A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model.

Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of goblet cells and smooth muscle, and subepithelial fibrosis. We examined the role of leukotrienes in a mouse model of allergen-induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on Days 0 and 14, received intranasal OVA periodically Days 14-75. The OVA-treated mice developed an extensive eosinophil and mononuclear cell inflammatory response, goblet cell hyperplasia, and mucus occlusion of the airways. A striking feature of this inflammatory response was the widespread deposition of collagen beneath the airway epithelial cell layer and also in the lung interstitium in the sites of leukocytic infiltration that was not observed in the saline-treated controls. The cysteinyl leukotriene(1) (CysLT(1)) receptor antagonist montelukast significantly reduced the airway eosinophil infiltration, mucus plugging, smooth muscle hyperplasia, and subepithelial fibrosis in the OVA-sensitized/challenged mice. The presence of Charcot-Leyden-like crystals in airway macrophages and the increased interleukin (IL)-4 and IL-13 mRNA expression in lung tissue and protein in BAL fluid seen in OVA-treated mice were also inhibited by CysLT(1) receptor blockade. These data suggest an important role for cysteinyl leukotrienes in the pathogenesis of chronic allergic airway inflammation with fibrosis.     

Differential effect of weight loss on insulin resistance in surgically treated obese patients

PURPOSE: To compare the effects of equivalent weight loss induced by two bariatric surgical techniques on insulin action in severely obese patients. METHODS: Eighteen nondiabetic patients with severe obesity (mean [+/- SD] body mass index: 53.5 +/- 9.0 kg/m(2)) and 20 sex- and age-matched lean subjects (body mass index: 23.8 +/- 3.0 kg/m(2)) underwent metabolic studies, including measurement of insulin sensitivity by the insulin clamp technique. Patients then underwent either vertical banded gastroplasty with Roux-en-Y gastric bypass, or biliopancreatic diversion, and were restudied at 5 to 6 months and again at 16 to 24 months postsurgery. RESULTS: At baseline, patients were hyperinsulinemic (194 +/- 47 pmol/L vs. 55 +/- 25 pmol/L, P < 0.0001), hypertriglyceridemic (1.56 +/- 0.30 mmol/L vs. 0.78 +/- 0.32 mmol/L, P < 0.0001), and profoundly insulin resistant (insulin-mediated glucose disposal: 20.8 +/- 4.4 micromol/min/kg fat-free mass vs. 52.0 +/- 10.1 micromol/min/kg, P < 0.0001) as compared with controls. Weight loss by the two procedures was equivalent in both amount (averaging -53 kg) and time course. In the gastric bypass group, insulin sensitivity improved (23.8 +/- 6.0 micromol/min/kg at 5 months and 33.7 +/- 11.3 micromol/min/kg at 16 months, P < 0.01 vs. baseline and controls). In contrast, in the biliopancreatic diversion group, insulin sensitivity was normalized already at 6 months (52.5 +/- 12.4 micromol/min/kg, P = 0.72 vs. controls) and increased further at 24 months (68.7 +/- 9.5 micromol/min/kg, P < 0.01 vs. controls) despite a persistent obese phenotype (body mass index: 33.2 +/- 8.0 kg/m(2)). CONCLUSION: In surgically treated obese patients, insulin sensitivity improves in proportion to weight loss with use of predominantly restrictive procedures (gastric bypass), but is reversed completely by predominantly malabsorptive approaches (biliopancreatic diversion) long before normalization of body weight. Selective nutrient absorption and gut hormones may interact with one another in the genesis of the metabolic abnormalities of obesity.     

Assessment,prevalence, and correlates of frailty among middle-aged adults with HIV in rural Uganda

Journal of NeuroVirology - We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44&nbsp;years)....     

Efficacy of mouthrinses with bovine milk and milk protein isolates to accumulate casein in the in situ pellicle

Clinical Oral Investigations - The adsorption of bovine milk caseins on the tooth surface might have a positive impact on the prevention of dental diseases. Therefore, the present study aimed to...     

Antibodies to prothrombin in antiphospholipid syndrome and inflammatory disorders

Antiphospholipid antibodies associated with the antiphospholipid syndrome (APS) have been shown to bind plasma proteins, particularly beta 2-glycoprotein I (β2-GPI). In this study the incidence of antibodies to solid-phase prothrombin was examined in patients with antiphospholipid syndrome and a variety of other inflammatory disorders.
Significantly elevated levels of IgG anti-prothrombin (anti-PT) antibodies were detected in 63% of patients with APS ( n  = 27, median 22 arbitrary units: AU), 33% with SLE ( n  = 92, median 14 AU), 45% with rheumatoid factor ( n  = 22, median 16 AU), 21% with carotid artery stenosis ( n  = 21, median 15 AU), 32% with stroke ( n  = 38, median 13 AU), 67% of patients with a false positive serology for syphilis ( n  = 21, median 24 AU), 37% with HIV ( n  = 30, median 14 AU), 29% with syphilis ( n  = 14, median 19 AU) and 3% with infectious mononucleosis ( n  = 30, median 9 AU). In addition, a group of lupus anticoagulant (LA) positive patients ( n  = 48) was examined for antibodies to prothrombin, β2-GPI and cardiolipin. 10 (21%) patients had raised levels of IgG anti-PT antibodies, 30 (62%) had significantly elevated levels of anti-β2-GPI antibodies and 15 (31%) had elevated levels of anticardiolipin antibodies (ACA). Of the LA-positive patients, 15 (43%) were identified with definite APS, eight (23%) with probable APS, two (6%) with possible APS and 10 (28%) patients had no clinical evidence of APS.
In conclusion, antibodies to prothrombin were found in a variety of inflammatory disorders and were therefore not specific for the APS. However, identification of the plasma proteins recognized by antibodies from patients with APS may provide insight into the pathogenic mechanisms involved in the heterogenous clinical manifestations of the APS.     

No “Magic Bullet”: Exploring Community Mobilization Strategies Used in a Multi-site Community Based Randomized Controlled Trial: Project Accept (HPTN 043)

As community-level interventions become more common in HIV prevention, processes such as community mobilization (CM) are increasingly utilized in public health programs and research. Project Accept, a multi-site community randomized controlled trial, is testing the hypothesis that CM coupled with community-based mobile voluntary counseling and testing and post-test support services will alter community norms and reduce the incidence of HIV. By using a multiple-case study approach, this qualitative study identifies seven major community mobilization strategies used in Project Accept, including stakeholder buy-in, formation of community coalitions, community engagement, community participation, raising community awareness, involvement of leaders, and partnership building, and describes three key elements of mobilization success.     

NIMH Project Accept (HPTN 043) HIV/AIDS Community Mobilization (CM) to Promote Mobile HIV Voluntary Counseling and Testing (MVCT) in Rural Communities in Northern Thailand: Modifications by Experience

Project Accept is a RCT designed to test the efficacy of community mobilization (CM), mobile voluntary counseling and testing (MVCT), and post-test support services (PTSS) in reducing HIV incidence in three African countries and Thailand. The intervention started in rural areas, northern Thailand in January 2006. CM initially included door-to-door visits during the daytime, small group discussions and joining organized meetings and followed by MVCT. In February 2007, CM strategy using HIV/AIDS "edutainment" (education and entertainment) during evening hours was introduced. After edutainment was initiated, the number of participants increased substantially. VCT uptake increased from 18 to 28 persons/day on average (t test; t = 7.87 P < 0.0001). Edutainment especially motivated younger people, as the median age of VCT clients decreased from 38 to 35 years old (median test; z = 6.74, P < 0.0001). Providing free MVCT in community settings along with edutainment during evening hours increased VCT uptake and was particularly attractive to younger adults.     

Mild hydrothermally treated brewer's spent grain for efficient removal of uranyl and rare earth metal ions

The increasing concerns on uranium and rare earth metal ion pollution in the environment require sustainable strategies to remove them from wastewater. The present study reports an eco-friendly approach to convert a kind of protein-rich biomass, brewer''s spent grain (BSG), into effective biosorbents for uranyl and rare earth metal ions. The employed method reduces the energy consumption by performing the hydrothermal treatment at a significantly lower temperature (150 °C) than conventional hydrothermal carbonization. In addition, with the aid of the Maillard reaction between carbohydrates and proteins forming melanoidins, further activation processes are not required. Treatment at 150 °C for 16 h results in an altered biosorbent (ABSG) with increased content of carboxyl groups (1.46 mmol g⁻¹) and a maximum adsorption capacity for La³⁺, Eu³⁺, Yb³⁺ (pH = 5.7) and UO₂²⁺ (pH = 4.7) of 38, 68, 46 and 221 mg g⁻¹, respectively. Various characterization methods such as FT-IR, ¹³C CP/MAS NMR, SEM-EDX and STA-GC-MS analysis were performed to characterize the obtained material and to disclose the adsorption mechanisms. Aside from oxygen-containing functional groups, nitrogen-containing functional groups also contribute to the adsorption. These results strongly indicate that mild hydrothermal treatment of BSG could be applied as a greener, low-cost method to produce effective adsorbents for uranyl and rare earth metal ion removal.

Effective biosorbent ABSG is obtained via hydrothermal treatment of BSG at low temperature without activation, minimizing energy consumption and environmental impact.     

Re-expression of a developmentally restricted potassium channel in autoimmune demyelination: Kv1.4 is implicated in oligodendroglial proliferation

Mechanisms of lesion repair in multiple sclerosis are incompletely understood. To some degree, remyelination can occur, associated with an increase of proliferating oligodendroglial cells. Recently, the expression of potassium channels has been implicated in the control of oligodendrocyte precursor cell proliferation in vitro. We investigated the expression of Kv1.4 potassium channels in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Confocal microscopy revealed expression of Kv1.4 in AN2-positive oligodendrocyte precursor cells and premyelinating oligodendrocytes in vitro but neither in mature oligodendrocytes nor in the spinal cords of healthy adult mice. After induction of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, Kv1.4 immunoreactivity was detected in or around lesions already during disease onset with a peak early and a subsequent decrease in the late phase of the disease. Kv1.4 expression was confined to 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive oligodendroglial cells, which were actively proliferating and ensheathed naked axons. After a demyelinating episode, the number of Kv1.4 and 2',3'-cyclic nucleotide 3'-phosphodiesterase double-positive cells was greatly reduced in ciliary neurotrophic factor knockout mice, a model with impaired lesion repair. In summary, the re-expression of an oligodendroglial potassium channel may have a functional implication on oligodendroglial cell cycle progression, thus influencing tissue repair in experimental autoimmune encephalomyelitis and multiple sclerosis.