Soft-sheath, stiff-core microfiber hydrogel for coating vascular implants.

Vascular implants remain clinically challenged due to often-occurring thrombosis and stenosis. Critical to addressing these complications is the design of implant material surfaces to inhibit the activities of platelets, smooth muscle cells (SMCs) and inflammatory cells. Recent mechanobiology studies accentuate the significance of material elasticity to cells and tissues. We thus developed and characterized an implant coating composed of hybrid, viscoelastic microfibers with coaxial core-sheath nanostructure. The coating over metallic stent material was formed by first depositing coaxially-electrospun fibers of poly(L-lactic acid) core and polyethylene glycol dimethacrylate sheath, and then polymerizing fibers with various UV times. Material characterizations were performed to evaluate the coating structure, mechanical property and biocompatibility. Results showed that coaxial microfibers exhibited arterial-like mechanics. The soft surface, high water content and swelling ratio of the coaxial fibers resemble hydrogels, while they are mechanically strong with an elastic modulus of 172-729 kPa. The coating strength and surface elasticity were tunable with the photopolymerization time. Further, the elastic fibers, as conformal coating on stent metal, strongly reduced SMC overgrowth and discouraged platelet adhesion and activation, compared to bare metals. Importantly, after 7-day subcutaneous implantation, coaxial fiber-coated implants showed more favorable in vivo responses with reduced tissue encapsulation, compared to bare stent metals or those coated with a two-layered fiber mixture composed of fibers from individual polymers. The excellent biocompatibility aroused from nanostructural interfaces of hybrid fibers offering hydrated, soft, nonfouling microenvironments. Such integrated fiber system may allow creation of advanced vascular implants that possess physico-mechanical properties of native arteries.

Are there differences between patients with and without the homozygous--13910CC genetic variant in the MCM-6 gene upstream from the lactase gene?--A non-randomised, two armed intervention study without control group.

BACKGROUND: Patients with chronic abdominal complaints are a diagnostic challenge for general practitioners (GP). Lactose intolerance (LI) often remains undiagnosed in these patients. Genetic testing for the homozygous -13910CC variant of the MCM-6 gene (LI+) combined with a lactose-restricted diet (LRD) seems to be an acceptable approach. The primary aim of the study was to determine the effect of a LRD in patients with chronic abdominal complaints without a definite diagnosis, with or without the homozygous -13910CC variant. The secondary aim was to determine in family practices the prevalence of undiagnosed LI in these patients. METHODS: In 25 practices around Düsseldorf (Germany) all patients presenting with chronic abdominal complaints for at least 12 months without definite diagnosis were identified by their GPs. Patients participating underwent a MCM-6 gene test and all, including those not genetically predisposed, were asked to keep a LRD for eight weeks. Symptoms were evaluated three times over two months using a standardized gastrointestinal Questionnaire (GIQLI, max. score 144). RESULTS: 210 patients were included. The gene test revealed 29.5% genetically positive for the homozygous T-13910-C mutation (LI+). All patients showed a significant increase in GIQLI scores (improvement) during the observation period, i.e. after four and eight weeks on the diet (p = 0.001, two-way repeated measures ANOVA). There was no significant difference between both groups (LI+/LI-) at any point of symptom measurement. CONCLUSIONS: A lactose-restricted diet showed an unspecific positive effect for patients with chronic abdominal pain without a defined diagnosis. For the LI-group, this could be explained by an unspecific effect of a diet in general, e.g., getting special attention. This can be important for a group of patients probably having psychosomatic complaints focussed on the abdomen.

TU-E-BRA-06: Evaluation of a New MV X-Ray Detector Designed for the TomoTherapy® System.

PURPOSE: To evaluate the performance of a new MV X-ray detector prototype specifically designed for use on the TomoTherapy® System. METHODS: A gas-filled detector array, similar in concept to existing TomoTherapy detector arrays, has been designed and fabricated for the TomoTherapy System. Unlike existing detector arrays, the prototype detector array has a radius of curvature that matches the source-to-detector distance. Also, the internal structure of the detector such as the septa material and geometry has been optimized for MV X-rays. The prototype detector performance was assessed by measuring the signal properties of each of the detector channel signals. Signal, noise, and signal-to-noise ratios (SNR) were measured. Finally, the resulting MVCT image quality was assessed. RESULTS: The signal profile across the prototype detector more closely matches the incident X-ray beam intensity and, in particular, is missing the characteristic trough in the center of signal profiles from existing TomoTherapy detector arrays. Compared to an existing detector, the mean signal is approximately equal outside the central region. Inside the 100 central channels (out of 576 total channels), the prototype detector signal is substantially larger than the existing detector. The variation in the pulse-to-pulse signal (noise), after accounting for output fluctuations, is substantially lower with the new detector. The resulting SNR is an average of 18% higher across all channels, with an improvement of up to 36% for the central channels. The prototype detector yielded MVCT images that, compared to one typical system with an existing detector array, had 7% lower image noise in the periphery and 36% lower noise at the center of the image. CONCLUSIONS: This evaluation indicates that the performance of a new MV X-ray detector array prototype exceeds the performance of an existing detector array in terms of signal-to-noise ratio and resulting MVCT image quality.

An e-learning platform for guideline implementation--evidence- and case-based knowledge translation via the Internet.

OBJECTIVES: Effective knowledge translation in medicine is an essential element of a modern health care system. Evidence-based clinical practice guidelines (CPGs) are considered relevant instruments for the transfer of knowledge into clinical practice. To improve this transfer we have created Internet-based continuing medical education (CME) modules and online case-based learning objects. METHODS: Building upon existing CPGs, an e-learning platform including a multi-step review process was developed to generate CME modules. These CME modules were presented through a modified content management system (CMS) that fulfils specific requirements of CME. An online questionnaire using a four-point Likert scale was designed to receive mandatory feedback from participating physicians. In the second step of development, case-based learning objects were added to the CMS. RESULTS: Existing clinical practice guidelines allowed a rapid development of CME modules specific to individual clinical indications. The modified CMS proved to be technically stable but also resource-intensive. 3105 physicians registered and used the platform between June 2003 and April 2005. 95% of the physicians expressed positive feedback in an evaluation questionnaire; only 35% of physicians actually used the corresponding CPGs in practice. Suggestions from the CME users led to the development of interactive medical case-based learning objects related to the main topics of the CPGs. CONCLUSIONS: To support the implementation of CPGs, an Internet platform for CME including case-based learning objects and examination tests was developed. An interactive online CME platform can support active learning and may establish an additional stimulus for knowledge translation into daily medical practice.

[Online continuing medical education based on national disease management guidelines. The e-learning platform leitlinien-wissen.de]. / Online-Fortbildung auf der Basis nationaler Versorgungsleitlinien : Die Fortbildungsplattform leitlinien-wissen.de.

Effective translation of relevant knowledge into clinical practice is essential for modern health care systems. National Disease Management Guidelines (NDMG) are considered relevant instruments to support this transfer. To implement NDMG Internet-based continuing medical education (CME), modules and online case-based learning objects were designed and published. To ensure high quality the contents are based on NDMG and subjected to multi-step review processes. Presentation on the web was realized through a modified content management system. To obtain a CME certificate, completing an online questionnaire using a four-point Likert scale was mandatory. Between June 2003 and April 2005, 3,105 physicians were registered and used the platform: 95% of the physicians expressed positive feedback in the evaluation questionnaire, and 35% actually used the corresponding NDMG in practice. This prompted the development of interactive medical case-based learning objects as a second learning pathway. An Internet platform for CME including case-based learning objects can be a helpful tool to assure the provision of scientific knowledge for patient care.

Research productivity in the areas of child abuse and domestic violence.

Research productivity in the areas of child abuse and domestic violence was reviewed for the years 1990-1996 by examining articles published in Child Abuse and Neglect, the Journal of Family Violence, and the Journal of Interpersonal Violence. To examine productivity across institutions, quantification of productivity was based on ordinal position of authorship as previously used. Productivity across these three journals was also summed based on the 1987 composite productivity index formula of Howard, et al., and the data were compared with a productivity assessment based on a search process in the PsycLIT database. Rank-order correlations between the raw productivity total, the composite measure, and productivity based on first-authored publications in PsycLIT were all significant. The findings suggest that the composite measure represents a good estimate of productivity across the three journals and that publication in these three journals provides a good representation of research in the general areas of child abuse and domestic and interpersonal violence. The findings, along with implications regarding the relative utility of such information for selection of graduate programs that have a strong research focus on child abuse or domestic violence, are discussed.

Taxol-dependent transcriptional activation of IL-8 expression in a subset of human ovarian cancer.

Taxol is important in the treatment of both primary and drug-resistant ovarian cancer. Although Taxol is known to stabilize microtubules and block cell mitosis, the effectiveness of this drug exceeds that of other antimitotic agents, suggesting it may have an additional mode of action. Stimulated by murine macrophage studies indicating cytokine induction by Taxol, we have investigated proinflammatory cytokine expression in a series of cell lines and recent explants of human ovarian cancer. Taxol induced secretion of interleukin (IL) 8 but not IL-6, IL-1alpha, or IL-1beta in 4 of 10 samples. Induction was dependent on transcriptional activation, and, in contrast to murine macrophage studies, was apparently independent of an active lipopolysaccharide signaling pathway. Confluent cultures secreted as much IL-8 as proliferating cells. Taxol did not induce IL-8 in breast carcinoma, endometrial stromal, or T-lymphocyte or monocyte cultures. We propose that the local expression of this chemokine in vivo may elicit a host response similar in effectiveness to that of cytokine gene therapy. These data are the first to suggest that a chemotherapeutic agent may have a direct effect on transcription of cytokine and/or growth factor genes in ovarian cancer, and that this effect may not be restricted to proliferating tumor cells.

Hypoxic induction of gene expression in chronic granulomatous disease-derived B-cell lines: oxygen sensing is independent of the cytochrome b558-containing nicotinamide adenine dinucleotide phosphate oxidase.

Reduced oxygenation of a variety of cells results in transcriptional upregulation of several genes, including the hematopoietic hormone erythropoietin, the angiogenic vascular endothelial growth factor (VEGF), and glycolytic enzymes such as aldolase. Recently, the heme protein cytochrome b558 of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex has been proposed as a key component of the oxygen-sensing mechanism. Cytochrome b558 consists of the p22phox and gp91phox subunits and is essential for superoxide generation in phagocytes and B lymphocytes. Mutations in these subunits result in cytochrome b558-negative chronic granulomatous disease (cytb- CGD), an inherited disorder in humans characterized by reduced microbicidal activity due to deficient superoxide generation. To test whether NADPH oxidase is involved in oxygen sensing, we exposed wild-type B-cell lines as well as cytb- CGD-derived B cell lines, deficient in either p22phox or gp91phox, to hypoxia (1% oxygen) or CoCl2 (100 mumol/L) and compared the mRNA levels of VEGF and aldolase with the untreated controls. Northern blot analysis revealed unimpaired basal and inducible expression of VEGF and aldolase mRNA in all four cytb- CGD-derived B-cell lines compared with wild-type cells. Furthermore, reconstitution of cytochrome b558 expression in cytb- CGD-derived B cells by transfection with p22phox or gp91phox expression vectors did not modify VEGF and aldolase mRNA expression. Thus, cytochrome b558 of the NADPH oxidase complex appears not to be essential for hypoxia-activated gene expression and can be excluded as a candidate for the putative universal oxygen sensor.

Colonic epithelial cell lines as a source of interleukin-8: stimulation by inflammatory cytokines and bacterial lipopolysaccharide.

Cytokines produced by intestinal epithelial cells may function as signals to neighbouring immune and inflammatory cells. We investigated production of the neutrophil and T-lymphocyte chemotactic cytokine interleukin-8 (IL-8) by intestinal epithelial cells using four colonic adenocarcinoma cell lines, T84, CaCo-2, HT29 and SW620, as a model system. These cell lines secreted substantial amounts of IL-8 if stimulated with IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma), except CaCo-2 cells, which responded only to IL-1 beta. Bacterial lipopolysaccharide (LPS) was also an efficient stimulus of IL-8 release in SW620 and HT29 cells, whereas T84 and CaCo-2 cells were completely unresponsive to LPS, IL-8 secretion was greater at 4 hr after stimulation and was accompanied by induction of IL-8 messenger RNA. In T84 cells IFN-gamma and epidermal growth factor (EGF) stimulated IL-8 secretion synergistically with TNF-alpha, whereas in SW620 cells this synergism occurred only between IFN-gamma and TNF-alpha. IL-4, IL-10 and transforming growth factor-beta (TGF-beta), which can down-regulate IL-8 production in macrophages, had no effect on IL-8 generation by our cell lines. Adenocarcinoma cell culture supernatants also induced rapid transients of intracellular calcium in neutrophils. Depending on cell line and stimulus, supernatant bioactivity was completely or partially abrogated by neutralizing antibodies to IL-8, indicating that the cell lines investigated also generate other neutrophil-activating factors. IL-8 and possibly other chemokines generated by colonic adenocarcinomas may help to attract tumour-infiltrating leucocytes. Possibly, normal intestinal epithelial cells also have the potential to secrete this potent chemoattractant and thus might contribute to inflammatory responses of the intestinal mucosa, for example in inflammatory bowel disease.

Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin 8.

BACKGROUND: To characterize the role of intestinal epithelial cells in mucosal host defense, we have examined constitutive cytokine expression and regulated expression of interleukin (IL)-8 by human colonic epithelial cells. METHODS: Cytokine expression by the human colonic epithelial cell lines, T84, Caco-2, SW620, and HT29 was assessed by using polymerase chain reaction amplification of reverse-transcribed RNA. Regulated IL-8 expression was analyzed by nuclear run-off assays, Northern blot analysis, and enzyme-linked immunosorbent assay. RESULTS: The cell lines constitutively expressed messenger RNA (mRNA) for IL-8 and transforming growth factor beta 1. In addition, some cell lines expressed mRNA for IL-1 alpha, IL-1 beta, IL-10 and tumor necrosis factor alpha (TNF alpha). None of the cell lines expressed mRNA for IL-2, IL-4, IL-5, IL-6, or interferon gamma. Cell lines secreted IL-8 either constitutively or after stimulation with the physiological agonists TNF alpha, IL-1 beta, or lipopolysaccharide. Increased IL-8 secretion after TNF alpha stimulation of T84 cells was accompanied by increased IL-8 mRNA levels and an increased transcription rate of the IL-8 gene. IL-8 was preferentially secreted at the basolateral surface of polarized T84 cells. In further studies, freshly isolated human colon epithelial cells also secreted IL-8. CONCLUSIONS: These results support the notion of bidirectional communication between intestinal epithelial cells and mucosal immune and inflammatory cells.

Restitution of superoxide generation in autosomal cytochrome-negative chronic granulomatous disease (A22(0) CGD)-derived B lymphocyte cell lines by transfection with p22phax cDNA.

The respiratory burst oxidase of phagocytes and B lymphocytes is a multicomponent enzyme that catalyzes the one-electron reduction of oxygen by NADPH. It is responsible for the O2-production that occurs when these cells are exposed to phorbol 12-myristate 13-acetate or physiologic stimuli, such as phagocytosis in phagocytes or cross-linking of surface immunoglobulin in B lymphocytes. The activity of this enzyme is greatly diminished or absent in patients with chronic granulomatous disease (CGD), an inherited disorder characterized by a severe defect in host defense against bacteria and fungi. In every CGD patient studied so far, an abnormality has been found in a gene encoding one of the four components of the respiratory burst oxidase: the membrane proteins p22phox or gp91phox which together form the cytochrome b558 protein, or the cytosolic proteins p47phox or p67phox. Autosomal recessive cytochrome-negative CGD (A22(0) CGD) is associated with mutations in the gene coding for p22phox. We report here that the capacity for O2- production and cytochrome b558 protein expression were restored to Epstein-Barr virus-transformed B lymphocytes from two A22(0) CGD patients by transfection with an expression plasmid containing a p22phox cDNA. No detectable O2- was generated by untransfected p22phox-deficient lymphocytes. The genetic reconstitution of the respiratory burst in A22(0) CGD B lymphocytes by transfer of the wild-type p22phox cDNA represents a further step towards somatic gene therapy for this subgroup of A22(0) CGD. This system will also be useful for expression of genetically engineered mutant p22phox proteins in intact cells, facilitating the structure-function analysis of cytochrome b558.

Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14.

Myeloid cell activation by lipopolysaccharides (LPS) involves two proteins, plasma LPS-binding protein (LBP) and cell-membrane CD14. Cell membrane CD14, anchored by a glycerophosphatidylinositol tail, is the cellular receptor for LPS-LBP complexes. Another form of CD14, without the lipid tail, circulates as a soluble plasma protein. In this work we show that soluble CD14 (sCD14) is required for activation of endothelial and epithelial cells by LPS. We propose that LPS-LBP complexes transfer LPS to sCD14, and the LPS-sCD14 complexes then bind to a cellular receptor. Support for this pathway comes from experiments in which LBP and CD14 in normal human serum are blocked by specific antibodies, experiments in which serum is replaced by purified LBP and sCD14, and experiments in which specific binding of [3H]LPS to epithelial cells is quantitated.

Interleukin-1 and experimental gastric ulcer healing in the rat.

The involvement of inflammation in peptic ulcer development and healing attracts growing interest. Since lymphokines, in particular interleukin-1 (IL-1), as ubiquitous mediators of inflammation are currently intensively studied in the gastrointestinal tract, we assessed the effect of this cytokine as well as that of a specific IL-1 release inhibitor (IX 207-887 (IX)) on development and healing of experimental gastric ulcers. After a single dose of IL-1, 4 micrograms/kg, i. p., basal acid secretion was almost completely inhibited for 4 hours in conscious chronic gastric fistula rats. In a first study, following induction of a 7 mm wide cryo-ulcer in the gastric corpus, three groups of 24 rats were treated either with a non-acid inhibitory dose of IL-1 (0.4 microgram/kg) or with an antisecretory regimen (4 micrograms/kg) b.i.d. or saline control. Ulcer size did not differ from that of control animals, neither after 24h nor 7 days. Similarly, IX applied daily (20 mg/kg/s.c) from 5 days before ulcer induction and continued thereafter for 15 days had no effect on ulcer development or healing. Despite its anti-inflammatory property IX produced no macroscopically visible damage on the gastric or intestinal mucosa and may therefore offer a higher safety profile within the gastrointestinal tract than conventional non-steroidal anti-inflammatory drugs.

Effect of acute and chronic acid suppression on plasma gastrin release in the rat.

The mechanisms by which administration of the H+,K(+)-ATPase inhibitor B 831-78 or intragastric perfusion with NaHCO3 induces plasma gastrin release were studied in the rat. Experiments were performed after a washout of residual intragastric contents in fasted animals provided with chronic gastric fistulae. Acute and chronic administration of B 831-78 elevated plasma gastrin dose-dependently up to 5-6 times above control levels, while the increase was only twofold with intragastric NaHCO3 infusion despite similar neutralization of gastric acidity. The profound hypergastrinaemia induced by the H+,K(+)-ATPase inhibitor, after both acute and chronic treatment, was completely prevented or reversed by intragastric perfusion with physiological amounts of acid (0.15 N HCl, 2.5 ml/h). The hypergastrinaemia was, however, largely resistant to high doses of atropine (4.3 mumol/kg) and of the M1 selective muscarinic antagonist telenzepine (10 mumol/kg). In contrast, the modest increase in plasma gastrin induced by gastric perfusion with NaHCO3 was completely suppressed by the high atropine dose and was attenuated by small doses of atropine or telenzepine (0.01 mumol/kg and 1 mumol/kg). These results demonstrate that, in the rat, blockade of the H+,K(+)-ATPase can potently induce gastrin release in the absence of a meal. Moreover, they suggest that interruption of the negative feedback between acid and gastrin release is the main mechanism through which this class of drugs releases gastrin in the rat. Since a similar degree of gastrin release cannot be achieved by alkalinization of gastric contents, additional hormonal or neural regulatory factors may contribute to the drug-induced hypergastrinaemia.

Interaction of liquid aluminium phosphate and aluminium hydroxide with the gastric acid profile. Influence of food components and timing of meals.

AlPO4 is generally perceived as a particularly weak antacid. Its neutralizing capacity, when evaluated with the classical Fordtran test at the pH 3 standard, is several times smaller than that of Al(OH)3, which is considered a particularly potent antacid. This difference of in vitro reactivity of the two antacids is largely due to the fact that the pKa value is considerably lower for AlPO4 than for Al(OH)3. The object of this study was to evaluate in vivo and in vitro the impact of the pKa value of these antacids on their efficacy at low pH values and the modulation of their neutralizing capacity through proteins. Since both preparations display a much closer antacid activity at pH 2, we felt it appropriate to reevaluate the comparative in vivo neutralizing capacity of the two antacids at doses matched with their in vitro reactivity at pH 2. In vivo antacid effects were measured by ambulant pH-metry in 18 healthy volunteers after randomized ingestion of carbohydrate or protein meals. Antacid or placebo medication was given 1 and 3 h after meals. At pH 3.0, the standard milieu of the Fordtran test, preparation A, composed of Al(OH)3 and a small fraction of Mg(OH)2, displayed in vitro a neutralizing capacity of 4.4 mmol/ml, whereas this was 0.18 mmol/ml for preparation B, composed solely of AlPO4 (p less than 0.001). When tested at pH 1, 1.5, and 2, however, the ratio between A and B was below 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspects of the role of prostaglandins in gastrin histamine regulation of gastric acid secretion.

There is convincing evidence from in vitro studies that prostaglandins interfere with the gastrin histamine regulation of gastric acid secretion in an opposing manner. They can inhibit the action of histamine on the parietal cell when given as single-dose treatment. Conversely, when given at high doses, they liberate endogenous histamine, probably from nonparietal cells. In in vivo experiments prostaglandins are potent inhibitors of acid secretion when studied with single-dose treatment but are capable of stimulating basal acid secretion when chronically applied to rats. Studies performed in whole animal preparations on the effect of cyclooxygenase inhibitors have not fully clarified which of these two histamine-modulating effects of prostaglandins is of prime physiologic significance but favour suppression of histamine activity with subsequent acid inhibition. It appears that somatostatin release is the mechanism through which prostaglandin can simultaneously inhibit acid secretion and release plasma gastrin. At least in the rat, the pattern of plasma gastrin and somatostatin release is, similarly to acid secretion, partly reversed during prolonged prostaglandin treatment.

Inflammation, capillary leakage and healing of experimental gastric ulcers in the rat.

Little information is available on the role of inflammation and small vessel alteration in the development and healing of peptic ulcers. We studied the spontaneous healing of experimental ulcers in the rat stomach with a novel radio-isotope technique for the monitoring of capillary damage in ulcer-related inflammation. Following ulcer induction, healing was assessed on days 1, 7 and 15 by macroscopical and histological determinations of ulcer size and lesion area, parietal cell counts in the ulcer margin and nuclear imaging of the lesion area using Nanocoll, a 99mTc-labelled colloid. The ulcers were re-epithelized after 15 days. However, Nonocoll activity was still significantly enhanced in the ulcer area, and regression of the microscopically visible lesion area, which, from day 1 on, occupied a zone considerably larger than the ulcer itself, was delayed and still incomplete at the end of the study. Compared to the intact mucosa, parietal cells were reduced in the scar tissue up to 15 days (24-40%). However, despite macroscopical and histological re-epithelization, small vessel leakage and substantial tissue alteration persisted in the ulcer scar.

Effect of 16.16 dimethyl prostaglandin E2, N-acetyl-cysteine and the proton pump inhibitor BY 831-78 on hydrogen peroxide-induced mucosal damage in the rat stomach.

Reactive oxygen species are noxious to gastrointestinal mucosa and contribute to a variety of gastrointestinal diseases. We examined whether 16.16 dimethyl prostaglandin E2 (PG) is protective against the oxidizing action of 6% H2O2 causing gross hemorrhagic lesions in rat gastric mucosa. Male Wistar rats were treated with PG, 0.005-5 micrograms/kg, either intragastrically (i.g.) or subcutaneously, 30 min prior to i.g. administration of 6% H2O2, 0.5 ml/100 g. Further animals received 25 mg of the mucus dissolvent N-acetyl-cystein (NAC) following oral PG treatment or 30 mumol/kg of the H+K(+)-ATPase inhibitor BY 831-78 (BY), 4 h before onset of the experiments. Volume, pH and beta-N-acetyl-glucosaminidase and lactate dehydrogenase as parameters of cell damage were determined in the gastric juice. i.g. PG treatment achieved 60 and 55% reduction of the mucosal lesions in doses between 5 and 0.05 micrograms/kg, respectively. i.p. PG administration was effective in all doses tested. Gastric juice volume was only slightly and enzymes were not significantly affected by PG treatment. NAC did not diminish PG efficacy or aggravate mucosal lesions. Gastric acid suppression did not increase PG-induced protection but was strongly protective by itself, reducing damage by 75%. Low-dose PG treatment achieves an effective protection against oxidative damage in gastric mucosa, which is not the result of dilution or enhanced mucus production.