Relationship between formaldehyde exposure, respiratory irritant effects and cancers: a review of reviews.

OBJECTIVES: Formaldehyde is an organic compound used in the production of resins, paper, wood plywood, solvents and cleaning products. Formaldehyde is also present when tobacco is smoked. Formaldehyde has been defined as an irritant and is classified as a human carcinogen by the International Agency for Research on Cancer. The purpose of this study was to demonstrate the following two distinct correlations: (1) the association between formaldehyde exposure and development of irritant diseases affecting the respiratory tract, mainly asthma; and (2) the association between formaldehyde exposure and development of neoplastic diseases. STUDY DESIGN: This was an umbrella review. METHODS: A search was conducted in the three main electronic databases of scientific literature: PubMed, Scopus and Web of Science. The search included systematic reviews and meta-analyses published in the previous 10 years. Initially, titles and abstracts of retrieved articles were evaluated, then full-text assessments of selected articles took place. Data extraction and quality assessment were performed according to Assessing the Methodological Quality of Systematic Reviews (AMSTAR) score. RESULTS: A total of 630 articles were initially collected. Nine articles concerning the association between formaldehyde exposure and asthma were included in the present review, and the majority of these reported good association. In addition, 27 articles investigating the association between formaldehyde exposure and neoplastic diseases were included in the review. These studies showed that nasopharyngeal cancer and leukaemia were the most represented neoplastic diseases; however, only a weak association was reported between formaldehyde exposure and cancer. CONCLUSIONS: Although the studies included in this review did not show a strong association between exposure to formaldehyde and irritant or neoplastic diseases, the World Health Organisation recommends that levels of formaldehyde do not exceed the threshold value of 0.1 mg/m3 (0.08 ppm) for a period of 30 min. It is recommended that preventive measures, such as ventilation in workplaces with high exposure to formaldehyde and environmental monitoring of formaldehyde concentrations, are implemented.

Return to work after kidney transplant: a systematic review.

BACKGROUND: Renal transplant is the gold standard treatment for patients with end-stage renal disease. Employment after transplant is an important marker of recovery and a key component of general well-being with important social implications. AIMS: To evaluate employment status after renal transplant and to investigate facilitators of and barriers to return to work for renal transplant patients. METHODS: We searched PubMed, Scopus and the Cochrane Library in March 2019 using the following algorithms: 'return to work' AND kidney AND transplant. Eligible studies were selected by two independent researchers. Quality assessment was performed using the following tools: International Narrative Systematic Assessment (INSA) and Newcastle-Ottawa Scale (NOS) for cross-sectional and cohort studies. RESULTS: The review included 18 papers: 10 cross-sectional studies, 6 cohort studies and 2 narrative reviews. The weighted mean percentage for return to work within 1 year was 39.4% (95% CI 39.3-39.6%). Employment status was influenced by modifiable and non-modifiable factors, such as pre-transplant employment, sociodemographic characteristics, clinical conditions and comorbidities, operative technique (invasive or not), type of transplants (living donor or cadaver), pre-transplant dialysis, psychosocial support, educational level and participation in education programmes. CONCLUSION: Return to work after kidney transplant is a dynamic process influenced by numerous factors. It is vital to implement multidimensional interventions focused on rehabilitation and influencing modifiable factors to improve return to work after kidney transplant. This systematic review updates knowledge in the field of transplant and of disability management.

"GiochiAMO": a school-based smoking and alcohol prevention program for children - a pilot randomized field trial. Part 2.

BACKGROUND: Young people who begin to smoke at an early age are at a higher risk of becoming occasional or regular smokers and establishing a premature dependence. It is fundamental to act as soon as possible, from very early childhood, to prevent harmful behaviors for health such as smoking and drinking alcohol. Young people must be encouraged to adopt healthy lifestyles. OBJECTIVES: The aim of the study is two-fold. First, increasing the knowledge about the negative health effects of cigarette smoking and alcohol consumption among children aged 9-10 years; and second, to introduce and reinforce life skills in order to learn how to tackle social influences that encourage children to smoke and to drink alcohol. METHODS: A pilot randomized field trial was conducted in May-June 2017. Four primary school classes in Rome were randomized to either the intervention or the control group. Both groups participated in an oral presentation about the risks and consequences of smoking and alcohol consumption, and the concept of life skills. The intervention group participated in two gaming sessions, each lasting 1.5 hours. Children were involved in six games aiming to deliver and reinforce knowledge about the target themes of the study. A 21 multi-response questions questionnaire was handed out to both groups at the beginning and at the end of the study. Eleven questions were about smoking; five questions about alcohol; five questions about life skills. Each question item included one correct answer. For each domain, a score was computed (total; smoking; alcohol; life skills). RESULTS: 67 children participated in the study (34 in the intervention and 33 in the control group). Univariate analyses showed significant differences among the intervention group before and after the intervention for total score (p<0.001), smoke score (p<0.001), and life skills score (p=0.003). No significant differences among the intervention group before and after the intervention were reported for alcohol score (p=0.076). Regarding the control group univariate analysis showed significant differences in total score (p=0,001) and life skills score (p=0.005). Multivariate analysis revealed that enrollment in the intervention was the only variable that had a significant positive influence on smoking knowledge score (beta=1.070, p=0.05). CONCLUSION: This pilot study shows that the intervention was effective among the intervention group for all the scores: total score, smoke score and life skills score, but ineffective for alcohol. Overall, the combination of a presentation and games was effective in increasing life skills knowledge.

Counseling interventions delivered in women with breast cancer to improve health-related quality of life: a systematic review.

BACKGROUND: Higher survival rates for breast cancer patients have led to concerns in dealing with short- and long-term side effects. The most common complications are impairment of shoulder functions, pain, lymphedema, and dysesthesia of the injured arm; psychological consequences concern: emotional distress, anxiety, and depression, thereby, deeply impacting/affecting daily living activity, and health-related quality of life. OBJECTIVE: To perform a systematic review for assessing the efficacy or effectiveness of interventions aiming at improving health-related quality of life, return to daily activity, and correct lifestyles among breast cancer patients. METHODS: A literature search was conducted in December 2016 using the databases PubMed and Scopus. Search terms included: (counseling) AND (breast cancer) AND (quality of life). Articles on counseling interventions to improve quality of life, physical and psychological outcomes were included. RESULTS: Thirty-five articles met the inclusion criteria. The interventions were grouped in five main areas: concerning lifestyle counseling interventions, related to combined interventions (physical activity and nutritional counseling), physical therapy, peer counseling, multidisciplinary approach, included psychological, psycho-educational interventions, and cognitive-behavior therapy (CBT). Exercise counseling as well as physical therapy are effective to improve shoulder mobility, healing wounds, and limb strength. Psychological therapies such as psychoeducation and CBT may help to realize a social and psychological rehabilitation. CONCLUSION: A multidisciplinary approach can help in sustaining and restoring impaired physical, psychosocial, and occupational outcomes of breast cancer patients.

Investigating the synergistic effect of socio-demographic fac- tors on behaviors and attitudes concerning alcohol and illicit drug use among Italian students: a large cross-sectional study.

Background: Alcohol, drug consumption and polysubstance use are some of the most important causes of illnesses and mortality among adolescents, who have been identified as common users of these substances. Aim of this study was to assess and describe the current scenery of alcohol and other drugs consumption habits among a wide sample of Italian high school and university students. Methods: A cross-sectional study was carried out using an online survey. The questionnaire was developed and administered via an internet forum for middle school, high school and university students named "Skuola.net". The statistical analysis included descriptive statistics, univariate and multivariate analysis. Additive interactions were assessed by calculating the synergy index. Results: A total of 11,379 Italian students answered the questionnaire. The prevalence of alcohol drinkers was 34.2%; among these, 17.8% of the individuals showed unhealthy drinking behaviors (frequency of alcohol use of four times or more per week); 10.3% of individuals declared daily assumption of six or more glasses of alcohol. Concerning drugs, 15.7% of the responders classified themselves as illicit drug users, with cannabis getting the highest prevalence rates (6.9%). Finally, concerning alcohol, a synergistic effect was recorded for male and adult individuals (SI = 1.04); while concerning illicit drugs, a synergistic effect was found between male gender and older age (SI = 1.42), and between university students and male gender (SI = 1.10). Conclusions: This study gives an overview about the attitudes of a wide sample of Italian students concerning alcohol and drugs habits. These results are in line with evidences from the scientific literature and will be helpful for developing future prevention strategies towards this target population.

Non-adherence to Mediterranean diet and synergy with lifestyle habits in the occurrence of breast cancer: a case-control study in Italy.

OBJECTIVE: The aim of this study was to assess the synergistic effect of non-adherence to the Mediterranean Diet (MD) and lifestyle habits on the occurrence of breast cancer (BC). PATIENTS AND METHODS: A case-control study was carried out from September 2018 to February 2019 at the Teaching Hospital "Umberto I" in Rome. A Food Frequency Questionnaire was used for assessing the level of adherence to MD, the IPAQ Questionnaire to measure physical activity, and AUDIT-C to estimate alcohol consumption. The possible interaction between risk factors was tested using the synergism index. RESULTS: A total of 94 cases and 88 controls were enrolled (median age 55.8 for cases and 57.9 for controls). The MD Score over 6 was associated with low odds of having breast cancer (OR = 0.29; 95% CI: 0.12-0.69). There is a clear indication for the additivity and synergism between non-adherence to MD and many risk factors on the occurrence of BC: current smoker (S = 2.02; 95% CI 0.62-8.07), physical inactivity (S = 2.14; 95% CI 0.71 2-8.28) and alcohol consumption (S = 3.02; 95% CI 0.91-12.95). CONCLUSIONS: Primary prevention of BC can benefit from intervention targeting nutritional and lifestyle factors that act synergistically.

Management of the early stage of Alzheimer's disease: a systematic review of literature over the past 10 years.

BACKGROUND: Alzheimer's disease is the most widespread senile dementia in the world and diagnoses are on the rise due to the aging of the world's population and this is causing a significant increase in health spending on the care of the disease. Current studies highlight the need for rapid diagnosis in order to prevent the therapeutic approach from being ineffective, and a comprehensive management of the disease, both with pharmacological and integrative therapies (safety of the environment, music therapy, diet, physical activity, recreational activities, etc.). Regarding the care provided by caregivers, the need to educate these figures is fundamental, to support them economically and psycho-socially (especially during the most difficult stages of the disease) and to provide them with technical skills to effectively and safely address the patient's care. OBJECTIVES: Aim of this study was to investigate the current evidence from scientific literature about the early stage of Alzheimer's disease in order to educate and support caregivers with specific technical and practical skills. MATERIAL AND METHODS: A systematic review of the scientific literature of the last 10 years, has been conducted in September 2019 through Medline (PubMed), Scopus and Cinahl databases, in accordance with the criteria of PRISMA Statement guideline (Preferred Reporting Items for Systematic reviews and Meta-Analyses). The included studies were related to Alzheimer's disease and patients' management. RESULTS: Thirty-six articles met the inclusion criteria but only for 26 of these it was possible to retrieve and access the full text. CONCLUSIONS: The evidences from this study provide information on how to effectively address Alzheimer's disease. The studies address different aspects of the disease, with different methodologies, thus providing heterogeneous evidence. Future studies with reproducible methodologies should be undertaken in order to achieve robustness in results.

Perception of Climate Change: validation of a questionnaire in Italy.

BACKGROUND AND AIMS: Climate Change (CC) is a worldwide concern with important consequences for Public Health. A more sustainable and responsible way of living is necessary in order to reduce CC consequences, and adequation to this is directly related to risk perception and knowledge about the phenomenon. The aim of this study was to validate a questionnaire to measure the knowledge of Italians on CC and its consequences. MATERIAL AND METHODS: The questionnaire was administered online to high school students, their parents and teachers that were participating to a meeting at Sapienza University. The questionnaire contained a sociodemographic section and 19 questions on causes and consequences of CC and ways to fight it. The statistical analysis was performed with Statistical Package for Social Sciences (SPSS) version 25. RESULTS: Sixty-four individuals answered the online questionnaire. The analysis of internal consistency was performed by 12 dichotomous variables that measured the knowledge level on CC. The analysis showed a standardized Cronbach's alpha equal to 0.39, corresponding to a low reliability. When females were excluded, the alpha value rose to 0.497, and ascended to the reliable value of 0.639 when refining the selection of the included questions. CONCLUSIONS: The Cronbach's alpha value found showed a low reliability but achieves acceptable levels when considering only males and excluding some of the initial questions. Future studies should be performed in order to highlight the reliability of this tool to assess the knowledge about CC among the population.

Counseling intervention to improve quality of life in patients with pre-existing acute myocardial infarction (AMI) or chronic obstructive pulmonary disease (COPD): a pilot study.

BACKGROUND: In the light of diagnostic and therapeutic advances, patients with a previous myocardial infarction or with a diagnosis of chronic obstructive pulmonary disease are vulnerable and need continuous monitoring over time. These pathological frameworks have a strong impact on the economy and on the status of the population and require effective and low-cost solutions. AIMS: The objective of this clinical trial is to evaluate the efficacy in the short term of a telephone counseling intervention to modify the lifestyles of these two patient populations. METHODS: In May 2015, all the patients included in the study underwent a questionnaire to evaluate their eating and smoking habits and their quality of life. After randomization in two groups, the intervention group received telephone counseling related to the correct lifestyles. The control group did not undergo any intervention. In September-October 2015, the same initial questionnaire was administered to evaluate changes in patients' behavior. RESULTS: 64 patients were included in the study: 34 were assigned to the intervention group and 30 to the control group. The outcomes evaluated were: quality of life, assessment of eating habits and smoking status. After the telephone counseling, the intervention group (34 persons) showed a significant improvement in the score of adherence to the Mediterranean diet (p = 0.01) and a significant reduction in the percentage of smokers (p = 0.01) compared to the population that did not receive any intervention (30 persons). On the other hand, the changes related to the quality of life questionnaire were not significant. CONCLUSIONS: A single telephone counseling intervention is effective in modifying the lifestyles of patients with a previous myocardial infarction or diagnosed with chronic obstructive pulmonary disease in the short term, reducing their risk profile.

Functional Assessment of Cancer Therapy Questionnaire for Breast Cancer (FACT-B+4): Italian version validation.

BACKGROUND: Improvements in breast cancer diagnosis and treatment led to an increased incidence of survivors' rate. The healthcare system has to face new problems related not only to the treatment of the disease, but also to the management of the quality of life after the diagnosis. The aim of this study was to validate the Italian version of the Functional Assessment of Cancer Therapy - Breast (FACT-B+4) questionnaire and to evaluate its reliability. METHODS: The questionnaire was administered twice, with an interval of three days between each administration, to a cohort of women of the Breast Surgical Unit, PoliclincoUmberto I. Cronbach's alpha was used as a measure of the internal consistency of the Italian version. RESULTS: The Italian version of the tool was administered to 55 subjects. The Cronbach's alpha for most scores registered values >0.7, both at baseline and at the follow-up analysis, therefore the subscale showed good internal consistency. CONCLUSIONS: The Italian version of FACT-B+4 demonstrated acceptable reliability properties in the Breast Unit patients. The use of this questionnaire seemed to be effective and in line with the results derived from the English and Spanishversions. Internal consistency and validity had similar performance results.

Returning to work after breast cancer: A systematic review of reviews.

BACKGROUND: Due to improvements in breast cancer diagnosis and treatment, the healthcare system faces a growing number of cancer survivors. Breast cancer survivors experience many difficulties when returning to work, including discrimination at work and lack of support by employers and colleagues. OBJECTIVE: To point out the knowledge in literature up to date about return to work (RTW) after breast cancer, the factors influencing it and the interventions to facilitate it. METHODS: A literature search was conducted in January 2017 using the databases Medline (PubMed) and Scopus. Studies were included if they analyzed the problem of RTW in women treated for breast cancer. RESULTS: Twenty-six articles met the inclusion criteria. The studies were divided into four themes: factors facilitating or impeding RTW; interventions to enhance RTW; lived experiences of RTW; economic aspects related to cancer survivors and RTW. CONCLUSIONS: The heterogeneity of the interventions suggests the need for a better definition of the concept of RTW. To compare interventions, studies should use a rigorous approach and better outcome measures should be identified to evaluate RTW.

Allergens of Parietaria judaica pollen--I. Purification and characterization of a hapten and a low molecular weight allergenic peptide.

A low mol. wt allergen (Pj-2) and a hapten (Pj-H3) were purified from Parietaria judaica pollen by means of long-term aqueous extraction, dialysis and gel filtrations. The yield of the Pj-2 allergen was 0.94% (w/v) of the total protein present in the aqueous extract of the pollen, while its allergenic activity was about 60% of the total dialyzable activity, as verified by skin prick tests, ELISA- and RAST-inhibition experiments. The homogeneity of this allergen was demonstrated by one single sharp peak on HPLC, one single band on PAGE-SDS and by one single arc on IEF. Its mol. wt, estimated by HPLC and amino acid composition, was 10,400. The amino acid analysis showed 73 amino acid residues, and lysine was predominant, with 20 residues. The hapten Pj-H3 was 0.2% (w/v) of the total protein found in the pollen aqueous extract. It was inactive in skin prick tests even at a protein concn of 2 mg/ml, while it was capable of inhibiting by 60% in ELISA- and RAST-inhibition experiments, suggesting an immunochemical relationship with both IgE and allergens specific to P. judaica. The homogeneity was demonstrated by one single sharp peak on HPLC and one single band on PAGE-SDS. The amino acid analysis showed 10 amino acid residues, with no specific traits, and the mol. wt determined by gel filtration and amino acid composition was 1000. An immunochemical relation between the allergen and the hapten was also suggested by the results of an ELISA-inhibition test, and by the ability of the hapten to partially inhibit the precipitin line between rabbit antibodies to whole P. judaica pollen extract and the Pj-2 allergen. The allergen and the hapten described above, purified at homogeneity and in an antigenically active state, both provide adequate material for further structural and immunological characterizations.

cDNA cloning, expression and primary structure of Par jI, a major allergen of Parietaria judaica pollen.

A 659 bp cDNA clone** coding for an allergen of Pj pollen has been isolated from a lambda gt11 library, and its DNA sequence determined. The cDNA insert showed an open reading frame of 429 bp coding for an allergenic protein of 14,866 Da and a deduced amino acid sequence containing 143 residues. The expressed recombinant protein represented the major allergen Par jI since it reacted with 95% of the sera from Pj-allergic patients (n = 22) and with two Par jI-specific monoclonal antibodies. No similarity with other known DNA and protein sequences has been detected.

cDNA cloning, sequence analysis and allergological characterization of Par j 2.0101, a new major allergen of the Parietaria judaica pollen.

A clone (P2) coding for an allergen of Parietaria judaica (Pj) pollen has been isolated and sequenced from a cDNA library in lambda ZAP using a pool of 23 sera from Pj-allergic patients. The clone contained an insert of 622 nucleotides with an open reading frame of 133 amino acids (aa) and a putative signal peptide of 31 aa giving a deduced mature processed protein of 102 aa with a molecular mass of 11344 Da. The expressed recombinant protein, named rPar j 2.0101, was a major allergen since it reacted with IgE of 82% (23/28) of the sera of Pj-allergic subjects analyzed. It was shown to be a new allergen since (i) the amino acid sequence homology with the already reported recombinant allergen Par j 1.0101 was 45% and (ii) there was no cross-inhibition between rPar j 2.0101 and rPar j 1.0101. In addition, rPar j 2.0101 inhibited 35% of the specific IgE for 10-14 kDa native allergens and preincubation of sera from Pj-allergic patients with both rPar j 2.0101 and rPar j 1.0101 fully abolished the IgE recognition of the 10-14 kDa native allergen region, suggesting that these two allergens contributed to the region.

Effect of substance P on uterine mast cell cytokine release during the reproductive cycle.

There is increasing evidence that neuropeptides, steroid hormones and inflammatory cytokines influence the immune response during the reproductive cycle. In the present study, we focus on the effects of neuropeptide Substance P (SP) during the pre-implantation stage of embryo development (day 4 of pregnancy), at pro-estrus and di-estrus (two phases with different hormonal states). We found heterogeneous responses to SP and anti-IgE by the rat uterine mast cells (MCs), as detected by ELISA. In fact, MCs purified from uteri on day 4 of pregnancy released histamine, granulocyte macrophage-colony stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) in response to anti-IgE, but not to SP. When pre-incubated with SP, the release to anti-IgE was significantly enhanced compared to anti-IgE alone. Exposure of SP to antibodies to SP, prior to pre-incubation with MCs, negated the SP effect on IgE-mediated release. At the pro-estrus phase SP showed similar behavior as on day 4 of pregnancy, whereas at the di-estrus phase SP alone was capable of inducing release of histamine and cytokines from purified uterine MCs. Moreover, non-quantitative RT-PCR analysis of the TNF-alpha mRNA level suggested an SP stimulation at the di-estrus phase, but neither on day 4 of pregnancy nor at the pro-estrus phase. Taken together, these data strongly suggest that SP can modulate IgE-mediated uterine MC release of histamine and inflammatory cytokines in different ways, depending on the phase of the reproductive cycle.

Mast cell production of TNF-alpha induced by substance P evidence for a modulatory role of substance P-antagonists.

Unregulated increasing of Tumor necrosis factor-alpha (TNF-alpha) could be pathogenic in inflammatory diseases. The aim of this study was to investigate the anti-inflammatory role of the Substance P-antagonists (SPAs) through the inhibition of histamine release (HR) and TNF-alpha production from mast cell. Rat peritoneal mast cells (PMC) stimulated with Substance P (SP), in the presence of SPAs or not, were analyzed for HR and TNF-alpha protein production. Competitive Polymerase Chain Reaction, with an internal standard competing with target cDNA for the same primers, was used to determine the TNF-alpha mRNA expression. We show that the increase of either HR and TNF-alpha levels in peritoneal (PMC) after induction with SP was inhibited by pre-incubation with SPA or with the Peptide 101 (P101), while the [D-Pro2, D-Phe7, D-Trp9]-SP (dSP) had no effect. Neuraminidase treatment suggests that dSP, as well as SP, interacts with sialic acid residues on the cell surface. Moreover, SPA and P101 also inhibit the release of histamine and TNF-alpha induced by dSP suggesting that a receptor-independent mechanism is involved. These data could be useful to better understand the mechanisms involved in the mast cell activation and TNF-alpha production in the inflammatory diseases where SP is involved.

Inhibitory effect of neuraminidase on SP-induced histamine release and TNF-alpha mRNA in rat mast cells: evidence of a receptor-independent mechanism.

The neuropeptide substance P (SP) is a mediator of neuro-inflammation and can play a role by induction of histamine release (HR) and TNF-alpha. However, its effect on the heterogeneous response of mast cells (MC) has not been completely studied. We have established that the SR can induce 25% of HR in highly purified rat uterine MC at diestrous but not at proestrous phases of the reproductive cycle and 88% of HR in peritoneal mast cells (PMC). We also found 2.2 fold increase in TNF-alpha mRNA at diestrous, in SP stimulated uterine MC versus control and 2.7 fold increase in PMC; RT and competitive PCR were used to amplify the TNF-alpha mRNA. We have thereafter investigated the mechanism whereby the binding of SP to sialic acid on the MC membrane, could trigger secretion of histamine and induction of TNF-alpha mRNA. The neuraminidase pretreatment (0.1 U/ml) inhibited SP-stimulated HR from either uterine MC and PMC (98% and 50%, respectively) and totally inhibited SP-stimulated TNF-alpha mRNA levels. The neuraminidase effect was not toxic, since it was not observed in IgE mediated HR and TNF-alpha mRNA levels. In conclusion, the inhibitory effect of the neuraminidase on the SP-mediated increase of histamine and TNF-alpha mRNA, suggests that the SP-sialic acid interaction could have a role in the MC heterogeneous response.

Immunosuppressive effect of early pregnancy factor on early expression of cell surface membrane IgG.

We have adopted a new assay to investigate the influence of early pregnancy factor (EPF) on the modulation of lymphocyte activity. Lymphocytes were attached to the plastic surfaces of microplates in serum-free medium in the presence of Sepharose-Con A. After 2-3 days incubation with EPF, and ELISA assay was used to detect the expression of surface membrane IgG (smIgG); this was done in the same microplates used for the culture, thus avoiding cell manipulation. Using only a few picograms of EPF a significant inhibition (in the range 26-40%) was obtained. The variation in the inhibition observed was mainly due to the different sources of lymphocytes used. Unrelated proteins and hormones, tested at the same concentration as EPF, did not show any inhibitory activity. Using the F(ab)2 fragment of anti-human IgG instead of the whole molecule the same levels of inhibition were obtained, suggesting that the observed inhibition by EPF was not due to a non-specific interaction between the anti-human IgG and the Fc receptors on the cell. Such inhibitory activity detected in vitro by this method provides additional support for a suppressive role for EPF during pregnancy.

Identification of a histamine-releasing factor secreted by human pre-implantation embryos grown in vitro.

Human pre-implantation stage embryos cultured in vitro spontaneously secreted a factor capable of inducing histamine-release from human blood basophils. The embryo-derived histamine-releasing factor (EHRF) has been isolated from the culture medium by means of heparin-Sepharose affinity chromatography. The factor bound to the column and was then eluted by increasing the buffer molarity to 1.5 M NaCl. EHRF was detected using an enzymatic-isotopic microassay and sensitized basophils known to undergo release with anti-IgE. The EHRF-induced histamine-release was calcium and temperature dependent and the relatively slow kinetics (10 min) were similar to those obtained with anti-IgE. EHRF caused the release of a substantial amount of histamine (48%, n = 18) in a dose-dependent manner. The equivalent fraction isolated from medium containing unfertilized oocytes gave less than 10% of histamine-release using the same source of basophils, suggesting that EHRF was secreted after fertilization. EHRF was very stable since it was resistant to boiling, lyophilization, and to several freeze and thaw treatments. The histamine-releasing activity induced by EHRF was measured in vitro also by means of purified leukocytes containing sensitized basophils. EHRF could represent a message sent by the embryo to the mother to induce histamine release at the time of implantation.

Dispersal of rat uterine mast cells and their functional response to an embryo-derived histamine releasing factor: a possible model for embryo implantation.

Rat uterine tissue was dissociated by enzymatic digestion with collagenase and viable mast cells were obtained. Their viability was assessed by the ability to exclude trypan blue dye and to respond functionally to different stimuli. Challenge with anti-IgE gave a calcium-dependent histamine release of 49%, whilst the undigested uterine fragments gave 23%. Moreover, they were capable of releasing histamine on challenge with the compound 48/80, suggesting a similarity with connective tissue mast cells. This similarity was further supported by their insensitivity to aldehyde blocking of dye binding. The final dispersed cell preparation contained 3 X 10(5) mast cells/g of uterine tissue, representing about 2% of total nucleated cells. The total histamine content of the undigested uterus was 2.5 micrograms/g of tissue, whilst after digestion the histamine determined was 1.2 pg per mast cell with a yield of 14%. The total histamine content of the uterus changed throughout the reproductive cycle, increasing before ovulation, reaching a maximum during ovulation and then decreasing after embryo implantation. This suggests that the implanting embryo, interacting with the uterus, may be capable of inducing the release of histamine. The embryo-derived histamine releasing factor (EHRF) that we have described previously is capable of inducing 22% histamine-release on uterine mast cells, thus supporting this hypothesis.