Multi-organ failures during septic shock from Escherichia coli urinary tract infection: catastrophic antiphospholipid syndrome?

INTRODUCTION: Although the presence of antiphospholipid antibodies is not an uncommon fact during infection, their responsibility in serious manifestations can still be debated and questions the existence of an actual catastrophic antiphospholipid syndrome or multivisceral faintings, triggered by the infection only, since the presence of antiphospholipid antibodies is not pathogenous. CASE: A 68-year-old man presented during an Escherichia coli urinary tract infection a septic shock with renal and cardiac insufficiencies, hepatic cytolysis and cholestasis and disseminated intravascular coagulation. There was a significant titer of antiphospholipid antibodies IgG (50 UGPL/ml) with an antibêta2-glycoprotein-1 positivity. The patient quickly recovered with antibiotherapy and intravenous immunoglobulins. DISCUSSION: Diagnosing the pathogeny of multivisceral faintings is founded of the clinical manifestations published during the catastrophic antiphospholipid syndrome, the evolution and the persistence of post recovery antibodies and the comparison with the visceral bouts that the sepsis exclusively as revealed.     

Anomaly and tumor of kidney and urinary tract

2007475 MRI manifestations of renal oncocytoma.JI Jiansong(纪建松) , et al. Dept Radiol, Sir Run RunShaw Hosp, Zhejiang Univ, Hangzhou 310016. Chin JRadiol 2007;41(10):1087 -1089. Objective To analyze the MRI findings of renal on-cocytoma, and to improve the ability for the diagnosis.Methods We retrospectively reviewed MRI findings ofsults Sixcases had a solitary lesion, and 1 of themac-companied with renal clear-cell carcinoma. Tumors ap-peared as round with diameter 1.5 to 3.8 cm,…     

Alterations of systemic endotoxemia over the course of acute edematous pancreatitis: Correlation to the advent of an infection?

Background/Aims: To define whether bacterial translocation occurs over the course of acute edematous pancreatitis and to correlate its presence to the advent of an infection since data in humans are lacking. Methods: Thirty-three patients hospitalized over the period January 2000–January 2001 were subjected to venipuncture at regular time intervals for the collection of blood samples for blood culture and for determination of endotoxins and of C-reactive protein. Endotoxins were measured by the Limulus assay and C-reactive protein by nephelometry. Results: A wide range of concentrations of endotoxins was observed over the first 3 days of the disease. Mean (±SE) of endotoxins was 4.01 B 1.36 and 2.42 ± 0.95 EU/ml 3 and 6 h, respectively, after admission of afebrile patients. Respective values 3 and 6 h after admission of febrile patients were 3.03 ± 1.14 and 5.84 ± 2.28 EU/ml (normal <0.1 EU/ml); these values gradually decreased after the second day. No correlation was found between endotoxins and C-reactive protein. Endotoxins were increased as a result of the occurrence of an infection on the third day. Conclusions: A significant level of endotoxemia is observed over the course of acute edematous pancreatitis, which might be correlated to the advent of the systemic inflammatory response.     

Prostatitis and urinary tract infection in men: what's new; what's true?

Urinary tract and prostatic infections are common in men, and most are treated by primary providers. Acute bacterial prostatitis is caused by uropathogens, presents with a tender prostate gland, and responds promptly to antibiotic therapy. Chronic bacterial prostatitis is a subacute infection, may present with a variety of pelvic pain and voiding symptoms, and is characterized by recurrent urinary tract infections. Effective treatment may be difficult and requires prolonged antibiotic therapy. Nonbacterial prostatitis and chronic pelvic pain syndrome are more common than bacterial prostatitis, and their etiologies are largely unknown. Treatment for both nonbacterial disorders is primarily symptomatic. An underlying anatomic or functional condition usually complicates urinary tract infections in men, but uncomplicated infections occur, often related to sexual activity. Gram-negative bacilli cause most urinary tract and prostate infections. Therapy for prostatic infections requires an agent that penetrates prostatic tissue and secretions, such as trimethoprim-sulfamethoxazole or, preferably, a fluoroquinolone. Duration of antibiotic therapy is typically 1 to 2 weeks for cystitis, 4 weeks for acute bacterial prostatitis, and 6 to 12 weeks for chronic bacterial prostatitis. Long-term suppressive antibiotic therapy and nonspecific measures aimed at palliation may be useful in selected patients with recurrent bacteriuria or persistent symptoms of chronic bacterial prostatitis.     

The loss of αSNAP downregulates the expression of occludin in the intestinal epithelial cell of acute pancreatitis model

Background and objectiveIntestinal barrier damage is an important event during the occurrence and progression of severe acute pancreatitis. The expression of occludin, one of the main components of the intestinal barrier proteins, is regulated by various factors related to intestinal barrier formation and the remodeling process. The αSNAP, as a novel membrane protein, is ubiquitously expressed in intestinal epithelial cells. This study aimed to investigate the role of αSNAP in acute pancreatitis and the relationship between occludin and αSNAP.MethodsMild and severe acute pancreatitis models were established by retrograde injections of 0.5% and 3.8% sodium taurocholate solutions, respectively, into rat pancreaticobiliary ducts. The animals were killed at 1, 2, and 3 days after the injection, and the pathological changes of the pancreas and intestinal mucosa, the changes in intestinal permeability, and the protein expression of occludin and αSNAP were assessed. Cultured epithelial IEC-6 cells were further infected with lentiviral αSNAP shRNA, cell apoptosis was determined with flow cytometry (FCM), and any changes in occludin expression were detected by Western blotting and immunofluorescent staining.ResultsThis pathologic study of a rat acute pancreatitis model indicated pancreatic tissue necrosis and inflammatory cell infiltration; the intestinal villi in the severe acute pancreatitis (SAP) group demonstrated edema, lodging, atrophy, and intestinal epithelial cell necrosis, and shedding. The intestinal permeability in rats with pancreatitis increased significantly. The SAP group showed significantly increased levels of serum TNF-α and endotoxins. The results of immunofluorescent staining and Western blotting revealed that compared with the SO (sham operation) and MAP (mild acute pancreatitis) groups, the SAP group displayed significantly downregulated protein expressions of αSNAP and occludin in the intestinal epithelial cells. After the lentiviral transduction of αSNAP shRNA, apoptosis in IEC-6 cells was drastically increased, whereas the expression of occludin was decreased significantly.ConclusionThe downregulated expression of αSNAP in intestinal epithelial cells leads to reduced occludin expression and enhanced apoptosis of intestinal epithelial cells. Hence, the permeability of the intestinal barrier may be increased in a severe acute pancreatitis model.     

Structural and functional insights into Escherichia coli α2-macroglobulin endopeptidase snap-trap inhibition

The survival of commensal bacteria requires them to evade host peptidases. Gram-negative bacteria from the human gut microbiome encode a relative of the human endopeptidase inhibitor, α₂-macroglobulin (α₂M). Escherichia coli α₂M (ECAM) is a ∼180-kDa multidomain membrane-anchored pan-peptidase inhibitor, which is cleaved by host endopeptidases in an accessible bait region. Structural studies by electron microscopy and crystallography reveal that this cleavage causes major structural rearrangement of more than half the 13-domain structure from a native to a compact induced form. It also exposes a reactive thioester bond, which covalently traps the peptidase. Subsequently, peptidase-laden ECAM is shed from the membrane and may dimerize. Trapped peptidases are still active except against very large substrates, so inhibition potentially prevents damage of large cell envelope components, but not host digestion. Mechanistically, these results document a novel monomeric “snap trap.”The human microbiome plays a crucial role in host health and disease (1). Successful commensalism requires microorganisms to neutralize damaging host factors, but the mechanisms to maintain symbiosis are only poorly understood (2). In particular, their habitat is rich in host proteolytic enzymes, which are generally held in check by protein inhibitors (3). Several Gram-negative proteobacteria, including human pathogens, contain genes similar to the widespread metazoan α₂-macroglobulins (α₂Ms) (4). These are large, multidomain glycoproteins that uniquely function as broad-spectrum endopeptidase inhibitors and mostly contain a reactive β-cysteinyl-γ-glutamyl thioester bond (5). The potential bacterial α₂Ms (bα₂Ms) occur in two independent forms: one provided with a thioester bond (represented by Escherichia coli α₂M; ECAM) and cotranscribed with penicillin-binding protein 1C, and the other lacking a thioester bond and transcribed from an operon further encoding other proteins (represented by E. coli YfaS).In humans, α₂M (hα₂M) circulates mostly in blood plasma as an abundant “native” ∼720-kDa tetramer. After cleavage in a “bait region” (6), the tetramer closes under large conformational rearrangement to yield an “induced” form, which encages the peptidase following an irreversible “Venus flytrap” mechanism (5, 7, 8). Inside the cage, within a large “central prey chamber,” peptidases still cleave small-to-medium substrates (<10–20 kDa) (9), which enter the tetramer through any of 12 entrances (8), but not large substrates. In some cases, prey lysines may be covalently bound through the thioester bond of mammalian α₂Ms. However, other α₂M-family inhibitors such as ovostatins lack thioester bonds and only encage, but they are as efficient inhibitors as hα₂M (10). Induction of tetrameric hα₂M exposes C-terminal receptor-binding domains (RBDs), which are bound by specific cell-surface receptors. This exposure triggers receptor-mediated endocytosis and clearance of the inhibitor and its prey from the circulation (11). For successful encaging, at least two protomers are required to wrap around a standard-size endopeptidase (12), but the detailed molecular mechanism of tetrameric α₂M inhibition is unknown, as only the molecular structure of induced hα₂M is available (8). Little is also known about the physiology and function of bα₂Ms, as only a YfaS-ortholog from Pseudomonas aeruginosa and ECAM have been partially studied to date (13–16). The crystal structure of native α₂M from Salmonella enterica (SEAM) is available (16), but its working mechanism is also unknown so far.To shed light on the structure and function of α₂Ms, we studied ECAM functionally, biophysically, and structurally by X-ray crystallography and cryoelectron microscopy (cryo-EM). We found that cleavage at the bait region of ECAM triggers major conformational rearrangement and covalent binding of the prey peptidase after a monomeric snap-trap mechanism, which differs from the encaging Venus flytrap mechanism of tetrameric hα₂M.     

Changes of plasma levels of gastrointestinal peptides over the course of acute pancreatitis. Any significance for the pathophysiology and treatment of acute pancreatitis?

BACKGROUND/AIMS: Acute pancreatitis may be accompanied by alterations of the secretion of pancreatic and gastrointestinal peptides as a result of pancreatic inflammation. These changes, that may constitute targets of therapeutic manipulation, led to the study of the serum levels of various pancreatic and gastrointestinal peptides over the course of acute pancreatitis before and after the administration of octreotide and ranitidine. METHODOLOGY: Concentrations of gastrin, glucagon, vasoactive intestinal peptide, neurotensin and pancreatic polypeptide were determined by radioimmunoassay in the plasma of 22 patients with acute pancreatitis on the first, sixth and 11th day of the disease. All patients were treated with octreotide s.c. while 14 of them were also administered ranitidine i.v. Treatment was initiated after taking the first blood sample. RESULTS: Mean gastrin levels in patients receiving ranitidine was 56.76 ng/L and in patients not receiving ranitidine 47.16 ng/L on the first day (pNS) remaining stable throughout the course of acute pancreatitis. Mean glucagon, vasoactive intestinal peptide, neurotensin and pancreatic polypeptide levels on the first day were 52.05 pmol/L, 8.90 pmol/L, 9.80 pmol/L and 22.06 pmol/L, respectively, and no changes were found through the course of acute pancreatitis. CONCLUSIONS: Plasma levels of gastrointestinal peptides remain constant over time and they are not significantly affected by the administration of octreotide or ranitidine. However more studies are necessary to document the significance of these findings.     

Smoking and inflammatory bowel diseases: what in smoking alters the course?

Epidemiological studies provide strong evidence to confirm the correlation between cigarette smoking and inflammatory bowel diseases. This relationship is proved to be positive in Crohn’s disease and negative in ulcerative colitis. What in smoking alters the course of inflammatory bowel diseases is still a mystery. Different smoking parts have different and may be opponent actions. Smoking has dual effects. Some of its activities are, sometimes, constructive as they are working in an antagonistic manner to the mechanism of the disease, such as reducing rectal blood flow and accordingly less recruitments of inflammatory mediators to the area of inflammation, enhancement of mucosal production, and consequently, strengthening the membranes, and inhibition of pro-inflammatory mediators’ liberation and activity in subjects with ulcerative colitis. Yet the outcome of smoking actions may be affected by the existence of other cofactors. Odd factors, such as shortage of zinc in subjects with Crohn’s disease, may facilitate liberation of pro-inflammatory mediators and their activities and accordingly exacerbates symptoms.     

COVID-19 and the gastrointestinal tract: Source of infection or merely a target of the inflammatory process following SARS-CoV-2 infection?

Gastrointestinal (GI) symptoms have been described in a conspicuous percentage of coronavirus disease 2019 (COVID-19) patients. This clinical evidence is supported by the detection of viral RNA in stool, which also supports the hypothesis of a possible fecal-oral transmission route. The involvement of GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is corroborated by the theoretical assumption that angiotensin converting enzyme 2, which is a SARS-CoV-2 target receptor, is present along the GI tract. Studies have pointed out that gut dysbiosis may occur in COVID-19 patients, with a possible correlation with disease severity and with complications such as multisystem inflammatory syndrome in children. However, the question to be addressed is whether dysbiosis is a consequence or a contributing cause of SARS-CoV-2 infection. In such a scenario, pharmacological therapies aimed at decreasing GI permeability may be beneficial for COVID-19 patients. Considering the possibility of a fecal-oral transmission route, water and environmental sanitation play a crucial role for COVID-19 containment, especially in developing countries.     

The course and therapy of acute hepatitis C viral infection. Is a prevention of its becoming chronic possible?

Due to the large number of patients chronically infected with hepatitis C virus and not responding to combination therapy with interferon-alfa 2 and ribavirin new therapeutic regimens are required. Early treatment of the viral infection might improve the response, as seen in treatment of HIV infection, thereby preventing progression to chronicity. The article reviews the natural course of an acute HCV infection after different modes of transmission like i.v.-drug abuse, transfusion, needle stick injury and blood products. As there are no good animal models for HCV infection, models of an acute infection with other noncytopathic viruses might improve our understanding of the mechanisms of viral clearance. Results from an acute infection of mice with the lymphocytic chorionmeningitis virus are demonstrating the development of a T-cell tolerance by anergy or deletion of virus specific T-cells as possible mechanisms for the failure of the immune system to clear the virus. These findings are compared to the results of CD4+ and CD8+ T-cell responses in patients with acute HCV infection. Several clinical trials have demonstrated a benefit of an early treatment of HCV infection. Although the natural course of acute HCV is changing during the last few years, even recent trials indicate that progression to chronicity might be prevented by early therapy. The studies show that therapy could be improved by daily dosing, higher single doses of interferon compared and prolongation of therapy up to six month. As most patients with acute HCV infection are rather seen in an outpatient practise than in hospitals cases of acute infections should be collected and treatment protocols be standardized to confirm these results in prospective trials. First results in 21 patients show that viral clearance under therapy was achievable in all of the patients.     

Chlamydia muridarum respiratory tract infection induces the proliferation of γδT cells and the secretion of IFN-γ and IL-17

<正>Objective To investigate the proliferation,activation and cytokine production ofγδT cells during different periods of Chlamydia muridarum(Cm)respiratory tract infection.Methods C57BL/6 mice were inoculated intranasally with 3×103inclusion-forming units(IFU)of Cm strains to induce the murine model of chlamydial     

Does co‐infection with multiple viruses adversely influence the course and outcome of sporadic acute viral hepatitis in children?

BACKGROUND: This study looked at the frequency of co-infection with multiple hepatotropic viruses and the effect of such infection on the course and outcome of acute sporadic viral hepatitis (AVH) and fulminant hepatic failure (FHF) in children. METHODS: Consecutive children up to 15 years of age presenting with AVH or FHF between January 1998 and July 2002 were evaluated prospectively. The following viral markers were assessed in all children: immunoglobulin M (IgM) anti-hepatitis A virus (HAV), IgM anti-hepatitis E virus (HEV), hepatitis B surface antigen (HBsAg), IgM anti-hepatitis B core (HBc), and anti-hepatitis C virus (HCV). RESULTS: A total of 149 children were included in the study, 122 with AVH and 27 with FHF. Co-infection with multiple viruses was detected in 30 (24.6%) AVH patients (A+E in 24, A+B in three, and E+B, A+C and A+E+B in one each) and seven (26%) FHF patients (A+E in five, and A+B and E+B in one each). The majority of single infections were due to HAV (AVH 70/92, FHF 14/20) followed by HEV (AVH 9/92, and FHF 5/20). HEV infection was associated with infection with another agent in 88% of patients with AVH (odds ratio 53, 95% confidence interval 15-186, P<0.0001). Frequency of anicteric state, prolonged cholestasis, relapsing hepatitis, ascites, hemolysis and mortality rates were similar in the single and multiple infection groups for both AVH and FHF patients. CONCLUSIONS: Co-infection with multiple viruses is observed in one-quarter of patients with sporadic AVH in childhood. Such infection does not produce a more severe disease. HEV positivity is a strong marker for multiple infections.     

Polarizing the T helper 17 response in Citrobacter rodentium infection via expression of resistin-like molecule α

Citrobacter rodentium infection is a murine model of pathogenic Escherichia coli infection that allows investigation of the cellular and molecular mechanisms involved in host-protective immunity and bacterial-induced intestinal inflammation. We recently demonstrated that following C. rodentium infection, the absence of Resistin-Like Molecule (RELM) α resulted in attenuated Th17 cell responses and reduced intestinal inflammation with minimal effects on bacterial clearance. In this addendum, we investigated the cytokine modulatory effects of RELMα and RELMα expression in the intestinal mucosa following C. rodentium infection. We show that in addition to promoting Th17 cytokine responses, RELMα inhibits Th2 cytokine expression and Th2-cytokine effector macrophage responses in the C. rodentium-infected colons. Second, utilizing reporter C. rodentium, we examined RELMα expression and macrophage recruitment at the host pathogen interface. We observed infection-induced macrophage infiltration and RELMα expression by intestinal epithelial cells. The influence of infection-induced RELMα on macrophage recruitment in the intestine is discussed.     

Construction and expression of the recombinant plasmid pET32α-Sj26GST of Schistosoma japonicum in Escherichia coli BL21(DE3)

Objective To construct and express the recombinant plasmid pET32α-Sj26GST of Schistosoma japonicum(sj)in Escherichia coli(E.coli)B121(DE3).Methods The total RNA was extracted from sj adult worms by ultrasound-breaking,Sj26GST antigen gene was amplified by RT-PCR from the total RNA,then cloned into prokaryotic expression plasmid pET32α(+) and transformed into E.coli B12(DE3)to construct pET32α-Sj26GST;BL21(pET32α-Sj26GST)WaS induced with isopropyl-β-D-thiogalactopyranosid(IPTG),and the expressed products were analyzed and identified by SDS-PAGE and Western blot.Results The 676 bp Sj26GST gene was successfully amplified by RT-PCR and cloned into pET32α(+)by restriction analysis and PCR identification,the recombinant plasmid pET32α-Sj26GST was successfully constructed;the relative molecular mass of the expressed recombinant protein was approximately 49×103 by SDS-PAGE,and the amount of the expressed protein was 24%of the total bacterial proteins;the fusion protein could be recognized by sera from rabbits infected with sj by Western blot.Conclusions The recombinant plasmid pET32α-Sj26GST is successfully constructed and highly expressed in E.coli in fused form with Trx-tag and His-tag,and the expressed fusion protein shows specific antigenicity.     

Construction and expression of the recombinant plasmid pET32α-Sj26GST of Schistosoma japonicum in Escherichia coli BL21(DE3)

Objective To construct and express the recombinant plasmid pET32α-Sj26GST of Schistosoma japonicum(sj)in Escherichia coli(E.coli)B121(DE3).Methods The total RNA was extracted from sj adult worms by ultrasound-breaking,Sj26GST antigen gene was amplified by RT-PCR from the total RNA,then cloned into prokaryotic expression plasmid pET32α(+) and transformed into E.coli B12(DE3)to construct pET32α-Sj26GST;BL21(pET32α-Sj26GST)WaS induced with isopropyl-β-D-thiogalactopyranosid(IPTG),and the expressed products were analyzed and identified by SDS-PAGE and Western blot.Results The 676 bp Sj26GST gene was successfully amplified by RT-PCR and cloned into pET32α(+)by restriction analysis and PCR identification,the recombinant plasmid pET32α-Sj26GST was successfully constructed;the relative molecular mass of the expressed recombinant protein was approximately 49×103 by SDS-PAGE,and the amount of the expressed protein was 24%of the total bacterial proteins;the fusion protein could be recognized by sera from rabbits infected with sj by Western blot.Conclusions The recombinant plasmid pET32α-Sj26GST is successfully constructed and highly expressed in E.coli in fused form with Trx-tag and His-tag,and the expressed fusion protein shows specific antigenicity.     

Impact of human immunodeficiency virus infection on the course of hepatitis C virus infection： A meta-analysis

AIM： TO analyze the influence of human immunodeficiency virus （HIV） infection on the course of hepatitis C virus （HCV） infection. METHODS： We performed a meta-analysis to quantify the effect of HIV co-infection on progressive liver disease in patients with HCV infection. Published studies in the English or Chinese-language medical literature involving cohorts of HIV-negative and -positive patients coinfected with HCV were obtained by searching the PUBMED, EMBASE and CBM. Data were extracted independently from relevant studies by 2 investigators and used in a fixed-effect meta analysis to determine the difference in the course of HCV infection in the 2 groups. RESULTS： Twenty-nine trails involving 16750 patients were identified including the outcome of histological fibrosis or cirrhosis or de-compensated liver disease or hepatocellular carcinoma or death. These studies yielded a combined adjusted odds ratio （OR） of 3.40 [95% confidence interval （CI） = 2.45 and 4.73]. Of note, studies that examined histological fibrosis/ cirrhosis, decompensated liver disease, hepatocellular carcinoma or death had a pooled OR of 1.47 （95% CI = 1.27 and 1.70）, 5.45 （95% CI = 2.54 and 11.71）, 0.76 （95% CI = 0.50 and 1.14）, and 3.60 （95% CI = 3.12 and 4.15）, respectively. CONCLUSION： Without highly active antiretroviral therapies （HAART）, HIV accelerates HCV disease progression, including death, histological fibrosis/ cirrhosis and decompensated liver disease. However, the rate of hepatocellular carcinoma is similar in persons who had HCV infection and were positive for HIV or negative for HIV.