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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis is a generalized inflammatory response, which involves organ systems remote from the locus of the initial infectious insult, accompanied by the release of cytokines and the subsequent formation of reactive oxygen and nitrogen species. The aim of this study was to investigate the possible protective effect of octreotide (OCT), a synthetic somatostatin analogue, against sepsis-induced oxidative damage in the uterine and ovarian tissues of rats. Sepsis was induced by caecal ligation and puncture method in female Wistar albino rats. Sepsis and sham operated (control) groups received either saline or OCT (50 microg/kg, i.p.; Novartis) immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and serum TNF-alpha levels and tissue malondialdehyde (MDA) content, glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the uterus and ovaries. Oxidant-induced tissue fibrosis was determined by tissue collagen contents, while the extent of tissue injuries was analyzed microscopically. Sepsis increased serum TNF-alpha levels and resulted in decreased GSH levels and increased MDA levels, MPO activity and collagen contents in both the uterus and the ovaries (p<0.05-0.001) indicating the presence of the oxidative damage, as also confirmed by histological analysis. On the other hand, OCT administration reversed these oxidant responses and reduced the severity of microscopic damage (p<0.001). In conclusion, OCT protects against sepsis-induced oxidative injury of the uterine and ovarian tissues by diminishing neutrophil infiltration, an important source of oxygen free radicals. Our results suggest that OCT may be of therapeutic value in ameliorating sepsis-associated pelvic inflammation.
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PMID:Octreotide ameliorates sepsis-induced pelvic inflammation in female rats by a neutrophil-dependent mechanism. 1565 56

In recent years, a number of articles have been published on the treatment of acute pancreatitis in experimental models and most of them were published about animals with mild disease. However, it is difficult to translate these results into clinical practice. For example, infliximab, a monoclonal TNF antibody, was experimentally tested in rats and it was able to significantly reduce the pathologic score and serum amylase activity, and also alleviate alveolar edema and acute respiratory distress syndrome; no studies are available in clinical human acute pancreatitis. Another substance, such as interleukin 10, was efficacious in decreasing the severity and mortality of lethal pancreatitis in rats, but seems to have no effect on human severe acute pancreatitis. Thus, the main problem in acute pancreatitis, especially in the severe form of the disease, is the difficulty of planning clinical studies capable of giving hard statistically significant answers regarding the benefits of the various proposed therapeutic agents previously tested in experimental settings. According to the pathophysiology of acute pancreatitis, we may re-evaluate the efficacy of the drugs already available, such as gabexate mesilate, lexipafant and somatostatin which should be probably administered in a different manner. Of course, also in this case, we need large studies to test this hypothesis. Another great problem is prevention of the infection of pancreatic necrosis. A randomized study has been published to test the hypothesis that probiotics and specific fibres used as supplements in early enteral nutrition may be effective in reducing pancreatic sepsis and the number of surgical interventions. A study named PROPATRIA (Probiotic Prophylaxis in Patients with Predicted Severe Acute Pancreatitis) has been planned to give a more robust confirmation to the previous study. Furthermore, the open question of the prevention of the fungal infection of necrosis is still being debated. Finally, the prevention of pain relapse after oral feeding in patients with mild or severe acute pancreatitis should be explored. Even if some studies exist on this issue, the question of optimal treatment is still unanswered. As in other diseases, obtaining results when treating patients with acute pancreatitis is difficult and will take continuous small steps.
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PMID:New approaches for the treatment of acute pancreatitis. 1640 25

The induction of immune tolerance is critical for the prevention of autoimmunity and the maintenance of immune homeostasis. The identification of factors involved in the maintenance or restoration of such tolerance has become the focus of new therapies for inflammatory and autoimmune diseases. Cortistatin, a recently discovered cyclic neuropeptide related to somatostatin, has emerged as a potential endogenous antiinflammatory factor based on its production by, as well as its binding to, immune cells. Thus, cortistatin has been found to downregulate the inflammatory response mediated by activated macrophages. The present work reviews various recent studies involving different experimental models of sepsis, rheumatoid arthritis and inflammatory bowel disease, demonstrating that cortistatin treatment offers great benefits at both the clinical and pathological levels. These include the downregulation of both inflammatory and Th1-mediated autoimmune disease components and the emergence of regulatory T cells (Treg) that suppress autoreactive T cells, both of which contribute to the restoration of immune tolerance. While many questions need to be resolved, cortistatin appears to be an exciting and promising candidate for the treatment of several chronic inflammatory diseases and autoimmune disorders.
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PMID:Cortistatin as a potential multistep therapeutic agent for inflammatory disorders. 1708 Feb 2

The entero-cutaneous fistulas (ECF) are abnormal communications between intestine and abdominal skin. They can occur spontaneously, or after an injury or a surgical procedure. They are associated with a high rate of morbidity and mortality. Spontaneous fistulas can mainly occur in patients affected by cancer, inflammatory bowel disease, diverticulitis, appendicitis, as a result of radiotherapy or injuries. Surgical procedures, carried out in case of neoplastic diseases, inflammatory bowel disease, adhesions removal, represent the primary cause in the development of a postoperative fistulas. Malnourishment, poor general conditions of the patient, high output fistula along with anatomical site of development, and the presence of abscesses, represent the negative factors influencing the spontaneous healing of fistulas. The experience reported here is about three ECF cases occurred after surgery and treated only with medical therapy. The first case is a woman in good general conditions who underwent surgery to remove a recurrent retroperitoneal myxoid liposarcoma situated in the right lower quadrant. The patient had never undergone surgery for an intestinal resection. The other two patients analyzed were affected by sepsis and metabolic unbalance and had developed a fistula after colonic resection. Fluids and electrolytes adjustments and sepsis management have preceded any other kind of therapy. Continuous infusion with somatostatin, fast, proton pump inhibitors and loperamide have been taken up to decrease secretions and intestinal motility. Total parenteral nutrition has been essential to recover nutritional status and improve patients' general conditions. In order to heal and protect peri-fistula skin we have used sterile washing solutions, absorbable ionic exchange resin, silver and polyurethanes based medications and colostomy bags adhesive systems. Since surgical treatment of ECF is associated with high rates of morbidity and mortality, conservative treatment should always be taken into consideration. When conservative treatment fails, delayed surgical intervention has been related to a higher rate of success. The purpose of this study is to describe diagnostic and therapeutic guidelines to general surgeons, like ourselves, whenever they have to deal with ECF cases.
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PMID:[Diagnostic and therapeutic guidelines for entero-cutaneous fistulas. Personal experience and literature review]. 1764 89

The use of reflectance spectrophotometry (RS) for mucosal hemodynamic measurement relies on the recognition of changes in indexes of mucosal hemoglobin concentration and oxygen saturation. Endoscopic application in clinical studies has confirmed important observations demonstrated in animal experiments. The vasoconstriction induced by propranolol, vasopressin, glypressin, or somatostatin in the portal hypertensive gastric mucosa and the reduction of gastroduodenal mucosal perfusion by nonsteroidal anti-inflammatory drugs (NSAIDs) or smoking, mesenteric venoconstriction associated with systemic hypoxia, and acid-induced duodenal hyperemia are important examples. Prognostic predictions include the development of stress-induced gastric ulcerations in patients with significant reductions in gastric perfusion after thermal or head injury, or the demonstration of delayed gastric or duodenal ulcer healing when the hyperemia at the ulcer margin fails to materialize. In mechanical-ventilator-dependent patients with sepsis, a significantly reduced gastric mucosal RS measurement portends a grave prognosis (mortality >80%). Recent advances in technology resulted in the construction and validation of instruments for visible light spectroscopy. Measurements focused on tissue oxygen saturation demonstrated epinephrine and vessel-ligation-induced vasoconstriction, the absence of ischemia in radiation-induced rectal telangiectasias, and gut ischemia responsive to revascularization treatment. Endoscopic RS and visible light spectroscopy are suitable for assessing the role of blood flow in conditions with a lesser degree of ischemia and for testing the hypothesis that functional dyspepsia and dysmotility syndromes may be due to gut ischemia.
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PMID:Endoscopic reflectance spectrophotometry and visible light spectroscopy in clinical gastrointestinal studies. 1793 61

Hemodynamic support of patients with septic shock is often complicated by a tachyphylaxis against exogenous catecholamines. Because an increase in somatotropic hormones may play a pivotal role in the regulation of the inflammatory response to endotoxin, intravenous supplementation of the neuroendocrine hormone somatostatin (SOMA) may attenuate hemodynamic dysfunction resulting from endotoxemia. The objective of the present study was to assess the short-term effects of SOMA alone and in combination with norepinephrine (NE) on cardiopulmonary hemodynamics, global oxygen transport, plasma nitrate/nitrite levels, and intestinal integrity compared with single NE therapy in ovine endotoxemia. After a baseline measurement in healthy sheep (n = 16) had been performed, Salmonella typhosa endotoxin was centrally infused (10 ng x kg(-1) x min(-1)) to induce a hypotensive-hyperdynamic circulation using an established protocol. Animals surviving 16 h of endotoxemia were randomly assigned to one of the two groups (each n = 6). Sheep allocated to the SOMA + NE group received SOMA as a loading dose of 10.5 microg x kg(-1) x min(-1) for 1 h, followed by a continuous infusion of 3.5 microg x kg(-1) x min(-1) for the next 2 h. After the SOMA loading dose had been given, NE was concurrently infused (0.3 microg x kg(-1) x min(-1)) for 2 h. In the NE group (control), NE (0.3 microg x kg(-1) x min(-1)) was continuously infused for 3 h. Endotoxemia caused a decrease in MAP and systemic vascular resistance index in both groups, but to a greater extent in the NE group. Arterial hypotension persisted despite administration of the study drugs. Infusion of SOMA alone and in combination with NE did not significantly increase systemic vascular resistance index. Neither SOMA nor NE infusion alone affected pulmonary vasoregulation. Plasma nitrate/nitrite levels did not differ between groups. However, combined infusion of SOMA and NE significantly increased arterial lactate concentrations, oxygen consumption index, and oxygen extraction rate (P < 0.05) and aggravated ileal mucosal injury. In conclusion, short-term treatment with SOMA failed to attenuate cardiocirculatory shock resulting from endotoxemia and did not improve vasopressor response to NE. In addition, combined SOMA and NE therapy resulted in intestinal injury. Therefore, SOMA does not seem to represent a therapeutic option to treat arterial hypotension resulting from sepsis and systemic inflammatory response syndrome.
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PMID:Somatostatin infusion increases intestinal ischemia and does not improve vasoconstrictor response to norepinephrine in ovine endotoxemia. 1839 53

Postoperative pancreatic fistula (POPF) is the most common major complication after pancreatoduodenectomy (PD) and it can lead to prolonged hospital stay, increased costs, and mortality. The POPF rate is strictly correlated to the definition applied, but there are so many different definitions in the literature that comparison between published series of patients is difficult. The International Study Group of Pancreatic Fistula (IGSPF) has developed a new definition, with a grading system able to stratify complicated patients into three groups, based upon the clinical implications and costs of their postoperative course. The most important risk factors identified are a soft pancreatic texture and a main pancreatic duct diameter of 3 mm or less. Several surgical techniques have been studied in order to prevent anastomotic leakage, but none has been demonstrated to be superior to others. The use of somatostatin analogues is still matter of controversy. Conservative management of POPF is usually effective, but in patients with deteriorating clinical status with evidence of sepsis, surgical management is needed.
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PMID:Pancreatic fistula: definition and current problems. 1853 60

Based on the modality of treatment, historically the management of enterocutaneous fistula has been grouped into three periods. The era of antibiotics (1945-1960), the era of intensive nurse care (1960-1970) and the era of intravenous hyperalimentation (1970-1975). Schein's modification of Sitges-Serra classification of enterocutaneous fistula is now preferred to the old classification of high-output type and low output type. A major cause of enterocutaneous fistula is technical failure. Serum level of short-turn over proteins such as albumin retinal-binding protein, thyroxin binding pre-albumin as serum transferring are predictors of mortality and spontaneous fistula closure. Immediate surgical correction of the fistula is not a priority of treatment. The control of sepsis and adequate nutrition are the two most important aspects of management. The use of somatostatin and octreotide has been shown to shorten the period of spontaneous closure of the fistula.
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PMID:Enterocutaneous fistula. 1986 68

We have previously shown in animals that somatostatin released from capsaicin-sensitive afferents in response to inflammation and tissue damage exerts systemic anti-nociceptive and anti-inflammatory actions. Since peptidergic sensory innervation of the airways and the joints are particularly dense, we aimed at investigating the alterations of plasma somatostatin-like immunoreactivity (SST-LI) in response to thoracic and orthopedic surgery, as well as sepsis. Thoracotomy, video-assisted thoracoscopy, hip and knee endoprosthesis were performed under general anesthesia. Blood was taken before, during and after the surgical procedures, as well as at admission and every consecutive morning from septic patients receiving exclusively total parenteral nutrition. SST-LI was determined from the plasma with specific and sensitive radioimmunoassay developed in our laboratory. Plasma SST-LI in healthy volunteers and preoperatively was 8-12fmol/ml. Both thoracotomy and thoracoscopy significantly increased SST-LI by 55-60% at the end of the procedures when the thoracic cavity and the skin were closed. Hip endoprosthesis implantation elevated SST-LI by 30% after skin incision, which increased further to 55% by the time the surgery was completed. In contrast, knee operations performed under tourniquet did not alter SST-LI in the systemic circulation. SST-LI was almost 3-fold higher in the plasma of septic patients than in healthy volunteers. This human study revealed that thoracic/hip surgery and sepsis elevate SST-LI in the systemic circulation, presumably by inducing its release from sensory fibres. It is concluded, that the endogenous protective mechanism mediated by neural somatostatin, which has been evidenced in animals, is likely to operate in patients.
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PMID:Surgery and sepsis increase somatostatin-like immunoreactivity in the human plasma. 2030 4

During the last two decades, research into the modulation of immunity by the neuroendocrine system has flourished, unravelling significant effects of several neuropeptides, including somatostatin (SRIH), and especially cortistatin (CST), on immune cells. Scientists have learnt that the diffuse neuroendocrine system can regulate the immune system at all its levels: innate immunity, adaptive immunity, and maintenance of immune tolerance. Compelling studies with animal models have demonstrated that some neuropeptides may be effective in treating inflammatory disorders, such as sepsis, and T helper 1-driven autoimmune diseases, like Crohn's disease and rheumatoid arthritis. Here, the latest findings concerning the neuroendocrine control of the immune system are discussed, with emphasis on SRIH and CST. The second part of the review deals with the immune response to neuroendocrine tumors (NETs). The anti-NET immune response has been described in the last years and it is still being characterized, similarly to what is happening for several other types of cancer. In parallel with investigations addressing the mechanisms by which the immune system contrasts NET growth and spreading, ground-breaking clinical trials of dendritic cell vaccination as immunotherapy for metastatic NETs have shown in principle that the immune reaction to NETs can be exploited for treatment.
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PMID:Diffuse endocrine system, neuroendocrine tumors and immunity: what's new? 2224 35


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