Involvement of CCR5 signaling in macrophage recruitment to porcine islet xenografts

BACKGROUND: Porcine antigen primed and CD4+ T-cell-activated macrophages are capable of both recognition and rejection of porcine xenografts. However, the specific signaling mechanisms involved remains to be addressed. The aim of this study was to examine the role of chemokine receptor and CD40 signaling in macrophage recruitment and graft destruction. METHODS: Macrophages were isolated from rejecting CCR2, CCR5, CD40 and control C57BL/6 mice that were recipients of neonatal porcine pancreatic cell cluster (NPCC) xenografts and were transferred to NPCC recipient NOD-SCID mice. RESULTS: Macrophages isolated from rejecting NPCC xenografts in CD40 and wildtype C57BL/6 mice demonstrated upregulated expression of macrophage activation markers as well as CCR5 and CCR2 genes, and caused pig islet xenograft destruction 8 days after transfer to NOD-SCID recipients. Graft infiltrating macrophages from rejecting CCR2 mice showed a similar activation phenotype and destroyed NPCC xenografts 10 days after transfer to NOD-SCID mice. Blockade of MCP-1 by anti-MCP-1 mAb did not prolong graft survival in CD4+ T cell reconstituted NPCC recipient NOD-SCID mice. By contrast, the graft infiltrating macrophages from rejecting CCR5 recipients showed impaired macrophage activation when compared to control C57BL/6 recipients, and transfer of these macrophages did not result in xenograft destruction in NOD-SCID recipients until day 16 after transfer. Analysis of graft infiltrating macrophages from these rejecting NOD-SCID mice showed an impaired activation phenotype. CONCLUSION: These results demonstrate that CCR5 is involved in both the activation and recruitment of macrophages to rejecting islet xenografts but other pathways are involved.     

Rivastigmine for Alzheimer's disease

Alzheimer's disease is the most common form of neurodegenerative dementia and poses considerable health challenges to both patients and their families. Rivastigmine is a powerful slow-reversible, noncompetitive carbamate cholinesterase inhibitor that is approved for the treatment of mild-to-moderate Alzheimer's disease. Randomized, double-blind, placebo-controlled trials of up to 6 months duration have shown beneficial effects of rivastigmine compared with placebo in measures of cognition and global functioning. Less rigorous but growing data suggest that the beneficial effects may endure for up to 5 years, extend to more advanced stages of Alzheimer's disease and may occur in noncognitive domains, such as activities of daily living and the behavioral symptoms of Alzheimer's disease. Evidence from controlled studies also supports the use of rivastigmine for cognitive and behavioral symptoms in Alzheimer's disease associated with vascular risk factors, dementia with Lewy bodies and Parkinson's disease dementia. Early and continued treatment of Alzheimer's disease with rivastigmine maximizes the observed beneficial effects. The most prominent adverse effect of rivastigmine is centrally mediated cholinergic gastrointestinal events, which can be minimized by slower dose-escalation intervals and administration with a full meal. Therapeutic dosing is 6-12 mg/day given twice daily, with higher doses having the potential for greater benefits.     

CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination

Here we demonstrate that a ubiquitin E3-ligase, FBXO21, targets the multidrug resistance transporter, ABCB1, also known as P-glycoprotein (P-gp), for proteasomal degradation. We also show that the Ser291-phosphorylated form of the multifunctional protein and stem cell marker, CD44, inhibits FBXO21-directed degradation of P-gp. Thus, CD44 increases P-gp mediated drug resistance and represents a potential therapeutic target in P-gp-positive cells.     

Incidental Thyroid Carcinoma

Objective: to find out the frequency of incidental thyroid carcinoma (ITC) in patients presumably operated for benign thyroid diseases. Methods: a total of 187 patients undergoing surgery for benign thyroid diseases were included in the study. All the patients underwent fine needle aspiration cytology (FNAC). Only those with benign diseases on FNAC were studied. Patients with undetermined cytology and follicular neoplasm were excluded. Results: Out of the 187 patients operated histology revealed ITC in 38 (20.3 %) of patients. The mean size of the nodule was 4.28 ± 1.48 cm in benign group and 4.21 ± 1.98 cm in ITC group. Papillary carcinoma was the commonest ITC (97.4 %) and follicular variant (16/38) was found more often than micropapillary variant (3/38). ITC was more common in patients with solitary nodule, 23 of 38 (60.5 %), although it wasn’t statistically significant (P value 0.262) 0.33 of 38 (86.8 %) were in euthyroid state (P value 0.029). Conclusions: the result of this study show, a high frequency of ITC (20.3 %). ITC was more frequent in euthyroid patients (P value 0.029). Incidence of ITC is not significantly different between patients presenting with SNG from those with MNG (P value 0.262). Papillary carcinoma was the commonest ITC (97.4 %) and follicular variant (16/38) was found more often than micropapillary variant (3/38).     

Prosthetic Rehabilitation of Oro-Nasal Defect

Maxillofacial defects may be due to congenital defect, trauma, tumor or infection. Among infections, fungal head and neck infections are common complication in patients with immunological or metabolic compromise. Cerebral extension of these infections often complicates the treatment plan. Treating these cases requires correction of the compromised state, local and systemic anti-fungal therapy and repeated radical debridement assisted by serial imaging. Following debridement, the resultant deformity can be corrected either surgically or prosthetically. Many factors are to be considered regarding the choice of the treatment. Here is a case report of a 55 year old male diabetic patient with oro-nasal mycosis, where debridement resulted in a gross morbid defect of the dorsum of the nose and the hard palate. Prosthetic rehabilitation was carried out with separate nasal prosthesis and a palatal feeding obturator.