Obesity drives adipose-derived stem cells into a senescent and dysfunctional phenotype associated with P38MAPK/NF-KB axis.

BACKGROUND: Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control. RESULTS: Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21WAF1/Cip1) up-regulation. We also observed increased senescence-associated ß-galactosidase (SA-ß-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16INK4A) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli. CONCLUSIONS: Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis.

Mono-, di-, and trichlorinated biphenyls (PCB 1-PCB 39) in the indoor air of office rooms and their relevance on human blood burden.

Exposure to polychlorinated biphenyls (PCBs) from indoor air can lead to a significant increase in lower chlorinated congeners in human blood. Lower chlorinated congeners with short biological half-lives can exhibit an indirect genotoxic potential via their highly reactive metabolites. However, little is known about their occurrence in indoor air and, therefore, about the effects of possible exposure to these congeners. We analyzed all mono-, di-, and trichlorinated biphenyls in the indoor air of 35 contaminated offices, as well as in the blood of the 35 individuals worked in these offices for a minimum of 2 years. The median concentration of total PCB in the indoor air was 479 ng/m3 . The most prevalent PCBs in the indoor air samples were the trichlorinated congeners PCB 31, PCB 18, and PCB 28, with median levels of 39, 31, and 26 ng/m3 , respectively. PCB 8 was the most prevalent dichlorinated congener (median: 9.1 ng/m3 ). Monochlorinated biphenyls were not detected in relevant concentrations. In the blood samples, the most abundant congener was PCB 28; nearly 90% of all mono-, di-, and trichlorinated congeners were attributed to this congener (median: 12 ng/g blood lipid).

Maternal environmental enrichment protects neonatal brains from hypoxic-ischemic challenge by mitigating brain energetic dysfunction and modulating glial cell responses.

There is evidence that maternal milieu and changes in environmental factors during the prenatal period may exert a lasting impact on the brain health of the newborn, even in case of neonatal brain hypoxia-ischemia (HI). The present study aimed to investigate the effects of maternal environmental enrichment (EE) on HI-induced energetic and metabolic failure, along with subsequent neural cell responses in the early postnatal period. Male Wistar pups born to dams exposed to maternal EE or standard conditions (SC) were randomly divided into Sham-SC, HI-SC, Sham-EE, and HI-EE groups. Neonatal HI was induced on postnatal day (PND) 3. The Na+,K+-ATPase activity, mitochondrial function and neuroinflammatory related-proteins were assessed at 24 h and 48 h after HI. MicroPET-FDG scans were used to measure glucose uptake at three time points: 24 h post-HI, PND18, and PND24. Moreover, neuronal preservation and glial cell responses were evaluated at PND18. After HI, animals exposed to maternal EE showed an increase in Na+,K+-ATPase activity, preservation of mitochondrial potential/mass ratio, and a reduction in mitochondrial swelling. Glucose uptake was preserved in HI-EE animals from PND18 onwards. Maternal EE attenuated HI-induced cell degeneration, white matter injury, and reduced astrocyte immunofluorescence. Moreover, the HI-EE group exhibited elevated levels of IL-10 and a reduction in Iba-1 positive cells. Data suggested that the regulation of AKT/ERK1/2 signaling pathways could be involved in the effects of maternal EE. This study evidenced that antenatal environmental stimuli could promote bioenergetic and neural resilience in the offspring against early HI damage, supporting the translational value of pregnancy-focused environmental treatments.

Complex pattern of the myelo-monocytic differentiation antigens MRP8 and MRP14 during chronic airway inflammation.

One of the characteristics of cystic fibrosis is the presence of the so-called cystic fibrosis antigen in the plasma of patients. The CF-antigen has been shown to consist of the two calcium-binding proteins MRP8 and MRP14. In the present study we investigate first whether elevated plasma titers of MRP8 and MRP14 are linked to the primary defect of CF or are rather a result of chronic airway inflammation; and second, whether the known complexes of these proteins may have in vivo relevance during inflammation. By employing the ELISA technique we measured MRP8 and MRP14 levels in the plasma of patients suffering from CF or nonspecific chronic bronchitis (CB) and of healthy controls, in sputum of CF and CB patients, and in saliva of CF patients and healthy controls, respectively. We found elevated plasma concentrations of both proteins in CF and CB patients compared to healthy controls. Levels correlated significantly with systemic and local signs of disease activity (i.e. c-reactive protein (CRP), daily sputum production). MRP8 and MRP14 both were found in high amounts at similar concentrations in sputum of CF and CB patients and, to a lesser extent, in saliva of CF patients and healthy donors. After covalent cross-linking at least three different complexes composed of MRP8 and MRP14 with approximate molecular weights of about 25, 35 and 48 kDa were detected in all samples. From this we conclude that the elevated plasma levels of MRP8 and MRP14 in CF and CB are the result of inflammatory processes. Further, possible biological functions of these proteins seem to be associated with complexed forms of MRP8 and MRP14 rather than with individual proteins.

Prevalence of excessive gambling before and after introduction of a national lottery in the United Kingdom: another example of the single distribution theory.

BACKGROUND: According to the single distribution theory advocated by Rose, the prevalence of a deviant condition such as excessive alcohol consumption depends upon the average level of the corresponding characteristic in the population. The objective of this study was to establish whether the single distribution theory applies to gambling behaviour. METHODS: Household gambling expenditure in the United Kingdom was examined using Family Expenditure Survey data collected before and after the introduction of a national lottery in November 1994. RESULTS: In cross-sectional analyses, the mean (or median) household expenditure on gambling for each region predicted the prevalence of excessive gambling in that region: the slope of the relationship in 1995-96 was equivalent to an increase of 1.2 (95% CI 0.7-1.7) points in the percentage of households gambling more than 10% of income for every increase of 1 Pound in mean household gambling expenditure. The introduction of the national lottery was associated with an increase in mean household gambling expenditure from 1.45 Pounds to 3.81 Pounds per week, and an increase in the proportion of households gambling more than 10% of total income four-fold from 0.4% to 1.7%. Among households with income of less than 200 Pounds/week, the proportion gambling more than 10% of their income increased from 0.6% to 3.2%. INTERPRETATION: The single distribution theory applies to gambling behaviour. The increase in average gambling expenditure associated with the introduction of a national lottery in the United Kingdom has led to a pronounced increase in the prevalence of excessive gambling, especially in low-income households. This is likely to increase the prevalence of gambling disorders and to exacerbate social inequalities in health.

Comparison of two methods of screening for genital chlamydial infection in women attending in general practice: cross sectional survey.

OBJECTIVES: To estimate the prevalence of Chlamydia trachomatis in asymptomatic women attending general practice: to assess the potential of the ligase chain reaction as a screening tool; and to evaluate selective screening criteria. DESIGN: Cross sectional survey. SETTING: Four general practices in northeast London. SUBJECTS: 890 women aged 18-35 years attending general practice for a cervical smear or a "young well woman" check between October 1994 and January 1996. The women were tested for C trachomatis with confirmed enzyme immunoassay (endocervical specimens) and ligase chain reaction assay on urine specimens. MAIN OUTCOME MEASURES: Prevalence of C trachomatis infection in women aged 18-35 on the basis of each test; sensitivity and specificity of both tests in this population. RESULTS: Prevalence of confirmed infection was 2.6% (95% confidence interval 1.6% to 3.6%) in all women. Prevalence on the basis of enzyme immunoassay was 1.6% (0.8% to 2.7%), with a sensitivity of 60% and a specificity of 100%. Prevalence on the basis of ligase chain reaction was 2.5% (1.5% to 3.9%), with 90% sensitivity and 99.8% specificity. Screening all women aged < or = 25 and all women who had had two or more partners in the past year would have detected 87% (20/23) of infections. CONCLUSION: Ligase chain reaction on urine samples performs at least as well as enzyme immunoassay on cervical specimens in this low prevalence population. It offers potential as a non-invasive screening tool. A simple selective screening strategy might be appropriate and would be able to detect most cases of infection. However, a rigorous economic evaluation of possible screening strategies is needed first.

[Quality assurance in the diagnosis of indoor fungi]. / Ringversuch "Innenraumrelevante Schimmelpilze".

In co-ordination with the Umweltbundesamt Berlin, the Landesgesundheitsamt Baden-Wurttemberg (LGA) initiated external quality assurance in the diagnosis of indoor fungi in autumn 2001. Four of six fungal strains commonly found indoors have to be fully identified (on the genus and species level). There are two distributions per year; the six distributions hitherto carried out resulted in correct identification by 46-89% of laboratories (40-71 participants, total 148). It is clear from the results that repeat participants were more successful. In addition to the pure cultures sent out we offered actual samples (two air samples, one wood material, one sample of house dust, hitherto); 43- 69% of participating laboratories also took part in this facultative investigation of actual samples and 29-62% were successful. Results that differed considerably revealed problems while treating and evaluating actual samples. Therefore, activities in this field should be enhanced. In conclusion, external quality assurance in the diagnosis of indoor fungi is a useful management aid in the maintenance and improvement of laboratory performance.

[Possibilities and limitations in the localisation of sources of infections (author's transl)]. / Möglichkeiten und Grenzen der Ermittlung von Infektionsquellen.

In latent microbial hospitalism environmental checks of the patients, the staff and objects permit detection of pathogenic or potentially pathogenic bacteria which are silent epidemiologically. "One's own body" as a source of infection has not yet been sufficiently investigated in connection with auto-infections. Taking two staphylococcal epidemics as examples, reference is made to the monogenic and heterogenic forms of hospitalism as well as to the necessity of accurately identifying the strains for the purpose of localising the source of infection. In the monogenic form only one type of bacterial species is present (Table 2). In heterogenic hospitalism, infections are caused by various different species of bacteria or also by a single species. If this is the case, various biotypes, serotypes and phagotypes exist (Table 1). In addition, simple possibilities of biotyping the staphylococci are demonstrated. Defensive measures can be adopted selectively only when the epidemiology and the source of infection are known.

Acceptability of shared care for asymptomatic HIV-positive patients.

In Britain, Human Immunodeficiency Virus (HIV) disease has been seen as an illness requiring specialist hospital care at all times. However, as its chronic nature has become apparent, the possibiliity that it could be managed more cost effectively in primary care has been raised. This has led to increasing interest in 'shared care', that is, care which is shared between a general practitioner and a specialist according to clear protocols, for this group of patients. However, for 'shared care' to be a success, it must be acceptable to all concerned: patients, GPs and specialists. This paper presents our experience of recruiting asymptomatic HIV-positive patients into a shared care programme: after 10 months' recruitment only 19 of 128 eligible patients had accepted the offer of shared care. The reasons for this, and alternative strategies for increasing GP involvement, are discussed.

[Disinfection of the inspired and expired air during artificial respiration with humified gases]. / Experimentelle Untersuchungen zur Desinfektion der In- und Exspirationsluft bei künstlich angefeuchteter Luft

The water in the nebulizer of respirators is a potential source of infection for patients receiving artificial respiration. Interposition of a special equipment that will produce ozone-free ultraviolet radiation will prevent infection of the patient by the inspired humidified air, even if the bacterial count in the nebulizer fluid is very high. Interposition of the same equipment on the expiratory side is also recommended to minimize the risk of infection of the environment by bacteria in the expired air.

[Bacteriological and parasitological investigations in public indoor swimming baths (author's transl)]. / Bakteriologisch-parasitologische Untersuchungen in öffentlichen Hallenbädern

The importance of the public swimming bath for the dissemination of Trichomonas vaginalis is disputed. 30 samples, each of 250 ml bath water from four indoor swimming baths, were examined for trichomonads. All the samples were negative. 218 smears taken from the wet places on the heated benches and other seating accommodation in these swimming baths were cultured for trichomonads and bacteria. Trichomonas vaginalis could not be demonstrated. Fecal organisms were found in 56 places, antibiotic-sensitive staphylococci were cultured from 20 samples and Ps. aeruginosa from 8. The negative tests for trichomonads suggests that the indoor swimming bath has no epidemiological importance in the dissemination of this parasite.

[Role of direct radiographic magnification in the evaluation of various morphological changes]. / Znachenie rentgenografii s priamym uvelicheniem v otsenke nekotorykh morfologicheskikh izmenenii.

Radiograms with direct enlargement of the image were performed by means of X-ray apparatus "PEIC" designed by the firm "Svetlana", Leningrad. The status of the hand bones was studied in persons with posttraumatic bone regeneration, as well as angioarchitectonics of organs in experimental animals. In radiograms with direct enlargement some details characterising the process of ageing in the hand bones are observed more distinctly than in routine radiograms. The investigators succeeded in obtaining age changes in the structure of spongy substance and of cortical layer of phalanxes. The apparatus "PEIC" presents new possibilities for vital investigation of bone ostructures in experimental and clinical work, as well as to examine preparations of organs and their histological sections.

[Recent methods for the detection of airborne microorganisms and source identification]. / Neuere Methoden zum Nachweis luftgetragener Mikroorganismen und zur Quellenidentifikation.

The detection of airborne microorganisms including selected cell constituents (e.g. allergens or endotoxins) depends on suitable methods and instruments for their collection. Furthermore, microbiological methods are necessary for their quantification and qualification. In the past these methods were largely based on the classical cultivation dependent approach. Modern molecular methods, e.g. direct staining procedures, hybridization assays with nucleic acids including the PCR-technology or immunological assays are promising new tools for a more sophisticated detection of bioaerosols. They allow a better detection rate, a more precise identification of certain members of the aerosol including cell constituents. With respect to speed and lower costs they are an important alternative to established detection methods.