors on glucose uptake. HYPOTHESIS: Artificial sweeteners increase glucose uptake via activating sweet taste receptors in the enterocyte to translocate GLUT2 to the apical membrane through the PLC ßII pathway. METHODS: Caco-2, RIE-1, and IEC-6 cells, starved from glucose for 1 h were pre-incubated with 10 mM acesulfame potassium (AceK). Glucose uptake was measured by incubating cells for 1 to 10 min with 0.5-50 mM glucose with or without U-73122, chelerythrine, and cytochalasin B. RESULTS: In Caco-2 and RIE-1 cells, 10 mM AceK increased glucose uptake by 20-30 % at glucose >25 mM, but not in lesser glucose concentrations (<10 mM), nor at 1 min or 10 min incubations. U-73122 (PLC ßII inhibitor) inhibited uptake at glucose >25 mM and for 5 min incubation; chelerythrine and cytochalasin B had similar effects. No effect occurred in IEC-6 cells. Activation of sweet taste receptors had no effect on glucose uptake in low (<25 mM) glucose concentrations but increased uptake at greater concentrations (>25 mM). CONCLUSIONS: Role of artificial sweeteners on glucose uptake appears to act in part by effects on the enterocyte itself.

Plasma insulin and glucose time courses after biliary pancreatic diversion in morbidly obese patients with and without diabetes.

BACKGROUND: The exact mechanism for the dramatic effect of surgical procedures for obesity on type 2 diabetes remains unknown. METHODS: Five diabetic morbidly obese patients and 5 nondiabetic morbidly obese patients undergoing biliopancreatic diversion were compared retrospectively. A 75-g trans-gastrostomy glucose tolerance test was administered on the fifth day postoperatively and a standard 75-g oral glucose tolerance test was performed on the seventh day postoperatively, with blood sampling for measuring plasma glucose and insulin levels at 0, 30, 60, 90, 120, and 180 minutes. RESULTS: All 5 diabetic patients were shown, at the same time, still to have diabetes or an impaired glucose tolerance test when tested through the biliopancreatic limb but patients were normal when tested through the new alimentary channel. No significant difference was seen in the nondiabetic patients. CONCLUSIONS: Biliopancreatic diversion can completely normalize the glycemic cycle in type 2 diabetes patients in the week after the intervention, even before any significant weight loss has occurred. The surgical procedure itself, designed to exclude most of the stomach, duodenum, and part of the jejunum, directly affects carbohydrate homeostasis.

Chronic toxicity and carcinogenicity of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame) in the rat.

Groups of 55 male and 55 female Han Wistar rats were administered advantame (98.9-99.8% purity) in the diet at concentrations of 0, 2000, 10,000, or 50,000 ppm for 104 weeks, following parental exposure to the same levels from prior to mating and throughout gestation. Additional groups of 20 rats/sex and 10 rats/sex were dosed for a period of 52 weeks and constituted the toxicity and reversibility phases of the study. Achieved doses of advantame over the carcinogenicity study were 0, 97, 488, and 2621 mg/kg body weight/day in males and 0, 125, 630, and 3454 mg/kg body weight/day in females, respectively. A high incidence of a pale and swollen anus and changes in fecal composition were observed in the high-dose groups. There was no effect of treatment on mortality. Body weight gain in the high-dose males (50,000 ppm) was slightly reduced compared to controls after 52 and 104 weeks of treatment; the decrease was not considered to be of toxicological significance, but due to the non-nutritive nature of the high dietary concentration of advantame. During the toxicity phase, food conversion efficiency was slightly decreased in both sexes, at the 50,000 ppm dose level. Given the non-nutritive content of the diet, this finding was not considered biologically significant. There were no relationships between treatment and the results of hematological or urinalysis investigations. Clinical chemistry evaluations showed consistently lower plasma urea concentrations in both sexes treated at 50,000 ppm, which was reversed during the 6-week recovery phase following 52 weeks of treatment, indicating a lack of permanent effects. Terminal investigations at both the 52 and 104-week revealed a number of intergroup differences in absolute and/or relative organ weights; however, the differences did not show dose-response relationships, were minor in nature, and/or occurred only in one sex, and were not associated with any pathological findings, and they were considered not to be treatment-related. Evaluation of the histopathology of the carcinogenicity phase animals revealed an increased incidence of pancreatic islet cell carcinomas in males (incidence rates of 0/55, 1/55, 2/55, and 3/55 in the 0, 2000, 10,000, or 50,000 ppm groups, respectively) and of mammary gland adenomas in the high-dose females (incidence rates of 0 in the control through 10,000 ppm dose groups and 4/41 in the 50,000 ppm dose group). The incidence rates of these tumors did not attain statistical significance and/or remained within background historical control values, and they were considered to be unrelated to advantame treatment. The no-observed-adverse-effect level was considered to be 50,000 ppm in the diet, the highest concentration tested, equivalent to 2621 and 3454 mg/kg body weight/day in males and females, respectively. Advantame was concluded to be without carcinogenic activity.

Determination of parabens in sweeteners by capillary electrochromatography

Parabens, common food preservatives, were analysed by capillary electrochromatography, using a commercial C18 silica (3 µm, 40 cm × 100 µm i. d.) capillary column as separation phase. In order to optimise the separation of these preservatives, the effects of mobile phase composition on the separation were evaluated, as well as the applied voltage and injection conditions. The retention behavior of these analytes was strongly influenced by the level of acetonitrile in the mobile phase. An optimal separation of the parabens was obtained within 18.5 minutes with a pH 8.0 mobile phase composed of 50:50 v/v tris(hydroxymethyl)aminomethane buffer and acetonitrile. The method was successfully applied to the quantitative analysis of paraben preservatives in sweetener samples with direct injection.

Os parabenos, empregados como conservantes em alimentos, foram analisados por eletrocromatografia capilar, empregando uma coluna comercial recheada com partículas de sílica-C18 (3 µm, 40 cm × 100 µm d. i.) como fase estacionária de separação. Para otimizar a separação destes conservantes foram avaliados os efeitos da composição da fase móvel na separação, bem como a voltagem e as condições de injeção. O comportamento de retenção dos analitos foi fortemente influenciado pela proporção de acetonitrila na fase móvel. A separação dos parabenos foi alcançada em 18,5 min com uma fase móvel contendo tampão tris(hidroximetil)aminometano e acetonitrila na proporção 50:50 v/v. O método foi aplicado na análise quantitativa de parabenos em adoçantes empregando a injeção direta das amostras.

Stevioside and related compounds: therapeutic benefits beyond sweetness.

Stevioside, an abundant component of Stevia rebaudiana leaf, has become well-known for its intense sweetness (250-300 times sweeter than sucrose) and is used as a non-caloric sweetener in several countries. A number of studies have suggested that, beside sweetness, stevioside along with related compounds, which include rebaudioside A (second most abundant component of S. rebaudiana leaf), steviol and isosteviol (metabolic components of stevioside) may also offer therapeutic benefits, as they have anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions. It is of interest to note that their effects on plasma glucose level and blood pressure are only observed when these parameters are higher than normal. As steviol can interact with drug transporters, its role as a drug modulator is proposed. This review summarizes the current knowledge of the pharmacological actions, therapeutic applications, pharmacokinetics and safety of stevioside and related compounds. Although much progress has been made concerning their biological and pharmacological effects, questions regarding chemical purity and safety remain unsolved. These issues are discussed to help guide future research directions.

Overview: the history, technical function and safety of rebaudioside A, a naturally occurring steviol glycoside, for use in food and beverages.

Rebaudioside A is a sweet tasting steviol glycoside extracted and purified from Stevia rebaudiana (Bertoni). Steviol glycosides can currently be used as a food ingredient in only a handful of countries. Questions on specifications, safety and special population effects have prevented steviol glycosides from obtaining a legal status permitting their use as a sweetener in most countries. A set of papers reporting results of research studies and reviews has been compiled in this Supplement to definitively answer unresolved questions. Specifically, recently completed studies on the general and reproductive toxicity of rebaudioside A corroborate studies carried out with purified steviol glycosides demonstrating safety at high dietary intake levels. Comparative metabolism studies provide further affirmation of the common metabolic pathway for all steviol glycosides and the common metabolism between rats and humans. Finally, clinical studies provide further evidence that purified rebaudioside A has no effect on either blood pressure or glucose homeostasis. This paper summarizes the information used to conclude that high purity rebaudioside A (rebiana) produced to food-grade specifications and according to Good Manufacturing Practices is safe for human consumption under its intended conditions of use as a general purpose sweetener.

l-Cysteine and glutathione restore the modulation of rat frontal cortex Na+, K+ -ATPase activity induced by aspartame metabolites.

BACKGROUND: Studies have suggested that aspartame (ASP) ingestion is implicated in neurological problems. AIM: The aim of this study was to evaluate rat frontal cortex Na+, K+ -ATPase and Mg2+ -ATPase activities after incubation with ASP or each of its metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (asp) separately. METHOD: Suckling rat frontal cortex homogenates or pure Na+, K+ -ATPase were incubated with ASP metabolites. Na+, K+ -ATPase and Mg2+ -ATPase activities were measured spectrophotometrically. RESULTS: Incubation of frontal cortex homogenate or pure Na+, K+ -ATPase with various ASP concentrations as expected in the cerebrospinal fluid (CSF) after ASP consumption of 34, 150 or 200mg/kg, decreased the frontal cortex enzyme activity by 33%, 53% or 57%, respectively, whereas pure enzyme was remarkably stimulated. Moreover, incubation of frontal cortex homogenate with each one of the expected ASP metabolites in the CSF, except MeOH, which are related to the intake of the above mentioned doses of the sweetener, resulted in an activation of the membrane Na+, K+ -ATPase, as well as pure enzyme. Frontal cortex Mg2+-ATPase remained unaltered. Addition of l-cysteine (cys) or reduced glutathione (GSH) to ASP metabolites mixtures, corresponding to 150 or 200mg/kg doses of the sweetener, completely or partially restored to normal the modulated membrane and pure Na+, K+ -ATPase activities. CONCLUSION: CSF concentrations of the sum of ASP metabolites corresponding to the intake of common, abuse or toxic doses (34 or 150 or 200mg/kg, respectively) of the additive significantly increased rat frontal cortex Na+, K+ -ATPase and pure enzyme activities. Cys or GSH completely or partially restored to normal both enzyme activities, possibly due to amelioration of the cellular GSH reduction from the action of MeOH, a metabolite of the sweetener and/or by their scavenging effect.

Altered intestinal function in patients with chronic heart failure.

OBJECTIVES: We evaluated morphology and function of the gut in patients with chronic heart failure (CHF). BACKGROUND: Intestinal translocation of bacterial endotoxin may contribute to the inflammatory state observed in patients with CHF. The morphology and function of the gut may be abnormal. METHODS: We studied 22 patients with CHF (age 67 +/- 2 years, left ventricular ejection fraction [LVEF] 31 +/- 1%, New York Heart Association functional class 2.3 +/- 0.1, peak VO2 15.0 +/- 1.0 ml/kg/min) and 22 control subjects (62 +/- 1 years, LVEF 68 +/- 2%, peak VO2 24.7 +/- 1.3 ml/kg/min). Bowel wall thickness was assessed by transcutaneous sonography, small intestinal permeability by the lactulose-mannitol test, passive carrier-mediated transport by D-xylose test, large intestinal permeability by sucralose test (5- and 26-h urine collection, high-performance liquid chromatography), and mucosal bacterial biofilm by fluorescence in situ hybridization in biopsies taken during sigmoidoscopy. RESULTS: Chronic heart failure patients, compared with control patients, showed increased bowel wall thickness in the terminal ileum (1.48 +/- 0.16 mm vs. 1.04 +/- 0.08 mm), ascending colon (2.32 +/- 0.18 mm vs. 1.31 +/- 0.14 mm), transverse colon (2.19 +/- 0.20 vs. 1.27 +/- 0.08 mm), descending colon (2.59 +/- 0.18 mm vs. 1.43 +/- 0.13 mm), and sigmoid (2.97 +/- 0.27 mm vs. 1.64 +/- 0.14 mm) (all p < 0.01). Chronic heart failure patients had a 35% increase of small intestinal permeability (lactulose/mannitol ratio: 0.023 +/- 0.001 vs. 0.017 +/- 0.001, p = 0.006), a 210% increase of large intestinal permeability (sucralose excretion: 0.62 +/- 0.17% vs. 0.20 +/- 0.06%, p = 0.03), and a 29% decrease of D-xylose absorption, indicating bowel ischemia (26.7 +/- 3.0% vs. 37.4 +/- 1.4%, p = 0.003). Higher concentrations of adherent bacteria were found within mucus of CHF patients compared with control subjects (p = 0.007). CONCLUSIONS: Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified. Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition.

Evaluation of intestinal mucosal permeability function in patients with acute pancreatitis.

This study aims to evaluate the intestinal mucosal permeability in patients with acute pancreatitis. The lactulose:mannitol (L:M) ratio was used to assess permeability. It is an inexpensive and quite reliable method. The intestinal permeability was increased in patients with acute pancreatitis compared with the controls. In addition, patients with severe pancreatitis had higher intestinal barrier dysfunction compared with patients with mild pancreatitis, the L:M ratio being .2 and .029, respectively. It was also concluded that the permeability increased gradually over the course of pancreatitis and was maximum at day 7 (P < .01). This provides a window of opportunity for therapeutic intervention to prevent the late observed increase in intestinal permeability.

Scanning electron microscopy of ciliae and saccharine test for ciliary function in septal deviations.

OBJECTIVE: To investigate the difference in mucociliary clearance and surface mucosal structure of the nasal septum and lateral nasal wall in patients with and without septal deviation. METHOD: The saccharine-dye test was used to measure the mucociliary clearance time in both nasal cavities of 20 patients with nasal septal deviation (study group) and was compared with that of 30 patients without septal deviation (control group). Bilateral septal and lateral nasal wall mucosal biopsies were taken from the study group during septoplasty, and unilateral biopsies were taken from 10 of the control group. These biopsies were studied under the scanning electron microscope. RESULTS: In the study group, mucociliary clearance on the side opposite the septal deviation was significantly slower than on the other side. Mucociliary clearance on both sides of the deviated septum of the study group was significantly slower than clearance in the control group. There was no statistically significant difference in the distribution of mucosal cilia of the cavities on either side of the deviated septum in the study group, nor between the distribution in the study group and controls. CONCLUSION: Patients with septal deviation display no change in mucosal surface anatomy but have decreased mucociliary activity on both sides of the deviation, the least activity being on the side opposite the deviation.

Intestinal permeability and systemic endotoxemia after laparotomic or laparoscopic cholecystectomy.

OBJECTIVE: Because laparoscopic cholecystectomy (LC) is widely recognized as a "mild" or "mini-invasive" kind of surgery, in this prospective nonrandomized study, we investigated the effect of intestinal manipulation on intestinal permeability and endotoxemia, in patients undergoing elective cholecystectomy by comparing the laparoscopic with the laparotomic approach. SUMMARY BACKGROUND DATA: The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. METHODS: Forty-three patients undergoing elective cholecystectomy were divided into either the laparotomic (n = 22) or laparoscopic (n = 21) approach. Intestinal permeability was measured preoperatively and at day 1 and day 3 after surgery using the lactulose/mannitol absorption test. Serial venous blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, and at 12, 24, and 48 hours after surgery, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay. RESULTS: Intestinal permeability was significantly increased at day 1 [0.106 +/- 0.005 (mean +/- SEM)] in the laparotomic group compared with the preoperative level (0.019 +/- 0.005, P < 0.05) and to the laparoscopic group at day 1 (0.019 +/- 0.005, P < 0.05), which showed no change in comparison with the preoperative level. A significantly higher concentration of systemic endotoxin was detected intraoperatively in the laparotomic group of patients in comparison to the laparoscopic group (P < 0.05). There was a significant positive correlation between systemic endotoxemia and intestinal permeability (r(s) = 0.958; P = 0.001). CONCLUSIONS: An increase in intestinal permeability and a greater degree of systemic endotoxemia are observed during laparotomic cholecystectomy. This suggests that intestinal manipulation may impair gut mucosal barrier function and contribute to the systemic inflammatory response see in open cholecystectomy.