Toll‐like receptor 6 mediated inflammatory and functional responses of zinc oxide nanoparticles primed macrophages

Macrophages are among the most sensitive immune cells because of their phagocytic activity and are prone to become dysfunctional or not able to perform properly if nanoparticle load increases. We have previously reported that zinc oxide nanoparticles (ZNPs) induce inflammatory responses in macrophages that contribute to their death. Recognition of ZNPs by pattern recognition receptors such as toll‐like receptors (TLRs) might be a factor in the initiation of these responses in macrophages. Therefore, in this study we explored the role played by TLR6 and mitogen‐activated protein kinase (MAPKs) pathways in the inflammatory responses of macrophages during ZNPs exposure. ZNPs‐activated macrophages showed enhanced expression of activation and maturation markers (CD1d, MHC‐II, CD86 and CD71). Among various TLRs screened, TLR6 emerged as the most potent activator for ZNPs‐induced inflammatory responses. Downstream signalling proteins myeloid differentiation 88, interleukin‐1 receptor associated kinase and tumour necrosis factor receptor‐associated factor were also enhanced. On inhibiting MAPKs pathways individually, the inflammatory responses such as interleukin‐1β, interleukin‐6, tumour necrosis factor‐α, cyclooxygenase‐2 and inducible nitric oxide synthase were suppressed. TLR6 silencing significantly inhibited the pro‐inflammatory cytokine levels, reactive nitrogen species generation and inducible nitric oxide synthase expression. Also, inhibition of MAPKs in the absence of TLR6 signalling validated the link between TLR6 and MAPKs in ZNPs‐induced inflammatory responses. TLR6 was found to be co‐localized with autophagosomes. Macrophages lacking TLR6 inhibited the autophagosome marker protein‐microtubule‐associated protein1 light chain 3‐isoform II formation and phagocytosis. These results demonstrate that inflammatory responses caused by ZNPs‐activated macrophages strongly depend on TLR6‐mediated MAPK signalling.     

Postextraction maintenance of the alveolar ridge: rationale and review

Alveolar ridge resorption has long been considered an unavoidable consequence of tooth extraction and can be a significant problem in implant and restorative dentistry. Postextraction maintenance of the alveolar ridge minimizes residual ridge resorption and allows placement of an implant that satisfies both esthetic and functional criteria. Guided bone-regeneration techniques and the use of bone-replacement materials have been shown to enhance socket healing and potentially modify the resorption process. The prime indication for socket preservation is the prevention of alveolar-bone and soft-tissue collapse, which would cause unacceptable prosthesis esthetics. This review describes the rationale behind socket preservation, and the various techniques and materials used for extraction site grafting.     

Reserpine modulates neurotransmitter release to extend lifespan and alleviate age-dependent Aβ proteotoxicity in Caenorhabditis elegans

Aging is a debilitating process often associated with chronic diseases such as diabetes, cardiovascular and neurodegenerative diseases like Alzheimer's disease (AD). AD occurs at a very high incidence posing a huge burden to the society. Model organisms such as C. elegans become essential to understand aging or lifespan extension - the etiology, molecular mechanism and identification of new drugs against age associated diseases. The AD model, manifesting Aβ proteotoxicity, in C. elegans is well established and has provided valuable insights. Earlier, we have reported that Reserpine, an FDA-approved antihypertensive drug, increases C. elegans lifespan with a high quality of life and ameliorates Aβ toxicity in C. elegans. But reserpine does not seem to act through the known lifespan extension pathways or inhibition of its known target, vesicular monoamine transporter, VMAT. Reserpine's mode of action and the pathways it activates are not known. Here, we have evaluated the presynaptic neurotransmitter(s) release pathway and identified acetylcholine (ACh) as the crucial player for reserpine's action. The corroborating evidences are: i) lack of lifespan extension in the ACh loss of function (hypomorphic) - synthesis (cha-1) and transport (unc-17) mutants; ii) mitigation of chronic aldicarb effect; iii) lifespan extension in dopamine (cat-2) and dopamine and serotonin (bas-1) biosynthetic mutants; iv) no rescue from exogenous serotonin induced paralysis in the AD model worms; upon reserpine treatment. Thus, modulation of acetylcholine is essential for reserpine's action.     

Noradrenergic Function in Suicide

Although abnormalities in serotonergic function have been the major focus of studies on suicidal behavior, several studies indicate that abnormalities of noradrenergic function may also be involved in the pathophysiology of suicide. In this paper, we have reviewed some of the noradrenergic studies in sucide, including studies of the biosynthetic enzyme for norepinephrine, tyrosine hydroxylase (TH), the receptors for norepinephrine, α- and β-adrenergic receptors, as well as the signaling cascades linked to β-adrenergic receptors. In general, these studies indicate that the protein expression of TH, as well as α₂- and β₂-adrenergic receptors, is increased in the postmortem brain of suicide victims. More studies are needed in order to examine extensively the role of noradrenergic function in suicidal behavior.     

Deep sclerectomy and trabeculectomy augmented with Mitomycin C: 2-year post-operative outcomes

Graefe's Archive for Clinical and Experimental Ophthalmology - Two-year post-operative outcomes of both deep sclerectomy (DS) and trabeculectomy surgery (Trab) augmented with Mitomycin C (MMC)...     

Penile Incarceration with Metallic Foreign Bodies: Management and Review of Literature

Introduction

Penile strangulation from constricting metallic objects disorders is an uncommon urological emergency which requires prompt intervention to prevent complications. The treatment modalities are diverse and characterized by lack of consensus.

Material and Methods

Three cases with penile incarceration due to constricting metallic objects who presented to our department were included in this study. All 3 patients required different management options highlighting the diversity of clinical presentation and need for customization of treatment as per the clinical scenario.

Results

The 3 patients required different approach for treatment. First patient could be managed by degloving of penile skin while second patient required mechanical removal of the foreign body and debridement of local necrotic tissues. The third patient had to undergo excision of gangrenous penile skin and skin grafting.

Conclusion

The study emphasizes the diversity of clinical presentations and the need for employing different surgical techniques to achieve the desired results.Key Words: Penile strangulation, Constricting objects, Penile amputation