Coexistence of at least three distinct beta-adrenoceptors in human internal mammary artery

The internal mammary artery (IMA) is currently the preferred conduit for myocardial revascularization. However, perioperative vasospasm and a hypoperfusion state during maximal exercise may limit its use as a bypass graft. The mechanism of spasm has not been clearly defined. Since beta-adrenoceptor activation plays a major role in vasorelaxation, the present study was carried out to investigate the beta-adrenoceptor responsiveness of human IMA smooth muscle. Isoproterenol produced a concentration-dependent relaxation in endothelium-denuded IMA segments, precontracted with phenylephrine (maximal relaxation 46.33±5.45%). Atenolol (10 –6 M) and propranolol (2×10 –7 M) inhibited isoproterenol-induced relaxation. While atenolol produced partial inhibition, propranolol caused a complete inhibition in a majority of the segments and a partial inhibition in a minority. BRL 37344, a selective beta 3-adrenoceptor agonist, produced a concentration-dependent relaxation in phenylephrine-precontracted rings of endothelium-denuded IMA (maximal relaxation 40.35±4.07%). Cyanopindolol, a beta-adrenoceptor partial agonist, produced a marked relaxation (58.65±6.2%) in endothelium-denuded IMA rings, precontracted with phenylephrine. Cyanopindolol-induced relaxation was resistant to blockade by propranolol (2×10 –7 M). Spontaneous contractions of IMA rings were also observed in some cases that were inhibited by isoproterenol and BRL 37344. This observation implies the important role of beta-adrenoceptor activation in prevention of human IMA spasm

MicroRNAs: effective elements in ear-related diseases and hearing loss

miRNAs are important factors for post-transcriptional process that controls gene expression at mRNA level. Various biological processes, including growth and differentiation, are regulated by miRNAs. miRNAs have been demonstrated to play an essential role in development and progression of hearing loss. Nowadays, miRNAs are known as critical factors involved in different physiological, biological, and pathological processes, such as gene expression, progressive sensorineural hearing loss, age-related hearing loss, noise-induced hearing loss, cholesteatoma, schwannomas, and inner ear inflammation. The miR-183 family (miR-183, miR-96 and miR-182) is expressed abundantly in some types of sensory cells in inner ear specially mechanosensory hair cells that exhibit a great expression level of this family. The plasma levels of miR-24-3p, miR-16-5p, miR-185-5p, and miR-451a were upregulated during noise exposures, and increased levels of miR-21 have been found in vestibular schwannomas and human cholesteatoma. In addition, upregulation of pro-apoptotic miRNAs and downregulation of miRNAs which promote differentiation and proliferation in age-related degeneration of the organ of Corti may potentially serve as a helpful biomarker for the early detection of age-related hearing loss. This knowledge represents miRNAs as promising diagnostic and therapeutic tools in the near futur

MicroRNA-183 family in inner ear: Hair cell development and deafness

miRNAs are essential factors of an extensively conserved post-transcriptional process controlling gene expression at mRNA level. Varoius biological processes such as growth and differentiation are regulated by miRNAs. Web of Science and PubMed databases were searched using the Endnote software for the publications about the role miRNA-183 family in inner ear: hair cell development and deafness published from 2000 to 2016. A triplet of these miRNAs particularly the miR-183 family is highly expressed in vertebrate hair cells, as with some of the peripheral neurosensory cells. Point mutations in one member of this family, miR-96, underlie DFNA50 autosomal deafness in humans and lead to abnormal hair cell development and survival in mice. In zebrafish, overexpression of the miR-183 family induces extra and ectopic hair cells, while knockdown decreases the number of hair cell. The miR-183 family (miR-183, miR-96 and miR-182) is expressed abundantly in some types of sensory cell in the eye, nose and inner ear. In the inner ear, mechanosensory hair cells have a robust expression level. Despite much similarity of these miRs sequences, small differences lead to distinct targeting of messenger RNAs targets. In the near future, miRNAs are likely to be explored as potential therapeutic agents to repair or regenerate hair cells, cell reprogramming and regenerative medicine applications in animal models because they can simultaneously down-regulate dozens or even hundreds of transcripts. © 2016 The Korean Audiological Society

Study of common mitochondrial mutations in patients with nonsyndromic hearing loss

Hearing loss is the most common sensorineural disorder involving one out of 1000 people. Around 50% of hearing losses occur due to genetic causes. Three mitochondrial mutations, A1555G in MTRNR1, A3243G in MTTL1, and A7445G in MTTS1, are the most important non-syndromic sensorineural causes of hearing loss in some populations. The aim of this review was to study common mitochondrial mutations in people with hearing loss in Iran. EVIDENCE ACQUISITION: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science were searched. EVIDENCE SYNTHESIS: Studies have indicated that the mitochondrial mutations A3243G, A1555G, and A7445G play no significant part in the development of hearing loss in Iran. Different variants of A7445C and G3316A have been identified in Iran. CONCLUSIONS: Further studies on other ethnicities and with a larger sample size are necessary to elucidate the role of these genes in hearing loss development in Iran

Proceedings- Computer Aided Molecular Modeling of Membrane Metalloprotease

Matrix metalloproteinases (MMP) are crucial for homeostasis (tissue remodelling and repair, bone growth, wound healing, etc.) and pathology (metastasis, angiogenesis, aneurysm rupture, etc.). Upregulated MMPs from macrophages are thus a two-edged sword, playing both defensive and aggressive roles. The related family of ADAMs (a disintegrin and a metalloproteinase) is sometimes overlooked because of classification peculiarities. The best-studied ADAM-17, tumor necrosis factor a convertase (TNF-a), is a membrane-bound "shedase" that releases a membrane-bound cytokine, tumor necrosis factor a (TACE). Many of the ADAMs have remarkable structural and mechanistic and inhibitor proclivities similar to the MMPs; the potential for inhibitor side reactions and drug toxicities abounds. Over the past 10 years the crystallographic study of proMMPs, MMPs, and ADAMs in free and complexed forms has revealed the mechanistic and structural nature of these macromolecules to atomic resolution. These results will be reviewed and indications for future work will be presented. Special attention will be given to visualization tools to assist with the conceptualization of complex molecular interactions. (Support provided by the Robert A. Welch Foundation, the US National Science Foundation, and the R.W. Johnson Pharmaceutical Research Institute). Powerpoint presentation available in PDF format onl

Toxicity of Peganum harmala: Review and a Case Report

Peganum harmala   L. is a plant, which grows in semi-arid rangeland. The plant is used traditionally as an emmenagogue and an abortifacient agent in the Middle East and North Africa. All parts of plant are thoughtto be toxic and sever intoxication occurs in domestic animals. Digestive and nervous syndromes have been observed in animals that consume sub-lethal amount of the plant. The toxicated animal appears in a narcotic state interrupted by occasional short period of excitement. Abortion is frequent in animals that digest this plant in a dry year. While this plant has traditionally been used in Middle East, it shows toxic effects in human. A case of human overdose with P. harmala seeds is reported in this paper. Symptomsexperienced by our patient found to be similar to what has been reported for domestic animals

An image processing technique for diagnosis of Alzheimer's disease

<ul><li><strong>BACKGROUND</strong>: Patients with Alzheimer's disease (AD) reportedly hibit hypersensitivity to much diluted tropicam solution (0.005%), a M4 muscarinic receptor antagonist. Therefore aocular application of 0.005% tropicamide ma be useful for screening dementia. The aim of this study was to simplify the pupil response test by using a new image analyzing system, which consists of a cheap, simple, and easy to use web-camera and a computer.</li><li><strong>METHODS</strong>: Intraocular tropicamide of 0.005% concentration was administered in 3 groups: Alzheimer's disease patients (n = 8, average age = 76 ± 5), non-Alzheimer's disease elderly (n = 6, average age = 65 ± 7), and young subjects (n = 8, average age = 28 ± 5). Every 5 minutes for 60 minutes, image of the eye's shape were taken, and the diameter of the pupils was measured.</li><li><strong>RESULTS</strong>: The results showed that differences in pupil dilation rate between Alzheimer's disease and non-Alzheimer's disease subjects were statistically significant. ROC analysis showed that after 35 minutes the sensitivity and specificity of the test were 100%.</li><li><strong>CONCLUSIONS</strong>: Based on our results, we concluded that this recording system might be an appropriate and reliable tool for pupil response diagnosis test of Alzheimer's disease.</li><li><strong>KEYWORDS</strong>: Alzheimer’s Disease, Tropicamide, Pupil.</li></ul&gt