ABSTRACT
Peritoneal metastases are one reason for the poor prognosis of scirrhous gastric cancer (SGC), and myofibroblast provides a favorable environment for the peritoneal dissemination of gastric cancer. The aim of this study was to determine whether myofibroblast originates from peritoneal mesothelial cells under the influence of the tumor microenvironment. Immunohistochemical studies of peritoneal biopsy specimens from patients with peritoneal lavage cytological (+) status demonstrate the expression of the epithelial markers cytokeratin in fibroblast-like cells entrapped in the stroma, suggesting that these cells stemmed from local conversion of mesothelial cells. To confirm this hypothesis in vitro, we co-incubated mesothelial cells with SGC or non-SGC to investigate morphology and function changes. As we expected, mesothelial cells undergo a transition from an epithelial phenotype to a mesenchymal phenotype with loss of epithelial morphology and decrease in the expression of cytokeratin and E-cadherin when exposed to conditioned medium from HSC-39, and the induction of mesothelial cells can be abolished using a neutralizing antibody to transforming growth factor-beta1 (TGF-ß1) as well as by pre-treatment with SB431542. Moreover, we found that these mesothelial cells-derived cells exhibit functional properties of myofibroblasts, including the ability to increase adhesion and invasion of SGC. In summary, our current data demonstrated that mesothelial cells are a source of myofibroblasts under the SGC microenvironment which provide a favorable environment for the dissemination of gastric cancer; TGF-ß1 produced by autocrine/paracrine in peritoneal cavity may play a central role in this pathogenesis.
Subject(s)
Adenocarcinoma, Scirrhous/secondary , Epithelial-Mesenchymal Transition , Epithelium/pathology , Fibroblasts/pathology , Peritoneal Neoplasms/secondary , Stomach Neoplasms/pathology , Adenocarcinoma, Scirrhous/metabolism , Cell Adhesion , Coculture Techniques , Culture Media, Conditioned , Fibroblasts/metabolism , Humans , Neoplasm Invasiveness , Peritoneal Neoplasms/metabolism , Peritoneum/pathology , Smad2 Protein/metabolism , Stomach Neoplasms/metabolism , Transforming Growth Factor beta1/metabolism , Tumor Cells, Cultured , Tumor MicroenvironmentABSTRACT
Therapeutic hypothermia (TH) is becoming a standard of care to mitigate neurologic injury in cardiac arrest survivors. Several cooling methods are available for use in TH. For maintaining a target temperature, intravascular cooling is superior to, more efficacious than, and safer than surface cooling methods. The use of an intravenous cooling catheter is independently associated with a higher odds ratio for survival. However, many techniques use commercially developed equipment that is expensive to purchase and use. The application and popularization of the intravascular cooling method have been difficult. In patients with pulmonary edema or cardiac insufficiency, liquid is restricted, so intravascular cooling systems cannot be used. Studies have shown abnormalities mimicking the immunologic and coagulation disorders observed in severe sepsis. Continuous renal replacement therapy has been widely used in the intensive care unit to improve clinical parameters and survival in patients with multiple-organ dysfunction of septic origin. Continuous renal replacement therapy can also be used as another type of core cooling method. We used continuous renal replacement therapy as a cooling method to induce TH in a patient who had a cardiac arrest, and the patient regained consciousness 52 hours later.
Subject(s)
Advanced Cardiac Life Support/methods , Heart Arrest/therapy , Hypothermia, Induced/methods , Hypoxia-Ischemia, Brain/prevention & control , Kidney Failure, Chronic/therapy , Renal Replacement Therapy/methods , Heart Arrest/complications , Humans , Kidney Failure, Chronic/complications , Male , Middle AgedABSTRACT
BACKGROUND: Severe burn-blast combined injury is a great challenge to medical teams for its high mortality. The aim of this study was to elucidate the clinical characteristics of the injury and to present our clinical experiences on the treatment of such cases. METHODS: Five patients with severe burn-blast combined injuries were admitted to our hospital 77 hours post-injury on June 7, 2005. The burn extent ranged from 80% to 97% (89.6% +/- 7.2%) of TBSA (full-thickness burns 75% - 92% (83.4% +/- 7.3%)). All the patients were diagnosed as having blast injury and moderate or severe inhalation injury. Functions of the heart, liver, kidney, lung, pancreas and coagulation were observed. Autopsy samples of the heart, liver, and lungs were taken from the deceased. Comprehensive measures were taken during the treatment, including protection of organ dys function, use of antibiotics, early anticoagulant treatment, early closure of burn wounds, etc. All the data were analyzed statistically with t test. RESULTS: One patient died of septic shock 23 hours after admission (four days after injury), the others survived. Dysfunction of the heart, liver, lungs, pancreas, and coagulation were found in all the patients on admission, and the functions were ameliorated after appropriate treatments. CONCLUSIONS: Burn-blast combined injury may cause multiple organ dysfunctions, especially coagulopathy. Proper judgment of patients' condition, energetic anticoagulant treatment, early closure of burn wounds, rational use of antibiotics, nutritional support, intensive insulin treatment, timely and effective support and protection of organ function are the most important contributory factors in successful treatment of burn-blast combined injuries.
Subject(s)
Blast Injuries/therapy , Burns/therapy , Adult , Anti-Bacterial Agents/therapeutic use , Blast Injuries/complications , Blast Injuries/physiopathology , Burns/complications , Burns/physiopathology , Humans , Male , Nutrition Therapy , Psychotherapy , RespirationABSTRACT
OBJECTIVE: To explore the regulative effect of lipopolysaccharide (LPS) on the mRNA expression of procollagen type I and type III and collagenase of normal skin fibroblasts of hypertrophic scar patients and its biological role in the formation of hypertrophic scar. METHODS: Scar tissue and normal skin were obtained from 20 patients with hypertrophic scar. Fibroblasts were isolated, underwent passaged culture, and exposed to LPS from Escherichia coli of the concentrations of (0.005 - 1.0) microg/ml till they reached stable phenotype (at the eighth passage). The expression of procollagen type I and type III and collagenase mRNAs were tested by RT-PCR. Fibroblasts from hypertrophic scar tissue obtained from the same patients and normal skin fibroblasts without stimulation of LPS in the same culture passage were used as positive control and negative control respectively. RESULTS: When LPS was of the concentrations of 0.005 - 0.5 microg/ml, the mRNA expression levels of procollagen type I and type III were markedly increased, but the mRNA expression of collagenase was significantly decreased, compared with negative control group (all P < 0.01). The effect reached the peak when the LPS concentration was 0.1 microg/ml. When the concentration of LPS reached 1.0 microg/ml, the mRNA expression levels of procollagen type I and type III were inhibited and the mRNA expression level of collagenase began to increase, but still lower than that of the negative control group (P < 0.01). When the concentration of LPS was 0.1 microg/ml, the mRNA expression levels of procollagen type I and type III and collagenase were similar to that of the positive control group (all P > 0.05). CONCLUSION: LPS enhances the mRNA expression of procollagen type I and type III, inhibits the mRNA expression of collagenase within certain range of concentrations. LPS may be a primitive factor in hypertrophic scar formation.
Subject(s)
Collagen Type III/genetics , Collagen Type I/genetics , Collagenases/genetics , Fibroblasts/drug effects , Lipopolysaccharides/pharmacology , Adolescent , Adult , Child , Child, Preschool , Cicatrix, Hypertrophic/genetics , Cicatrix, Hypertrophic/pathology , Female , Fibroblasts/metabolism , Gene Expression/drug effects , Humans , Male , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Skin/drug effects , Skin/metabolismABSTRACT
OBJECTIVE: To observe the effects of carbon fiber dressing on burn wounds. METHODS: Two hundreds and seventy seven burn patients were randomly divided into treatment group (group T) and control group (group C). The burn wounds were covered with carbon fiber dressing in T group, and with povidone iodine gauze in C group, respectively. The absorption capability of the dressing, inflammatory reaction and bacteria quantitation of wound tissues and wound healing time were observed, and biopsy of wounds were performed. RESULTS: The absorption capability of the dressing was higher, the wound inflammatory reaction was milder, and bacteria quantitation of wound tissues was lower in the group T than that in group C. The wound healing time in the group T was shorter than that in group C. CONCLUSIONS: Carbon fiber dressing is a new model dressing, it can absorb wound exudation, lessen inflammatory reaction and improve wound healing.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Bandages , Burns/therapy , Carbon/therapeutic use , Adolescent , Adult , Aged , Carbon Fiber , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
OBJECTIVE: To study the effects of enteral administration of carbachol on organ dysfunction induced by partial ischemia/reperfusion injury to the intestine. METHODS: Seventy-five white rabbits were randomized into four groups: ischemia/reperfusion (I/R), carbachol+ I/R and sham operation. The superior mesenteric artery (SMA) was partially blocked with self-designed blocker, producing 50% decrease in SMA blood flow, lasting for 4 hours. One hour after SMA occlusion, carbachol was injected into gut in carbachol+I/R group. Sham group was treated as same as I/R group except without SMA occlusion. The levels of alanine aminotransferase (ALT), creatinine (Cr), MB isoenzyme of creatine kinase (CK-MB) and tumor-necrosis factor-alpha (TNF-alpha) were measured by automatic analyzer and with radio-immunology method before SMA occlusion, and at 2, 4, 6, 8, 24, 48 and 72 hours after occlusion. The pathological changes of the intestinal tissue were observed with hematoxylin and eosin stained sections. RESULTS: In I/R groups, the levels of TNF-alpha, Cr, ALT, CK-MB in plasma were increased dramatically after partial ischemia/reperfusion injury to the gut. Severe pathological changes were observed in the hearts, livers, and kidneys. While in carbachol treatment groups, the levels of TNF-alpha, Cr, ALT, CK-MB in plasma were decreased dramatically after enteral administration of carbachol during ischemia stage. The pathological injuries were alleviated in the heart, liver, and kidney. CONCLUSION: Enteral administration of carbachol may alleviate after the systemic inflammatory response and pathological changes in various organs, thus provide a protective effect on gut and remote organs partial ischemia/reperfusion of the intestine.
Subject(s)
Carbachol/pharmacology , Intestines/blood supply , Reperfusion Injury/prevention & control , Systemic Inflammatory Response Syndrome/prevention & control , Animals , Disease Models, Animal , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Male , Multiple Organ Failure/etiology , Multiple Organ Failure/prevention & control , Rabbits , Random Allocation , Reperfusion Injury/blood , Reperfusion Injury/complications , Reperfusion Injury/pathology , Systemic Inflammatory Response Syndrome/etiology , Tumor Necrosis Factor-alpha/bloodABSTRACT
OBJECTIVE: To investigate the potential effect of bifidobacterial supplement on intestinal mucosal immunity associated with severe burns. METHODS: Wistar rats were randomly divided into burn control group (BC group, n = 30), treatment group (BT group, n = 30), and sham-burn group (NC group, n = 10). Rats in BT group were fed bifidobacterial preparation (5 x 10(9) CFU/ml) after 30% total body surface area full-thickness burns, 1.5 ml, twice daily. Rats in BC group and NC group were fed normal saline, 1.5 ml, twice daily. Samples were taken on post-burn 1-, 3-, and 5-day. The incidence of bacterial translocation and bifidobacteria counts in the cecum mucosa were determined with standard methods. The sIgA levels in the mucus of the small intestine were measured by RIA. The positive sIgA expression in the lamina propria was detected by immunohistochemical staining. RESULTS: The incidence of bacterial translocation was 42% and 16% in BC and BT groups on post-burn day 3 (P = 0.004), 30% and 8% on day 5 (P = 0.002), respectively. Plasma endotoxin levels were markedly higher in BC and BT groups than in NC group at the early stage post-burn. There was a significant decrease between BT group and BC group on post-burn day 1 (P = 0.0412). Bifidobacteria counts in cecum mucosa were reduced by 10- to 60-fold after thermal injury, but there was a remarkable increase in bifidobacteria counts in animals fed with bifidobacteria. sIgA levels in the intestinal mucus were significantly decreased in group BC, but they returned to normal range in BT group on post-burn day 5. Similarly, sIgA expression in the lamina propria was also weakened after burns, and had a tendency to recover after prescription of a 5-day bifidobacteria-supplemented formula. A strong positive correlation was observed between the counts of bifidobacteria in the cecal mucosa and the levels of sIgA in the intestinal mucus (r = 0.7534, P = 0.0000). CONCLUSIONS: The expression and excretion of sIgA in the intestine appear to be markedly inhibited following a severe thermal injury. The supplement of exogenous bifidobacteria could improve sIgA formation in the small intestine, thereby reducing the incidence of bacterial/endotoxin translocation secondary to major burns.
Subject(s)
Bifidobacterium/physiology , Burns/immunology , Immunoglobulin A, Secretory/biosynthesis , Intestinal Mucosa/immunology , Probiotics , Animals , Bacterial Translocation , Burns/microbiology , Disease Models, Animal , Female , Intestinal Mucosa/microbiology , Male , Random Allocation , Rats , Rats, WistarABSTRACT
Metastasis is unequivocally the most lethal aspect of breast cancer and the most prominent feature associated with disease recurrence, the molecular mechanisms whereby epithelial-to-mesenchymal transition (EMT) mediates the initiation and resolution of breast cancer metastasis remains poorly understood. Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine that is intimately involved in regulating numerous physiological processes, including cellular differentiation, homeostasis and EMT. Recent findings have implicated high levels of TGF-ß1 were associated with poor outcome, whereas inhibition of TGF-ß signaling reduces metastasis in breast cancer, suggesting that the chemo-therapeutic targeting of TGF-ß1 or TGF-ß signaling may offer new inroads in ameliorating metastatic disease in breast cancer patients. In this study, we showed immunohistochemical evidence for EMT, which is associated with TGF-ß1 expression, at the invasion front of breast cancer in vivo. The data also indicated that human breast cancer cell lines, MCF-7 and MDA-MB-435S, of epithelial cell characteristics were induced to undergo EMT by TGF-ß1 and dependent on the Smad2 signaling pathway. Following TGF-ß1 treatment, cells showed dramatic morphological changes assessed by phase contrast microscopy, accompanied by decreased epithelial marker and increased mesenchymal markers. Importantly, cell invasion was also enhanced in the EMT process, while knockdown of the Smad2 gene by silencing siRNA partially inhibited these effects in MDA-MB435S (P<0.05). These data suggested that EMT of breast cancer induced by TGF-ß1 is dependent on Smad2 signaling and promotes breast cancer cell metastasis.
Subject(s)
Apoptosis , Breast Neoplasms/pathology , Cell Movement , Epithelial-Mesenchymal Transition , Smad2 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Blotting, Western , Breast Neoplasms/metabolism , Cell Adhesion , Cell Proliferation , Female , Humans , Immunoenzyme Techniques , Neoplasm Invasiveness , Phosphorylation , RNA, Small Interfering/genetics , Smad2 Protein/antagonists & inhibitors , Smad2 Protein/genetics , Tissue Array Analysis , Tumor Cells, CulturedABSTRACT
The study focused on the chemical element compositions of river water and groundwater in Lijiang Basin. Water samples were collected in Baishui, Sanshu, Geji and Shuhe rivers in Lijiang Basin to analyze pH, conductivity and ion concentration, in order to understand the contributions of anthropogenic activities and rock weathering to river solutes. The results show that all water samples are mildly alkaline and are rich in Ca2+ and HCO3-, which account for 54.8 and 92.4 percentage of total ion concentration respectively. Obvious variations have been perceived during monsoon and westward wind season. The ion concentration of river water is lower than that of groundwater. With decreasing elevation, the ion concentrations are found to increase considerably in the study region. According to source study of major ions, water chemistry is mainly influenced by precipitation rock weathering and dissolving processes. In addition, precipitation is an important factor in monsoon seasons whereas the anthropogenic inputs have lead to light pollution on water in residential district.
Subject(s)
Environmental Monitoring/methods , Groundwater/chemistry , Rain/chemistry , Rivers/chemistry , Water Pollutants, Chemical/analysis , Calcium/analysis , Carbonates/analysis , China , Hydrogen-Ion Concentration , Iron/analysisABSTRACT
OBJECTIVE: To investigate the influence of enteral administration of carbachol on the intestinal dysfunction of both severely burn patients and rabbits with partial intestinal ischemia/reperfusion (I/R) injury. METHODS: Seventy-five white rabbits were inflicted with I/R injury and randomized into intestinal I/R (I, n=25), carbachol [C, n=25, with 3g/L carbachol (3 mg/kg) injection into duodenum 1 h after SMA occlusion] and sham operation (SO, n=25, with SMA isolation but no occlusion) groups, and 5 other as normal controls. The blood flow of intestinal mucosa was detected before and after SMA occlusion or admission of carbachol. Changes in diamine oxidase (DAO), D-lactate, xylopyranose absorption, blue dextran discharging time were measured at 2, 4, 6, 8, 24, 48, 72 h after SMA occlusion. In addition, eight severe burn patients with TBSA of 84 +/- 12% were enrolled in the study, and carbachol (15 microg/kg) was administered to patients when abdominal distension or bowel sound was lower than 2 times/min, then the number of abdominal distension and bowel sounds per minute were observed. RESULTS: The blood flow in intestinal mucosa of rabbits without SMA occlusion was (102 +/- 5) PU, reduced to (48 +/- 6) PU after SMA occlusion, and increased to (77 +/- 3) PU after injection of carbachol. The plasma DAO activity and D-lactic acid content in I group began to increase 4 hours after SMA occlusion, and they reached the peak 24 hours after SMA occlusion (4.63 +/- 0.27 U/ml, 7.9 +/- 2.4 mg/L) , after that they decreased gradually, but still higher than the normal value (0.89 +/- 0.14 U/ml, 2.0 +/- 1.1 mg/L, P < 0.05). In carbachol group, data showed the same trends as that in intestine I/R group with lower values, while no obvious changes were in sham operation group (P > 0.05). The content of D-lactic decreased dramatically 2 hours after D-lactic administration in both I and C groups, increased 6 hours after SMA occlusion, then decreased gradually, but it in C group was always higher than normal values, and little fluctuation was in sham operation group. There was no blue dextran discharge 2 hours after SMA occlusion. The discharging distance increased 6 hours later, but it was obviously shorter than the normal value 24 hrs after operation (P < 0.05) , then it returned to normal 48 to 72 hrs after operation. In the C group, blue dextran discharge was found immediately after its injection, with obvious increase in the discharging distance to peak value (43 +/- 6 cm) 6 hours after injury, and returning to normal (28 +/- 3 cm) gradually. In severe burned patients, the bowel sounds was (1.6 +/- 1.1) per minutes before carbachol administration, then increased dramatically to (6.9 +/- 1.7) per minutes 10 mins after administration, reached to a higher level 30 minutes after administration (8.3 +/- 2.4 ) times/min, and it maintained to (6.1 +/- 1.3) times/min 1 hour after administration. Abdominal distension was ameliorated 2 hours after carbachol administration, six patients were able to defecate. CONCLUSION: Enteral administration of Carbachol can increase the blood flow of intestine mucosa, help to improve the movement, absorption and barrier functions of intestine, and ameliorate intestinal dysfunction in patients with severe burns.
Subject(s)
Burns/drug therapy , Carbachol/therapeutic use , Intestinal Mucosa/blood supply , Intestines/physiopathology , Reperfusion Injury/drug therapy , Adolescent , Adult , Animals , Burns/physiopathology , Disease Models, Animal , Female , Humans , Intestinal Mucosa/metabolism , Male , Rabbits , Reperfusion Injury/physiopathologyABSTRACT
OBJECTIVE: To investigate the dynamic expression of platelet-derived growth factor-A (PDGF-A) and its receptor alpha (PDGFR-alpha) in different acute radiation-induced skin ulcers, and to explore the underlying mechanism involved in retarded healing of the ulcer. METHODS: The model of acute radiation-induced skin ulcers in rats was replicated with 50 Gy 60Co gamma rays to the skin (radiation group, R, n = 55), rats with full - thickness skin excision wounds as control group (T, n = 55), and 5 normal rats to serve as normal control (NC) group. The expression of PDGF-A and PDGFR-alpha protein and PDGF-A mRNA was respectively assessed by means of histochemistry and in situ RT-PCR. RESULTS: No PDGF-A expression was identified in the rat skin in NC group. The expression of PDGF-A and PDGFR were reduced in R group during inflammatory responsive and granulation formation periods (14 - 28 days after radiation, the IA value of PDGF-A varied from 14.0 +/- 1.2 to 20.3 +/- 1.2 compared with that in T group in which the IA value of PDGF-A at the same period (3 - 9 days after injury) varied from 20.0 +/- 1.6 to 28.3 +/- 1.0, and reduced gradually during scar formation period (55 days after radiation). CONCLUSION: The reduction of PDGF-A and PDGFR-expression may be partially involved in the mechanism of retarded healing of acute radiation-induced skin ulcers.