Articles: chronic.
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Am. J. Respir. Crit. Care Med. · Jul 2014
Tuberculosis, pulmonary cavitation and matrix metalloproteinases.
Tuberculosis (TB), a chronic infectious disease of global importance, is facing the emergence of drug-resistant strains with few new drugs to treat the infection. Pulmonary cavitation, the hallmark of established disease, is associated with very high bacillary burden. Cavitation may lead to delayed sputum culture conversion, emergence of drug resistance, and transmission of the infection. ⋯ MMP concentrations are elevated in human TB and are closely associated with clinical and radiological markers of lung tissue destruction. Immunomodulatory therapies targeting MMPs in preclinical and clinical trials are potential adjuncts to TB treatment. Strategies targeting patients with cavitary TB have the potential to improve cure rates and reduce disease transmission.
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Journal of neurotrauma · Jul 2014
Delayed Increases in Microvascular Pathology Following Experimental Traumatic Brain Injury Are Associated with Prolonged Inflammation, Blood Brain Barrier Disruption and Progressive White Matter Damage.
Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. ⋯ Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased understanding of mechanisms underlying delayed microvascular damage following TBI could provide novel insights into chronic pathological responses to TBI and potential common mechanisms underlying TBI and neurodegenerative diseases.
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It is well established that prolonged, controlled mechanical ventilation is associated with contractile dysfunction of the diaphragm due to impaired function of the mitochondrial respiratory chain as a result of aggravated oxidative and nitrosative stress. Sepsis and circulatory failure induce a similar response pattern. Callahan and Supinski now show that streptozotocin-induced insulin-dependent diabetes causes a comparable response pattern, both with respect to function and physiology - that is, reduced fiber force and, consequently, muscle contractility - but also as far as the underlying mechanisms are concerned. ⋯ It remains to be elucidated whether the underlying co-morbidity (for example, diabetes) adds to or even synergistically enhances the effect of an acute stress situation (for example, sepsis, mechanical ventilation). In addition, extending their previous work during shock states, the authors also show that administration of a preparation of the enzymatic anti-oxidant superoxide dismutase can reverse the deleterious effects of diabetes. These data are discussed in the context of the fundamental role of hyperglycemia in relation to metabolism-dependent formation of reactive oxygen species.