Protective role of brain derived neurotrophic factor (BDNF) in obstructive sleep apnea syndrome (OSAS) patients.

Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by repeated episodes of upper airways collapse during the sleep. The following intermittent hypoxia triggers a state of chronic inflammation, which also interests the nervous system leading to neuronal damage and increased risk of cognitive impairment. Brain derived neurotrophic factor (BDNF) is a growth factor often associated with neuroplasticity and neuroprotection whose levels increase in several condition associated with neuronal damage. However, whether patients affected by OSAS have altered BDNF levels and whether such alteration may be reflective of their cognitive impairment is still controversial. Here we show that, when compared to healthy control volunteers, OSAS patients have increased serum levels of BDNF. Moreover, OSAS patients with the higher levels of BDNF also have reduced neurocognitive impairment as measured by The Montreal Cognitive Assessment (MoCA) questionnaire. Treatment with standard non-invasive mechanical ventilation (CPAP) also was able to ameliorate the level of cognitive impairment. Altogether our results indicate that BDNF levels represent a neuroprotective response to intermittent hypoxia in OSAS patients.

Cognitive status in the oldest old and centenarians: a condition crucial for quality of life methodologically difficult to assess.

Human life expectancy and the number of the oldest old are rapidly increasing worldwide. Advanced age is the main risk factor for dementia, representing one of the major causes of disability/dependency among older people with a strong impact on their families/caregivers. Centenarians have reached the extreme limits of human life escaping or delaying the major age-related diseases. Thus, these extraordinary individuals embody the best model to answer the crucial question if cognitive decline and dementia are progressive and unavoidable occurrences of increasing age. Despite a growing amount of data underlines the importance of cognitive function for quality of life and survival in old age, studies on centenarians have paid more attention to their physical condition rather than the assessment of their actual cognitive abilities. Accordingly, this work aims to summarize available data on the prevalence of dementia in centenarians and to critically address topics which can have a relevant impact on the cognitive assessment/status of the oldest old: (i) lack of standardized tools for cognitive assessment; (ii) criteria and threshold to establish the presence of dementia; (iii) influence of birth cohort and education; (iv) role of depression or positive attitude towards life; (v) gender differences.

Impact of vitamin D receptor polymorphisms in centenarians.

Vitamin D is a seco-sterol produced endogenously in the skin or obtained from certain foods. It exerts its action through binding to intracellular vitamin D receptor (VDR). Lately, the role of vitamin D has been revised regarding its potential advantage on delaying the process of aging. The aim of this study was to assess the contribution of VDR gene polymorphisms in healthy aging and longevity. We evaluated the frequency of four polymorphisms of the VDR gene (FokI, BsmI, ApaI, and TaqI) in centenarians (102 subjects, mean age: 102.3 ± 0.3 years), compared to septuagenarians (163 subjects, mean age: 73.0 ± 0.6 years) and we analyzed a variety of pathophysiologically relevant functions in centenarians. BsmI and ApaI provided a significant association with longevity: there was a highly significant difference in the frequency of BsmI genotypes (p = 0.037), ApaI genotypes (p = 0.022), and ApaI alleles (p = 0.050) in centenarians versus septuagenarians. Furthermore, we found a significant correlation of all the VDR gene polymorphisms in centenarians with some measured variables such as hand grip strength, body mass index, blood pressure, HDL cholesterol, and mini-mental state examination. We also found a correlation with the prevalence of medical history of hypertension, acute myocardial infarction, angina, venous insufficiency, dementia, chronic obstructive pulmonary disease, and arthrosis. In conclusion, this study proposes a new scenario in which the variability of the VDR gene is relevant in the aging process and emphasizes the role of VDR genetic background in determining healthy aging.

Leukocyte telomere length and prevalence of age-related diseases in semisupercentenarians, centenarians and centenarians' offspring.

Centenarians and their offspring are increasingly considered a useful model to study and characterize the mechanisms underlying healthy aging and longevity. The aim of this project is to compare the prevalence of age-related diseases and telomere length (TL), a marker of biological age and mortality, across five groups of subjects: semisupercentenarians (SSCENT) (105-109years old), centenarians (CENT) (100-104years old), centenarians' offspring (CO), age- and gender-matched offspring of parents who both died at an age in line with life expectancy (CT) and age- and gender-matched offspring of both non-long-lived parents (NLO). Information was collected on lifestyle, past and current diseases, medical history and medication use. SSCENT displayed a lower prevalence of acute myocardial infarction (p=0.027), angina (p=0.016) and depression (p=0.021) relative to CENT. CO appeared to be healthier compared to CT who, in turn, displayed a lower prevalence of both arrhythmia (p=0.034) and hypertension (p=0.046) than NLO, characterized by the lowest parental longevity. Interestingly, CO and SSCENT exhibited the longest (p<0.001) and the shortest (p<0.001) telomeres respectively while CENT showed no difference in TL compared to the younger CT and NLO. Our results strengthen the hypothesis that the longevity of parents may influence the health status of their offspring. Moreover, our data also suggest that both CENT and their offspring may be characterized by a better TL maintenance which, in turn, may contribute to their longevity and healthy aging. The observation that SSCENT showed considerable shorter telomeres compared to CENT may suggest a progressive impairment of TL maintenance mechanisms over the transition from centenarian to semisupercentenarian age.

Is asthma caused by atopy (positive skin prick tests)? Epidemiologic evidence suggests a negative answer.

In this paper we shortly discuss epidemiological data on the relationship between asthma and atopy according to recent personal and literature epidemiological publications. The coexistence in several subjects of asthma (and of other "atopic" diseases) and IgE hyperproduction generated the dogma that these two biological conditions are mainly genetic in origin and are linked by a strong casual relationship. In the last decades atopy increased at 5-10 % annual rate and at present atopy prevalence, although variable in different countries, reaches somewhere the prevalence of more than 60 %. Similarly, asthma prevalence increased in the last decades, especially so in western and English speaking countries, reaching in certain countries prevalence values higher than 40 %. For these reasons, although certainly dependent on a genetic predisposition, atopy and asthma can nowadays be considered to be largely determined by environmental factors. Moreover, the analysis of epidemiological data derived from studies conducted worldwide, showed that the prevalence of the two conditions were clearly not correlated so that in certain countries with a 50-60% prevalence of atopy asthma prevalence is lower than 2-6 %, while in other countries asthma prevalence is double than atopy prevalence. Further, in countries with high atopy, the prevalence this conditions is high both in asthmatics and in normal subjects and in the places where asthma prevalence reaches high levels this condition is high both in atopic and non atopic people. In conclusion, epidemiological data show that environmental factors affecting asthma prevalence are different from those affecting atopy prevalence and that subjects bearing one of the two conditions don't show any preferential tendency to develop the other one. From aetiological and pathogenetic point of view asthma and atopy appear to be independent conditions We therefore believe that the association between asthma and atopy demonstrated in almost all the "population studies" (atopy prevalence has always been found 20-30 % higher in asthmatics than in non asthmatic subjects) doesn't prove the existence of a "causal" relationship between the two conditions: this could be a kind of association without causative meaning as is the association between blond hair and blue eyes which in no way can be considered a prove that one of the two conditions is the cause of the other.

Relationship between atopic asthma and the population prevalence rates for asthma or atopy in children: atopic and nonatopic asthma in epidemiology.

Innumerable articles have tried to solve the "continuing enigma of atopic and nonatopic asthma" but notwithstanding the strenuous efforts to substantiate the few well-known clinico-epidemiologic differences between these two forms of asthma most studies have hitherto generated inconclusive statements. In a recent study based on the review of epidemiologic studies conducted worldwide in unselected populations of children, we documented that the prevalence of atopic asthma (AA) was high in the populations with a high prevalence of atopy. We systematically reviewed 36 articles that studied 48 populations of unselected children and reported prevalence rates for asthma and atopy in the total sample and in the subpopulations. No significant difference was found in the prevalence of asthma cases in the quartiles of childhood populations subdivided for the prevalence of atopy. In addition, atopy did not increase significantly in the subgroups of populations subdivided by asthma quartiles. In both subgroups, however, AA increased with increasing atopy or with increasing asthma (p < 0.001). Using a positive skin-prick test reaction to define cases of asthma as cases of AA is misleading because the prevalence of subjects so defined is heavily influenced by the environmentally generated changes in the prevalence of atopy or asthma. Asthma in a child should be labeled as a case of AA only if skin-prick tests yield a positive reaction and the clinical history documents asthma symptoms triggered by allergen exposure.

Adenosine deaminase polymorphism and the relationship of total immunoglobulin E with skin prick test: a study on school children.

Recent studies suggest that genetic polymorphism modulates immunoglobulin E (IgE)-mediated atopic reactions. Adenosine is an important local hormone influencing immune function and tissue reactivity; because adenosine concentration is regulated by adenosine deaminase (ADA), we have investigated the possible effect of ADA polymorphism on the relationship between IgE and positive prick test. A random sample of 160 schoolchildren from the population of Viterbo (Italy) were studied. Prick testing was performed with a panel of local allergens. Total IgE assay was performed according to standard clinical procedure. ADA phenotype was determined according to Spencer et al. A highly significant correlation between prick test and IgE was observed. However, the strength of correlation was moderate (eta2 = 0.16), indicating that positive prick testing depends on other variables besides IgE. The relationship between IgE and positive prick testing is stronger in carriers of ADA*2 allele than in ADA*1/*1 subjects. Also, sensitivity and predictive values are higher in ADA*2 carriers than in homozygous ADA*1/*1 children. The data suggest that the effect of IgE level on local reactivity is influenced by ADA polymorphism; at low level of IgE, the presence of the ADA*2 allele seems to protect from positive prick testing.

Digital hearing aids for high-frequency sensorineural hearing loss: preliminary experience with the RetroX device.

CONCLUSIONS: The RetroX outer ear hearing aid seems to represent a means of overcoming problems with understanding speech in noise in patients with high-frequency sensorineural hearing loss (SNHL) without the need to wear conventional completely-in-the-canal (CIC) hearing aids, which are usually reported to annoy patients as a result of the occlusion effect. OBJECTIVE: To present preliminary data from a study carried out to compare the efficacy, in the same individual, of a standard digital CIC hearing aid and a new implantable outer ear canal device, the RetroX. MATERIAL AND METHODS: Three out of 15 adults affected by high-frequency SNHL who were candidates for auditory rehabilitation were evaluated by using speech audiometric tests in quiet and noise as well as a questionnaire shortly after use of a CIC hearing aid and the RetroX device, i.e. at 7 and 14 days. The efficacy of the RetroX was anticipated by testing all the subjects using a RetroX simulating system before starting the study protocol. RESULTS: In all three implanted patients, the RetroX provided better audiological benefit for speech understanding in noise. These findings were corroborated by the results of the questionnaire, which showed greater satisfaction with the RetroX, especially regarding the absence of the occlusion effect.

Why Chlamydia pneumoniae is associated with asthma and other chronic conditions? Suggestions from a survey in unselected 9 yr old schoolchildren.

Despite numerous studies demonstrating an association between asthma and many other chronic conditions and signs of Chlamydia pneumoniae (Cp) infection, the role of Cp in the pathogenesis of these illness remain still unclear. We investigated the prevalence of Cp antigen in the upper airways and the prevalence of detectable Cp serum antibodies in an unselected population of 207 9-yr-old schoolchildren. We also sought the presence of asthma, chronic or recurrent respiratory symptoms by means of questionnaire completed by the parents. Nasal aspirate, blood sampling and allergen skin prick tests were also performed. None of the children had obvious signs of acute infection at physical examination. Cp DNA was detected in nasal aspirates from 20 of the 207 children tested and serum IgG antibodies for Cp in 68 children. No association was found between atopy or history of atopic illness and the presence of Cp DNA or antibody production. This finding is explained by the fact that our study was conducted in an unselected childhood population, inherently including few children with asthma. A strong association between the status of antigen carrier and the presence of detectable Cp serum immunoglobulin (Ig)G or IgM suggests that subjects with detectable Cp antibodies have an impaired ability to eliminate this pathogen when infected. Because Cp eradication requires a strong Th1 lymphocyte response, the previously proven association between Cp and asthma, might reflect the known association of asthma with Th2-oriented lymphocytic activity.

Detection of Chlamydia pneumoniae in cholesteatoma tissue: any pathogenetic role?

BACKGROUND: Acquired cholesteatoma is a complication of chronic otitis media that is usually associated with an intense local inflammatory reaction. Cholesteatoma probably arises from epithelial migration close to an ongoing host inflammatory response attributable to a chronic bacterial infection. Chlamydia pneumoniae is an intracellular microorganism associated with several pathologic conditions originally considered noninflammatory, including asthma, atherosclerosis, and Alzheimer disease. To investigate a possible relationship between C. pneumoniae and the development of cholesteatoma, tissue was studied in three different layers by polymerase chain reaction analysis. The results were compared with those relative to other two common middle-ear pathogens, Mycoplasma pneumoniae and Haemophilus influenzae. METHODS: Cholesteatoma specimens were collected from 32 patients undergoing middle ear surgery. A series of 5 microm-thick specimens were obtained at three different tissue levels, internal (matrix), intermediate (perimatrix), and external (granulation tissue), and processed by polymerase chain reaction for detection of C. pneumoniae, H. influenzae, and M. pneumoniae. Fragmentation and polymerase chain reaction amplification were carried out using two substantially different techniques. RESULTS: C. pneumoniae was detected with either polymerase chain reaction techniques in the internal layers in 16 of the 32 cholesteatomas (50%), associated with a positive finding in the intermediate layer in two cases and in the external layer in one case. Four specimens contained H. influenzae, always in the external layer, whereas none contained M. pneumoniae. CONCLUSIONS: The close relationship between cholesteatoma and C. pneumoniae demonstrated by the findings of this study could suggest a direct cause and effect link between the pathogen action and the clinical manifestations. Otherwise, a facilitated colonization by C. pneumoniae and chronic pathology of the ear could both take origin from a peculiar immunologic background of the host.

Release of transforming growth factor beta-1 in a vestibular schwannoma cell line.

Vestibular schwannoma (VS) often displays an irregular growth pattern due to factors which remain unknown. In this study, VS cell lines from tissue removed during surgery were cultured in order to assess the presence of transforming growth factor beta-1 (TGFbeta-1) a multifunctional polypeptide that has different pleiotropic effects on various tissues. The antibody-binding inhibition assay technique was used. The proliferation rate of VS cell lines in vitro was assessed by [3H]thymidine incorporation, with determinations carried out on days 0, 1, 2 and 4 after removal of fetal calf serum (FCS) from the medium. After 48 h of FCS deprivation, cell growth decreased. TGFbeta-1 release also decreased progressively 24 h after removing FCS from the medium, reaching an overall decrease of 50% after 3 days. The cell culturing procedure appeared suitable for VS cells, in that VS cultures were viable for at least 4 months. TGFbeta-1 was initially shown to be released in significant amounts, but also to decrease progressively to values five times lower after 4 days. These data thus support the possibility of a significant association between TGFbeta-1 release and VS cell replication.

Nasal cellularity in 183 unselected schoolchildren aged 9 to 11 years.

OBJECTIVE: Although rhinitis is extremely frequent in children, methods for assessing the severity of nasal inflammation produce results with wide variability and hence weak clinical significance. We designed this epidemiologic investigation to define the clinical usefulness of assessing nasal cellularity in children. METHODS: We studied 183 of 203 eligible unselected schoolchildren who were aged 9 to 11 years and whose parents gave informed consent and completed a questionnaire on the history of atopic and respiratory symptoms. In all children, nasal swabs were obtained from both nostrils and eluted in saline and slides were prepared from cytospin preparations for staining and white cell counts. Children also underwent determination of nasal volume, skin prick tests with 7 common local allergens, flow volume curves, and nitric oxide measurement in expired air. Blood samples were drawn for the measurement of total immunoglobulin E, eosinophil percentage, and detection of Chlamydia pneumoniae antibodies. C pneumoniae DNA was also sought in eluates from nasal swabs. The percentage, standard deviations, and percentiles of the various nasal white cell populations were determined. RESULTS: No correlation of the percentage of these cells was found with the history of allergies or respiratory disease or with functional or laboratory finding. Repeat nasal swabs obtained 1 month after the initial examination in 31 children (20 with neutrophils higher and 11 lower than 14%) in 77.4% of the cases confirmed the previous (high or normal) result. Twelve of the 16 eligible children with persistently high nasal neutrophil counts completed a 15-day cycle of intranasal flunisolide therapy (200 micro g twice a day). Therapy significantly reduced nasal neutrophil percentage and increased nasal volume. CONCLUSIONS: Increased nasal neutrophils, although related neither to the clinical history nor to laboratory variables, are a common important finding in children. A 15-day cycle of intranasal flunisolide is sufficient to restore normal nasal neutrophilia.