Cordycepin prevents the esophageal stricture formation in the alkali-burn rat model by exerting anti-inflammatory and antifibrotic effects

ABSTRACT Purpose To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. Methods Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. Results Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). Conclusions The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

Caustic ingestion in children in south of Iran: Retrospective study from Shiraz - Iran / Ingestión de cáusticos en niños del sur de Irán: Estudio retrospectivo de Shiraz - Irán

Caustic ingestion is a major health concern in both developed and developing countries, that may lead to serious esophageal injury. The clinical presentation of caustic ingestion in children vary from asymptomatic to serious and fatal sequelae, such as perforation and stricture formation. Objective: Due to the lack of a comprehensive study in our area, this study has evaluated clinical and endoscopic manifestations and complications of caustic ingestion in children in south of Iran. Materials and methods: In this retrospective study, we reviewed 75 children with caustic ingestion who admitted in Nemazee Hospital of Shiraz University of Medical Science during 6 years (2006-2011). Sign and symptoms were recorded for each case. Results: The most common symptoms were dysphagia, oral lesions, vomiting, and drooling. Esophageal injuries were detected in both acid and alkali ingestion, but gastric injuries was significantly more in acid ingestion. During follow up period, 20% of all cases developed esophageal stricture. Conclusion: Dysphagia, oral lesions, vomiting, and drooling were the most common findings. Esophageal stricture was found in 20% of cases during 3 months of follow up.

La ingestión de cáusticos es una gran preocupación de salud tanto en países desarrollados como en vías de desarrollo, que puede llevar a lesiones esofágicas graves. La presentación clínica de la ingestión de cáusticos en niños varía desde asintomática hasta tener secuelas fatales, como perforación y/o estenosis. Objetivo: Debido a la ausencia de estudios en nuestra área, este estudio ha evaluado las manifestaciones clínicas, endoscópicas y las complicaciones de la ingesta de cáusticos en niños en el sur de Irán. Materiales y métodos: En estudio retrospectivo, revisamos 75 niños con ingesta de cáusticos que ingresaron al Nemazee Hospital of Shiraz University of Medical Science durante 6 años (2006-2011). Los signos y síntomas fueron recolectados para cada caso. Resultados: Los síntomas más frecuentes fueron disfagia, lesiones orales, vómitos y salivación. Las lesiones esofágicas se detectaron tanto en ingestión de ácido como de álcali, pero las lesiones gástricas fueron definitivamente más frecuentes con la ingestión de ácidos. Durante el periodo de seguimiento el 20% de los casos desarrolló estrechez esofágica. Conclusión: La disfagia, lesiones orales, vómitos y salivación fueron los hallazgos más comunes. La estrechez esofágica se encontró en el 20% de los casos durante los tres meses de seguimiento de los pacientes.

Effect and mechanism of intermittent alkaline stimulation on high phosphorus induced calcification in vascular smooth muscle cells of rats / 中华心血管病杂志

Objective@#To explore the effect and possible mechanisms of intermittent alkaline on rat vascular smooth muscle cells (VSMCs) calcification induced by high phosphorus.@*Methods@#VSMCs were isolated from rat thoracic aorta and cultured in vitro. The fourth generation VSMCs were randomly divided into control group, high phosphorus+ pH7.4, high phosphorus+ pH7.5, high phosphorus+ pH7.6 and high phosphorus+ pH7.7 group with random number table. The control group was cultured in DMEM with 10% fetal bovine serum. Other groups were cultured in DMEM with 10 mmol/L β-glycerophosphate and alkalized by 7.4% NaHCO3 to adjust the pH respectively. After the intervention of 4 hours, the control group was replaced with the normal medium containing 10% fetal bovine serum, the other 4 groups were replaced with high phosphorus based on the pH value of the culture medium, and then replaced the culture medium every other day. After 4 days intervention, the mRNA and protein expression of L type calcium channel β3 subunit(LTCC β3) and Runt related transcription factor 2 (Runx2) were detected by RT-PCR and Western blot. After 4 days intervention, the level of VSMC calcium ion was detected by Fluo-3/AM. After 14 days intervention, alkaline phosphatase (ALP) activity was measured by enzyme linked immunosorbent assay (ELISA) and the calcification was observed by measuring calcium content.@*Results@#(1) Compared with control group, the gene and protein expressions of LTCC β3 were higher in high phosphorus+ pH7.4 group (0.49±0.03 vs. 0.23±0.02 and 0.45±0.03 vs. 0.26±0.02 respectively, all P<0.05). Compared with high phosphorus+ pH7.4 group, the mRNA(0.86±0.05) and protein(0.62±0.04) expressions of LTCC β3 were higher in high phosphorus+ pH7.5 group (P<0.05). Compared with high phosphorus+ pH7.5 group, the mRNA(0.99±0.05) and protein(0.80±0.03) expressions of LTCC β3 were higher in high phosphorus+ pH7.5 group (all P<0.05). Compared with high phosphorus+ pH7.6 group, the mRNA(1.16±0.05) and protein(0.93±0.03) expressions of LTCC β3 were higher in high phosphorus+ pH7.7 group (all P<0.05). (2) Compared with control group, calcium ion influx were higher in high phosphorus+ pH7.4 group (124.61±6.06 vs. 75.68±7.82, P<0.05). Compared with high phosphorus+ pH7.4 group, calcium ion influx was higher in high phosphorus+ pH7.5 group(210.85±9.75, P<0.05). Compared with high phosphorus+ pH7.5 group, calcium ion influx was higher in high phosphorus+ pH7.6 group(298.44±11.42, P<0.05). Compared with high phosphorus+ pH7.6 group, calcium ion influx was higher in high phosphorus+ pH7.7 group(401.13±11.41, P<0.05). (3) Compared with control group, the mRNA and protein expressions of Runx2 and ALP were higher in high phosphorus+ pH7.4 group (0.60±0.04 vs. 0.34±0.03, 0.42±0.04 vs. 0.21±0.02, 67.2±4.3 vs. 23.2±2.3 respectively, all P<0.05). Compared with high phosphorus+ pH7.4 group, the mRNA(0.76±0.05) and protein(0.68±0.03) expressions of Runx2 and ALP(102.1±5.4) were higher in high phosphorus+ pH7.5 group (all P<0.05). Compared with high phosphorus+ pH7.5 group, the mRNA(0.90±0.05) and protein(0.90±0.05) expressions of Runx2 and ALP(139.3±4.9) were higher in high phosphorus+ pH7.6 group (all P<0.05). Compared with high phosphorus+ pH7.6 group, the mRNA(1.11±0.05) and protein(1.08±0.06) expressions of Runx2 and ALP(197.0±6.7) were higher in high phosphorus+ pH7.7 group (all P<0.05). (4) Compared with control group, the calcium content were higher in high phosphorus+ pH7.4 group ((75.4±4.3)mg/g pro vs.(25.2±2.1)mg/g pro, P<0.05). Compared with high phosphorus+ pH7.4 group, the calcium content were higher in high phosphorus+ pH7.5 group ((100.8±5.7) mg/g pro, P<0.05). Compared with high phosphorus+ pH7.5 group, the calcium content were higher in high phosphorus+ pH7.6 group ((143.5±6.1) mg/g pro, P<0.05). Compared with high phosphorus+ pH7.6 group, the calcium content were higher in high phosphorus+ pH7.7 group ((205.1±8.2) mg/g pro, P<0.05).@*Conclusion@#Intermittent alkaline stimulation can promote high phosphorus induced rat VSMCs calcification possibly through upregulating LTCC β3 subunit gene and protein expression, increasing calcium ion influx and enhancing VSMCs phenotypic transformation.

Evaluation and Management of Caustic Injuries from Ingestion of Acid or Alkaline Substances

Although the numbers have decreased compared with in the past, cases of patients who ingest caustic substances and visit the emergency room are not rare. However, well-summarized data about caustic injuries are insufficient. Therefore, in this article, I will discuss the etiologic causative agents, injury mechanism, and clinical characteristics, as well as the endoscopic evaluation of the degree of injury and proper management of the patient, in gastrointestinal caustic injury.

The expression and significance of connective tissue growth factor after rat corneal alkali burn / 中国医师杂志

Objective To evaluate the effects of connective tissue growth factor (CTGF) on corneal neovascularization.Methods Twenty-five Wistar rats were divided into control and experimental groups.Corneal neovascularization (CNV) was induced by alkaline burn of the cornea with 1 mmol/L NaOH.On the 1st,4th,7th,and 14th day,CNV was observed,and the expression of CTGF was investigated with immunohistochemical method in rat cornea at the different time point.Results On the 4th day,7th day and 14th day after alkaline burn,the areas of CNV were (12.740 ±2.536) mm2,(26.068 ± 10.028) mm2,and (37.588 ± 8.066) mm2,respectively.CTGF was rarely expressed in the cornea of normal rats,and then CTFG expression was quickly increased after alkaline burn,reached the highest level on the 4th day (1.714 ± 0.185),and then declined remarkably on the 7th day (1.334 ± 0.198).Conclusions CTGF might be involved in the formation process of corneal neovascularization after corneal alkali burn.

The Effects of Neutralization Therapy for Acute Alkali Ingestion in Rabbits

PURPOSE: To evaluate temperature changes in the gastric lumen and the efficacy of weak acid neutralization against the ingestion of a strong alkaline commercial agent. METHODS: A total of 23 male New Zealand White rabbits were anesthetized with an intramuscular injection of ketamine and xylazine. After gastric lavage, anoro-gastric catheter and an electric thermometer probe were inserted into the stomach. Then 3 mL/kg of room-temperature (24~26degrees C) 1M sodium hydroxide (NaOH) disinfectant was instilled into the gastric lumen. The rabbits were divided into three groups: Group 1 (n=8) was treated with NaOH only and Group 2 (n=7) and Group 3 (n=8) were treated with 39 mL/kg of room-temperature orange juice or water after 5 minutes, respectively. Intra-gastric temperature was continuously measured and compared with arterial pH before alkali insult and 30 minutes later. Gastric pH was measured, and pathological examination of the esophagus, stomach, and duodenum performed after animal sacrifice. RESULTS: Gastric lumen temperatures gradually increased from 32.6degrees C to 38.7degrees C after alkali instillation. Significant decreases in lumen temperature, 7.5degrees C or 12.0degrees C, were observed following treatment with water or orange juice, respectively (p<0.01). Post-treatment temperature did not exceed pre-treatment temperature for the entire observation period. The gastric pH of the neutralization group was much lower than the alkali alone group or the dilution group (7.0+/-0.7 vs. 11.6+/-0.2, or 10.6+/-0.4, respectively, mean+/-SD, p<0.01). In gastric microscopic findings, only mucosal injuries were observed in the neutralization groups, while there were no significant differences among groups in terms of esophageal or duodenal injury. CONCLUSION: Neutralization therapy with room-temperature orange juice for acute gastrointestinal injuries caused by liquid alkali did not cause additional thermal injury and might have protective effects against local tissue destruction in the stomach.

Carbon monoxide produced from degradation of desflurane reacting with different carbon dioxide absorbents in a closed anesthesia circuit / 中华麻醉学杂志

soda lime). It took significant less time to reach the peak CO concentration with baralyme than with the other two CO2 absorbents. The temperature of top canister went up faster than that of the bottom one with soda lime; whereas with baralyme the temperature of the bottom canister went up faster. Conclusion In a simulated closed circuit the risk of CO poisoning was higher with baralyme than with soda lime. But KOH-free soda lime which still contains NaOH, such as sofnolime, may produce more CO than standard soda lime.