Exposure to a farming environment has allergen-specific protective effects on TH2-dependent isotype switching in response to common inhalants

BACKGROUND: IgE synthesis by human B cells results from allergen-dependent, T(H)2-mediated isotype switching. Exposure to a farming environment protects against IgE responses. OBJECTIVE: We reconstructed allergen-dependent switching patterns in vivo to identify the level or levels at which farm exposure acts to protect against atopy. METHODS: Serum IgG1 to IgG4 and IgE to grass (rPhl p 1 and rPhl p 5), cat (rFel d 1), and mite (rDer p 2) were assessed by means of ELISA in the Allergy and Endotoxin study population (812 children). Farm exposure was defined as currently living on a farm, exposure to stables/farm milk in the first year of life, or both. RESULTS: Farm exposure did not affect allergen-specific IgG2 and IgG3 levels but had complex allergen-specific effects on IgG1, IgG4, and IgE levels. Exposure protected against grass-specific responses at every step along the IgG1/IgG4/IgE switching pathway but had no significant effect on mite responses. Protection from cat responses was concentrated at the IgG1 level. For all allergens, failure to express IgG1 was associated with low prevalence of IgG4 or IgE responses. Notably, coexpression of IgG1, IgG4, and IgE to grass was associated with increased risk of allergic disease and higher IgE levels compared with production of IgG1 and IgE without IgG4, suggesting IgG4 coexpression marks stronger activation of T(H)2-dependent events. CONCLUSION: The protective effects of farm exposure were confined to T(H)2-dependent IgG1, IgG4, and IgE expression and were allergen and switch stage specific, suggesting that distinct mechanisms regulate individual steps within allergen-induced class switching in vivo. CLINICAL IMPLICATIONS: Environmental interventions to prevent IgE expression might need to be tailored to specific allergens.     

Release studies of undecylenoyl phenylalanine from topical formulations

The aim of this study was to characterize the stability of new vehicles for the undecylenoyl phenylalanine that is used as skin-lightening agent in the melasma treatment. The purpose of this research was also to analyse the release kinetics of phenylalanine derivative from topical preparations through different synthetic membranes. Topical formulations such as two different macroemulsions, hydrogels (based on carbomer and hydroxyethylcellulose) and microemulsions were characterized in terms of stability by laser diffraction method. Additionally, multiple light scattering assessed the stability of macroemulsions. The release rates of active substance through different membranes (such as Cuprophan, nitrocellulose, cellulose acetate and Strat-M) were determined using enhancer cell. In order to explain the mechanism of release process the results were fitted with different kinetic models. New stable vehicles for Ude-Phe were successfully obtained. The results proved that the membrane structure had the influence on the release rate of undecylenoyl phenylalanine. The slowest release rate of Ude-Phe was observed when Strat-M membrane was applied. The highest amount of active substance was released from the hydrogel based on carbomer. The release of undecylenoyl phenylalanine from both macroemulsions and hydrogel based on hydroxyethylcellulose followed the Higuchi model. Whereas the release results of Ude-Phe from both microemulsion-based hydrogels and carbomer hydrogel can be described by using Korsmeyer-Peppas model. Hydrogels and microemulsion-based hydrogels could be recommended as proper vehicles for the derivative of phenylalanine.     

Effect of long-term administration of ranitidine,a histamine H2 receptor antagonist,on bone metabolism in young growing rats

Background

Histamine regulates function of osteoclasts and osteoblasts, however data regarding the influence of histamine H2 receptors antagonists on bone tissue are ambiguous. Factors that influence growing skeleton may have an important impact on the peak bone mass and future risk of fractures. The aim of our study was the assessment of influence of ranitidine, on growing bones.

Triple (GGTA1, CMAH,B2M) modified pigs expressing an SLA class Ilow phenotype—Effects on immune status and susceptibility to human immune responses

Porcine xenografts lacking swine leukocyte antigen (SLA) class I are thought to be protected from human T cell responses. We have previously shown that SLA class I deficiency can be achieved in pigs by CRISPR/Cas9‐mediated deletion of β₂‐microglobulin (B2M). Here, we characterized another line of genetically modified pigs in which targeting of the B2M locus did not result in complete absence of B2M and SLA class I but rather in significantly reduced expression levels of both molecules. Residual SLA class I was functionally inert, because no proper differentiation of the CD8⁺ T cell subset was observed in B2M^low pigs. Cells from B2M^low pigs were less capable in triggering proliferation of human peripheral blood mononuclear cells in vitro, which was mainly due to the nonresponsiveness of CD8⁺ T cells. Nevertheless, cytotoxic effector cells developing from unaffected cell populations (eg, CD4⁺ T cells, natural killer cells) lysed targets from both SLA class I⁺ wildtype and SLA class I^low pigs with similar efficiency. These data indicate that the absence of SLA class I is an effective approach to prevent the activation of human CD8⁺ T cells during the induction phase of an anti‐xenograft response. However, cytotoxic activity of cells during the effector phase cannot be controlled by this approach.     

Correlations Between Demographics,Knowledge, Beliefs,and Attitudes Regarding Organ Transplantation Among Academic Students in Poland and Their Potential Use in Designing Society-wide Educational Campaigns

Background

Family objection precludes 10% of cadaveric donations in Poland. Academic students represent a socially influential demographic group. Educational campaigns improving their attitudes may increase overall donation rates. The aim of this study was to assess correlations between knowledge, beliefs, and attitudes regarding organ transplantation and the identification of the most critical factors affecting one's donation preferences.

Methods

Eight hundred students from 4 public universities in Krakow, Poland, participated in the study; participants were diverse in age, sex, hometown population, and academic discipline (400 medical, 400 non-medical). This cross-sectional study was conducted with the use of a group-administered questionnaire inquiring into demographics, general and professional knowledge, beliefs, and attitudes toward organ transplantation.

Results

Attitudes toward organ donation correlate positively with beliefs (ρ = 0.36), general knowledge (ρ = 0.48), and professional knowledge (ρ = 0.23) scores. Beliefs were proven to correlate with general (ρ = 0.21) and professional (ρ = 0.26) knowledge as well. Misconceptions about the medical criteria allowing cadaveric organ recovery, distrust for brain death reliability, fear of “do not resuscitate” approach toward Organ Donor Card holders, a strong belief in organ trafficking, and unawareness of family members' attitudes are the most important factors influencing one's refusal/uncertainty to donate.

Conclusions

Knowledge, attitudes, and refusal rates differ, depending on the academic discipline as well as other demographics, indicating a need for a specifically targeted approach in designing educational campaigns. Sources of knowledge are related to donation rates, with pre-academic education evaluated as unfavorable, as opposed to healthcare providers and the media.     

Dopamine and Noradrenaline Are Unrelated to Renalase,Heart Rate,and Blood Pressure in Heart Transplant Recipients

Introduction

Renalase may degrade catecholamines and regulate sympathetic tone and blood pressure. The aim of this study was to assess dopamine, norepinephrine, and renalase in 80 heart transplant recipients and 22 healthy volunteers and their correlations with heart rate, blood pressure control, type of hypotensive therapy, and renal function.

Patients and Methods

Renalase, dopamine, and norepinephrine were studied by using commercially available assays.

Results

Renalase levels were higher in heart transplant recipients compared with healthy volunteers, and noradrenaline levels were lower in the studied cohort patients than in the healthy volunteers. Noradrenaline was correlated with white blood cell count (r = −0.21, P < .05), copeptin (r = 0.41, P < .01), and left ventricular diameter (r = −0.29, P < .05), whereas dopamine was correlated in univariate analysis with white blood cell count (r = −0.22, P < .05), posterior wall of left ventricular diameter (r = 0.58, P < .01), and left atrium diameter (r = −0.31, P < .05). Neither noradrenaline nor dopamine was correlated with heart rate, blood pressure, kidney function, or New York Heart Association class. Noradrenaline was significantly higher in patients with elevated diastolic blood pressure (>90 mm Hg) compared with those with normal diastolic blood pressure (P < .05). Renalase was related to kidney function but was unrelated to catecholamines.

Conclusions

Elevated renalase levels in heart transplant patients were related to kidney function but not linked to the sympathetic nervous system activity in this study population. In heart transplant recipients, these findings might suggest that sympathetic denervation and the modulation of β-receptors persist.     

Inadequate Blood Pressure Control in Orthotopic Heart Transplant: Is There a Role of Kidney Function and Immunosuppressive Regimen?

Introduction

Cardiac transplantation is the definitive therapy for eligible patients with end-stage heart failure. Hypertension is a widely accepted risk factor for its outcome.

Patients and Methods

We analyzed 169 heart transplant recipients. The diagnosis of hypertension was made on the basis of information gathered at 3 consecutive visits. Complete blood count, urea, serum lipids, fasting glucose, creatinine, and N-terminal pro–B-type natriuretic peptide were also studied.

Results

In the orthotopic heart transplantation (OHT) population, 11% had diabetes and 68% had chronic kidney disease. Hypertension was diagnosed and treated in 68% of the OHT patients. Hypertensive patients were significantly older, with a lower estimated glomerular filtration rate and higher serum creatinine and erythrocyte count. Thirty-three percent of patients did not achieve target blood pressure despite optimal medical treatment. Patients treated with tacrolimus had similar systolic blood pressure compared with those treated with cyclosporine (with a tendency to have lower values). Patients treated with mammalian target of rapamycin inhibitors had similar systolic and diastolic blood pressures compared with those treated without these inhibitors. In the group of patients given steroids, systolic and diastolic blood pressures were significantly lower than in the group not treated with steroids. In addition, steroid-treated patients had a significantly lower estimated glomerular filtration rate, hemoglobin, and erythrocyte count and higher serum creatinine, N-terminal pro–B-type natriuretic peptide, and New York Heart Association class. Chronic kidney disease was also more prevalent in this group. Blood pressure was not related to the kidney function.

Conclusions

Despite polytherapy, optimal blood pressure control was not achieved in the majority of patients. OHT patients have a high prevalence of hypertension, which should be treated adequately. More efforts should be made to optimize blood pressure control, particularly when other comorbidities are present. Blood pressure was not related to patient kidney function.     

Fibroblast Growth Factor 23 and Klotho as Cardiovascular Risk Factors in Heart Transplant Recipients

Background

Fibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality. Klotho is an essential coreceptor for FGF23 and at the same time it is known as a “longevity” hormone. There are no data considering FGF23 and Klotho roles in heart transplant (HT) recipients. The aim of this study was to assess Klotho and FGF23 serum concentration in heart transplant recipients depending on immunosuppressive therapy regimen and comorbidities.

Methods

Eighty-four stable heart transplant recipients were enrolled in the study; 22 healthy volunteers served as control subjects. FGF23 and Klotho protein concentration, markers of renal function, such as cystatin C and neutrophil gelatinase–associated lipocalin (NGAL), and heart failure markers, such as copeptine and N-termiinal pro–B-type natriuretic peptide (NT-proBNP), were evaluated.

Results

FGF23 concentration was significantly higher in the HT group whereas Klotho protein was significantly lower. FGF23 correlated with creatinine level (r = 0.72; P < .001), estimated glomerular filtration rate (eGFR; r = −0.32; P < .01), cystatin C (r = 0.36; P < .01), NGAL (r = 0.51; P < .001), hemoglobin (r = −0.39; P < .001), NT-proBNP (r = 0.51; P < .001), high-density lipoprotein (HDL; r = 0.27; P < .05), intraventricular septum thickness (r = 0.42; P < .01) and right ventricular systolic pressure (r = 0.34; P < .05). Klotho protein correlated only with age (r = −0.21; P < .05), creatinine (r = −0.21; P < .05), and eGFR (r = −0.31; P < .01). FGF23 concentration was significantly higher in patients with eGFR <60 mL/min whereas Klotho protein was significantly lower. FGF23 predictors were renal function (creatinine concentration; β = 0.45; P = .0001), HDL (β = 0.33; P = .003), intraventricular septum thickness (β = 0.38; P = .0003), and right ventricular systolic pressure (β = 0.34; P = .003), explaining 70% of FGF23 variability.

Conclusions

FGF23/Klotho system disorders in HT recipients are related to cardiovascular system function and kidney failure and could cause increased risk of cardiovascular disease.     

YKL-40, a Novel Marker of Cardiovascular Complications,Is Related to Kidney Function in Heart Transplant Recipients

Background

YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesions of atherosclerosis. Elevated serum YKL-40 levels are independently associated with the presence and extent of coronary artery disease and cardiovascular mortality. Because there are no data on heart transplant recipients and because they are prone to cardiovascular complications, the aim of this study was to assess YKL-40 in this population with particular attention to its relationship with endothelial damage. We studied 84 patients after heart transplantation. Healthy volunteers served as control subjects.

Methods

Complete blood count, urea, creatinine, lipids, fasting glucose, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and iron status were studied with the use of standard laboratory methods. We assessed YKL-40, copeptin, markers of inflammation high sensitivity C-reactive protein (hsCRP) and interleukin (IL) 6, and markers of endothelial cell injury von Willebrand factor (vWF) and midkine with the use of commercially available assays.

Results

Mean levels of YKL-40, IL-6, vWF, and hsCRP were significantly higher in heart allograft recipients than in the control group (P < .001). In univariate analysis, YKL-40 was related to kidney function (creatinine, r = 0.63 [P < .001]; estimated glomerular filtration rate, r = −0.44 [P < .001]), NT-proBNP (r = 0.45; P < .001), age (r = 0.33; P < .01), time after transplantation (r = 0.23; P < .05), copeptin (r = −0.42; P < .001), soluble transferrin receptor (r = 0.24; P < .05), hemoglobin (r = −0.42; P < .001), transferrin (r = −0.31; P < .01), haptoglobin (r = 0.39; P < .001), cystatin C (r = 0.55; P < .001), ejection fraction (r = −0.28; P < .05), New York Heart Association functional class (r = −0.41; P < .01), hsCRP (r = 0.26; P < .05), IL-6 (r = 0.23; P < .05), vWF (r = −0.40; P < .001), and midkine (r = 0.33; P < .01). In multivariate analysis, only creatinine was found to be a predictor of YKL-40 (β = 0.59; P = .02), explaining 56% of the variation in YKL-40 levels in heart allograft recipients.

Conclusions

YKL-40 may contribute to the enhanced risk of cardiovascular complications mainly owing to impaired renal function in patients after heart transplantation.     

Contamination Resulting From Aerosolized Fluid During Laparoscopic Surgery

Background and Objectives:

Aerosolized droplets of blood can travel considerable distances on release of intra-abdominal pressure during laparoscopic surgery. This creates an environmental hazard for members of the surgical team. This study describes and provides a method of measurement of aerosolized blood contamination during evacuation of the pneumoperitoneum in laparoscopic surgery.

Methods:

Samples were measured by removing a trocar from the abdomen while a pneumoperitoneum of 15 mm Hg was present. A white poster board was placed 24 inches above the incision to catch the released blood spatter. By use of machine vision, luminol fluorescence, and computerized spatial analysis, data from the boards were recorded, analyzed, and scored based on the distance, size, and quantity of particulate contamination.

Results:

We analyzed 27 boards. Spatter was present on every board. The addition of luminol to the boards increased the amount of visible spatter. Most tests created <1000 blood spatters. Fluids are typically ejected as a fine mist. Every test included at least 1 blood spatter. The range of the average blood spatter size was 0.53 × 10^–3 to 7.11 × 10^–3 sq in. The amount of spatter detected did not show any apparent correlation with the patient''s body mass index, the estimated blood loss, or the type of operation performed.

Conclusions:

Evacuation of the pneumoperitoneum during laparoscopic surgery results in consistent contamination. Most blood spatter is not visible to the naked eye. Our results suggest that all surgical participants should wear appropriate protective barriers and conscious measures should be undertaken to prevent environmental contamination during pneumoperitoneal evacuation.