Natural alkaloid 8-oxo-epiberberine inhibited TGF-ß1-triggred epithelial-mesenchymal transition by interfering Smad3.

Epithelial-mesenchymal transition (EMT), the transition of epithelial cells into mesenchymal cells, plays important roles in the metastasis of solid tumors. 8-Oxo-epiberberine (OPB) is a natural alkaloid extracted from the roots of Coptis chinensis Franch. In this study, The effect and the underlying mechanism of OPB on EMT in a TGF-ß1-induced model and the inhibitory effect of OPB on lung metastasis were investigated. TGF-ß1-stimulated lung cancer cells were co-treated with OPB, the morphological changes were examined. The protein expression of EMT biomarkers E-cadherin and N-cadherin was determined by Western blotting and immunofluorescence. The transcription activity of smad2/3 promoter was analyzed by a luciferase reporter assay. The effect of OPB on cell migration, invasion, and adhesion was detected by wound-healing, adhesion, and transwell assays. The in vivo anti-metastatic effect of OPB was evaluated using a 4 T1 cell xenograft mouse model. Results showed that OPB significantly reversed TGF-ß1-triggered morphological changes, expression of EMT biomarkers, and migration, adhesion, and invasion. Furthermore, OPB suppressed TGF-ß1-induced Smad2/3 activation, Smad3 phosphorylation and nuclear translocation, and interaction of Smad3 with Smad4. Besides, OPB dramatically decreased the metastatic nodules in the lung without affecting the growth of primary tumors. In conclusion, OPB inhibited TGF-ß1-induced EMT possibly by interfering with Smad3. OPB might have therapeutic potentials for the treatment of metastatic cancers.

Gastric perforation following improper cardiopulmonary resuscitation in out-of-hospital cardiac arrest.

Gastric perforation is a rare complication of cardiopulmonary resuscitation (CPR), mostly resulting from incorrect airway management. If left unrecognized, it is associated with high mortality and morbidity. We present a case of gastric perforation after improper CPR. A 56-year-old drunken male was sent to the emergency department due to coma after fall onto the ground. He was thought to have cardiac arrest at scene and was saved with CPR maneuver by his friends who has never been trained before. He was taken to the hospital by emergency medical service personnel and presented with abdominal distention and extensive pneumoperitoneum. Emergency laparotomy was performed which revealed gastric perforation at the lesser curvature of the stomach. The laceration was repaired without any difficulty and the patient was discharged home without any neurological deficit. The aim of this report is to remind the public and emergency physicians that gastric perforation should be suspected in patients with distended abdomen and pneumoperitoneum after CPR. Because the most common risk factor for CPR-related gastric perforation is the bystander-provided resuscitation, it is encouraged for the public to take formal CPR training.

Ideal target arterial pressure after control of bleeding in a rabbit model of severe traumatic hemorrhagic shock: results from volume loading-based fluid resuscitation.

BACKGROUND: Previously reported ideal target mean arterial pressure (MAP) after control of bleeding in traumatic hemorrhagic shock (THS) requires further verification in more clinically related models. The authors explored this issue via gradient volume loading without vasopressor therapy. As certain volume loading can induce secretion of atrial natriuretic peptide (ANP), which has been shown to be protective, the authors also observed its potential role. MATERIALS AND METHODS: Fifty male New Zealand rabbits were submitted to 1.5 h of uncontrolled THS (with another eight rabbits assigned to the sham group). After bleeding control, treated rabbits were randomly (n = 10, respectively) resuscitated with blood and Ringer lactate (1:2) to achieve target MAP of 50, 60, 70, 80, and 90 mm Hg within 1 h. During the following 2 h, they were resuscitated toward baseline MAP. Rabbits were observed until 7 h. RESULTS: After resuscitation, infused fluid was lower and oxidative stress injury was milder in the 70 mm Hg group. Fluid volume loaded during the initial hour after hemostasis was negatively correlated with pH, oxygen saturation, and base excess at the end of resuscitation. It also correlated positively with proinflammatory responses in bronchoalveolar lavage fluid at 7 h and 7-h mortality. Moreover, after volume loading, the 80 mm Hg group showed significantly increased serum ANP level, which correlated with the expression of Akt protein in the jejunum at 7 h. CONCLUSIONS: In rabbits the ideal target MAP during the initial resuscitation of severe THS after hemostasis was 70 mm Hg. ANP may have a critical role in gut protection.

Early fluid loading in acute respiratory distress syndrome with septic shock deteriorates lung aeration without impairing arterial oxygenation: a lung ultrasound observational study.

INTRODUCTION: The study was designed to assess the impact of fluid loading on lung aeration, oxygenation and hemodynamics in patients with septic shock and acute respiratory distress syndrome (ARDS). METHODS: During a 1-year period, a prospective observational study was performed in 32 patients with septic shock and ARDS. Cardiorespiratory parameters were measured using Swan Ganz (n = 29) or PiCCO catheters (n = 3). Lung aeration and regional pulmonary blood flows were measured using bedside transthoracic ultrasound. Measurements were performed before (T0), at the end of volume expansion (T1) and 40 minutes later (T2), consisting of 1-L of saline over 30 minutes during the first 48 h following onset of septic shock and ARDS. RESULTS: Lung ultrasound score increased by 23% at T2, from 13 at baseline to 16 (P < 0.001). Cardiac index and cardiac filling pressures increased significantly at T1 (P < 0.001) and returned to control values at T2. The increase in lung ultrasound score was statistically correlated with fluid loading-induced increase in cardiac index and was not associated with increase in pulmonary shunt or regional pulmonary blood flow. At T1, PaO2/FiO2 significantly increased (P < 0.005) from 144 (123 to 198) to 165 (128 to 226) and returned to control values at T2, whereas lung ultrasound score continued to increase. CONCLUSIONS: Early fluid loading transitorily improves hemodynamics and oxygenation and worsens lung aeration. Aeration changes can be detected at the bedside by transthoracic lung ultrasound, which may serve as a safeguard against excessive fluid loading.

Biosynthesis of CdS nanoparticles in banana peel extract.

Cadmium sulfide (CdS) nanoparticles (NPs) were synthesized by using banana peel extract as a convenient, non-toxic, eco-friendly 'green' capping agent. Cadmium nitrate and sodium sulfide are main reagents. A variety of CdS NPs are prepared through changing reaction conditions (banana extracts, the amount of banana peel extract, solution pH, concentration and reactive temperature). The prepared CdS colloid displays strong fluorescence spectrum. X-ray diffraction analysis demonstrates the successful formation of CdS NPs. Fourier transform infra-red (FTIR) spectrogram indicates the involvement of carboxyl, amine and hydroxyl groups in the formation of CdS NPs. Transmission electron microscope (TEM) result reveals that the average size of the NPs is around 1.48 nm.

Evaluation of the inflammatory response in a two-hit acute lung injury model using [18F]FDG microPET.

The aim of this study was to investigate whether a two-hit acute lung injury (ALI) model is better than a one-hit model in simulating ALI, and to evaluate the inflammatory response in the lungs in these two models using micro-positron emission tomography (microPET) with [18F]fluorodeoxyglucose (FDG). Sprague Dawley rats were divided into four groups; rats in the lipopolysaccharide (LPS; n=10) and LPS-HCl (n=10) groups were challenged by the intraperitoneal administration of 5 mg/kg LPS, while rats in the normal saline (NS; n=3) and HCl (n=10) groups received the same volume of normal saline solution. Sixteen hours following the administration, the rats in the HCl and LPS-HCl groups received an acid instillation (IT) of 0.5 ml/kg HCl (pH=1.2), while the rats in the remaining two groups received the same volume of normal saline solution. The mean arterial blood pressure (MAP) and blood gas concentrations were measured in all four groups. MicroPET was performed 4 h following HCl IT and the lungs were excised for histopathological examination. The rats in the LPS-HCl group exhibited a higher arterial PaO2 and a lower arterial PaCO2 compared with the rats in the remaining groups. The MAP decreased markedly in the LPS-HCl group, but remained stable in the LPS, HCl and NS groups. MicroPET results identified that the region of interest ratio in the LPS-HCl group (9.00±1.41) was significantly higher compared with those in the LPS (4.01±0.60) and HCl (3.33±0.55) groups (P<0.01). In addition, histological examination showed that the mean lung injury score in the LPS-HCl group (12.70±0.95) was significantly higher compared with those in the HCl (8.40±1.26) and LPS (7.00±0.82) groups (P<0.01). The present study demonstrates that LPS pretreatment significantly magnifies and prolongs the inflammatory response to subsequent acid IT in the lungs. Moreover, it is simpler to induce ALI using the two-hit model than with the one-hit model, and [18F]FDG microPET is a useful tool for evaluating the inflammatory reaction during ALI.

Risk factors and clinical significance of trauma-induced coagulopathy in ICU patients with severe trauma.

OBJECTIVE: To investigate the incidence and risk factors for trauma-induced coagulopathy (TIC) and the impact of TIC on outcomes of patients with severe trauma admitted to an emergency intensive care unit. METHODS: We retrospectively reviewed clinical data from 223 patients with severe trauma admitted to emergency intensive care unit within 24 h after injury. Injury Severity Score (ISS), Acute Physiology and Chronic Health Evaluation II score, coagulation function, routine blood and biochemical tests, and blood gas parameters were obtained from medical records. Patients were divided into two groups according to the presence or absence of coagulopathy. ISS, Acute Physiology and Chronic Health Evaluation II score, and the incidence rates of hypothermia and tissue hypoperfusion were compared. The risk factors of TIC were analyzed and a multivariate logistic regression equation was developed. Coagulation function and the incidence of TIC were also compared between surviving and dead patients. RESULTS: Overall, 52/223 (23.3%) patients fulfilled the diagnostic criteria for TIC. Their mortality rate was significantly higher than that of patients without coagulopathy (36.5 vs. 9.4%, P<0.01). ISS, incidence rates of hypothermia and tissue hypoperfusion, and the prevalence of severe traumatic brain injury were significantly higher (P<0.01), whereas Glasgow Coma Scale, hemoglobin, hematocrit, and platelet counts were significantly lower (P<0.01) in patients with coagulopathy than those without. Base deficit at least 6, Glasgow Coma Scale 8 or less, and platelet count were independent risk factors for TIC. Compared with surviving patients, the patients who died had significantly reduced coagulation function. CONCLUSION: The incidence of TIC is particularly high among patients with severe trauma. TIC is associated with increased ISS, brain injury, shock and hypothermia, and mortality.

Rapid detection of recurrent intraventricular hemorrhage by ultrasound in a multiple trauma patient who had undergone craniectomy.

Ultrasound may be a useful tool to evaluate intracranial abnormalities in critically ill patients undergoing decompressive craniectomy. We present a multiple trauma patient who had undergone craniectomy and in whom recurrent intraventricular hemorrhage and patterns of cerebral blood flow were rapidly detected by ultrasound.

Bis(µ-5-nitro-2-oxidobenzoato)bis-[triaqua-zinc(II)].

The title complex mol-ecule, [Zn(2)(C(7)H(3)NO(5))(2)(H(2)O)(6)], is a centrosymmetric dimer containing two zinc(II) cations with distorted octa-hedral geometries provided by the O atoms of three water mol-ecules and the two bridging bidentate 5-nitro-salicylate ligands. The separation between the metal centres in the dimer is 3.1790 (11) Å. The crystal structure is stabilized by O-H⋯O hydrogen bonds, one of which intra-dimeric, linking the dimers into a three-dimensional network.

Protective effect of raloxifene on lipopolysaccharide and acid- induced acute lung injury in rats.

AIM: To evaluate the protective effect of oral raloxifene on acute lung injury. METHODS: Thirty adult, male Sprague-Dawley rats each weighing 180-210 g were used and divided into 3 groups: the raloxifene-lipopolysaccharide (LPS)-HCl group (n=10), the LPS-raloxifene-HCl group (n=10), and the placebo group (n=10). All the rats were injected intraperitoneally (ip) with 5 mg/kg LPS, and raloxifene (30 mg/kg) was orally administered 1 h before and 14 h after LPS injection into the raloxifene-LPS-HCl and the LPS-raloxifene-HCl groups, respectively; the placebo group received nothing. Sixteen hours after LPS injection, all the animals were anesthetized and the femoral artery was cannulated. All the rats received a direct intratracheal (IT) injection of HCl (pH 1.2; 0.5 mL/kg). The mean arterial pressure (MAP) and blood gas concentrations were measured. Fifteen rats (5 in each group, respectively) underwent a micro positron emission tomography (microPET) scan of the thorax 4 h after HCl instillation. The wet/dry (W/D) weight ratio determination and histopathological examination were also performed. RESULTS: The rats in the LPS-raloxifene-HCl group had a lower [18F]fluorodeoxyglucose uptake compared with the rats in the placebo group (4.67+/-1.33 vs 9.01+/-1.58, respectively, P<0.01). The rats in the LPS-raloxifene-HCl group also had a lower histological lung injury score (8.20+/-1.23 vs 12.6+/-0.97, respectively, P<0.01) and W/D weight ratio (5.335+/-0.198 vs 5.886+/-0.257, respectively, P<0.01) compared to the placebo group. The rats in this group also showed better pulmonary gas exchange and more stable mean arterial pressure (MAP) compared to the placebo group. CONCLUSION: Raloxifene provides a significant protective effect on acute lung injury in rats induced first by LPS ip injection and then by HCl IT instillation.