Properties of the amniotic membrane for potential use in tissue engineering

An important component of tissue engineering (TE) is the supporting matrix upon which cells and tissues grow, also known as the scaffold. Scaffolds must easily integrate with host tissue and provide an excellent environment for cell growth and differentiation. Most scaffold materials are naturally derived from mammalian tissues. The amniotic membrane (AM) is considered an important potential source for scaffolding material. The AM represents the innermost layer of the placenta and is composed of a single epithelial layer, a thick basement membrane and an avascular stroma. The special structure and biological viability of the AM allows it to be an ideal candidate for creating scaffolds used in TE. Epithelial cells derived from the AM have the advantages of stem cells, yet are a more suitable source of cells for TE than stem cells. The extracellular matrix components of the basement membrane of the AM create an almost native scaffold for cell seeding in TE. In addition, the AM has other biological properties important for TE, including anti-inflammatory, anti-microbial, anti-fibrosis, anti-scarring, as well as reasonable mechanical property and low immunogenicity. In this review, the various properties of the AM are discussed in light of their potential use for TE

Anti-Inflammatory Effects of Morphine on Carrageenan Iinduced Hind Paw Edema in Mice Model of Aacute Inflammation

Background: Using the systemic opioids in pain relief has been known during the history. Several evidences indicate that exogenous opioids such as morphine can produce anti-nociceptive effects by interacting with local opioid receptors in peripheral inflamed tissues; in addition to analgesic effects of morphine, less clear is potential anti-inflammatory effects of it. Materials and Methods: In the present study we examined effects of intra-peritoneal (i.p.) injection of morphine (7 mg/kg) on carrageenan (0.05 ml, 3% W/V in saline) induced paw edema in mice. Results: Carrageenan induced paw edema were measured by mercury plethysmometer and was maximal at hour 3 and pretreatment with morphine could reduce the edema significantly. At the same time the serum levels of interleukin-1 alpha (IL-1α) were increased. Pretreatment with naloxone (2&10 mg/kg, i.p.) at 45 min before and 165 min after carrageenan, respectively, blocked the effects of morphine sulfate on edema in each groups. Pretreatment with naloxone abolished morphine anti-inflammatory while decreased IL-1α serum levels, significantly. Although, administration of anti mouse IL-1α (7, 14 & 28 µg/mice, i.p.) abolished morphine anti-inflammatory effects. Conclusion: These findings showed that increase in serum levels of IL-1α play important roles in anti-inflammatory effect of morphine. The results indicated that morphine exert significant anti-inflammatory activity. Presumably, the anti-inflammatory action of morphine may be due to change on the cytokine production and/or release by host immune system

Increase in formalin-induced tonic pain by 5alpha-reductase and aromatase inhibition in female rats

Little is known about the role of steroidogenic enzymes in pain modulation. This study examined the effects of 5α-reductase and aromatase inhibition on formalin-induced tonic pain (FITP) in adult female rats. The animals received subcutaneous injection (5 mg/kg) of finasteride (an inhibitor of 5α-reductase) and letrozole (an inhibitor of aromatase), either separately or in combination, 15 min before formalin injection at a low (0.25%) and high (2.5%) concentration. Pretreatment with inhibitors increased FITP evoked by injection of 0.25% formalin, but they were not effective on 2.5% formalin pain. The enhancing effects of finasteride and letrozole on FITP induced by 2.5% formalin was demonstrated by inhibitory actions of these drugs on morphine (7 and 10 mg/kg, intraperitoneal) induced antinociception. The nervous system could be considered as the main target of the enzymes inhibition, since the pronociceptive effect was also observed after administration of inhibitors to ovariectomized rats. Altogether, these findings suggest that the biological activity of the enzymes 5α-reductase and aromatase modulates FITP and may help to develop effective therapeutic strategies to counteract pain. © 2010 Elsevier Inc

A simple, low cost and fast improved fluorimetric method for Histamine measurement

The well-known fluorimetric method for histamine measurement which is one of the common methods in diagnostic laboratories was modified to accelerate and facilitate measurement of serum histamine levels and decrease the costs and restrictions. The modified method needs only 1 ml of whole blood (or serum) instead of about 10 ml in original method which is difficult almost or impossible specially for children. In addition, very small amounts of the expensive materials are needed and the samples are saved for about 15 days in -20°C which makes no significant changes. Because in most cases, sample can not be read at sampling day, the saving possibility is an advantage for improved method

NEUROPEPTIDES (SP AND CGRP) AUGMENT IL-1 BETA PRODUCTION IN HSV-INFECTED MACROPHAGES

Neuropeptides, possessing specific and functional receptors on various cells of the immune system, have the potential to regulate immune responses; and the macrophages as important components of defense against various agents, are at their influence. In this study the effect of neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) on IL-1 beta production by herpes sim¬plex type-1 (HSV-1 )-infected and also uninfected mouse peritoneal macrophages were considered. Each neuropeptide separately has upregulated IL-1 beta produc¬tion by HSV-1 infected macrophages with the greatest effect at the concentrations of 10'9M for both SP and CGRP, but no synergistic effect on IL-1 production has been observed in the presence of both neuropeptides at optimal concentrations. IL-ip production by uninfected macrophages was also moderately enhanced in the presence of each neuropeptide, but not in the presence of both neuropeptides simultaneously. It can be concluded that IL-1 S3 production, which is part of mac¬rophage mediated inflammatory response to HSV-1, is enhanced by specific doses of neuropeptides

Association of serotonin receptor 2a haplotypes with obsessive–compulsive disorder and its treatment response in Iranian patients: a genetic and pharmacogenetic study

Marzie Sina,1 Abolhassan Ahmadiani,1 Sareh Asadi,2 Jamal Shams3 1Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Behavioral Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Introduction: Obsessive–compulsive disorder (OCD) is a debilitating psychiatric disorder causing intrusive thoughts or repetitive behaviors. Serotonin reuptake inhibitors are used for OCD treatment, but 40%–60% of patients do not respond to them adequately. In this study, the associations of serotonin receptor 2a polymorphisms rs6311 and rs6313 with OCD, its familial form and fluvoxamine treatment response in Iranian population were investigated. Patients and methods: Association analyses were conducted in 293 OCD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR and 245 controls. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150–300 mg). Treatment response was considered as >25% reduction in Yale–Brown Obsessive Compulsive Scale score. Genotyping was performed by means of PCR-RFLP. Results: The results showed no association of rs6311 or rs6313 with OCD, but their haplotypes had different distribution patterns in cases and controls. Moreover, rs6313 was associated with the familial form of OCD in females significantly (P=0.005) under the recessive genetic model. Moreover, rs6311–rs6313 haplotypes were associated with fluvoxamine treatment response in OCD patients with more AC and less AT in responders. Conclusion: HTR2A haplotypes are associated with OCD and its treatment response with a fluvoxamine in Iranian patients. Furthermore, the observed association of rs6313 with the familial form of OCD in females suggests different genetic background of OCD familial and non-familial forms, which needs further investigation. Keywords: family history, fluvoxamine, treatment response, rs6311, rs631

Lack of bioequivalence between two aciclovir tablets in healthy subjects

Objective: This study aimed to compare the systemic bioavailability of two aciclovir tablets, Rouz-Aciclovir (test) and Zovirax® (reference), in 12 healthy volunteers. Methods: In a crossover design, each subject received a single oral dose of aciclovir 400 mg followed by a 7-day washout period. Plasma concentrations of aciclovir were measured for up to 12 hours using a validated high-performance liquid chromatography method with a lower limit of quantification of 50 μg/L. Results: The mean values of maximum plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve from time 0 to 12 hours (AUC12) and from time 0 to infinity (AUC∞), and plasma half-life following administration of the test product were 999.6 μg/L, 2.08 h, 4911.2 μg/L • h, 5417.7 μg/L • h and 3.08 h, respectively, and for the reference product 775.8 μg/L, 2.58 h, 3862.1 μg/L • h, 4295.4 μg/L • h and 3.14 h, respectively. The test/reference geometric ratio for Cmax (90% CI) was 1.30 (97.1, 174.8). The test/reference geometric ratios for AUC12 (90% CI) and AUC∞ (90% CI) were 1.26 (99.7, 159.1) and 1.24 (98.9, 155.6), respectively. Therefore, the 90% CIs of Cmax, AUC12 and AUC∞ were not within the acceptable range of 80 and 125 suggested by the US FDA bioequivalence guideline. Conclusion: The results of the present study suggest that the aciclovir test product was not bioequivalent to the reference product. The exact reasons for this remain to be determined. However, we think the difference should be attributed to the difference in the type and amounts of ingredients used in the formulation that probably affect the contact time of aciclovir with the sites of absorption in the gut. © 2008 Adis Data Information BV. All rights reserved

Differentiation factors that influence neuronal markers expression in vitro from human amniotic epithelial cells

The differentiation of neural cells from embryonic stem cells is influenced by several growth factors. Amniotic epithelial cells (AECs) share many of the same characteristics as embryonic stem cells, and therefore those factors may similarly affect the derivation of neural cells from AECs. In this study, we examined the differentiation of neural cells in vitro from AECs following AECs treatment with retinoic acid (RA), basic fibroblast growth factor (bFGF) as well as investigation of bFGF withdrawal on neuronal differentiation. We also studied whether blocking bone morphogenetic protein (BMP) signaling using its antagonist, noggin, affects the derivation of neuronal cells from AECs. The effects of serum on the rate of neural markers expression were also examined. Analysis of AECs derived neurons was performed at some neural markers expression level by immunocytochemistry. All cultures treated with noggin showed the higher levels of neural markers expression than noggin free cultures. Combined treatment with bFGF and RA showed the highest level of neural markers in all treatment groups with or without noggin. bFGF withdrawal did not promote expression of neural markers, while its maintenance increased the expression of these markers. Serum-free condition decreased the viability of cells but increased the rate of neural markers expression. These results show the capability of AECs to express neural cell markers and this ability is affected by some factors including serum, noggin, bFGF and RA