Amlodipine-induced gingival hyperplasia

Drug-induced gingival hyperplasia is a serious concern both for the patient and the clinician. A 45 year-old Caucasian male patient with hypertension, who received amlodipine (10 mg/day, single dose orally) for two months, sought medical attention because of the new-onset gingival enlargement. On clinical examination a generalized and firm overgrowth of the gingival throughout the maxilla and the mandible were evident. The lack of gingival inflammation and purulent discharge were other features of the clinical scenario. Histological assessment of the biopsy specimen revealed the hyperplasia of connective tissue, epithelial acanthosis, and elongated rete ridges along with few inflammatory cells. The histological and the clinical evidences were consistent with amlodipine-induced gingival hyperplasia. We believe that the present report indicates the most rapidly developed case of amlodipine-induced gingival hyperplasia reported to date. The related literature is reviewed and the underlying pathogenic mechanisms of this rare side-effect are discussed here

Existential Features of the Body in Merleau-Ponty Phenomenology

In this article, we try to show that Maurice Merleau-Ponty, as the patron saint of the body, offers a phenomenological analysis of the body that is neither psychological nor rational, but existential in nature. Influenced by Heidegger's philosophy, Merleau-Ponty presents an existential analysis of man and his corporeality as the corporeal subject relates to the world. In this article, focusing on concepts such as location, body schema, flesh, absent body, and body perspective, we show that Merleau-Ponty's phenomenological analysis of these existential concepts has important role in understanding of the lived-body. Merleau-Ponty, by criticizing Descartes' body and abandoning his duality of soul and body, turns to the existential union of the two in the form of a bodily subject, showing that human existence can be understood through this bodily. He contrasts this analysis with philosophical analyzes, including Cartesian philosophy, in which he believes that sensory perception and the body as the foundation of human consciousness play an important role in his pre-reflective understanding of himself and the world

Factitial pemphigus-like lesions

The maxillofacial region is rarely subjected to self-inflicted conditions such as factitious disease. Nasal ulceration, facial emphysema, periorbital ecchymosis, mandibular subluxation, gingival and mucosal ulceration, dental and salivary gland pain and glossopharyngeal neuralgia have been reported as possible manifestations of factitious disease. We report a case of a young woman who presented with unilateral bullous and ulcerative oral and erythematous facial lesions that were initially diagnosed as pemphigus vulgaris but was later determined to be secondary to self-inflicted injuries. To the best of the authors? knowledge, this clinical scenario has not been previously reported in the context of a factitious disease and, therefore, may be considered in the differential diagnosis of oral vesiculobullous disorders

Fiber manipulation and post-assembly nanobody conjugation for adenoviral vector retargeting through SpyTag-SpyCatcher protein ligation

For adenoviruses (Ads) to be optimally effective in cancer theranostics, they need to be retargeted toward target cells and lose their natural tropism. Typically, this is accomplished by either engineering fiber proteins and/or employing bispecific adapters, capable of bonding Ad fibers and tumor antigen receptors. This study aimed to present a simple and versatile method for generating Ad-based bionanoparticles specific to target cells, using the SpyTag-SpyCatcher system. The SpyTag peptide was inserted into the HI loop of fiber-knob protein, which could act as a covalent anchoring site for a targeting moiety fused to a truncated SpyCatcher (SpyCatcherΔ) pair. After confirming the presence and functionality of SpyTag on the Ad type-5 (Ad5) fiber knob, an adapter molecule, comprising of SpyCatcherΔ fused to an anti-vascular endothelial growth factor receptor 2 (VEGFR2) nanobody, was recombinantly expressed in Escherichia coli and purified before conjugation to fiber-modified Ad5 (fmAd5). After evaluating fmAd5 detargeting from its primary coxsackie and adenovirus receptor (CAR), the nanobody-decorated fmAd5 could be efficiently retargeted to VEGFR2-expressing 293/KDR and human umbilical vein endothelial (HUVEC) cell lines. In conclusion, a plug-and-play platform was described in this study for detargeting and retargeting Ad5 through the SpyTag-SpyCatcher system, which could be potentially applied to generate tailored bionanoparticles for a broad range of specific targets; therefore, it can be introduced as a promising approach in cancer nanotheranostics

Prevalence of Merkel cell polyomavirus in Tehran: An age-specific serological study

Background: Several new types of polyomavirus have been discovered in recent years mainly because of the recent state-of-the-art detection technologies. Among the polyomaviruses, Merkel cell polyomavirus (MCPyV) has attracted the most attention because of its possible role in the etiology of Merkel cell carcinoma, a rare but lethal form of skin cancer. Objectives: This study aimed to determine age-specific seroprevalence of MCPyV in Tehran. Patients and Methods: In this cross-sectional study, we collected 440 serum samples from healthy individuals 2 to 78 years of age who visited the Pasteur Institute�s clinic in Tehran, Iran, using a convenience sampling strategy. We developed a virus-like particle-based enzyme-linked immunosorbent assay that uses VP1, the major capsid protein of MCPyV, to detect and quantitate serum antibodies to MCPyV. We compared the prevalence of MCPyV between males and females and across eight age groups. Results: A total of 255 (57.9) of the serum samples were MCPyV positive. The seroprevalence in children under 10 years of age was 25. The seroprevalence increased to 56 over the next decade of life (10 - 19 years of age). The seroprevalence rate in males and females was 56.1 and 59.7 respectively, and a binary logistic regression showed no significant difference between males and females (P = 0.77). However, the prevalence of MCPyV increased with age (P = 0.012). Conclusions: Our results suggest that human exposure to MCPyV occurs throughout life. The MCPyV antibody levels remained high among older adults in our population, consistent with reports from other populations. © 2016, Iranian Red Crescent Medical Journal

Oncolytic adenovirus: A tool for cancer therapy in combination with other therapeutic approaches

Cancer therapy using oncolytic viruses is an emerging area, in which viruses are engineered to selectively propagate in tumor tissues without affecting healthy cells. Because of the advantages that adenoviruses (Ads) have over other viruses, they are more considered. To achieve tumor selectivity, two main modifications on Ads genome have been applied: small deletions and insertion of tissue- or tumor-specific promoters. Despite oncolytic adenoviruses ability in tumor cell lysis and immune responses stimulation, to further increase their antitumor effects, genomic modifications have been carried out including insertion of checkpoint inhibitors and antigenic or immunostimulatory molecules into the adenovirus genome and combination with dendritic cells and chemotherapeutic agents. This study reviews oncolytic adenoviruses structures, their antitumor efficacy in combination with other therapeutic strategies, and finally challenges around this treatment approach. © 2018 Wiley Periodicals, Inc

Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers.

In this study, Taguchi design was used to determine optimal parameters for the preparation of bovine serum albumin (BSA)-loaded nanoparticles (NPs) using a biodegradable polymer poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL). NPs were prepared, using BSA as a model protein, by the double emulsion evaporation process followed by spray-drying from leucine to form nanocomposite microparticles (NCMPs). The effect of various parameters on NP size and BSA loading were investigated and dendritic cell (DC) uptake and toxicity. NCMPs were examined for their morphology, yield, aerosolisation, in vitro release behaviour and BSA structure. NP size was mainly affected by the polymer mass used and a small particle size ≤500 nm was achieved. High BSA (43.67 ± 2.3 μg/mg) loading was influenced by BSA concentration. The spray-drying process produced NCMPs (50% yield) with a porous corrugated surface, aerodynamic diameter 1.46 ± 141 μm, fine particle dose 45.0 ± 4.7 μg and fine particle fraction 78.57 ± 0.1%, and a cumulative BSA release of 38.77 ± 3.0% after 48 h. The primary and secondary structures were maintained as shown by sodium dodecyl sulphate poly (acrylamide) gel electrophoresis and circular dichroism. Effective uptake of NPs was seen in DCs with >85% cell viability at 5 mg/mL concentration after 4 h. These results indicate the optimal process parameters for the preparation of protein-loaded PGA-co-PDL NCMPs suitable for inhalation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci

Pulmonary delivery of Nanocomposite Microparticles (NCMPs) incorporating miR-146a for treatment of COPD.

The treatment and management of COPD by inhalation to the lungs has emerged as an attractive alternative route to oral dosing due to higher concentrations of the drug being administered to site of action. In this study, Nanocomposite Microparticles (NCMPs) of microRNA (miR-146a) containing PGA-co-PDL nanoparticles (NPs) for dry powder inhalation were formulated using l-leucine and mannitol. The spray-drying (Buchi B290) process was optimised and used to incorporate NPs into NCMPs using mix of l-leucine and mannitol excipients in different ratios (F1; 100:0% w/w, F2; 75:25% w/w, F3; 50:50% w/w, F4; 25:75% w/w, F5; 0:100% w/w) to investigate yield %, moisture content, aerosolisation performance and miR-146a biological activity. The optimum condition was performed at feed rate 0.5 ml/min, aspirator rate 28 m3/h, atomizing air flow rate 480 L/h, and inlet drying temperature 70 °C which produced highest yield percentage and closest recovered NPs size to original prior spray-drying. The optimum formulation (F4) had a high yield (86.0 ± 15.01%), recovered NPs size after spray-drying 409.7 ± 10.05 nm (initial NPs size 244.8 ± 4.40 nm) and low moisture content (2.02 ± 0.03%). The aerosolisation performance showed high Fine Particle Fraction (FPF) 51.33 ± 2.9%, Emitted Dose (ED) of 81.81 ± 3.0%, and the mass median aerodynamic diameter (MMAD) was ≤5 µm suggesting a deposition in the respirable region of the lungs. The biological activity of miR-146a was preserved after spray-drying process and miR-146a loaded NCMPs produced target genes IRAK1 and TRAF6 silencing. These results indicate the optimal process parameters for the preparation of NCMPs of miR-146a-containing PGA-co-PDL NPs suitable for inhalation in the treatment and management of COPD