Tumor-induced senescent T cells promote the secretion of pro-inflammatory cytokines and angiogenic factors by human monocytes/macrophages through a mechanism that involves Tim-3 and CD40L.

Solid tumors are infiltrated by immune cells where macrophages and senescent T cells are highly represented. Within the tumor microenvironment, a cross-talk between the infiltrating cells may occur conditioning the characteristic of the in situ immune response. Our previous work showed that tumors induce senescence of T cells, which are powerful suppressors of lympho-proliferation. In this study, we report that Tumor-Induced Senescent (TIS)-T cells may also modulate monocyte activation. To gain insight into this interaction, CD4+ or CD8+TIS-T or control-T cells were co-incubated with autologous monocytes under inflammatory conditions. After co-culture with CD4+ or CD8+TIS-T cells, CD14+ monocytes/macrophages (Mo/Ma) exhibit a higher expression of CD16+ cells and a reduced expression of CD206. These Mo/Ma produce nitric oxide and reactive oxygen species; however, TIS-T cells do not modify phagocyte capacity of Mo/Ma. TIS-T modulated-Mo/Ma show a higher production of pro-inflammatory cytokines (TNF, IL-1ß and IL-6) and angiogenic factors (MMP-9, VEGF-A and IL-8) and a lower IL-10 and IP-10 secretion than monocytes co-cultured with controls. The mediator(s) present in the supernatant of TIS-T cell/monocyte-macrophage co-cultures promote(s) tubulogenesis and tumor-cell survival. Monocyte-modulation induced by TIS-T cells requires cell-to-cell contact. Although CD4+ shows different behavior from CD8+TIS-T cells, blocking mAbs against T-cell immunoglobulin and mucin protein 3 and CD40 ligand reduce pro-inflammatory cytokines and angiogenic factors production, indicating that these molecules are involved in monocyte/macrophage modulation by TIS-T cells. Our results revealed a novel role for TIS-T cells in human monocyte/macrophage modulation, which may have deleterious consequences for tumor progression. This modulation should be considered to best tailor the immunotherapy against cancer.

Analysis of environmental endocrine disrupting chemicals using the E-screen method and stir bar sorptive extraction in wastewater treatment plant effluents.

Endocrine disrupting chemicals (EDCs) have become a major issue in the field of environmental science due to their ability to interfere with the endocrine system. Recent studies show that surface water is contaminated with EDCs, many released from wastewater treatment plants (WWTP). This pilot study used biological (E-screen assay) and chemical (stir bar sorptive extraction-GC-MS) analyses to quantify estrogenic activity in effluent water samples from a municipal WWTP and in water samples of the recipient river, upstream and downstream of the plant. The E-screen assay was performed on samples after solid phase extraction (SPE) to determine total estrogenic activity; the presence of estrogenic substances can be evaluated by measuring the 17-beta-estradiol equivalency quantity (EEQ). Untreated samples were also assayed with an acute toxicity test (Vibrio fischeri) to study the correlation between toxicity and estrogenic disruption activity. Mean EEQs were 4.7 ng/L (+/-2.7 ng/L) upstream and 4.4 ng/L (+/-3.7 ng/L) downstream of the plant, and 11.1 ng/L (+/-11.7 ng/L) in the effluent. In general the WWTP effluent had little impact on estrogenicity nor on the concentration of EDCs in the river water. The samples upstream and downstream of the plant were non-toxic or weakly toxic (0

Varicella and its complications as cause of hospitalization.

Varicella is an acute contagious disease that most commonly occurs in childhood. Although normally benign, varicella can occasionally develop into a more serious illness. Moreover, the infection can lead to serious complications, such as Staphylococcus aureus infections, otitis media, endocarditis, pneumonia, and rare central nervous system (CNS) events like cerebellar ataxia and encephalitis. This study was conducted to analyze the hospitalization rate due to varicella or its complications in a tertiary care hospital in Italy, where varicella vaccination has not yet been implemented. The review was carried out on cases of children with varicella identified by ICD9 and ICD9-CM diagnostic codes and admitted to the Giannina Gaslini Children's Research Hospital of Genoa, Italy, from January 1st, 1995 to December 31st, 2004. For each case reporting complications, the clinical report form was extracted and the events recorded. Varicella was recorded in 346 (0,16%) out of 212,647 total hospital discharges. Chickenpox with detailed complications and cerebrovascular diseases accounted for 56 discharges (12.14%), for a total of 728 days. Fifteen patients needed more than one hospitalization because of severe sequelae as result of CNS involvement. We reported three particular cases of invasive infections and four children affected with cerebrovascular diseases following varicella. Our retrospective data regarding a single tertiary care pediatric hospital shows that hospitalization due to varicella or its sequelae may present an important medical and indirect economic problem.

An economic evaluation of universal pertussis vaccination in Italy.

An economic evaluation was performed of universal acellular pertussis vaccination in Italy, where until recently the overall coverage of pertussis vaccination was estimated at 50%. Over the last two years coverage seems to have increased rapidly. By means of a mathematical simulation model, the consequences of pertussis vaccination in terms of both health effects and economic costs were calculated for a single birth cohort followed for 6 years. Incremental analyses were performed for each additional 10% increase in coverage from 50-90%. The results indicate that a 50% coverage rate of pertussis vaccination in Italy was not optimal on the basis of cost-effectiveness and cost-benefit considerations. Additional increases in coverage were found to yield extra health gains at modest net costs or even potential net savings to the health care sector. For example, an increase in coverage to 90% would yield direct net savings of US$42 per extra vaccinee in comparison to a situation of 50% coverage. The total net savings for this strategy would be well over US$100 per additional vaccinee. In the sensitivity analysis, the positive relationship between incremental coverage and incremental efficiency remained unchanged.

ELISA to determine anti-K99 pilus antibody in the sera of normal and diarrhoeic calves.

An ELISA to detect circulating antibodies against K99 pili, a major attachment factor to intestinal epithelial cells of Escherichia coli in calves, was performed. Two methods of K99 pili purification were attempted. Best results in terms of purity of the K99 antigen were achieved following the method described by Karkhanis and Bhogal (1986). This procedure included a heat shock at 65 degrees C during 25 min to release the pili and ultracentrifugation steps to purify the antigen. SDS-PAGE showed an 18 KDa major band, identified as the K99 pilus antigen after immunoblotting against reference antisera. The purified K99 antigen was then adsorbed to the ELISA microplates. High optical density was obtained in the ELISA using a pool of sera from immunized cows. No differences in antibody levels (P > or = 0.05) could be detected between clinically healthy calves and those showing diarrhoea.

[Taste disorders in forensic medicine]. / Alterazioni del gusto in medicina legale.

Taste disorders can a rise from lesions of peripheral receptors, taste control pathways or cortical area involvement. Among peripheral lesions, trauma of the tongue and oropharynx are the most common. Iatrogenic lesions of facial and glossopharingeal nerves are very important in Forensic Medicine, while there are different opinions about taste alterations due to head injuries; hypogeusia associated to smell disorders are found in 0.4-0.5% of patient after head trauma with good prognosis (90% healing) while qualitative disorders are more common (30%). The Authors describe clinical methodologies for taste evaluation and their application in Forensic Medicine. Forensic estimation of taste disorders con be classified by two main groups: study of cause relation between the occurrence and damage and quantitative valuation of the damage in three different juridical ambits: Penal, Civil, Insurance and foresight. In Penal Right taste damages could be classified among personal lesion crimes and can be classified as serious (permanent injury of taste) ore very serious (complete lost of taste function). Italian Legislation equipare the 5 sense organs. In Civil Right evaluation the so-called "biologic damage" and working ability are considered; this means very different evaluations. In the most recent baremes, generic damage is estimated by different Authors from 0 to 10% while with regard to specific working capacity, common evaluation criteria does not exist. In Insurance taste disorders evaluation is based only on working ability and not on biologic damage. In the previdenzial ambit, taste disorders are not even included in the most recent tables of permanent invalidity estimation. The Authors propose new and more efficacious valutation criteria for taste disorders in all ambits, hoping for more interest in the Forensic aspects of taste, a too often forgotten sensory function.

Autoradiographic assessment of pineal gland glucose utilization and capillary permeability in the unanesthetized rat.

Pineal gland glucose utilization (GU) and capillary permeability (CP) were measured in unanesthetized rats, using complementary quantitative autoradiographic techniques. GU values within the pineal tissue were homogeneously distributed around 70 mumol of glucose/100 g each min, i.e., they were approximately 30% lower than in the cortical gray structures. The blood-to-brain transfer constant of [14C]-alpha-aminoisobutyric acid, as an index of CP, was up to ten orders of magnitude higher than that for the rest of the brain. These measurements were carried out at that point in the circadian rhythm that corresponds to the minimum level of neurosecretory activity of the pineal gland.