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.     

Neonatal Severe Hyperparathyroidism due to Compound Heterozygous Mutation of Calcium Sensing Receptor (CaSR) Gene Presenting as Encephalopathy

The authors report a 14-d-old neonate who presented with lethargy, polyuria and dehydration and was found to have severe hypercalcemia with hyperparathyroidism. This neonate was treated with saline hydration, diuresis and injection pamidronate. Genetic analysis revealed a compound heterozygous mutation of CaSR.     

Depression in patients receiving pharmacotherapy for epilepsy: An audit in a tertiary care centre

BackgroundThe association of depression and epilepsy is thought to be bidirectional. The present study aimed to evaluate the prevalence of depression in patients on antiepileptic drugs (AEDs) and factors affecting it.MethodsIn this preliminary cross sectional study, patients at epilepsy clinic of a tertiary care centre were studied for occurrence of depression, using Hospital Anxiety and Depression Scale (HADS-D) and Patient Health Questionnaire (PHQ-2) scales. Correlation analysis was carried out to determine the factors associated with presence of depression in these patients.ResultsA total of 12 AEDs (maximum 5 per patient including older and newer) were prescribed to 933 patients in different treatment regimens over a period of 3 years. The median age of the patients was 22 years (10–77) and among them 63.5% were men. Mild and clinically relevant depression occurred in 279 (29.9%) and 223 (23.9%) patients, respectively. Mean HADS-D and PHQ-2 score was significantly higher with polytherapy as compared to monotherapy (p < 0.001). Patients on levetiracetam exhibited significantly higher HADS-D score in comparison to phenytoin (p < 0.001), carbamazepine (p < 0.001) and sodium valproate (p < 0.05). However, there was no significant difference in PHQ score among patients on monotherapy of different AEDs. Multivariate regression analysis suggested correlation between depression and seizure frequency, total number of AEDs and their load (p < 0.001).ConclusionDepressive symptoms were found to be present in more than half of the patients with epilepsy which require detailed work up for depression. Levetiracetam was found to be associated with a higher incidence of subclinical depression which needs further investigation.     

Indoleamine 2,3-dioxygenase (IDO) induced by Leishmania infection of human dendritic cells

Dendritic cells (DC) play a pivotal role in regulating immunity, establishing immunologically privileged tissue microenvironments and maintaining homoeostasis. It is becoming increasingly clear that one key mechanism that mediates many DC functions is production of the immunomodulatory enzyme indoleamine 2,3‐dioxygenase (IDO). For pathogens that cause chronic infection, exploitation of host DCs is a solution to establish and persist within a host. Leishmania parasites cause a range of clinical manifestations, all involving chronic infection, and are proficient at avoiding immune responses. We demonstrate here that infection of human myeloid‐derived DC with L. major and L. donovani induces IDO expression using a mechanism that involves autocrine or paracrine stimulation with a DC‐secreted factor. Leishmania‐induced IDO suppresses allogeneic and tetanus toxoid–specific lymphocyte proliferation, an inhibition that is reversed with the IDO inhibitor, 1‐methyl tryptophan (1‐MT). Furthermore, IDO expression by human DC does not require live Leishmania infection, as parasite lysates also up‐regulate IDO mRNA production. Our data suggest that one mechanism Leishmania parasites utilize to circumvent immune clearance may be to promote the induction of IDO among host DC within the infection microenvironment.     

Effect of sociodemographic variables on complete denture satisfaction

PURPOSE

The objective of this study was to evaluate the effect of sociodemographic factors on quality of satisfaction towards denture treatment.

MATERIALS AND METHODS

One hundred subjects (filling inclusion criteria) who were wearing a denture for at least two months were enrolled and divided into five groups on the basis of sociodemographic variables (age, gender, literacy level, socio-economic and marital status). Questionnaires consisting of 38 questions (positive and negative attitude towards denture satisfaction) related to patients'' perception of clinical outcome in different domains such as mastication, appearance, speech, comfort, health, denture care and social status were scored by the subjects. Questions reflecting positive attitude were scored as 2, 1, or 0 (yes, uncertain and no, respectively) and reversely for the negative questions. Statistical analysis was done by using Statistical Package for Social Sciences (α = .05).

RESULTS

Level of denture satisfaction was higher in age subgroup belonging to 45 - 65 years of age in relation to comfort, health and denture care. Female and male showed significant priority for denture treatment because of esthetic and function respectively. Level of satisfaction was statistically significant with literacy level. Upper high income group showed significantly higher level of satisfaction only in case of social status. Married group showed significantly higher satisfaction level only with comfort.

CONCLUSION

Patients'' sociodemographic variables were influential factors on denture satisfaction.     

Effect of occlusal splint therapy on maximum bite force in individuals with moderate to severe attrition of teeth

ObjectiveThe purpose of the pilot study was to determine the effect of restoring lost occlusal vertical dimension (OVD) due to attrition on maximum bite force in humans.MethodologyA total of 124 subjects in age range of 25–40 years, with moderate to severe attrition, having full complement of teeth were screened according to inclusion and exclusion criteria. After consent, occlusal vertical dimension was assessed by employing mechanical and physiological methods in the experimental group and a maxillary canine guided hard splint was fabricated for each subjects fulfilling inclusion criteria and with positive consent (78). Bite force in experimental group was measured before, immediately after delivery of splint and subsequently at an interval of four, eight, and twelve weeks. Due loss during follow up, only 50 subjects could be available for bite force recording till 12 weeks. Bite force of age, gender, height and weight matched controls with no signs of attrition was also measured for comparison.ResultsBite force of the experimental group was found to be significantly less than the matched controls (P = 0.000) initially. After delivery of splint, bite force values increased progressively till twelve weeks. However comparison of bite force values of experimental group with control group showed no significant difference at end of eight (P = 0.008) and twelve weeks (P = 0.162).ConclusionIt was concluded that maximum bite force increases with restoration of lost vertical using splint therapy. A time period of 8–12 weeks is required to restore the maximum bite force value approximately similar to matched controls.