Immunomodulation by biphalin,dimeric synthetic opioid peptide,and its analog

The opioid pentapeptides called enkephalins were originally described as the endogenous ligands for the opioid receptors. Although their precise physiological significance still remains elusive, the enkephalins have been reported to exhibit analgesic, antidepressant, antianxiety and anticonvulsant activities. In addition, enkephalins have also been shown to act as immunomodulator. The first generation of dimeric peptides was derived from enkephalins. Biphalin [(Tyr-D-Ala-Gly-Phe-NH)2] is a bivalent opioid analog containing two tyrosine residues. We have evaluated the immunomodulatory properties of biphalin and its analogs in various in vitro tests. We report that biphalin and one of its analogs [Tyr-D-Ala-Gly-Phe-NH.NH-Phe(p-Cl)-H] stimulate human T cell proliferation, natural killer (NK) cell cytotoxicity in vitro and interleukin-2 (IL-2) production. Biphalin and its analog also released chemokine like factor in the culture supernatant that was responsible for increased chemotaxis of monocytes. Furthermore, these peptides inhibited tumor necrosis factor (TNF-alpha) production in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) and nitric oxide (NO) production in mouse macrophage cells, RAW 264.7. Our observations suggest immunomodulatory property of biphalin and its analog.     

Selenium improves cardiac function by attenuating the activation of NF-kappaB due to ischemia-reperfusion injury

Although selenium, an essential trace element and a component of glutathione peroxidase, is known to protect the heart from ischemia-reperfusion (I/R)-induced injury, the mechanisms of this protection are not fully understood. For this purpose, isolated rat hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion; sodium selenite (25-1,000 nM) was added in the perfusion medium 10 min prior to ischemia, as well as during reperfusion. Selenium caused a dose-dependent improvement in cardiac performance and attenuated the decrease in the ratio of reduced glutathione to oxidized glutathione, as well as the increased level of malondialdehyde in I/R heart. Elevated ratios of nuclear factor-kappaB (NF-kappaB) in particulate and cytosolic fraction and of phosphorylated NF-kappaB and total NF-kappaB in I/R hearts were reduced by selenium. Cardiac dysfunction in hearts perfused with xanthine plus xanthine oxidase mixture, as well as hydrogen peroxide, or subjected to Ca2+ paradox was also attenuated by selenium. These data suggest that selenium protects the heart against I/R injury due to its action on the redox state and deactivation of NF-kappaB in I/R hearts.     

Inflammation: the link between insulin resistance, obesity and diabetes

Recent data have revealed that the plasma concentration of inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), is increased in the insulin resistant states of obesity and type 2 diabetes, raising questions about the mechanisms underlying inflammation in these two conditions. It is also intriguing that an increase in inflammatory mediators or indices predicts the future development of obesity and diabetes. Two mechanisms might be involved in the pathogenesis of inflammation. Firstly, glucose and macronutrient intake causes oxidative stress and inflammatory changes. Chronic overnutrition (obesity) might thus be a proinflammatory state with oxidative stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated with obesity and type 2 diabetes, might interfere with insulin action by suppressing insulin signal transduction. This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.     

The role of arthroscopy in the treatment of functional instability of the ankle

BackgroundAnkle sprains are common, the majority resolving with functional rehabilitation. Some patients are left with symptoms of functional instability (FI). Ankle arthroscopy in those with symptoms of FI is not well covered in the literature. Our aim was to assess its role in FI of the ankle.MethodsRetrospective case note analysis of patients with FI following an ankle sprain from 2005 to 2007. All underwent arthroscopy, provided mechanical instability was excluded (EUA and stress X-rays), and there were no signs of soft tissue impingement. These patients had exhausted all options of conservative therapy.ResultsSeventy-seven patients with a mean age of 38.1: five had true mechanical instability and were excluded. 72 underwent arthroscopy: 67 (93.1%) had significant amounts of scar tissue needing debridement, most commonly in the antero-lateral corner (58.3%). 52 patients improved (72.2%) at a minimum of 6 months follow-up.ConclusionOur study supports the role of ankle arthroscopy in the treatment of FI following trauma. It should be considered when conservative measures have failed.