Insulin-Induced Electrophysiology Changes in Human Pleura Are Mediated via Its Receptor

Background. Insulin directly changes the sheep pleural electrophysiology. The aim of this study was to investigate whether insulin induces similar effects in human pleura, to clarify insulin receptor's involvement, and to demonstrate if glibenclamide (hypoglycemic agent) reverses this effect. Methods. Human parietal pleural specimens were mounted in Ussing chambers. Solutions containing insulin or glibenclamide and insulin with anti-insulin antibody, anti-insulin receptor antibody, and glibenclamide were used. The transmesothelial resistance (RTM) was determined. Immunohistochemistry for the presence of Insulin Receptors (IRa, IRb) was also performed. Results. Insulin increased RTM within 1st min (P = .016), when added mesothelially which was inhibited by the anti-insulin and anti-insulin receptor antibodies. Glibenclamide also eliminated the insulin-induced changes. Immunohistochemistry verified the presence of IRa and IRb. Conclusion. Insulin induces electrochemical changes in humans as in sheep via interaction with its receptor. This effect is abolished by glibenclamide

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p<00001), age 70 years or older versus younger than 70 years (230 [165-322], p<00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p<00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Human parietal pleura present electrophysiology variations according to location in pleural cavity

The aim of the study was to investigate if human pleura from different anatomical locations presents electrophysiology differences. Specimens were stripped over the 2nd-5th rib (cranial), 8th-10th rib (caudal), and mediastinum during open surgery and were mounted between Ussing chambers. Amiloride and ouabain were added towards mesothelial surface and trans-mesothelial potential difference (PDTM) was measured after 1, 5, 10 and 20 min. Trans-membrane resistance (RTM) was calculated from Ohm's law. R TM increased after amiloride addition, for cranial (net increase of 0.40 Ω·cm2) and caudal (1.16 Ω·cm 2) pleural pieces. Mediastinal pleura RTM remained unchanged (0.09 Ω·cm2). RTM increase was higher for caudal than cranial (P = 0.029) or mediastinal tissues (P = 0.002). RTM increased after ouabain addition for caudal (1.35 Ω·cm2) and cranial (0.56 Ω·cm2) pleural pieces. Mediastinal pleural tissue did not respond (0.20 Ω·cm2). Caudally located pleura responded greater than cranial (P = 0.043) or mediastinal (P = 0.003) pleural tissues. Human pleura shows electrophysiology differences according to the location within the pleural cavity. Surgeons may waste mediastinal pleura when needed but should leave intact caudal parietal pleura, which seems to be electrophysiologically the most important part of the pleural cavity

Blind on table internal iliac artery embolization in severe post partum hemorrhage: a case report

A case of a woman that had been transferred to our hospital in hemorrhagic shock secondary to post partum hemorrhage due to uterine atony, automatic abortion and extended vaginal lacerations has been described. Subtotal hysterectomy had already been performed but failed to control bleeding. The authors performed on table blind embolisation of internal iliac arteries in order to control hemorrhage as a life-saving procedure that was successful

Role of Electrolytes and Glucose in the Insulin-Induced Electrochemical Effect in Sheep Pleura

Aim: Insulin induces electrochemical alterations in sheep visceral and parietal pleura, an effect abolished by the Na(+)-channel blocker amiloride and the Na(+)-K(+) pump inhibitor ouabain. The aim of this study was to further investigate the role of different electrolytes and glucose in these electrochemical changes. Materials and methods: Sheep pleural specimens were mounted in Ussing chambers. Insulin (10(-7) M) was added mesothelially in Na(+), K(+), Ca(2+)-free, low H(+) and glucose solutions. In other experiments, specimens were pretreated with K(+) and Ca(2+)-free Krebs solutions. Trans-mesothelial Resistance was determined. Results: Insulin did not increase Trans-mesothelial Resistance of visceral and parietal pleura in K(+)-free (p = 0.008 and p = 0.028 respectively), Ca(2+)-free (p = 0.006 and p = 0.012 respectively) and low glucose (p = 0.009 and p = 0.03 respectively) solutions. This effect was totally inhibited in Na(+)-free solutions or in specimens pretreated with Ca(2+)-free Krebs solution and partially inhibited, when low H(+) solutions were used (p = 0.042 for visceral and p = 0.045 for parietal). Conclusion: Insulin-induced electrochemical changes in sheep pleura are mainly associated with alterations in Na(+) and Ca(2+) concentrations. Since amiloride and ouabain abolish these electrochemical changes, it may be suggested that insulin could influence the pleural fluid recycling, mainly via the Na(+) transportation system, irrespective of the glucose content

Insulin Alters the Permeability of Sheep Pleura

Aim: Insulin promotes ion transportation across epithelia, mainly kidneys, leading to water and electrolyte abnormalities, possibly causing 'insulin oedema syndrome', which rarely presents as pleural effusion. Direct stimulation of sheep pleura by insulin and the possible electrophysiology mechanisms involved were investigated. Material and Methods: Sheep visceral and parietal pleural specimens were mounted between Ussing chambers. Insulin solutions (10(-9) to 10(-5) M), L-NAME, Nitroprussid sodium, amiloride and ouabain were used. Trans-mesothelial Resistance was determined. Immunohistochemistry for presence of Insulin Receptors was performed. Results: Insulin increased Trans-mesothelial Resistance within 1st minute when added mesothelially of visceral (p = 0.008) and parietal pleura (p = 0.046) for concentrations higher than 10(-7) M. L-NAME or Nitroprussid sodium didn't but amiloride and ouabain inhibited insulin's effect. Immunohistochemistry revealed the presence of Insulin Receptors. Conclusion: Insulin changes the permeability of sheep pleura by altering its electrophysiology and may interfere in pleural effusion formation. Involvement of Insulin Receptors may be suggested

Insulin-Induced Electrochemical Changes in Pleura are Associated with the Location within the Pleural Cavity

Aim: We investigated the effects of insulin on the electrophysiology of sheep pleural specimens obtained from the upper and lower parts of the pleural cavity and the insulin receptor abundance in these regions. Materials and methods: Sheep pleural specimens were obtained from the upper and lower lung lobes and from the 1(st)-4(th) and 8(th)-12(th) ribs and were mounted between Ussing chambers. Insulin 10(-7)M was added on the mesothelial surface with Insulin Receptor (IR) inhibitor in some experiments. Trans-mesothelial Resistance (R(TM)) was determined. Immunohistochemistry for the presence of IR differences was performed. Results: Insulin increased the R(TM) of all pleural regions. Higher R(TM) increase was demonstrated in lower lobe visceral and in caudal parietal specimens. The R(TM) increase demonstrated in caudal parietal had the tendency to be higher than that observed in the lower lobe visceral specimens. IR inhibitor abolished insulin's effect in all regions. Immunostaining was more intense for parietal and for caudal parietal specimens when compared with the visceral and lower lobe visceral specimens. Conclusion: Insulin induces electrochemical alterations that vary depending on the location of specimens within the pleural cavity which possibly is not correlated with insulin receptors variations

IGF-1 alters the human parietal pleural electrochemical profile by inhibiting ion trans-cellular transportation after interaction with its receptor

Objective: The effect of IGF-1 in the human pleural permeability and the underlying mechanisms involved were investigated. Design: Specimens from thoracic surgical patients were mounted in Ussing chambers. Solutions containing IGF-1 (1 nM-100 nM) and IGF-1 Receptor Inhibitor (1 mu M), amiloride 10 mu M (Na+ channel blocker) and ouabain 1 mM (Na+-K+ pump inhibitor) were used in order to investigate receptor and ion transporter involvement respectively. Trans-mesothelial Resistance (R-TM) across the pleural membrane was determined as a permeability indicator. Immunohistochemistry for IGF-1 receptors was performed. Results: IGF-1 increased R-TM when added on the interstitial surface for all concentrations (p = .008, 1 nM-100 nM) and decreased it on the mesothelial surface for higher concentrations (p = .046, 100 nM). Amiloride and ouabain inhibited this effect. The IGF-1 Receptor Inhibitor also totally inhibited this effect. Immonuhistochemistry demonstrated the presence of IGF-1 receptors in the pleura. Conclusions: It is concluded that IGF-1 changes the electrophysiology of the human parietal pleura by hindering the normal ion transportation and therefore the pleural fluid recycling process. This event is achieved after IGF-1 interaction with its receptor which is present in the human pleura. (C) 2012 Elsevier Ltd. All rights reserved

Nonsteroidal Anti-Inflammatory Drugs Alter the Human Mesothelial Pleural Permeability via Ion Cellular Transportation by Inhibiting Prostaglandin Synthesis

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in clinical practice as analgesics or anti-inflammatory drugs. Studies have implicated them in participating in permeability throughout various tissues such as the kidneys and lungs. Objective: The effect of NSAIDs on the pleural permeability and the underlying mechanisms whereby this effect is mediated were investigated. Methods: Parietal pleural specimens were obtained from patients subjected to thoracic surgery and were mounted in Ussing chambers. Solutions containing paracetamol, acetylsalicylic acid, diclofenac, lornoxicam, parecoxib and ibuprofen were added in the chambers facing the pleural and the outer-pleural surface. Prostaglandin E-2 was similarly used to investigate prostaglandin synthesis involvement at low and high doses. Amiloride- and ouabain-pretreated specimens were used in order to investigate ion transportation involvement. Transmesothelial resistance (R-TM) was determined as a permeability indicator. Results: Paracetamol, acetylsalicylic acid, diclofenac, lornoxicam and ibuprofen increased R-TM on the pleural and outer-pleural surface, inhibited by amiloride and ouabain. Parecoxib had no effect on the R-TM. Prostaglandin decreased R-TM on the pleural and outer-pleural surface inhibited by amiloride, ouabain and ibuprofen. Conclusion: NSAIDs, except parecoxib, induce a rapid decrease of the pleural permeability by inhibiting cellular transportation, an effect that is mediated by prostaglandin synthesis inhibition. Copyright (C) 2012 S. Karger AG, Base

Low glucose level and low pH alter the electrochemical function of human parietal pleura

The aim of the present study was to investigate whether low glucose and pH level, which are usually measured in complicated pleural effusions, alter the electrochemical function of healthy human parietal pleura. Parietal pleural pieces were stripped from 66 patients during thoracic surgery and were mounted in Ussing chambers. Krebs' solutions containing different glucose levels (0, 40 and 100 mg) and balanced at different pH levels (7.4, 7.3 and 7.2) were added to the pleural cavity surface of the pieces. Transmesothelial potential difference was measured at various time-points as an electrophysiological variable and transmesothelial resistance (R-rm) was calculated using Ohm's law. When normal-glucose Krebs at pH 7.45 was used, R (TM) remained unchanged over time, but when low-glucose Krebs was used, R (TM) decreased. Krebs without glucose caused the greatest decrease in R (TM). Use of low-pH Krebs decreased RTM. The lower the pH of the Krebs, the faster the decrease in R (TM) and the greater the effect. The decrease in R-rm was greater with low-pH than with low-glucose Krebs. Low glucose and low pH caused an additive decrease in R (TM). Low glucose concentration and low pH cause alteration of the electrochemical function of human parietal pleura and could act as agents that lead to further exudate progression