The disconnect between animal models of sepsis and human sepsis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141189/1/jlb0137.pd

Evidence for a functional role of the second C5a receptor C5L2

During experimental sepsis in rodents after cecal ligation and puncture (CLP), excessive C5a is generated, leading to interactions with C5aR, loss of innate immune functions of neutrophils, and lethality. In the current study, we have analyzed the expression of the second C5a receptor C5L2, the putative â defaultâ or nonsignaling receptor for C5a. Rat C5L2 was cloned, and antibody was developed to C5L2 protein. After CLP, blood neutrophils showed a reduction in C5aR followed by its restoration, while C5L2 levels gradually increased, accompanied by the appearance of mRNA for C5L2. mRNA for C5L2 increased in lung and liver during CLP. Substantially increased C5L2 protein (defined by binding of 125Iâ antiâ C5L2 IgG) occurred in lung, liver, heart, and kidney after CLP. With the use of serum ILâ 6 as a marker for sepsis, infusion of antiâ C5aR dramatically reduced serum ILâ 6 levels, while antiâ C5L2 caused a nearly fourfold increase in ILâ 6 when compared with CLP controls treated with normal IgG. When normal blood neutrophils were stimulated in vitro with LPS and C5a, the antibodies had similar effects on release of ILâ 6. These data provide the first evidence for a role for C5L2 in balancing the biological responses to C5a.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154410/1/fsb2fj043424fje.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154410/2/fsb2fj043424fje-sup-0040.pd

Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis

INTRODUCTION: Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis. METHODS: Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls. RESULTS: Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group. CONCLUSIONS: Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis

Various forms of educational work in schools during the mathematics classes

Diplomdarbā ir iekļauta teorētiskā daļa par pamatizglītības un vidējās izglītības programmas galvenajiem mērķiem un uzdevumiem. Nodaļā par vispārīgās pedagoģijas problēmām ir analizēta netradicionālas mācību stundas ietekme uz skolēnu mācību rezultātiem. Diplomdarba praktiskā daļā ir izstrādāti matemātikas stundu projekti klases un ārpusklases darbam. Stundu projekti ir veidoti no 7. – 12. klasei: 7., 8., 9., 10. un 11. klasei ir katrai vienas stundas projekts, bet 12. klasei ir divi stundu projekti.The theoretical part of the Diploma Paper holds information about the main objectives and tasks of the elementary education and secondary education programs. The Paper holds a chapter regarding general pedagogy and how the untraditional classes affect pupils. The practical part contains mathematics class’s projects. Class projects have been elaborated for 7th to 12th class. One class project has been elaborated for 7th, 8th, 9th, 10th and 11th class, but two class projects for 12th class

The disconnect between animal models of sepsis and human sepsis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141189/1/jlb0137.pd