Diphtheria toxoid-containing microparticulate powder formulations for pulmonary vaccination: preparation, characterization and evaluation in guinea pigs

In this study, the potential of N-Trimethyl chitosan (TMC, degree of quaternization 50%) and dextran microparticles for pulmonary delivery of diphtheria toxoid (DT) was investigated. The antigen-containing microparticles were prepared by drying of an aqueous solution of polymer and DT through a supercritical fluid (SCF) spraying process. The median volume diameter of the dry particles, as determined by laser diffraction analysis, was between 2 and 3 microm and the fine particle mass fractions smaller than 5 microm, as determined by cascade impactor analysis, were 35 and 56% for the dextran and TMC formulations, respectively. The water content of the particles as measured by Karl-Fischer titration was 2-3% (w/w). Pulmonary immunization with DT-TMC microparticles containing 2 or 10 Lf of DT resulted in a strong immunological response as reflected by the induction of IgM, IgG, IgG subclasses (IgG1 and IgG2) antibodies as well as neutralizing antibody titers comparable to or significantly higher than those achieved after subcutaneous (SC) administration of alum-adsorbed DT (2 Lf). Moreover, the IgG2/IgG1 ratio after pulmonary immunization with DT-TMC microparticles was substantially higher as compared to SC administered alum-adsorbed DT. In contrast, pulmonarily administered DT-dextran particles were poorly immunogenic. Among the tested formulations only pulmonarily administered DT-containing TMC microparticles induced detectable pulmonary secretory IgA levels. In conclusion, in this paper it is demonstrated that TMC microparticles are a potent new delivery system for pulmonary administered DT antigen.     

Evaluation of the efficacy of topical sucralfate on healing haemorrhoidectomy incision wounds and reducing pain severity: A randomised clinical trial

The healing of haemorrhoidectomy wounds is a main concern of surgeons and patients. Various modalities can improve the quality of wound care after surgery. Antibiotics and topical agents, such as solutions and ointments, have been evaluated. The current research investigates the effects of sucralfate ointment on wound healing (epithelialisation) and postoperative pain after open haemorrhoidectomy. This trial involves two groups of randomly collected patients (n = 40) who underwent open haemorrhoidectomy surgery by the Milligan‐Morgan method. A 10% topical sucralfate ointment was applied to the investigated group''s wounds, while the control group patients used Vaseline as a placebo. The present work measured the two outcomes as follows: pain severity by a Visual Analogues Scale (VAS) score and epithelialisation by a surgeon''s visual inspection. During the postoperative phase, the mean VAS was 3.70 for the investigated group and 6.90 for the control group. On the average, the completion of epithelialisation for the investigated group was on day 13 as opposed to day 20 for the control group. The topical application of sucralfate ointment on post‐haemorrhoidectomy wound is an effective method for the promotion of healing, also lessens the severity of pain, and reduces the need for analgesics.     

Interstitial lung disease in polymyositis and dermatomyositis: longitudinal evaluation by pulmonary function and radiology

OBJECTIVE: To estimate predictors and long-term outcome of interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM). METHODS: We conducted a prospective study in which newly diagnosed PM/DM patients, regardless of clinical symptoms of pulmonary disease, were investigated with repeated chest radiography, high-resolution computed tomography (HRCT) of the lungs, and pulmonary function test (PFT). Clinical, radiologic, and lung function outcome was based on the last followup results. RESULTS: Twenty-three patients with a mean followup period of 35 months were included. Findings on radiographic examination and/or PFT compatible with ILD were recorded in 18 patients (78%). Patients with ILD had lower lung function, higher radiologic scores, and higher creatine kinase values than those without ILD. All patients were treated with high-dose glucocorticoids and other immunosuppressive agents. Two patients died due to ILD, both with active myositis. During the followup, total lung capacity (TLC) improved in 33%, remained stable in 39%, and deteriorated in 28%. Changes in TLC correlated only partially with HRCT findings, which persisted even after normalizing for lung function. CONCLUSION: ILD associated with PM/DM is in most cases mild, chronic, and has a nonprogressive course during immunosuppressive treatment. PFT can be normalized during treatment with immunosuppressive therapy, even if radiologic signs of ILD persist. The course of ILD could not be predicted on the first examination. Therefore, myositis patients with ILD need careful evaluation of clinical features as well as PFT and radiologic features during followup.     

Heart and lung organ offer acceptance practices of transplant programs are associated with waitlist mortality and organ yield

Variation in heart and lung offer acceptance practices may affect numbers of transplanted organs and create variability in waitlist mortality. To investigate these issues, offer acceptance ratios, or adjusted odds ratios, for heart and lung transplant programs individually and for all programs within donation service areas (DSAs) were estimated using offers from donors recovered July 1, 2016, and June 30, 2017. Logistic regressions estimated the association of DSA‐level offer acceptance ratios with donor yield and local placement of organs recovered in the DSA. Competing risk methodology estimated the association of program‐level offer acceptance ratios with incidence and rate of waitlist removals due to death or becoming too sick to undergo transplant. Higher DSA‐level offer acceptance was associated with higher yield (odds ratios [ORs]: lung, _1.041.11_1.19; heart, _1.091.21_1.35) and more local placement of transplanted organs (ORs: lung, _1.011.12_1.24; heart, _1.471.69_1.93). Higher program‐level offer acceptance was associated with lower incidence of waitlist removal due to death or becoming too sick to undergo transplant (hazard ratios [HRs]: heart, _0.800.86_0.93; lung, _0.670.75_0.83), but not with rate of waitlist removal (HRs: heart, _0.910.98_1.06; lung, _0.890.99_1.10). Heart and lung offer acceptance practices affected numbers of transplanted organs and contributed to program‐level variability in the probability of waitlist mortality.     

Correlation between ST segment shift and cardiac diastolic function in patients with acute myocardial infarction

Background

Diastolic dysfunction is the early sign of myocardial ischemia that usually occurs earlier than ECG changes.

Selective immunoglobulin A deficiency in Iranian blood donors: prevalence, laboratory and clinical findings

Selective deficiency of immunoglobulin A (IgA) is the most frequent primary hypogammaglobulinemia. As some IgA-deficient patients have IgA antibodies in their plasma which may cause anaphylactic reactions, blood centers usually maintain a list of IgA-deficient blood donors to prepare compatible blood components. In this study we determined the incidence of selective IgA deficiency (SIgAD) in normal adult Iranian population. 13022 normal Iranian blood donors were included in this study. The assay which we used was adapted to the manual pipetting system and ELISA reader was used for screening. Other classes of immunoglobulins (G, M), as well as secretory IgA and IgG subclasses were tested in IgA deficient cases by ELISA. SPSS was used for statistical analysis.Among 13022 studied cases, 11608 blood donors were males (89.14%) and 1414 were females (10.86%). Their mean (+/-SD) age and weight were 38.5+/-11 years and 82+/-12 Kg respectively. Twenty of the screened samples were found by means of ELISA to be IgA-deficient (less than 5mg/dl), (frequency; 1:651). The data could indicate a compensation for IgA deficiency by serum IgM in one of our IgA deficient cases (Patient 5). We observed a correlation between IgG3 and serum IgA in deficient cases (r=0.498, P=0.025). Our results indicate that in present study the prevalence of S IgA D is in agreement with data from other Caucasians populations (from 1:300 to 1:700). In conclusion, Selective IgA Deficiency could be almost asymptomatic in most cases in general population. Our study suggests that; due to high frequency of IgA deficiency in Iran, it seems necessary to measure IgA levels for every blood donor and blood recipient to find IgA deficient cases.     

Ankylosing spondylitis monocyte-derived macrophages express increased level of A<Subscript>2A</Subscript> adenosine receptor and decreased level of ectonucleoside triphosphate diphosphohydrolase-1 (CD39), A<Subscript>1</Subscript> and A<Subscript>2B</Subscript> adenosine receptors

Macrophages play an important role in the ankylosing spondylitis (AS) auto-inflammatory responses and fibrocartilage destruction. Adenosine is a key modulator of inflammatory conditions. The various effects of adenosine are mediated by its interaction with adenosine receptors (AR). In this study, we investigated the mRNA expression of A₁, A_2A, A_2B, and A₃ adenosine receptors, ectonucleoside triphosphate diphosphohydrolase-1 (CD39), and ecto-5′-nucleotidase (CD73) in the monocyte-derived macrophages from AS patients in comparison to healthy controls. We also explored the correlation between analyzed gene expression and patients’ clinical manifestations. Whole blood-separated monocytes from 23 healthy controls and 23 active AS patients were stimulated by macrophage colony-stimulating factor (M-CSF) for 7 days and differentiated to macrophages. Monocyte and macrophage markers were analyzed by flow cytometry. Analysis of adenosine receptors (ADORA1? ADORA2A? ADORA2B? ADORA3), CD39 and CD73 gene expression was performed by SYBR green real-time PCR. Our results demonstrated monocyte-derived macrophages from AS patients expressed increased level of A_2AAR and reduced level of A₁, A_2BAR, and CD39 mRNA compared to healthy controls. We found an inverse correlation between A_2AAR mRNA expression and Bath Ankylosing Spondylitis Functional Index (BASFI) score in AS patients. According to our results, altered expression level of adenosine-relying system would be involved in AS macrophage dysfunction and inflammation and correlated with functional status in AS patients.     

Physiologic role of decidual beta1 integrin and focal adhesion kinase in embryonic implantation

Implantation refers to a series of interactions between embryo and endometrium including hatching, attachment, and outgrowth. We investigated the expression and function of beta1 integrin and focal adhesion kinase (FAK) in human decidual cells during implantation. Immunofluorescent staining localized beta1 integrin to surfaces of cultured decidual cells. Double staining for beta1 integrin and mediators of intracellular signaling involving beta1 integrin, such as FAK and vinculin, colocalized beta1 integrin with these substances, suggesting that human decidual cells express beta1 integrin in the focal adhesion region. We next investigated the actions of beta1 integrin and FAK in implantation by co-culturing mouse embryos and human decidual cells. Mouse blastocysts attached to cultured decidual cells after embryo hatching, usually within 24 h of culture initiation. Blastocysts attached to decidual cells exhibited extensive outgrowth at 48 h. Treatment of decidual cells with an antibody against beta1 integrin or with an antisense FAK oligonucleotide did not affect hatching or attachment of blastocysts, but either one could inhibit outgrowth. Thus, it was concluded that human decidual beta1 integrin and FAK participate in this final step of implantation.