Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the prevalence of congenital malaria among neonates with suspected sepsis and its outcome at the University of Calabar Teaching Hospital, Calabar, Nigeria. All in-born neonates admitted to the newborn unit with clinical features suggestive of sepsis were recruited. They were screened for bacterial sepsis and malaria. The mothers of the neonates that had parasitaemia were further screened for malaria and anaemia. A total of 546 in-born neonates were admitted to the neonatal unit and 202 (37%) presented with clinical signs suggested of sepsis. Of these, 71 babies (35% of 202 or 13% of the total in-born nursery admissions) had congenital malaria and 14 also had sepsis. Sixty-three (88.7%) of the parasitaemic babies were delivered by mothers who received antenatal care at our centre. Eighty-six percent of the mothers of the 71 babies also had the malaria parasite in their blood. The majority (67%) of the 71 mothers were gravidae 2 and below. Thirty (42.3%) of the affected neonates were anaemic and 5 (7%) of them required a blood transfusion. Congenital malarial is not uncommon in Calabar among babies with suspected sepsis. It appears that the antenatal chemoprophylaxis with pyrimethamine (25 mg weekly) currently used for malaria in our centre no longer protects the mother and fetus. An alternative is needed in order to stem maternal, fetal and neonatal morbidity and wastage. Babies with features of sepsis should be routinely screened for malaria.
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PMID:The prevalence of congenital malaria among neonates with suspected sepsis in Calabar, Nigeria. 1845 88

Although acute lung injury (ALI) is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM); however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar-capillary membrane barrier-the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36(-/-) mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality.
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PMID:Parasite burden and CD36-mediated sequestration are determinants of acute lung injury in an experimental malaria model. 1848 51

Hypercytokinemia is gaining recognition as the mechanism of fatality from influenza. No work to date has addressed the role of high mobility group box 1 protein (HMGB1) in influenza, the parallel being that in other severe proinflammatory cytokine syndromes (e.g., sepsis and malaria) levels of circulating HMGB1 are elevated and may correlate with death. Using a commercially available ELISA for HMGB1, we found that HMGB1 was not increased in the plasma of influenza virus-infected mice (A/Japan/305/57) on day 7 post infection, about the time of peak mortality, and peak levels of HMGB1 in the plasma did not occur until relatively late in infection, on day 9 post infection. In keeping with the late peak of HMGB1 being unassociated with mortality, administration of ethyl pyruvate, which inhibits active secretion but not passive release of HMGB1, to influenza virus-infected mice, did not affect their survival. Further work is required to determine whether influenza virus infection induces passive release of HMGB1, and whether HMGB1 neutralization with a specific Ab would improve survival.
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PMID:Systemic release of high mobility group box 1 protein during severe murine influenza. 1860

Eryptosis, the suicidal death of erythrocytes, is characterised by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are recognised by macrophages, which engulf and degrade the affected cells. Reported triggers of eryptosis include osmotic shock, oxidative stress, energy depletion, ceramide, prostaglandin E(2), platelet activating factor, hemolysin, listeriolysin, paclitaxel, chlorpromazine, cyclosporine, methylglyoxal, amyloid peptides, anandamide, Bay-5884, curcumin, valinomycin, aluminium, mercury, lead and copper. Diseases associated with accelerated eryptosis include sepsis, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency, hemolytic uremic syndrome and Wilsons disease. Eryptosis may be inhibited by erythropoietin, adenosine, catecholamines, nitric oxide (NO) and activation of G-kinase. Most triggers of eryptosis except oxidative stress are effective without activation of caspases. Their signalling involves formation of prostaglandin E(2) with subsequent activation of cation channels and Ca2+ entry and/or release of platelet activating factor (PAF) with subsequent activation of sphingomyelinase and formation of ceramide. Ca2+ and ceramide stimulate scrambling of the cell membrane. Ca2+ further activates Ca2+-sensitive K+ channels leading to cellular KCl loss and cell shrinkage and stimulates the protease calpain resulting in degradation of the cytoskeleton. Eryptosis allows defective erythrocytes to escape hemolysis. On the other hand, excessive eryptosis favours the development of anemia. Thus, a delicate balance between proeryptotic and antieryptotic mechanisms is required to maintain an adequate number of circulating erythrocytes and yet avoid noneryptotic death of injured erythrocytes.
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PMID:Erythrocyte programmed cell death. 1872 Apr 18

Malaria is an important treatable cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in the tropics and in the returning traveller in the non-endemic areas. ARDS is an important complication in severe, complicated falciparum malaria and has been described in P. vivax and P. ovale malaria also. Malarial ALI/ARDS is more common in adults than in children. Pregnant women and non-immune individuals are more prone to develop this condition. Increased alveolar capillary permeability resulting in intravascular fluid loss into the lungs appears to be the key pathophysiologic mechanism. In malaria, ARDS can develop either at initial presentation or after initiation of treatment when the parasitaemia is falling and the patient is improving. Patients present with acute onset dysnoea that can rapidly progress to respiratory failure. The diagnosis of malaria is confirmed by slide microscopy supported by the use of rapid antigen tests. Patients with malarial ARDS should be managed in an intensive care unit. Careful attention must be paid to haemodynamic stabilisation and optimising fluid balance. Currently, specific treatment choices for malaria include parenteral artemisinins or intravenous quinine along with doxycycline. Respiratory failure requires endotracheal intubation and assisted mechanical ventilation. Co-existent bacterial sepsis is frequently present in patients with malarial ARDS eventhough an obvious focus may not be evident. Appropriate broad spectrum antibiotic therapy must be started when there is a clinical suspicion after procuring the microbiological specimens. ARDS in malaria is a disease with a high mortality. Early diagnosis, institution of specific antimalarial treatment and assisted ventilation can be life-saving.
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PMID:Acute lung injury and acute respiratory distress syndrome in malaria. 1880 74

Certain distinctive components of the severe systemic inflammatory syndrome are now well-recognized to be common to malaria, sepsis, viral infections, and post-trauma illness. While their connection with cytokines has been appreciated for some time, the constellation of changes that comprise the syndrome has simply been accepted as an empirical observation, with no theory to explain why they should coexist. New data on the effects of the main pro-inflammatory cytokines on the genetic control of sickness behaviour can be extended to provide a rationale for why this syndrome contains many of its accustomed components, such as reversible encephalopathy, gene silencing, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia. It is thus proposed that the pattern of pathology that comprises much of the systemic inflammatory syndrome occurs when one of the usually advantageous roles of pro-inflammatory cytokines--generating sickness behaviour by moderately repressing genes (Dbp, Tef, Hlf, Per1, Per2 and Per3, and the nuclear receptor Rev-erbalpha) that control circadian rhythm--becomes excessive. Although reversible encephalopathy and gene silencing are severe events with potentially fatal consequences, they can be viewed as having survival advantages through lowering energy demand. In contrast, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia may best be viewed as unfortunate consequences of extreme repression of these same genetic controls when the pro-inflammatory cytokines that cause sickness behaviour are produced excessively. As well as casting a new light on the previously unrationalized coexistence of these aspects of systemic inflammatory diseases, this concept is consistent with the case for a primary role for inflammatory cytokines in their pathogenesis across this range of diseases.
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PMID:Sickness behaviour pushed too far--the basis of the syndrome seen in severe protozoal, bacterial and viral diseases and post-trauma. 1885 46

Cerebral malaria is responsible for a high proportion of mortality in human Plasmodium falciparum infection. Previous studies have reported the presence of apoptosis in endothelial cells, astrocytes, neurons, and glial cells in experimental murine cerebral malaria caused by infection with Plasmodium berghei ANKA. Using this model, we tested two strategies, which have been shown to improve survival in murine models of sepsis: 1) treatment with z-VAD, a pancaspase inhibitor; and 2) overexpression of Bcl-2 using transgenic mice expressing human Bcl-2 (which prevents the release of apoptotic mediators from the mitochondria) from a myeloid cell promoter. Neither of these anti-apoptotic strategies, previously shown to provide therapeutic benefit in sepsis, improved survival in experimental cerebral malaria.
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PMID:Failure of two distinct anti-apoptotic approaches to reduce mortality in experimental cerebral malaria. 1905 86

Where malaria is endemic, there is an unexpected association between haemoglobinopathies and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Their coexistence in a patient with sickle cell disease (SCD) can lead to hemolytic anemia, hemoglobinuria, sepsis, renal failure and vaso-occlusive attacks (VOA). The aim of this research was to determine the impact of G-6-PD deficiency in SCD patients. That is why, we screened haemoglobinopathies and G-6-PD deficiency in 7 villages and at 10 primary schools in Kadiogo Province, Burkina Faso. Hemoglobin electrophoresis was performed on blood from 18,383 people. From these results, we chose 342 subjects for a hemogram and the measure of the G-6-PD activity. The results were analyzed with Epilnfo-6 and Spss-10. Statistical significance was set at p < 0.05. We found a prevalence of 28.9% of Sickle Cell Trait (SCT), 1.3% of Major Sickle Cell Syndromes (MSCS), 12.3% of G-6-PD deficiency among women and 20.5% among men. We did not detect a statistically significant difference for counts of erythrocytes (p = 0.773), leucocytes (p = 0.227) and reticulocytes (0.292); hemoglobin levels (p = 0.998); annual vasoocclusive attacks (p = 0.869) between persons with SCD having a G-6-PD deficiency and those with normal G-6-PD activity. According to this study, G-6-PD deficiency does not seem to increase the severity of SCD. However, these patients should know their G-6-PD genotype in order to avoid consuming oxidative drugs that might provoke oxidative stress.
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PMID:Glucose-6-phosphate dehydrogenase deficiency and sickle cell disease in Burkina Faso. 1906 10

Gelsolin is a highly conserved, multifunctional actin-binding protein initially described in the cytosol of macrophages and subsequently identified in many vertebrate cells. A unique property of gelsolin is that in addition to its widely recognized function as a cytoplasmic regulator of actin organization, the same gene expresses a splice variant coding for a distinct isoform, plasma gelsolin, which is secreted into extracellular fluids. The secreted form of gelsolin has been implicated in a number of processes such as the extracellular actin scavenging system and the presentation of lysophosphatidic acid and other inflammatory mediators to their receptors, in addition to its function as a substrate for extracellular matrix-modulating enzymes. Consistent with these proposed functions, blood gelsolin levels decrease markedly in a variety of clinical conditions such as acute respiratory distress syndrome, sepsis, major trauma, prolonged hyperoxia, malaria, and liver injury. This correlation between blood gelsolin levels and critical clinical conditions suggests the potential utility of gelsolin as a prognostic marker as well as the possibility for therapeutic replenishment of gelsolin to alleviate the injurious cascades in these settings. This review summarizes current data supporting a role of plasma gelsolin in extracellular fluids and the potential for its use as a diagnostic marker or therapeutic treatment in several medical conditions.
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PMID:Plasma gelsolin: function, prognostic value, and potential therapeutic use. 1907 45

Viral hepatitis is common in Nigeria and may present with jaundice in pregnancy. The objective of this study was to determine the contribution of viral hepatitis among other aetiological factors, to the development of jaundice during pregnancy. Data on viral hepatitis among gravidae with jaundice in pregnancy over a 10-year period from 1st January 1992 through 31st December 2001 were retrieved and analyzed. Fifty-two cases of jaundice in pregnancy were seen among 16,566 pregnancies registered in the hospital over the 10-year period. Of the 52 cases of jaundice in pregnancy, only 48 case records were retrievable, on which this analysis is based. Viral hepatitis (VH) occurred in 1 in 591.6 pregnancies and was diagnosed in 28 (58.3%) cases of jaundice in pregnancy. Other causes of jaundice were malaria 8 (16.7%), sickle-cell anaemia in pregnancy 6 (12.5%) and sepsis 2 (4.2%). Of the 28 patients with viral hepatitis, 8 (28.5%) were positive for HBsAg. The liver function tests (LFTs) were done in 26 of the 28 patients and it showed hyperbilirubinaemia in 24, 11 had serum albumin >3.5 g/dl. All had spontaneous vaginal delivery with no maternal death. Complications associated with viral hepatitis were, anaemia 14 (50%), intrauterine growth retardation (14.3%), intrauterine foetal death 2 (7.1%), congestive cardiac failure 1 (3.57%) early neonatal death 1 (3.57%) and 2 (7.1%) cases of systemic hypertension. Viral hepatitis contributes significantly to jaundice in pregnancy and there is associated fetal and maternal morbidity.
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PMID:Viral hepatitis in the aetiogenesis of jaundice in pregnancy at the University College Hospital, Ibadan. 1920 72


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