Impairment of gamma/delta T lymphocytes in elderly: implications for immunosenescence

Gamma/delta T lymphocytes cells recognize the antigen in a non-classical way and are considered the third branch of the immune system devoted to defend the integrity of the body. Ageing is characterized by an impairment of the main way of protection (the adaptive branch) but, successfully aged people show compensatory mechanisms of defense such as proneness to inflammation. Moreover, very old subjects show an increased number of NK cells. We have previously demonstrated that gamma delta T lymphocytes are reduced in elderly. In the present paper we have studied some characteristics of these cells to evaluate the possibility that these cells might balance the decreased action of the adaptive branch in successfully aged people. Cytofluorimetric analysis of cells collected from young, old and centenarian subjects has been used to evaluate the ability of these cells to expand in vitro. Here we demonstrate that gamma delta T cells are impaired in the ability to proliferate to different stimuli such as isopentenyl pyrophoshate, that select gamma delta T lymphocytes bearing delta 2 chain, other than to phytohemagglutinin and anti-CD3 that are polyclonal activators. Moreover, we demonstrate that gamma delta T cells in aged and centenarians show an enhanced sensitivity to undergo apoptosis induced both by alpha-Fas and TNF-alpha. All together these data suggest that gamma delta T lymphocytes are impaired in elderly and suggest that the reduced ability to proliferate and the reduced number of circulating gamma delta T lymphocytes is due to the proneness to apoptosis. Finally on the basis of these data, we conclude that gamma delta T lymphocytes, do not participate in the remodeling of the immune system due to the reduction of classical T cell response and replacement by NK cells in elderly.     

Pregnancy as a risk factor for restless legs syndrome

Pregnant women have at least two or three times higher risk of experiencing restless legs syndrome (RLS) than the general population. These data come from few epidemiological studies finding an 11-27% prevalence of RLS during pregnancy. Women affected by pre-existing RLS often complain of worsening symptoms during pregnancy. This is usually a benign form of RLS, with the highest degree of severity in the third trimester and a tendency to disappear around delivery. The causes of the association between RLS and pregnancy are unknown. The most debated hypotheses are: metabolic alterations, with particular regard to iron and folate deficiency; hormonal influences related to the increase of prolactin, progesterone and estrogens during late pregnancy; and the changing motor habits and psychological state of pregnant women. The importance of folate and iron supplementation during pregnancy in preventing RLS is unclear. RLS in pregnant women is frequently unrecognized; they are often worried about the symptoms and do not receive an adequate explanation by doctors.     

Mutational analysis of 206 families with cavernous malformations

OBJECT: A gene contributing to the autosomal-dominant cerebral cavernous malformation (CCM) phenotype, KRIT1 (an acronym for Krev Interaction Trapped 1), has been identified through linkage analysis and mutation screening. The authors collected blood samples from 68 patients with familial CCM and 138 patients with apparently sporadic CCM as well as from their families, in an effort to characterize the prevalence and spectrum of disease-causing sequence variants in the KRIT1 gene. METHODS: The authors used single-strand conformational polymorphism analysis to identify genomic variants in KRIT1, which were sequenced to determine the specific mutation. Among 43 Hispanic-American kindreds who immigrated to the southwestern US from northern Mexico, 31 share an identical founder mutation. This Q455X mutation is found in 18 (86%) of 21 persons with a positive family history and in 13 (59%) of 22 persons with apparently sporadic CCM. This mutation was not found among 13 persons with CCM who were recruited from Mexico. These findings establish the key role of a recent founder mutation in Hispanic persons with CCM who live in the US. Although nearly all Hispanic families in the US in which there are multiple CCM cases linked to the CCM1 locus, only 13 of 25 non-Hispanic CCM-carrying families have displayed evidence of linkage to the CCM1 locus. Among these 13 families, the authors identified eight independent mutations in nine kindreds. They identified four additional mutations among 22 familial CCM kindreds with no linkage information, bringing the total number of independent mutations to 12. Inherited KRIT1 mutations were not detected among 103 non-Hispanic persons in whom a family history of CCM was rigorously excluded. CONCLUSIONS: All mutations were nonsense mutations, frame-shift mutations predicting premature termination, or splice-site mutations located throughout the KRIT1 gene, suggesting that these are genetic loss-of-function mutations. These genetic findings, in conjunction with the clinical phenotype, are consistent with a two-hit model for the occurrence of CCM.     

Non-invasive mechanical ventilation in patients with acute cardiogenic pulmonary edema

AIM: To evaluate the use of noninvasive mechanical ventilation (NIMV) in patients with acute cardiogenic pulmonary edema. METHODS: Design: prospective study. Setting: Emergency Department at a University hospital. Patients: 84 patients with acute respiratory distress due to pulmonary edema. Interven-tions: NIMV, using a pressure support mode and positive end-expiratory pressure (PEEP). A "weaning test" to evaluate clinical stability. Measurements: heart rate, arterial blood pressure, respiratory rate, arterial blood gases, electrocardiogram and incidence of myocardial infarction before and after NIMV. Mortality and duration of hospital stay were also considered. RESULTS: A total of 84 patients received NIMV with 14+/-3.6 cm H2O pressure support over PEEP of 8.3+/-2.1 cm H2O and FiO2 1. At the end of the study period, 16 patients (19%) were considered "non responders" and required invasive ventilation; 62 patients (74%) were considered "responders" and subsequently transferred to the medical ward. The hospital mortality was 14% and 25% in the "responder" and "non responder" groups, respectively; the length of stay was 15.7+/-10.1 days in the "responder" group vs 16+/-10.6 days in the "non responder" group. We never found new episodes of myocardial infarction related to NIMV. The only significant difference between "responder" and "non responder" patients was arterial blood pressure. CONCLUSIONS: We hypothesize that "non responder" patients, characterized by blood pressure values lower than "responders", are less "cardiocompetent" and thus unable to cope with the increased work of breathing. NIMV avoided Intensive Care Unit admission for 74% of the observed patients.     

Leishmania antibodies in children’s serum samples in correlation with the disease in dogs

Sera of 489 children from Northern Greece aged between 6 months and 15 years of age and aflicted with different clinical entities, were tested for anti ? Leishmania infantum specific IgG and IgM antibodies, using an ELISA (enzyme linked immunosorbent assay) technique. In this survey, a remarkably high percentage (8.5%) of hospitalized children reacted positively to this method. Twenty three out of 489 children (4.7%) had IgG antibodies, seventeen (3.5%) IgM, while two (0.4%) had both IgG and IgM antibodies against soluble antigen of L. infantum promastigotes. Females had a higher seropositivity than males. The highest prevalence was observed in males aged between 6 months and 5 years old (10 out of 19), while the lowest was observed also in males aged between 11 and 15 years old (5 out of 11). Seropositivity rate was higher in children below 5 years of age. Some epidemiologic, as well as clinical data of canine Leishmaniosis from Northern Greece are discussed.     

Toxocarosis as zoonosis. A review of literature and the prevalence of Toxocara canis antibodies in 511 serum samples

A total of 511 serum samples from children aged between 6 months to 15 years old, with different clinical signs-living in the region of Northern Greece - were tested by ELISA (enzyme links immunosorbent assay) technique, for the detection of specific IgG and IgM antibodies against T. canis antigen. The reason IgM was detected was because IgM levels are elevated in the acute phase of toxocara infection, in spite of their notorious non-specificity. In this seroepidemiologic survey of children, a remarkably high percentage (12.5%) reacted positively to this method. Sixteen (3.1%) out of 511 sera showed IgG antibodies, 43 (8.4%) showed IgM, while 5 (1%) showed both IgG and IgM antibodies against T. canis E/S (excretory - secretory) antigen. Females were significantly more infected than males. Seropositivity rate was highest in children over the age of 10.