Assessment of fertility among mustard-exposed residents of Sardasht, Iran: a historical cohort study

BACKGROUND: Mustard gas (HD) is an alkylating agent with mutagenic and carcinogenic effects. Previous reports have demonstrated the ability of this class of compounds to cause adverse reproductive effects, however as of the time of this writing, few correlations have been established between HD exposure and human infertility. In the present study we hypothesize that infertility among mustard-exposed individuals is higher than among the general population. METHODS: 117 couples, 90 with at least one partner, and 27 with both partners exposed to HD in June 1987, were evaluated for occurrence of infertility (defined as the failure to conceive after 12 months of unprotected intercourse). Two groups of subjects were considered in order to establish dose-responsive effect of HD on fertility. One cohort was married at the time of exposure and were evaluated in a time period 12 months from that date. The second cohort married after the date of exposure and each couple was evaluated for a year during a period following marriage. Measurements of these subjects were compared with worldwide incidence of fertility. RESULTS: A 7.5% rate of infertility was observed among couples who were married at the time of exposure; and a rate of 10.3% was noted among individuals single at exposure and subsequently married, for an overall rate of 8.3%, which compares with a worldwide rate of 10-15%. Conclusions: This study showed that within a population of HD-exposed individuals, elevated environmental levels of the agent during a time period in which couples were actively attempting to conceive, failed to correlate with increased risk of infertility. However, these results must be interpreted with caution based on experimental design which limits the definition of infertility to one 12 month time period.     

Cell surface association of matrix metalloproteinase-9 (gelatinase B)

Matrix metalloproteinase (MMP)-9 (gelatinase B) belongs to the MMP family of zinc-dependent endopeptidases that has been associated with tumor cell invasion and metastasis and tumor-induced angiogenesis. As a secreted MMP, pro-MMP-9 is released into the extracellular environment by both tumor and stroma cells, where it fulfills its proteolytic functions degrading both extracellular matrix (ECM) and non-ECM proteins. A major dilemma in our understanding of MMP-9 function is how the released protease is targeted to the right location and how its activity is controlled at the pericellular space. It has been proposed that MMP-9 interact with cell surface components and that this type of interaction positively regulates enzymatic activation and activity. However, recent evidence shows that association of MMP-9 with the cell surface is mediated by a distinct array of surface proteins that serve to regulate multiple aspects of the enzyme function including localization, inhibition and internalization. How these distinct mechanisms regulate the overall MMP-9 activity at the pericellular space remains an important goal in our understanding of MMP-9 function at the cell surface. Furthermore, the study of surface-associated MMP-9 imposes new conceptual and methodological challenges with particular consideration to the unique structural and functional characteristics of this key enzyme.     

Effect of Normal Saline Infusion on the Diagnostic Utility of Base Deficit in Identifying Major Injury in Trauma Patients

Background
Base deficit (BD) is a reliable marker of metabolic acidosis and is useful in gauging hemorrhage after trauma. Resuscitation with chloride-rich solutions such as normal saline (NS) can cause a dilutional acidosis, possibly confounding the interpretation of BD.
Objectives
To test the diagnostic utility of BD in distinguishing minor from major injury after administration of NS.
Methods
This was a prospective observational study at a Level 1 trauma center. The authors enrolled patients with significant mechanism of injury and measured BD at triage (BD-0) and at four hours after triage (BD-4). Major injury was defined by any of the following: injury severity score of ≥15, drop in hematocrit of ≥10 points, or the patient requiring a blood transfusion. Patients were divided into a low-volume (NS < 2L) and a high-volume (NS ≥ 2L) group. Data were reported as mean (±SD). Student's t- and Wilcoxon tests were used to compare data. Receiver operating characteristic (ROC) curves tested the utility of BD-4 in differentiating minor from major injury in the study groups.
Results
Four hundred eighty-nine trauma patients (mean age, 36 [± 18] yr) were enrolled; 82% were male, and 34% had penetrating injury. Major-(20%) compared with minor-(80%) injury patients were significantly (p = 0.0001) more acidotic (BD-0 mean difference: −3.3 mmol/L; 95% confidence interval [CI] =−2.5 to −4.2). The high-volume group (n = 174) received 3,342 (±1,821) mL, and the low-volume group (n = 315) received 621 (±509) mL of NS. Areas under the ROC curves for the high-volume (0.63; 95% CI = 0.52 to 0.74) and low-volume (0.73; 95% CI = 0.60 to 0.86) groups were not significantly different from each other.
Conclusions
Base deficit was able to distinguish minor from major injury after four hours of resuscitation, irrespective of the volume of NS infused.     

A review of key challenges of electrospun scaffolds for tissue‐engineering applications

Tissue engineering holds great promise to develop functional constructs resembling the structural organization of native tissues to improve or replace biological functions, with the ultimate goal of avoiding organ transplantation. In tissue engineering, cells are often seeded into artificial structures capable of supporting three‐dimensional (3D) tissue formation. An optimal scaffold for tissue‐engineering applications should mimic the mechanical and functional properties of the extracellular matrix (ECM) of those tissues to be regenerated. Amongst the various scaffolding techniques, electrospinning is an outstanding one which is capable of producing non‐woven fibrous structures with dimensional constituents similar to those of ECM fibres. In recent years, electrospinning has gained widespread interest as a potential tissue‐engineering scaffolding technique and has been discussed in detail in many studies. So why this review? Apart from their clear advantages and extensive use, electrospun scaffolds encounter some practical limitations, such as scarce cell infiltration and inadequate mechanical strength for load‐bearing applications. A number of solutions have been offered by different research groups to overcome the above‐mentioned limitations. In this review, we provide an overview of the limitations of electrospinning as a tissue‐engineered scaffolding technique, with emphasis on possible resolutions of those issues. Copyright © 2015 John Wiley & Sons, Ltd.     

Cell‐mediated immune responses to α‐fetoprotein and other antigens in hepatocellular carcinoma

Cell‐mediated immune responses play an important role in the control of tumour growth. CD4 and CD8 T cells recognise tumour antigens presented via major histocompatibility complex molecules of antigen presenting cells and develop into effector cells with the ability to identify and kill tumour cells. Here, we re‐examine the adaptive immune response to tumour antigens expressed by hepatocellular carcinoma (HCC) and discuss approaches that could be applied in future T‐cell‐based immunotherapy schedules to induce a potent and effective antitumour immunity. Moreover, we discuss cytotoxic T lymphocyte and Th1 responses to tumour antigens in patients with HCC and evaluate the effects of conventional treatments on antitumour T‐cell responses.     

Induction of latency-associated peptide (transforming growth factor-β(1)) expression on CD4+ T cells reduces Toll-like receptor 4 ligand-induced tumour necrosis factor-α production in a transforming growth factor-β-dependent manner

CD4(+) T cells expressing the latent form of transforming growth factor-β [latency-associated peptide (LAP) (TGF-β(1))] play an important role in the modulation of immune responses. Here, we identified a novel peptide ligand (GPC(81-95) ) with an intrinsic ability to induce membrane-bound LAP (TGF-β(1)) expression on a subpopulation of human CD4(+) T cells (using flow cytometry; ranging from 0·8% to 2·6%) and stimulate peripheral blood mononuclear cells to release LAP (TGF-β(1) ) (using ELISPOT assay; ranging from 0·03% to 0·16%). In spite of this low percentage of responding cells, GPC(81-95) significantly reduced Toll-like receptor 4 ligand-induced tumour necrosis factor-α production in a TGF-β(1) - and CD4(+) T-cell-dependent manner. The results demonstrate that GPC(81-95) is a useful tool to study the functional properties of a subpopulation of LAP (TGF-β(1))(+) CD4(+) T cells and suggest a pathway that can be exploited to suppress inflammatory response.