CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection

Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis. The existing therapies fail to control the inflammation-driven tissue damage that occurs during Pseudomonas aeruginosa infection. Antibiotic treatment reduces bacterial burdens, but better interventions are needed to alleviate tissue damage resulting from local inflammation. We have previously documented that inhibition of macrophage migration inhibitory factor (MIF) reduces the bacterial levels and the inflammatory damage during keratitis. Here, we report that mice deficient for CD74, the putative MIF receptor, developed milder Pseudomonas aeruginosa-induced disease, characterized by decreased proinflammatory mediators and reduced bacterial presence in the cornea. However, topical inhibition of MIF using antibodies applied to the cornea further promoted recovery from disease, suggesting that in addition to MIF-dependent signaling events, MIF-triggered CD74-independent signaling pathways regulate sensitization to P. aeruginosa-induced infection

Inhibition of Macrophage Migration Inhibitory Factor Ameliorates Ocular Pseudomonas aeruginosa-Induced Keratitis

Pseudomonas aeruginosa causes severe sight-threatening corneal infections, with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity. We found that mice deficient for macrophage migration inhibitory factor (MIF), a key regulator of inflammation, had significantly reduced consequences from acute P. aeruginosa keratitis. This improvement in the outcome was manifested as improved bacterial clearance, decreased neutrophil infiltration, and decreased inflammatory responses when P. aeruginosa-infected MIF knock out (KO) mice were compared to infected wild-type mice. Recombinant MIF applied to infected corneas restored the susceptibility of MIF deficient mice to P. aeruginosa-induced disease, demonstrating that MIF is necessary and sufficient to cause significant pathology at this immune privileged site. A MIF inhibitor administered during P. aeruginosa-induced infection ameliorated the disease-associated pathology. MIF regulated epithelial cell responses to infection by enhancing synthesis of proinflammatory mediators in response to P. aeruginosa infection and by promoting bacterial invasion of corneal epithelial cells, a correlate of virulence in the keratitis model. Our results uncover a host factor that elevates inflammation and propagates bacterial cellular invasion, and further suggest that inhibition of MIF during infection may have a beneficial therapeutic effect

Ethnobotanical study of medicinal plants used by people in Zegie Peninsula, Northwestern Ethiopia

An ethnobotanical study was conducted from October 2005 to June 2006 to investigate the uses of medicinal plants by people in Zegie Peninsula, northwestern Ethiopia. Information was gathered from 200 people: 70 female and 130 males, using semistructured questionnaire. Of which, six were male local healers. The informants, except the healers, were selected randomly and no appointment was made prior to the visits. Informant consensus factor (ICF) for category of aliments and the fidelity level (FL) of the medicinal plants were determined. Sixty-seven medicinal plants used as a cure for 52 aliments were documented. They are distributed across 42 families and 64 genera. The most frequently utilized plant part was the underground part (root/rhizome/bulb) (42%). The largest number of remedies was used to treat gastrointestinal disorder and parasites infections (22.8%) followed by external injuries and parasites infections (22.1%). The administration routes are oral (51.4%), external (38.6%), nasal (7.9%), and ear (2.1%). The medicinal plants that were presumed to be effective in treating a certain category of disease, such as 'mich' and febrile diseases (0.80) had higher ICF values. This probably indicates a high incidence of these types of diseases in the region, possibly due to the poor socio-economic and sanitary conditions of this people. The medicinal plants that are widely used by the local people or used as a remedy for a specific aliment have higher FL values (Carissa spinarum, Clausena anisata, Acokanthera schimperi, Calpurnia aurea, Ficus thonningii, and Cyphostemma junceum) than those that are less popular or used to treat more than one type of aliments (Plumbago zeylanicum, Dorstenia barnimiana)

Indigenous use and bio-efficacy of medicinal plants in the Rasuwa District, Central Nepal

<p>Abstract</p> <p>Background</p> <p>By revealing historical and present plant use, ethnobotany contributes to drug discovery and socioeconomic development. Nepal is a natural storehouse of medicinal plants. Although several ethnobotanical studies were conducted in the country, many areas remain unexplored. Furthermore, few studies have compared indigenous plant use with reported phytochemical and pharmacological properties.</p> <p>Methods</p> <p>Ethnopharmacological data was collected in the Rasuwa district of Central Nepal by conducting interviews and focus group discussions with local people. The informant consensus factor (F_IC) was calculated in order to estimate use variability of medicinal plants. Bio-efficacy was assessed by comparing indigenous plant use with phytochemical and pharmacological properties determined from a review of the available literature. Criteria were used to identify high priority medicinal plant species.</p> <p>Results</p> <p>A total of 60 medicinal formulations from 56 plant species were documented. Medicinal plants were used to treat various diseases and disorders, with the highest number of species being used for gastro-intestinal problems, followed by fever and headache. Herbs were the primary source of medicinal plants (57% of the species), followed by trees (23%). The average F_IC value for all ailment categories was 0.82, indicating a high level of informant agreement compared to similar studies conducted elsewhere. High F_ICvalues were obtained for ophthalmological problems, tooth ache, kidney problems, and menstrual disorders, indicating that the species traditionally used to treat these ailments are worth searching for bioactive compounds: <it>Astilbe rivularis</it>, <it>Berberis asiatica</it>, <it>Hippophae salicifolia, Juniperus recurva</it>, and <it>Swertia multicaulis</it>. A 90% correspondence was found between local plant use and reported plant chemical composition and pharmacological properties for the 30 species for which information was available. Sixteen medicinal plants were ranked as priority species, 13 of which having also been prioritized in a country-wide governmental classification.</p> <p>Conclusions</p> <p>The <it>Tamang </it>people possess rich ethnopharmacological knowledge. This study allowed to identify many high value and high priority medicinal plant species, indicating high potential for economic development through sustainable collection and trade.</p

Late Onset CNS Immune Reconstitution Inflammatory Syndrome in an Immunocompetent Patient

IRIS refers to the presence of paradoxical clinical deterioration attributable to immune system recovery during highly active antiretroviral therapy (HAART). We present an immunocompetent patient with multifocal leukoencephalopathy on HAART, with central nervous system (CNS) IRIS pathology of unknown infectious etiology. CNS IRIS pathology should be suspected in patients on longstanding HAART without immune reconstitution, presenting with unexplained leukoencephaphalopathy

Pre-tissue plasminogen activator blood pressure levels and risk of symptomatic intracerebral hemorrhage

BACKGROUND AND PURPOSE-: From small pilot studies, uncontrolled pretreatment systolic blood pressure &gt;185 mm Hg and diastolic blood pressure &gt;110 mm Hg in patients with acute ischemic stroke were introduced in the National Institute of Neurological Diseases and Stroke rtPA Stroke Study as a contraindication for thrombolysis. We sought to determine if pretreatment blood pressure protocol violations in patients with acute ischemic stroke receiving intravenous tissue plasminogen activator are related to the subsequent risk of symptomatic intracranial hemorrhage (sICH). METHODS-: We reviewed medical records of consecutive ischemic stroke admissions treated with intravenous thrombolysis over a 10-year period at our tertiary care hospital. The National Institutes of Health Stroke Scale score on admission was used to determine baseline stroke severity. The closest documented blood pressure values to the time of tissue plasminogen activator bolus (range, 0 to 10 minutes) were considered as pretreatment blood pressure. Pretreatment blood pressure protocol violations were identified as systolic blood pressure &gt;185 or diastolic blood pressure &gt;110 mm Hg prebolus. sICH was defined as brain imaging evidence of intracranial hemorrhage with clinical worsening by the National Institutes of Health Stroke Scale score increase of ≤4 points. RESULTS-: Among 510 patients with ischemic stroke treated with intravenous tissue plasminogen activator (282 men; mean age, 65±15 years), sICH occurred in 31 patients (6.1%). Blood pressure protocol violations were present in 63 patients (12.4%) and they were more frequent in patients with sICH (26% versus 12%; P=0.019). After adjusting for demographic characteristics, onset-to-treatment time, baseline National Institutes of Health Stroke Scale, stroke risk factors and medications, pretreatment blood pressure protocol violations were independently associated with a higher likelihood of sICH (OR, 2.59; 95% CI, 1.07 to 6.25; P=0.034). CONCLUSIONS-: These data support current guidelines advising not to use intravenous tissue plasminogen activator when pretreatment blood pressure exceeds the prespecified thresholds by showing that blood pressure protocol violations are independently associated with a higher likelihood of sICH. © 2009 American Heart Association, Inc