Comparative pharmacodynamics of flunixin, ketoprofen and tolfenamic acid in calves

The pharmacodynamics of the non-steroidal anti-inflammatory drugs flunixin, tolfenamic acid and ketoprofen were studied in calves after intravenous administration. An acute inflammatory reaction was induced in tissue cages by the intracaveal injection of the mild irritant carrageenan, and the inhibition of inflammatory mediators and enzymes was investigated. The substances measured in the exudate included the enzymes (active and total metalloproteases, serine and cysteine proteases, acid phosphatase [AP], lactate dehydrogenase [LDH] and beta-glucuronidase) and the eicosanoids (prostaglandin [PG]E2 and leukotriene [LT]B4). Studies were also made of inhibition of the synthesis of serum thromboxane (Tx)B2 ex vivo, of bradykinin-induced oedema in vivo and of the generation of superoxide anions (O2-) in vitro. None of the drugs affected the concentration of LTB4, or the activities of metalloproteases, cysteine and serine proteases, AP or LDH in the exudate. All the drugs inhibited the synthesis of serum TxB2 and exudate PGE2 and inhibited the release of beta-glucuronidase. They also decreased the oedematous response to intradermally injected bradykinin and inhibited the generation of O2- ions by neutrophils in vitro. These actions may contribute to the anti-inflammatory effects of the drugs and hence to their clinical efficacy.     

Optical bandwidth considerations in p-i-n multiple quantum-wellmodulators

We investigate the optical bandwidth of p-i(multiple quantum well [MQW])-n modulators employing various MQW designs. The optical bandwidth translates directly into an operating temperature range due to the shift of the band gap with temperature. We find that although greater maximum modulation may be obtained with narrow (~90 Å) quantum wells operating below the band edge (absorption increases with field), uniform large performance may be obtained over a larger bandwidth using wider (~110 Å) quantum wells operating at the exciton (absorption decreases with field). We obtain a usable bandwidth of 7.7 nm, which translates into a operating temperature range of 27°C     

Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain

Laminins are the major noncollagenous glycoproteins of all basal laminae (BLs). They are alpha/beta/gamma heterotrimers assembled from 10 known chains, and they subserve both structural and signaling roles. Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic development. Here, we show that the laminin alpha5 chain is required during embryogenesis. The alpha5 chain is present in virtually all BLs of early somite stage embryos and then becomes restricted to specific BLs as development proceeds, including those of the surface ectoderm and placental vasculature. BLs that lose alpha5 retain or acquire other alpha chains. Embryos lacking laminin alpha5 die late in embryogenesis. They exhibit multiple developmental defects, including failure of anterior neural tube closure (exencephaly), failure of digit septation (syndactyly), and dysmorphogenesis of the placental labyrinth. These defects are all attributable to defects in BLs that are alpha5 positive in controls and that appear ultrastructurally abnormal in its absence. Other laminin alpha chains accumulate in these BLs, but this compensation is apparently functionally inadequate. Our results identify new roles for laminins and BLs in diverse developmental processes.     

Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells

Inadequate presentation of tumor antigens by host professional antigen-presenting cells (APCs), including dendritic cells (DCs), is one potential mechanism for the escape of tumors from the host immune system. Here, we show that human cancer cell lines release a soluble factor or factors that dramatically affect DC maturation from precursors without affecting the function of relatively mature DCs. One factor responsible for these effects was identified as vascular endothelial growth factor (VEGF). Thus, VEGF may play a broader role in the pathogenesis of cancer than was previously thought, and therapeutic blockade of VEGF action may improve prospects for immunotherapy as well as inhibit tumor neovasculature.     

A new analytical approach to the long term behaviour of moisture concentrations in building cavities—I. Non-condensing cavity

This paper, the first of two, presents a conceptual model of moisture concentrations in a building cavity. The model is comprehensive and general considering air infiltration, vapour diffusion and material hygroscopicity under non-steady state conditions. The resulting linearised coupled differential equations are analytically solved to study the case of long term cavity moisture behaviour. Dimensionless parameters and algebraic formulae are presented describing all important moisture performance parameters for a non-condensing cavity. Two primary time constants are identified, and a third, which governs the drying rate, derived. This allows the identification of three drying regimes based on cavity tightness. Some general design recommendations are given.     

The pathomechanics of compression injuries in the cervical spine. Nondestructive and destructive investigative methods

Biomechanical analysis using nondestructive and destructive investigative methods was performed to evaluate the mechanisms of cervical compression injuries. These injuries produce two basic modes of failure: 1) anterior dislocation; and 2) rupture of the anterior ligamentous complex of the vertebral body. Distribution of these two failure patterns was determined by the initial cervical spine position; translational alignment did not have a significant effect. Different results were observed between spines positioned in flexion and extension, indicating that the most important factor determining the mode of failure was rotational alignment in the sagittal plane.     

Conditioning and extinction of tolerance to the hypothermic effect of ethanol in rats.

Examined the contribution of classical conditioning to tolerance to the hypothermic effect of ethanol in 56 male albino rats. During the tolerance acquisition phase, Ss were exposed at 4-day intervals to a distinctive set of environmental cues paired with injections of ethanol (1.4 g/kg, ip). Interspersed between these drug trials were exposures to an alternate set of cues paired with injections of saline. In addition, 3 groups experienced different amounts of stimulation and activity during drug exposure in order to determine whether "behavioral augmentation" of tolerance would occur. In subsequent tests, Ss were tolerant only in the presence of cues previously paired with ethanol. Moreover, this environmentally specific tolerance was associated with a conditioned hyporthermic response to placebo (saline) injections in the drug environment. An extinction procedure designed to weaken tolerance mediated by classical conditioning was also found to be effective. Evidence for conditioned tolerance was weakest in Ss experiencing low levels of activity during the initial drug exposure periods. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)