Bioactive sucralfate-based microneedles promote wound healing through reprogramming macrophages and protecting endogenous growth factors.

Impaired wound healing due to insufficient cell proliferation and angiogenesis is a significant physical and psychological burden to patients worldwide. Therapeutic delivery of exogenous growth factors (GFs) at high doses for wound repair is non-ideal as GFs have poor stability in proteolytic wound environments. Here, we present a two-stage strategy using bioactive sucralfate-based microneedle (SUC-MN) for delivering interleukin-4 (IL-4) to accelerate wound healing. In the first stage, SUC-MN synergistically enhanced the effect of IL-4 through more potent reprogramming of pro-regenerative M2-like macrophages via the JAK-STAT pathway to increase endogenous GF production. In the second stage, sucralfate binds to GFs and sterically disfavors protease degradation to increase bioavailability of GFs. The IL-4/SUC-MN technology accelerated wound healing by 56.6 % and 46.5 % in diabetic mice wounds and porcine wounds compared to their respective untreated controls. Overall, our findings highlight the innovative use of molecular simulations to identify bioactive ingredients and their incorporation into microneedles for promoting wound healing through multiple synergistic mechanisms.

Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination.

PURPOSE: To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. METHODS: Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. RESULTS: There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. CONCLUSIONS: The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.

Effectiveness of the polyphenols-rich Sedum dendroideum infusion on gastric ulcer healing in rats: Roles of protective endogenous factors and antioxidant and anti-inflammatory mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. AIM OF THE STUDY: Here, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. MATERIAL AND METHODS: Rats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. RESULTS: Oral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1ß levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. CONCLUSIONS: The gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.

A Controlled Study to Examine the Effect of Topical Sucralfate on Radiofrequency-induced Burn Wounds in Rats

Several preclinical studies have shown topical sucralfate facilitates wound repair. PURPOSE: This study aimed to evaluate the effect of 10% topical sucralfate on healing radiofrequency-induced burn wounds in rats. METHODS: Twenty (20) male rats were divided into 2 equal groups. Using radiofrequency, 4 full-thickness, 1 cm in diameter round burns were created on the backs of the rats that then were randomized to receive twice-daily treatment for 30 days with 10% sucralfate or neutral cream. Biopsies were taken on days 4, 7, 14, and 21 to analyze fibrin-leukocyte crut, edema density, epidermal-dermal cell infiltration, amount of fibroblast and collagen fibers, amount of elastic fibers, neovascularization-angiogenesis, and reepithelialization-granulation tissue. Data were collected to a spreadsheet and entered into statistical software for analysis. Histopathological features were classified as categorical variables and compared using the χ2 test and Fisher's exact test. When χ2 was used, Yates' correction for continuity was performed. All reported P values were 2-tailed; P less than .05 was considered statistically significant. RESULTS: On day 4, improvement in edema density (P = .034), epidermal detachment (P = .020), epidermal-dermal cell infiltration (P = .007), and polymorphonuclear leukocyte infiltration (P = .021) were statistically more significant in the sucralfate than control group. On day 7, epidermal-dermal cell infiltration (P = .007) and elastic fibers P = .050) were statistically more significant in the sucralfate group. On day 14, angiogenesis (P = .029), reepithelialization (P = .035), and granulation tissue (P = .003) were statistically more significant in the sucralfate group. By the end of the study (day 30), angiogenesis (P = .010), reepithelialization (P <.001), fibroblast density (P = .016), granulation tissue (P = .035), and collagen density (P = .002) were significantly improved in the sucralfate group versus the control group. CONCLUSION: In a rat wound model, 10% topical sucralfate was found to histopathologically facilitate the healing process compared to the control group. Controlled clinical studies are needed to elucidate the effect of this treatment in human wounds.

Oral Viscous Sucralfate Gel for Post-procedural Treatment of Barrett's Esophagus.

Barrett's esophagus refers to an abnormal change in the cells of the lower portion of the esophagus. It is characterized by the replacement of the normal stratified squamous epithelium lining of the esophagus by columnar epithelium cells which are usually found lower in the gastrointestinal tract. The medical significance of this pathology is approximately 0.5% risk to develop esophageal adenocarcinoma (per patient diagnosed with Barrett's esophagus per year). Diagnosis requires endoscopy and biopsy. In general, high-grade dysplasia and early stages of adenocarcinoma can be treated by endoscopic resection and/or endoscopic ablative therapy, whereas advanced stages (submucosal) are generally advised to undergo surgical treatment. Patients who undergo endoscopic resection and/or endoscopic ablative therapy might suffer from retrosternal discomfort and transient dysphagia, adverse effects that sometimes accompanies these procedures. One of the common post-procedural treatments is sucralfate 1 g 3 to 4 times daily for two weeks after the procedure. The rational for this treatment is to enhance the wound-healing process in the esophagus tissues and to coat the wounded tissues with a cytoprotective agent. As no clinical trials have been performed in order to prove the efficacy of sucralfate in the postprocedural treatment of Barrett's esophagus, this article summarizes the clinical experience accumulated from the treatment with sucralfate as a wound-healing enhancer. In addition, the article deals with the hypothesized mechanism of action of sucralfate and gives one option for compounding sucralfate oral viscous gel.

Medicina antienvelhecimento: notas sobre uma controvérsia sociotécnica / Anti-aging medicine: notes on a socio-technical controversy

Após algumas décadas de batalha, a geriatria e a gerontologia se tornaram as legítimas ciências do envelhecimento. Hoje surge uma contestação a tal condição. Em sua breve história, a medicina antienvelhecimento se afirmou como prática médica que questiona o modo de se endereçar o envelhecimento biológico. Com isso, toda a medicina é questionada. Aqui, exploramos especialmente como essa controvérsia se estrutura em torno dos fundamentos das ciências do envelhecimento. Há bases para esses questionamentos? Como eles foram tratados por aqueles que os receberam? Tendo em vista uma perspectiva sociotécnica, é interessante pensar que, para geriatras e gerontólogos, a necessária crítica à medicina antienvelhecimento também traz uma importante reflexão sobre o modo como as ciências do envelhecimento vêm tratando seu objeto.

After some decades of struggle, geriatrics and gerontology have become the legitimate sciences of aging. Today, their status is being questioned. In its short history, anti-aging medicine has taken root as a medical practice that questions how to address biological aging. In so doing, all medicine is questioned. Here, we explore in particular how this controversy is structured around the founding principles of the sciences of aging. Is there any basis for these questionings? How have they been treated by those who have received them? Taking a socio-technical viewpoint, it is worth considering that for geriatricians and gerontologists, the need to criticize anti-aging medicine also raises some important reflections about how the sciences of aging address their subject.

Evaluation of the application of enemas containing sucralfate in tissue content of neutral and acid mucins in experimental model of diversion colitis

PURPOSE: To evaluate the effects of sucralfate on tissue content of neutral and acids mucins in rats with diversion colitis. METHODS: Thirty-six rats were submitted to a proximal right colostomy and a distal mucous fistula. They were divided into two groups according to sacrifice to be performed two or four weeks after intervention. Each group was divided into three subgroups according daily application of enemas containing saline, sucralfate at 1.0 g/kg/day or 2.0 g/kg/day. Colitis was diagnosed by histological analysis and neutral and acid mucins by Periodic Acid Schiff and Alcian Blue techniques, respectively. The contents of mucins were quantified by computer-assisted image analysis. Student's t paired and ANOVA test were used to compare the contents of both types of mucins among groups, and to verify the variance with time, establishing level of signification of 5% for both (p<0.05). RESULTS: Enemas containing sucralfate improves the inflammation and increases the tissue contents of neutral and acid mucins. The content of neutral mucins does not change with the time or concentration of sucralfate used, while acid mucins increases with concentration and time of intervention. CONCLUSIONS: Sucralfate enemas improve the inflammatory process and increase the tissue content of neutral and acid mucins in colon without fecal stream. .

Anti-secretory and cyto-protective effects of peganine hydrochloride isolated from the seeds of Peganum harmala on gastric ulcers.

Gastroprotective mechanism of peganine hydrochloride isolated from Peganum harmala seeds was investigated. Peganine hydrochloride was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of peganine was observed against CRU (50.0%), AS (58.5%), AL (89.41%) and PL (62.50%) induced ulcer models. The reference drug omeprazole (10mg/kg, p.o.) showed 77.45% protection against CRU, 49.97% against AS and 69.42% against PL model. Sucralfate, another reference drug (500mg/kg, p.o.) showed 62.50% protection in AL induced ulcer model. Peganine significantly reduced free acidity (33.38%), total acidity (38.09%) and upregulated mucin secretion by 67.91%, respectively. Further, peagnine significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 73.47µg/ml as compared to the IC50 value of omeprazole (30.24µg/ml) confirming its anti-secretory activity.

Antemortem diagnosis and successful management of noncompressive segmental myelopathy in a Siberian-Bengal mixed breed tiger.

A 10-yr-old female spayed mixed breed tiger presented for a 9-day history of acute and nonprogressive paralysis of the pelvic limbs. Magnetic resonance imaging revealed a lesion suggestive of fibrocartilaginous embolic myelopathy with regional spinal cord edema, decreased disk signal intensity at L2-L3, and mild intervertebral disk protrusion at L1-L2 and L2-L3. Cerebral spinal fluid analysis showed no overt evidence of infection or neoplasia. Medical therapy was instituted, including corticosteroids and gastroprotectants as well as nursing care and physical therapy. The tiger began showing clinical improvement 2 wk after initiating treatment, progressing to the point where the animal was standing and intermittently walking. Three months after diagnosis, the tiger had regained muscle strength of its hind limbs and walked regularly with improving coordination. This case is the first report of antemortem diagnosis and successful medical management of suspected fibrocartilaginous embolic myelopathy in a large exotic felid.

Radiodermatitis prevention with sucralfate in breast cancer: fundamental and clinical studies.

BACKGROUND: Acute radiodermatitis induced by radiotherapy may affect the quality of life and in some cases requires withholding treatment. The present study concerns the protective effect of a 1% sucralfate lotion. We propose joint fundamental and clinical points of view. METHODS: The free radical scavenging capacity of sucralfate was measured with electron spin resonance and was supported by theoretical calculations. The clinical effects of sucralfate lotion were evaluated on 21 women treated for breast cancer. Breast skin response was evaluated at 0, 10, 20, 30, 40, and 50 Gy, according to (1) the radiation therapy oncology group (RTOG) acute toxicity scale and (2) spectrophotometry data obtained with X-Rite SP60. RESULTS AND CONCLUSIONS: Sucralfate appeared as a relatively poor free radical scavenger (compared to reference compounds such as vitamin E). The sucralfate-containing lotion used in the present study did not provide systematic radiodermatitis prevention. Spectrophotometric evaluation of the skin response to irradiation appeared to be a very effective and more sensitive technique than the RTOG scale. Its use should be recommended to study cutaneous radioprotective action.

Estudio comparativo de la cicatrización en piel de conejo entre sucralfato y tartrato de ketanserin / Comparative study of wound healing in rabbit skin between sucralfate and ketanserin tartrate

Al sanar una herida se activa un proceso de reepitelización para generar una epidermis. Este proceso de cicatrización debe ocurrir rápido y efectivamente para prevenir los ataques provenientes del medio ambiente. Existe una gran variedad de cremas regeneradoras, dentro de las cuales se encuentran sucralfato (Cicalfate ®), de utilidad en medicina humana, y tartrato de ketanserin (Vulketan ®), utilizado como tratamiento convencional en medicina veterinaria. El objetivo general de este estudio fue comparar el grado de cicatrización y reacción inflamatorio entre sucralfato y tartrato de ketanserin en heridas quirúrgicas en piel del área superior de la pared torácica de conejos (Oryctologus cuniculis), los cuales se utilizaron como modelos animales para medir parámetros cicatriciales que son complicados de evaluar en forma rutinaria en estudios clínicos en el ser humano. Se emplearon 15 conejos machos. Sucralfato y tartrato de ketonserin fueron aplicados simultáneamente en 10 animales. Sucralfato se aplicó en el lado derecho y tartrato de ketanserin, en el lado izquierdo. Cinco conejos fueron tratados con suero fisiológico como grupo control. La evaluación se realizó mediante la Escala de Vancouver durante 19 días. Los resultados revelan que en el caso de ambas cremas regeneradoras no existe diferencia significativa en torno a los signos de vascularidad. Con respecto o los signos de plegabilidad, altura, pigmentación y dolor, sí existe diferencia significativa (P < 0,05) contribuyendo mejor sucralfato, por lo que se concluye que éste presento ventaja comparativa con respecto o tartrato de ketanserin al momento de realizar un tratamiento tópico para heridas en piel.

In healing o process of reepithelialization to generate epidermis start. This process must take place quickly and effectively to prevent attacks from the environment. There is a great variety of regenerative creams available such as sucralfate (Ciclalfate®) in human medicine and ketaserin tartrate (Vulketan®) used as a conventional treatment in veterinary medicine. The main objective of this study was to compare the healing degree and inflammatory reaction between sucralfate and ketanserin tartrate in surgical wounds on skin of the upper thoracic wall of rabbits (Oryctolagus cuniculis), which were used as animal models for measuring cicatricial parameters that are complicated to evaluate routinely in clinical trials in humans. Fifteen male rabbits were used Sucralfate and ketanserin tartrate were used simultaneously in 10 animals. Sucralfate was used on right side and ketanserin trartrate on the left side. Five rabbits were treated with physiological saline solution (control group). Wound evaluation were compared with the Scale of Vancouver during 19 days. The results showed that both regenerative creams had no significant differences in vascularity. In relation to pliability height, pigmentation and pain there was a significant difference (P < 0,05) between the two products in favor of sucralfate in the topical treatment of skin injuries.

Sucralfate modulates uPAR and EGFR expression in an experimental rat model of cervicitis.

Sucralfate is a drug used in the treatment of gastric and duodenal ulcer; it is cytoprotective and able to increase the bioavailability of several growth factors, modulating the wound healing process. In this study we tested the possible therapeutic effect of Sucralfate in the treatment of ulcerative lesions occurring in uterine cervix; to investigate such effect we used an experimental rat model of cervicitis in which the uPAR and EGFR expression were evaluated. Cervicitis was induced in wild and ovariectomized Wistar female rats by an acetic acid-soaked tampon. The animals were divided into two main groups (4 and 7 days) and Sucralfate was administered topically until the day they were sacrificed. In order to distinguish physiological and drug-induced healing, quantitative and qualitative uPAR and EGFR expression were evaluated by using Western blot and Immunohistochemistry techniques. Western blot analysis demonstrated an increased expression of both receptors after 4 days from wounding in wild and ovariectomized animals. In particular in ovariectomized animals the expression of uPAR and EGFR increased after 4 days while it reduced following the administration of Sucralfate. In wild rats the same was observed for uPAR expression, while EGFR was different; in fact, its expression increased significantly at day 4 in the animals treated with the drug and only at day 7 in those untreated. Immunohistochemistry highlighted a noteworthy epithelial colocalization of EGFR and uPAR after 4 days in the animals treated with Sucralfate. We conclude that Sucralfate can promote the healing of ulcerative cervicitis and moreover, it reduces the normal healing time because of its modulatory property on uPAR and EGFR expression.

Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: possible new targets of pharmacologic agents.

AIM: To investigate the role of major non-protein and protein sulfhydryls and disulfides in chemically induced gastric hemorrhagic mucosal lesions (HML) and the mechanism of gastroprotective effect of sucralfate. METHODS: Rats were given 1 mL of 75% ethanol, 25% NaCl, 0.6 mol/L HCl, 0.2 mol/L NaOH or 1% ammonia solutions intragastrically (i.g.) and sacrificed 1, 3, 6 or 12 min later. Total (reduced and oxidized) glutathione (GSH + GSSG), glutathione disulfide (GSSG), protein free sulfhydryls (PSH), protein-glutathione mixed disulfides (PSSG) and protein cystine disulfides (PSSP) were measured in gastric mucosa and liver. RESULTS: Reduced glutathione (GSH) was depleted in the gastric mucosa after ethanol, HCl or NaCl exposure, while oxidized glutathione (GSSG) concentrations increased, except by HCl and NaOH exposure. Decreased levels of PSH after exposure to ethanol were observed, NaCl or NaOH while the total protein disulfides were increased. Ratios of reduced to oxidized glutathione or sulfhydrils to disulfides were decreased by all chemicals. No changes in thiol homeostasis were detected in the liver after i.g. abbreviation should be spelled out the first time here administration of ethanol. Sucralfate increased the concentrations of GSH and PSH and prevented the ethanol-induced changes in gastric mucosal thiol concentrations. CONCLUSION: Our modified methods are now suitable for direct measurements of major protein and non-protein thiols/disulfides in the gastric mucosa or liver. A common element in the pathogenesis of chemically induced HML and in the mechanism of gastroprotective drugs seems to be the decreased ratios of reduced and oxidized glutathione as well as protein sulfhydryls and disulfides.

Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats.

AIM: To compare the effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing. METHODS: Male Spraque-Dawley rats (n=48) were divided into four groups. Group1 served as control group, group 2 as gastric ulcer group without treatment, groups 3 and 4 as gastric ulcer treatment groups with sucralfate and Aloe vera. The rats from each group were divided into 2 subgroups for study of leukocyte adherence, TNF-alpha and IL-10 levels and gastric ulcer healing on days 1 and 8 after induction of gastric ulcer by 20% acetic acid. RESULTS: On day 1 after induction of gastric ulcer, the leukocyte adherence in postcapillary venule was significantly (P<0.05) increased in the ulcer groups when compared to the control group. The level of TNF-alpha was elevated and the level of IL-10 was reduced. In the ulcer groups treated with sucralfate and Aloe vera, leukocyte adherence was reduced in postcapillary venule. The level of IL-10 was elevated, but the level of TNF-alpha had no significant difference. On day 8, the leukocyte adherence in postcapillary venule and the level of TNF-alpha were still increased and the level of IL-10 was reduced in the ulcer group without treatment. The ulcer treated with sucralfate and Aloe vera had lower leukocyte adherence in postcapillary venule and TNF-alpha level. The level of IL-10 was still elevated compared to the ulcer group without treatment. Furthermore, histopathological examination of stomach on days 1 and 8 after induction of gastric ulcer showed that gastric tissue was damaged with inflammation. In the ulcer groups treated with sucralfate and Aloe vera on days 1 and 8, gastric inflammation was reduced, epithelial cell proliferation was enhanced and gastric glands became elongated. The ulcer sizes were also reduced compared to the ulcer group without treatment. CONCLUSION: Administration of 20% acetic acid can induce gastric inflammation, increase leukocyte adherence in postcapillary venule and TNF-alpha level and reduce IL-10 level. Aloe vera treatment can reduce leukocyte adherence and TNF-alpha level, elevate IL-10 level and promote gastric ulcer healing.

[The effect of selective bowel decontamination and mechanical bowel preparation on bacterial translocation due to intraabdominal hypertension]. / Kariniçi hipertansiyon modelinde gelisen bakteriyel translokasyon üzerine selektif bagirsak dekontaminasyon ve mekanik bagirsak temizliginin etkileri.

BACKGROUND: The objective of our study is to evaluate the preventive effects of selective digestive decontamination (SDD) and mechanical bowel preparation in rats with experimentally induced bacterial translocation. METHODS: Fourty adult male Sprague Dowley rats weighing 250-300 g. were divided equally into four groups as Group 1 (sham [control]), Group 2 (experimentally induced IAH at 19 mmHg), Group 3 ( SDD group) and Group 4 (SDD and mechanical bowel preparation with 19 mmHg intraabdominal pressure). Group 3 and 4 were treated at 12 hours intervals with oral gentamycine 5 mg/kg and IM sefotaxime 100mg/kg Mechanical bowel preparation was performed by oral administration of sodium phosphate. After 24 hours all rats were sacrified; mesenteric lymph nodes, spleen and liver biopsy specimens were harvested aseptically. Specimens were diluted and cultured in McConkey medium and the colony-forming units (CFU/gr ) were calculated. RESULTS: In Kruskal Wallis tests there were no significant differences between Group 1 and 3 or 4, and also Group 3 and 4 (p>0.05, p=0.872 respectively), while differences between Group 1 and 2, and also Group 3 and 4 were statistically significant (p<0.001) with respect to CFU/g estimates. CONCLUSION: These data indicate that selective intestinal decontamination and mechanical bowel preparation prevent bacterial translocation due to intraabdominal hypertension.

Teprenone, but not H2-receptor blocker or sucralfate, suppresses corpus Helicobacter pylori colonization and gastritis in humans: teprenone inhibition of H. pylori-induced interleukin-8 in MKN28 gastric epithelial cell lines.

BACKGROUND: The role of teprenone in Helicobacter pylori-associated gastritis has yet to be determined. To investigate the effect of teprenone on inflammatory cell infiltration, and on H. pylori colonization of the gastric mucosa in H. pylori-infected patients, we first compared the effect of teprenone with that of both histamine H2 receptor antagonists (H2-RA) and sucralfate on the histological scores of H. pylori gastritis. We then examined its in vitro effect on H. pylori-induced interleukin (IL)-8 production in MKN28 gastric epithelial cells. MATERIALS AND METHODS: A total of 68 patients were divided into three groups, each group undergoing a 3-month treatment with either teprenone (150 mg/day), H2-RA (nizatidine, 300 mg/day), or sucralfate (3 g/day). All subjects underwent endoscopic examination of the stomach before and after treatment. IL-8 production in MKN28 gastric epithelial cells was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Following treatment, the teprenone group showed a significant decrease in both neutrophil infiltration and H. pylori density of the corpus (before vs. after: 2.49 +/- 0.22 vs. 2.15 +/- 0.23, p =.009; 2.36 +/- 0.25 vs. 2.00 +/- 0.24, p =.035, respectively), with no significant differences seen in either the sucralfate or H2-RA groups. Teprenone inhibited H. pylori-enhanced IL-8 production in MKN28 gastric epithelial cells in vitro, in a dose-dependent manner. CONCLUSIONS: Teprenone may modify corpus H. pylori-associated gastritis through its effect on neutrophil infiltration and H. pylori density, in part by its inhibition of IL-8 production in the gastric mucosa.

[The effect of bFGF and sucralfate on cell proliferation during continuous tissue expansion].

OBJECTIVE: To investigate the effect of local application of bFGF combined with sucralfate on the cell proliferation during continuous tissue expansion (CTE). METHODS: Nine white pigs were selected to undergo the continuous tissue expansion in this study and treated with bFGF and sucralfate, respectively as the following groups: group 1 with both bFGF and sucralfate, group 2 only with bFGF, group 3 with only sucralfate, and group 4 with saline as control. Fifteen samples were taken in each pig for immunohistochemistry analysis 1-14 days and 6 weeks after the operation. RESULTS: In the group with both bFGF and sucralfate, the epidermic basal cells proliferated significantly after the operation and reached top level in 3 days, which was statistical higher than the control group, but the multiplication of basal cell was the lowest 14 days after the operation, still more than the control group. In dermal layer, proliferation of fibroblasts, vessel endothelial cells, hair follicles epidermic cells and sweat gland epicytes was also significant higher in the group with both bFGF and sucralfate than that the control group and reached top level 7 day after the operation, but the proliferation of cells decreased obviously 14 days after the operation, still higher than the control group. The mitotic activity of cells returned to the basal level in 42 days. There were no significant differences among the group 2, group 3 and group 4. CONCLUSION: Local application of both bFGF and sucralfate could be more effect to induce cells multiplication during early skin expansion to facilitate the growth of neoformed skin soft tissue.

Does sucralfate prevent apoptosis occurring in the ischemia/reperfusion-induced intestinal injury?

BACKGROUND/PURPOSE: We have shown in a previous study that sucralfate is beneficial in the prophylaxis and treatment of hypoxia/reoxygenation-induced intestinal injury. The aim of this study is to investigate whether sucralfate has any effect on the prevention of apoptosis in the ischemia/reperfusion (I/R)-induced intestinal injury. METHODS: Rats were randomized into three groups. Group 1 and 2 were subjected to I/R. Group 1 (treatment group) received sucralfate while group 2 (treatment control group) did not. Group 3 served as a normal control group (sham group). The terminal ileum was harvested for histopathologic investigation by light microscopy. The presence of apoptotic enterocytes (DNA fragmentation in cell nuclei) was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) reaction. RESULTS: In treatment control group, 3 of 7 rats had severe inflammation. None of the sucralfate-treated rats showed severe inflammation, 6 of them only showed mild inflammatory changes (p < 0.05). The apoptotic percentage was found to be 37.1 +/- 9.4 in the sucralfate-treated group (group 1), whereas it was 45.4 +/- 3.9 in the untreated group (group 2) (p < 0.05). The sham group had a completely normal intestinal architecture. CONCLUSIONS: The present study shows that 1) the experimental model of I/R-induced intestinal injury induces enterocyte apoptosis; 2) sucralfate decreases enterocyte apoptosis in the experimental model of I/R-induced intestinal injury which may play a key role in the pathophysiological events leading to failure of the intrinsic gut barrier defense mechanisms.

[Local application of bFGF and sucralfate during continuous tissue expansion].

OBJECTIVE: To investigate the effect of local application of bFGF and sucralfate during continuous tissue expansion (CTE). METHODS: CTE combined with local administration of bFGF and sucralfate was used in twelve patients with scar and nasal tip defects. Twenty three expanders were placed in the subcutaneous pockets through intralesion short incisions. Continuous expansion began at 1-3 days after expander implantation. The histomorphological changes and epidermal cell proliferation were observed. The clinical results were investigated. RESULTS: The average inflation time was 8.9 days. The average interval of the two operations was 13.5 days. The average hospitalization was 28.4 days. The average immediate stretch-back rate of the expanded skin was 25.7%. The clinical results were satisfactory without any complications. Histological examinations showed that the epidermal, granular and spinous layer became thicker. The basal cells increased significantly. The dermis thinned slightly and the collagen fibers became thicker. The elastic fiber regenerated significantly. Fibroblast and capillary density increased obviously. The immunohistochemistry analysis showed that the proliferation of epidemic basal cells was significant postoperatively. CONCLUSION: Local application of exogenous bFGF and sucralfate during CTE was feasible in patients. It could accelerate tissue expansion and improve the quality of expanded skin flap.

Sucralfate mouthwash for prevention and treatment of 5-fluorouracil-induced mucositis: a randomized, placebo-controlled trial.

A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of a sucralfate mouthwash in preventing and alleviating oral mucositis induced by 5-fluorouracil (5FU). A total of 81 patients with colorectal cancer were enrolled. Patients were studied during their first cycle of chemotherapy with 5FU and leucovorin (LV) daily for 5 days every 4 weeks (Mayo Clinic schedule). Patients were randomly allocated to receive either a sucralfate suspension or a placebo suspension that was identical in appearance. Patients were instructed to use the suspension as a mouthwash four times daily from the beginning of the chemotherapy cycle. All patients received oral cryotherapy. Patients graded the severity of their own symptoms on a daily basis, and this was the primary outcome measure. There was no difference in the frequency or severity of oral mucositis between the sucralfate- and the placebo-treated group. Some mucositis was reported by 79% of the patient group. Assessment of mucositis by trial staff underestimated the incidence of this problem. Results of this trial do not support the hypothesis that a sucralfate mouthwash can prevent or alleviate oral mucositis induced by 5FU. Patient reporting of mucositis is a more sensitive instrument for assessment of mucositis than review by medical staff.