a-mouse-model-for-pathogen-induced-chronic-inflammation-at-local

A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites

Chronic inflammation is a major driver of pathological tissue damage and a unifying characteristic of many chronic diseases in humans including ...

Boston University School of Medicine

Endourological techniques are used more often nowadays in the treatment of ureteric strictures of various etiologies. Advances in technology have provided new tools to the armamentarium of the endoscopic urological surgeon. Numerous studies exist that investigate the efficiency and safety of each of the therapeutic modalities available. In this review, we attempt to demonstrate the available and contemporary evidence supporting each minimally invasive modality in the management of ureteric strictures.

Current status of minimally invasive endoscopic management of ureteric strictures.

To report the early and long-term results of Vascu-Guard bovine pericardium (BP) for patch angioplasty in carotid endarterectomy (CEA).

Use of the vascu-guard bovine pericardium patch for arteriotomy closure in carotid endarterectomy. Early and long-term results.

Neurosyphilis presenting as primary progressive aphasia.

To investigate the evidence for the use of hyoscine N-butylbromide (HBB) in the treatment of acute renal colic.

Hyoscine N-butylbromide (Buscopan®) in the treatment of acute ureteral colic: what is the evidence?

To investigate the role of centrally recorded P300 in patients suffering from mesial temporal sclerosis-temporal lobe epilepsy (MTS-TLE).

Auditory event-related potentials (P300) and mesial temporal sclerosis in temporal lobe epilepsy patients.

Type 1 diabetes as an autoimmune disease: the evidence.

To examine the distribution of cervical length (Cx) in the late second and third trimester of pregnancy and construct survival models for spontaneous delivery (SpD).

Cervical length in late second and third trimester: a mixture model for predicting delivery.

Thirty to fifty percent of critically ill patients admitted to the intensive care unit suffer from generalized neuromuscular weakness due to critical illness polyneuropathy, critical illness myopathy, or a combination of them, thus prolonging mechanical ventilation and their intensive care unit stay. A distinction between these syndromes and other neuromuscular abnormalities beginning either before or after ICU admission is necessary. These intensive care unit-related diseases are associated with both elevated mortality rates and increased morbidity rates. Generally, over 50 % of patients will completely recover. Most of them recover after 4-12 weeks, but some patients have been reported to keep on suffering from muscle weakness for at least 4 months. Prevention has a key role in the management of critical illness neuromuscular disorders, as no specific therapy has been suggested. Either prevention or aggressive treatment of sepsis can prevent critical illness polyneuropathy and critical illness myopathy. The dose and duration of the administration of neuromuscular blocking drugs should be limited, and their concurrent administration with corticosteroids should be avoided. Intensive insulin therapy has also been proven to reduce their incidence. Finally, early mobilization via active exercise or electrical muscle stimulation plays a significant role in their prevention.

Intensive care unit-related generalized neuromuscular weakness due to critical illness polyneuropathy/myopathy in critically ill patients.

Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS) structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4) agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune detection at TLR4 facilitating chronic inflammation in the vasculature. These studies support the emerging concept that pathogen-mediated chronic inflammatory disorders result from specific pathogen-mediated evasion strategies resulting in low-grade chronic inflammation.

Article	Year
Current status of minimally invasive endoscopic management of ureteric strictures. Therapeutic advances in urology\| PubMed ID: 24294293	2013
Use of the vascu-guard bovine pericardium patch for arteriotomy closure in carotid endarterectomy. Early and long-term results. Annals of vascular surgery\| PubMed ID: 24370503	2014
Neurosyphilis presenting as primary progressive aphasia. The Journal of neuropsychiatry and clinical neurosciences\| PubMed ID: 24515700	2014
Hyoscine N-butylbromide (Buscopan®) in the treatment of acute ureteral colic: what is the evidence? Urologia internationalis\| PubMed ID: 24576895	2014
Auditory event-related potentials (P300) and mesial temporal sclerosis in temporal lobe epilepsy patients. Epileptic disorders : international epilepsy journal with videotape\| PubMed ID: 24691299	2014
Type 1 diabetes as an autoimmune disease: the evidence. Diabetologia\| PubMed ID: 24705607	2014
Cervical length in late second and third trimester: a mixture model for predicting delivery. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology\| PubMed ID: 24817155	2014
Intensive care unit-related generalized neuromuscular weakness due to critical illness polyneuropathy/myopathy in critically ill patients. Journal of anesthesia\| PubMed ID: 24981564	2014
Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation. PLoS pathogens\| PubMed ID: 25010102	2014

George Papadopoulos

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