bluuebunny/crossref_metadata_2025 huggingface dataset:
Breath analysis during one-lung ventilation in cancer patients
Authors: Kischkel Sabine , Miekisch Wolfram , Fuchs Patricia , Schubert Jochen K.
Published: January 2012

Noninvasive breath analysis may provide valuable information for cancer recognition if disease-specific volatile biomarkers could be identified. In order to compare nondiseased and diseased tissuein vivo, this study took advantage of the special circumstances of one-lung ventilation (OLV) during lung-surgery.

15 cancer patients undergoing lung resection with OLV were enrolled. From each patient, alveolar breath samples were taken separately from healthy and diseased lungs before and after tumour resection. Volatile substances were pre-concentrated by means of solid-phase microextraction, and were separated, identified and quantified by means of gas chromatography–mass spectrometry.

Different classes of volatile substances could be identified according to their concentration profiles. Due to prolonged fasting and activation of lipolysis, concentrations of endogenous acetone significantly increased during surgery. Exogenous substances, such as benzene or cyclohexanone, showed typical washout exhalation kinetics. Exhaled concentrations of potentially tumour associated substances, such as butane or pentane, were different for nondiseased and diseased lungs and decreased significantly after surgery.

Separate analysis of volatile substances exhaled from healthy and diseased lungs in the same patient, together with thorough consideration of substance origins and exhalation kinetics offers unique opportunities of biomarker recognition and evaluation.
Costs of childhood asthma due to traffic-related pollution in two California communities
Authors: Brandt Sylvia J. , Perez Laura , Künzli Nino , Lurmann Fred , McConnell Rob
Published: January 2012

Recent research suggests the burden of childhood asthma that is attributable to air pollution has been underestimated in traditional risk assessments, and there are no estimates of these associated costs. We aimed to estimate the yearly childhood asthma-related costs attributable to air pollution for Riverside and Long Beach, CA, USA, including: 1) the indirect and direct costs of healthcare utilisation due to asthma exacerbations linked with traffic-related pollution (TRP); and 2) the costs of health care for asthma cases attributable to local TRP exposure.

We calculated costs using estimates from peer-reviewed literature and the authors’ analysis of surveys (Medical Expenditure Panel Survey, California Health Interview Survey, National Household Travel Survey, and Health Care Utilization Project). A lower-bound estimate of the asthma burden attributable to air pollution was US$18 million yearly. Asthma cases attributable to TRP exposure accounted for almost half of this cost. The cost of bronchitic episodes was a major proportion of both the annual cost of asthma cases attributable to TRP and of pollution-linked exacerbations.

Traditional risk assessment methods underestimate both the burden of disease and cost of asthma associated with air pollution, and these costs are borne disproportionately by communities with higher than average TRP.
Measurement of parasternal intercostal electromyogram during an infective exacerbation in patients with cystic fibrosis
Authors: Reilly Charles C. , Jolley Caroline J. , Elston Caroline , Moxham John , Rafferty Gerrard F.
Published: January 2012

The parasternal intercostal muscle electromyogram (sEMGpara) is a measure of neural respiratory drive and reflects lung disease severity in stable cystic fibrosis (CF). The aim of the study was to measure sEMGpara in acute infective exacerbations of CF and compare changes in sEMGpara with those in conventional lung function measures.

12 patients with CF admitted to hospital with an acute chest infection were studied.

There was a significant reduction in mean±sdsEMGpara (ΔsEMGpara -38±19%, p<0.001) between admission and discharge. Spirometery also improved significantly from admission to discharge; Δforced expiratory volume in 1 s % predicted 39±30%, p<0.001 and Δvital capacity % pred 22±18%, p<0.001.

sEMGpara has potential value as a nonvolitional measure of change in respiratory function in CF.
GenoType MTBDRslperformance on clinical samples with diverse genetic background
Authors: Miotto Paolo , Cabibbe Andrea M. , Mantegani Paola , Borroni Emanuele , Fattorini Lanfranco , Tortoli Enrico , Migliori Giovanni B. , Cirillo Daniela M.
Published: January 2012

We evaluate the performance of the GenoType® MTBDRsl(Hain Lifescience Nehren, Germany) for the detection of second-line resistant tuberculosis and we correlate the frequency of mutations to differentMycobacterium tuberculosisgenotypes.

We tested 175 strains and 59 clinical specimens interpreting the results according to the Standards for Reporting of Diagnostic Accuracy recommendations. All the strains were also investigated by spoligotyping and Mycobacterial Interspersed Repetitive Units–Variable Number of Tandem Repeats typing.

The performances of the MTBDRslin detecting resistance to fluoroquinolones (FQ), second-line injectable drugs (SLID), and ethambutol (EMB) on clinical isolates were similar (specificity ∼99%, sensitivity ∼70%, and positive predictive value (PPV) ∼99%).

Of the 59 respiratory specimens, three samples were classified as “indeterminate”. The specificity in detecting resistances was similar for FQs and EMB 100% (95% CI 92.7–100%) and 100% (95% CI 83.9–100%), respectively with a PPV of 100% (95% CI 64.6–100%) and 100% (95% CI 87.9–100%), respectively. Detection of SLID showed a specificity of 89.1% (95% CI 77.0–95.3%) and a PPV of 58.3% (95% CI 32.0–80.7%). Sensitivity for FQ-resistance detection was 100% (95% CI 64.6–100%), whereas for SLID and EMB it was 89.1% (95% CI 77.0-95.3%) and 86.1% (95% CI 71.3-93.9%), respectively. We detected a significant association between mutations in therrsgene and Beijing lineage.

The MTBDRslcan be used to “rule in” extensively drug-resistant strains of tuberculosis in a high risk group; the low sensitivity and negative predicted value (NPV) make confirmation by conventional drug susceptibility testing mandatory when mutations are not identified. NPV for SLID is higher in Beijing strains, showing that the predictive values of the molecular tests are related to the genetic background.
Community-acquired pneumonia in outpatients: aetiology and outcomes
Authors: Cillóniz Catia , Ewig Santiago , Polverino Eva , Marcos Maria Angeles , Prina Elena , Sellares Jacobo , Ferrer Miquel , Ortega Mar , Gabarrús Albert , Mensa Josep , Torres Antoni
Published: January 2012

The purpose of this study was to establish the microbial aetiology and outcomes of patients with community-acquired pneumonia (CAP) treated as outpatients after presenting to a hospital emergency care unit.

A prospective observational study was carried out in the Hospital Clinic of Barcelona (Barcelona, Spain). All consecutive cases of CAP treated as outpatients were included.

568 adult outpatients with CAP were studied (mean±sdage 47.2±17.6 yrs; 110 (19.4%) were aged ≥65 yrs). Aetiological diagnoses were established in 188 (33.1%) cases.Streptococcus pneumoniaewas the most frequent pathogen followed byMycoplasma pneumoniaeand respiratory viruses.Legionellawas detected in 13 (2.3%) cases. More than one causative agent was found in 17 (9.0%) patients. Mortality was low (three (0.5%) patients died) and other adverse events were rare (30 (5.2%) patients had complications, 13 (2.3%) were re-admitted and treatment failed in 13 (2.3%)). Complications were mostly related to pleural effusion and empyema, and re-admissions and treatment failures to comorbidities.

Outpatients with CAP have a characteristic microbial pattern. Regular antipneumococcal coverage remains mandatory. Treatment failures and re-admissions are rare and may be reduced by increased attention to patients requiring short-term observation in the emergency care unit and in the presence of pleural effusion and comorbidities.
Increased oxygen pulse after lung volume reduction surgery is associated with reduced dynamic hyperinflation
Authors: Lammi Matthew R. , Ciccolella David , Marchetti Nathaniel , Kohler Malcolm , Criner Gerard J.
Published: January 2012

Stroke volume augmentation during exercise is limited in chronic obstructive pulmonary disease patients because of decreased preload from dynamic hyperinflation (DH). We hypothesised that oxygen pulse and pulse pressure (PP) improve following lung volume reduction surgery (LVRS), and the magnitude of improvement correlates with reduction in DH.

We compared 16 emphysema patients undergoing LVRS with six emphysema patients not undergoing LVRS. Oxygen pulse and PP were calculated from maximal cardiopulmonary exercise tests at baseline and 6 months. End-expiratory lung volume (EELV)/total lung capacity (TLC) represented DH. Comparisons were made between baseline and 6 months at metabolic isotimes (per cent maximal carbon dioxide production (V′CO2,max)).

At baseline, the LVRS group was older with higher forced expiratory volume in 1 s, but had similar hyperinflation to the non-LVRS group. At 6 months, oxygen pulse (50%, 75%, and 100%V′CO2,max) and PP (50% and 75%V′CO2,max) increased in the LVRS, but not in the non-LVRS group. Baseline functional residual capacity/TLC inversely correlated with resting oxygen pulse (r= -0.449, p=0.04). Decreased EELV/TLC correlated with increased oxygen pulse at 75% (r= -0.487, p=0.02) and 100%V′CO2,max(r= -0.548, p=0.008).

LVRS led to increased oxygen pulse and PP during exercise at metabolic isotimes 6 months following surgery. Reductions in DH correlated with increases in oxygen pulse during exercise. Reducing lung volume may improve stroke volume response to exercise by decreasing DH.
Massive monoclonal expansion of CD4 T-cells specific for aMycobacterium tuberculosisESAT-6 peptide
Authors: Hodapp Tobias , Sester Urban , Mack Ulrich , Singh Mahavir , Meier Thomas , Wiech Elisabeth , Fisch Paul , Ehl Stephan , Sester Martina
Published: January 2012

T-cell responses towards tuberculin (purified protein derivative; PPD) or theMycobacterium tuberculosis-specific antigens early secretory antigenic target (ESAT)-6 and culture filtrate protein-10 are indicative of prior contact with mycobacterial antigens. In this study, we investigated the exceptional case of a 75-yr-old patient who devoted more than one-third of his CD4 T-cells against PPD and ESAT-6.

Antigen-specific T-cells were characterised using flow cytometric intracellular cytokine staining, ELISPOT assay, proliferation assays, and T-cell receptor spectratyping.

T-cell frequencies were far above those found in age-matched controls (median 0.33%, range 0.05–6.32%) and remained at high levels for >2 yrs. The patient initially presented with haemoptysis, but active tuberculosis was ruled out by repeated analysis of sputum and bronchoalveolar lavage fluid. Skin testing was negative and haemoptyses did not have aM. tuberculosis-related aetiology. Phenotypical and functional properties of specific T-cells were consistent with a terminally differentiated effector-memory phenotype with capacity to produce interferon-γ, interleukin-2 and tumour necrosis factor-α. Epitope mapping showed that the CD4 T-cells were directed against a single peptide from ESAT-6 (amino acid 5–20) that was presented in context of HLA-DR. T-cell receptor Vβ-spectratyping and sequencing of specific CD4 T-cells revealed a prominent peak fraction of monoclonal origin.

In conclusion, similar to monoclonal gammopathies of undetermined significance, this may represent the first T-cell counterpart with known specificity againstM. tuberculosis.
Effects of 8 weeks of continuous positive airway pressure on abdominal adiposity in obstructive sleep apnoea
Authors: Sivam Sheila , Phillips Craig L. , Trenell Michael I. , Yee Brendon J. , Liu Peter Y. , Wong Keith K. , Grunstein Ronald R.
Published: January 2012

The aim of the present study was to investigate the effect of continuous positive airway pressure (CPAP) treatment on regional adipose tissue distribution in patients with moderate or severe obstructive sleep apnoea.

Patients received both therapeutic and sham CPAP in a random order for 2 months each with an intervening 1-month washout. Abdominal subcutaneous, visceral and liver fat were quantified using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Liver enzymes and plasma glucose were also determined. Measurements were obtained at baseline and at the end of both treatment arms.

38 eligible patients were randomly assigned to a treatment order, with 27 patients having complete MRI/MRS data. No significant difference was observed in subcutaneous (-28.6 cm3; p=0.49) or visceral (-16.8 cm3; p=0.59) adipose tissue, intrahepatic lipid (-0.2%; p=0.21), or fasting glucose measurements (-0.1 mmol·L−1; p=0.46) between treatment modalities. Alkaline phosphatase decreased (-3.1 U·L−1; p=0.02) while on therapeutic CPAP compared with sham CPAP but other liver enzymes, including aspartate aminotransferase (0.3 U·L−1; p=0.82), alanine aminotransferase (1.34 U·L−1; p=0.59) and γ-glutamyltransferase (-2.3 U·L−1; p=0.33), remained unchanged.

In this first randomised, sham-controlled trial, there was no change in adipose tissue distribution after 8 weeks of therapeutic CPAP compared with 8 weeks of sham CPAP. Longer duration of CPAP use may be necessary to demonstrate a difference.
Social determinants of tuberculosis in Europe: a prospective ecological study
Authors: Ploubidis George B. , Palmer Melissa J. , Blackmore Charlotte , Lim Tek-Ang , Manissero Davide , Sandgren Andreas , Semenza Jan C.
Published: January 2012

Tuberculosis (TB) is considered to be a disease of poverty, since its incidence is exacerbated by socioeconomic factors, inconsistent or partial treatment practices, and immigration from endemic countries.

A prospective country level study, using a comprehensive dataset of TB incidence and prevalence taken from countries within the World Health Organization (WHO) European region, was conducted. We employed quintile regression to investigate the prospective association between baseline (measured in 2000) and a nation’s wealth, level of egalitarianism, migration rate, health-related lifestyle and social capital with TB incidence and prevalence over a 10-yr period (2000–2009).

We found that ∼50% of TB variation is accounted for by a nation's wealth and level of egalitarianism. We observed a negative prospective association between logged gross domestic product and TB rates, and a positive prospective association between income inequality and TB.

National income levelsper capitaand income inequality are important predictors for TB incidence and prevalence in the WHO European region. They account for 50% of country-level variation, indicating the importance of a combined absolute and relative socioeconomic disadvantage in the development of TB. These findings also provide a tool for forecasting potential fluctuations in the level of TB epidemics in the WHO European region, with respect to socioeconomic changes.
Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis
Authors: Elborn J. Stuart , Perrett John , Forsman-Semb Kristina , Marks-Konczalik Joanna , Gunawardena Kulasiri , Entwistle Neil
Published: January 2012

The aim of this study was to evaluate the safety and effect on clinical outcomes and biomarkers of inflammation and tissue damage of the neutrophil elastase inhibitor AZD9668 (60 mg twice daily orally for 4 weeks) in cystic fibrosis.

This was a randomised, double-blind, placebo-controlled study. Primary outcome measures were sputum neutrophil count, lung function, 24-h sputum weight, BronkoTest® diary card data and health-related quality-of-life (revised cystic fibrosis quality-of-life questionnaire). Secondary end-points included sputum neutrophil elastase activity, inflammatory biomarkers in sputum and blood, urine and plasma desmosine (an elastin degradation marker), AZD9668 levels and safety parameters (adverse events, routine haematology, biochemistry, electrocardiogram and sputum bacteriology).

56 patients were randomised, of which 27 received AZD9668. There was no effect for AZD9668 on sputum neutrophil counts, neutrophil elastase activity, lung function or clinical outcomes, including quality of life. In the AZD9668 group, there was a trend towards reduction in sputum inflammatory biomarkers with statistically significant changes in interleukin-6, RANTES and urinary desmosine. The pattern of adverse events was similar between groups.

Consistent reductions in sputum inflammatory biomarkers were seen in the AZD9668 group, and reduction in urinary desmosine suggests that AZD9668 impacts elastin cleavage by neutrophil elastase.
Effects of C-reactive protein on human pulmonary vascular cells in chronic thromboembolic pulmonary hypertension
Authors: Wynants Marijke , Quarck Rozenn , Ronisz Alicja , Alfaro-Moreno Ernesto , Van Raemdonck Dirk , Meyns Bart , Delcroix Marion
Published: January 2012

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by proximal pulmonary vascular obstruction by thrombo-fibrotic material, the origin of which has not been elucidated. Enhanced inflammation could contribute to persistent obstruction by impairing pulmonary vascular cell function in CTEPH. We investigated C-reactive protein (CRP) effects on pulmonary vascular cell functionin vitro.

Primary cultures of proximal pulmonary endothelial cells (ECs) and smooth muscle cells (SMCs) from CTEPH and nonthromboembolic pulmonary hypertension (PH) patients were established. Recombinant CRP effects on mitogenic activity, adhesion capacity, endothelin-1 and von Willebrand factor (vWF) secretion and intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1 expression were investigated in ECs and/or SMCs. Expression of the CRP receptor, lectin-like oxidised low-density lipoprotein receptor (LOX)-1, was evaluated in proximal pulmonary arterial tissue and cells by Western blotting and immunofluorescence.

CRP increased CTEPH-SMC proliferation by 250%. CRP increased adhesion capacity, endothelin-1 and vWF secretion by CTEPH-ECs by 37%, 129% and 694%, respectively. CRP-induced adhesion of CTEPH-ECs to monocytes was mediated by ICAM-1. CRP had no effect on cells from nonthromboembolic PH patients, probably because of overexpression of LOX-1 in CTEPH. Local expression of CRP was detected in ECs and SMCs within pulmonary arterial tissue.

CRP may contribute to persistent obstruction of proximal pulmonary arteries in CTEPH by promoting vascular remodelling, endothelial dysfunction andin situthrombosis.
The role of MglA for adaptation to oxidative stress of Francisella tularensis LVS
Authors: Honn Marie , Lindgren Helena , Sjöstedt Anders
Published: January 2012

Background

The Francisella tularensis protein MglA performs complex regulatory functions since it influences the expression of more than 100 genes and proteins in F. tularensis. Besides regulating the igl operon, it has been suggested that it also regulates several factors such as SspA, Hfq, CspC, and UspA, all important to stress adaptation. Therefore, it can be hypothesized that MglA plays an important role for Francisella stress responses in general and for the oxidative stress response specifically.

Results

We investigated the oxidative stress response of the ΔmglA mutant of the live vaccine strain (LVS) of F. tularensis and found that it showed markedly diminished growth and contained more oxidized proteins than the parental LVS strain when grown in an aerobic milieu but not when grown microaerobically. Moreover, the ΔmglA mutant exhibited an increased catalase activity and reduced expression of the fsl operon and feoB in the aerobic milieu. The mutant was also found to be less susceptible to H2O2. The aberrant catalase activity and gene expression was partially normalized when the ΔmglA mutant was grown in a microaerobic milieu.

Conclusions

Altogether the results show that the ΔmglA mutant exhibits all the hallmarks of a bacterium subjected to oxidative stress under aerobic conditions, indicating that MglA is required for normal adaptation of F. tularensis to oxidative stress and oxygen-rich environments.
The prevalence of metabolic syndrome and cardiovascular risk factors in adults in southern China
Authors: Lao Xiang Qian , Zhang Yong Hui , Sang Wong Martin Chi , Xu Yan Jun , Xu Hao Feng , Nie Shao Ping , Ma Wen Jun , Thomas G Neil , Sun Yu Ignatius Tak
Published: January 2012

Background

The metabolic syndrome has been shown to increase the incidence of cardiovascular disease. Little information exists on the prevalence of the metabolic syndrome for southern Chinese. We therefore investigate the prevalence of the metabolic syndrome in a southern Chinese population with 85 million residents.

Methods

The Guangdong Nutrition and Health Survey 2002 is a cross-sectional survey designed to assess the health and nutritional status of 85 million residents in Guangdong province located in southern China. Stratified multistage random sampling method was applied in this survey and a provincial representative sample of 6,468 residents aged 20 years or above was obtained in the present study. The participants received a full medical check-up including measurement of blood pressure, obesity indices, fasting lipids and glucose levels. Data describing socioeconomic and lifestyle factors was also collected through interview. Metabolic syndrome was defined in accordance with the International Diabetes Federation criteria.

Results

The prevalence of metabolic syndrome was 7.30%, translating into a total of 4.0 million residents aged 20 years or above having the condition in this southern Chinese population. The urban population had higher prevalence of the syndrome than the rural population (10.57% vs 4.30%). Females had a higher prevalence of metabolic syndrome than males (8.99% vs 5.27%). More than 60% of the adults had at least one component of the metabolic syndrome.

Conclusions

Our results indicate that a large proportion of southern Chinese adults have the metabolic syndrome and associated risk factors. The metabolic syndrome has become an important public health problem in China. These findings emphasize the urgent need to develop population level strategies for the prevention, detection, and treatment of cardiovascular risk in China.
Do positive or negative experiences of social support relate to current and future health? Results from the Doetinchem Cohort Study
Authors: Croezen Simone , Picavet H Susan J , Haveman-Nies Annemien , Verschuren WM Monique , de Groot Lisette CPGM , van't Veer Pieter
Published: January 2012

Background

Cross-sectional studies have reported associations between social support and health, but prospective evidence is less conclusive. This study aims to investigate the associations of positive and negative experiences of social support with current and future lifestyle factors, biological risk factors, self-perceived health and mental health over a 10-year period.

Methods

Data were from 4,724 Dutch men and women aged 26-65 years who participated in the second (1993-1997) and in the third (1998-2002) or fourth (2003-2007) study round of the Doetinchem Cohort Study. Social support was measured at round two using the Social Experiences Checklist. Health was assessed by several indicators such as smoking, alcohol consumption, physical activity, fruit and vegetable intake, overweight, hypertension, hypercholesterolemia, self-perceived health and mental health. Tertiles of positive and negative experiences of social support were analysed in association with repeated measurements of prevalence and incidence of several health indicators using generalised estimating equations (GEE).

Results

Positive and negative experiences of social support were associated with prevalence and incidence of poor mental health. For the lowest tertile of positive support, odds ratios were 2.74 (95% CI 2.32-3.23) for prevalent poor mental health and 1.86 (95% CI 1.39-2.49) for incident poor mental health. For the highest tertile of negatively experienced support, odds ratios for prevalent and incident poor mental health were 3.28 (95% CI 2.78-3.87) and 1.60 (95% CI 1.21-2.12), respectively. Low levels of positive experiences of social support were also associated with low current intake of fruits and vegetables, but not with future intake. Negative experiences of social support were additionally associated with current smoking, physical inactivity, overweight and poor self-perceived health. Furthermore, high levels of negative experiences of social support were associated with future excessive alcohol consumption (OR 1.42; 95% CI 1.10-1.84), physical inactivity (95% CI 1.28; 1.03-1.58) and poor self-perceived health (OR 1.36; 95% CI 1.01-1.82).

Conclusions

This study showed that social support might have a beneficial effect on lifestyle and health, with negative experiences of social support affecting lifestyle and health differently from positive experiences of social support.
Environmental manipulation for edible insect procurement: a historical perspective
Authors: Van Itterbeeck Joost , van Huis Arnold
Published: January 2012

Throughout history humans have manipulated their natural environment for an increased predictability and availability of plant and animal resources. Research on prehistoric diets increasingly includes small game, but edible insects receive minimal attention. Using the anthropological and archaeological literature we show and hypothesize about the existence of such environmental manipulations related to the procurement of edible insects. As examples we use eggs of aquatic Hemiptera in Mexico which are semi-cultivated by water management and by providing egg laying sites; palm weevil larvae in the Amazon Basin, tropical Africa, and New Guinea of which the collection is facilitated by manipulating host tree distribution and abundance and which are semi-cultivated by deliberately cutting palm trees at a chosen time at a chosen location; and arboreal, foliage consuming caterpillars in sub-Saharan Africa for which the collection is facilitated by manipulating host tree distribution and abundance, shifting cultivation, fire regimes, host tree preservation, and manually introducing caterpillars to a designated area. These manipulations improve insect exploitation by increasing their predictability and availability, and most likely have an ancient origin.
A forgotten collection: the Libyan ethnobotanical exhibits (1912-14) by A. Trotter at the Museum O. Comes at the University Federico II in Naples, Italy
Authors: De Natale Antonino , Pollio Antonino
Published: January 2012

Background

The Ethnobotanical Collection from the Libyan territories of the botanist Alessandro Trotter is included in the Oratio Comes Botanical Museum at the Faculty of Agraria at the University Federico II in Naples. Trotter explored different territories of Libya, mainly Tripolitania, between 1912-1924, collecting plant specimens and the drugs most frequently sold in the markets. The Libyan herbarium currently includes over 2300 sheets of mounted and accessioned plants. The drugs, mostly acquired by Trotter from Tripolitanian markets, were identified and packed in 87 paper sheets or boxes. Trotter added ethnobotanical information for each species when available.

Methods

A database of the herbarium species and the drugs has been carried out, after a taxonomic update. Nomenclature has been revised according to the African flowering plants database and the World Checklist of selected plant families, and a comparison with currently available ethnopharmacological data from North African has been attempted.

Results

In this study, ethnopharmacological data related to about 80 species of flowering plants and to 4 lichens are presented. The plants are mainly from Mediterranean or Sub-Saharan habitats and belong to 37 different families; Lamiaceae was the most cited family, with 10 accessions. Generally, the aerial parts of the plants are the most frequently used (28 species), followed by leaves (15 species), flowers and seeds (9 species), fruits (7 species) and hypogean organs (roots, rhizomes, tubers: 5 species). Plants were generally processed in very simple ways: infusion or decoction of the plants were prepared and orally administered or used for topical applications. A wide range of conditions was treated, ranging from mental disorders to skin affections. All the organs of human body are considered, but the pathologies of gastro-intestinal tract, respiratory system and those related to traumatic accidents were the most frequently mentioned. The comparison with the recent ethnopharmacological research in Maghreb and its neighboring countries reveals a high correspondence; almost all the plants cited by Trotter are still used in the folk medicine of at least one of the North African countries, and the therapeutic uses of each plant appear consistent over time.

Conclusions

The information collected by Trotter is an important contribution to tracing plant utilization in Libyan folk medicine over the last century.
Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism
Authors: Song Ju-Xian , Choi Mandy Yuen-Man , Wong Kavin Chun-Kit , Chung Winkie Wing-Yan , Sze Stephen Cho-Wing , Ng Tzi-Bun , Zhang Kalin Yan-Bo
Published: January 2012

Background

Two active compounds, baicalein and its glycoside baicalin were found in the dried root of Scutellaria baicalensis Georgi, and reported to be neuroprotective in vitro and in vivo. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism.

Methods

Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS) and loss of mitochondrial membrane potential (ΔΨm) were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots.

Results

Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2.

Conclusion

The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells.
Epidemiological, clinical features and susceptibility pattern of shigellosis in the buea health district, Cameroon
Authors: Njunda Anna L , Assob Jules CN , Nsagha Dickson S , Kamga Henri LF , Awafong Maghah P , Weledji Elroy P
Published: January 2012

Background

Shigellosis is an acute invasive enteric infection caused by bacteria belonging to the genus Shigella; it is clinically manifested by bloody diarrhoea. Shigellosis is endemic in many developing countries including Cameroon and also occurs in epidemics causing considerable morbidity and mortality. This study evaluated the epidemiological and clinical features of Shigella and the resistance pattern of isolates to commonly used antibiotics in the Buea Health District in Cameroon, from April to August, 2010.

Results

Of the 223 stool samples cultured, 10 (4.5%) yielded Shigella species. Isolation rate was observed to be more in children below 15 years (7.89%), and also higher in rural areas (6.35%). All 10 isolates showed resistance to at least two antibiotics and 9 (90%) were multi-drug resistant. The highest resistance rates were encountered with cotrimoxazole (90%) and amoxicillin (80%). Least resistance was observed with azithromycin (10%).

Conclusion

Shigellosis is more prevalent in children below 15 years in the Buea District. There is a high level of resistance to most of the antibiotics used for the treatment of shigellosis including extended-spectrum beta-lactamases (ESBLs) as well as evidence of resistance to quinolones. Azithromycin was found to be the drug of choice for shigellosis in this setting.
Beta-catenin is selectively required for the expansion and regeneration of mature pancreatic acinar cells
Authors: Keefe Matthew , Wang Hui , De La O Jean-Paul , Khan Ameena , Firpo Matthew A. , Murtaugh L. Charles
Published: January 2012

The size of the pancreas is determined by intrinsic factors, such as the number of progenitor cells, and by extrinsic signals that control the fate and proliferation of those progenitors. Both the exocrine and endocrine compartments of the pancreas undergo dramatic expansion after birth, and are capable of at least partial regeneration following injury. Whether the expansion of these lineages relies on similar mechanisms is unknown. Although we have shown that the Wnt signaling component β-catenin is selectively required for generation of exocrine acinar cells in utero, this gene has been ascribed various functions in the postnatal pancreas including proliferation and regeneration of islet as well as acinar cells. To address whether β-catenin remains important for the maintenance and expansion of mature acinar cells, we have established a system to follow the behavior and fate of β-catenin-deficient cells during postnatal growth and regeneration. We find that β-catenin is continuously required for the establishment and maintenance of acinar cell mass, extending from embryonic specification through juvenile and adult self-renewal and regeneration. This requirement is not shared with islet cells, which proliferate and function normally in the absence of β-catenin. These results make distinct predictions for the relative role of Wnt/β-catenin signaling in the etiology of human endocrine and exocrine disease. We suggest that loss of Wnt/β-catenin activity is unlikely to drive islet dysfunction, as occurs in type 2 diabetes, but that β-catenin is likely to promote human acinar cell proliferation following injury, and may therefore contribute to the resolution of acute or chronic pancreatitis.
TOR complex 2 (TORC2) in Dictyostelium suppresses phagocytic nutrient capture independently of TORC1-mediated nutrient sensing
Authors: Rosel Daniel , Khurana Taruna , Majithia Amit , Huang Xiuli , Bhandari Ramanath , Kimmel Alan R.
Published: January 2012

The TOR protein kinase functions in two distinct complexes, TOR complex 1 (TORC1) and 2 (TORC2). TORC1 is required for growth in response to growth factors, nutrients and the cellular energy state; TORC2 regulates AKT signaling, which can modulate cytoskeletal polarization. In its ecological niche, Dictyostelium engulf bacteria and yeast for nutrient capture. Despite the essential role of TORC1 in control of cellular growth, we show that nutrient particle capture (phagocytosis) in Dictyostelium is independent of TORC1-mediated nutrient sensing and growth regulation. However, loss of Dictyostelium TORC2 components Rictor/Pia, SIN1/RIP3 and Lst8 promotes nutrient particle uptake; inactivation of TORC2 leads to increased efficiency and speed of phagocytosis. In contrast to phagocytosis, we show that macropinocytosis, an AKT-dependent process for cellular uptake of fluid phase nutrients, is not regulated by either of the TOR complexes. The integrated and balanced regulation of TORC1 and TORC2 might be crucial in Dictyostelium to coordinate growth and energy needs with other essential TOR-regulated processes.
Regulation of local expression of cell adhesion and motility-related mRNAs in breast cancer cells by IMP1/ZBP1
Authors: Gu Wei , Katz Zachary , Wu Bin , Park Hye Yoon , Li Deling , Lin Stanley , Wells Amber L. , Singer Robert H.
Published: January 2012

Metastasis involves tumor cell detachment from the primary tumor, and acquisition of migratory and invasive capabilities. These capabilities are mediated by multiple events, including loss of cell–cell contact, an increase in focal adhesion turnover and failure to maintain a normal cell polarity. We have previously reported that silencing of the expression of the zipcode-binding protein IMP1/ZBP1 in breast tumor patients is associated with metastasis. IMP1/ZBP1 selectively binds to a group of mRNAs that encode important mediators for cell adhesion and motility. Here, we show that in both T47D and MDA231 human breast carcinoma cells IMP1/ZBP1 functions to suppress cell invasion. Binding of ZBP1 to the mRNAs encoding E-cadherin, β-actin, α-actinin and the Arp2/3 complex facilitates localization of the mRNAs, which stabilizes cell–cell connections and focal adhesions. Our studies suggest a novel mechanism through which IMP1/ZBP1 simultaneously regulates the local expression of many cell-motility-related mRNAs to maintain cell adherence and polarity, decrease focal adhesion turnover and maintain a persistent and directional motility.
Sumoylated protein tyrosine phosphatase 1B localizes to the inner nuclear membrane and regulates the tyrosine phosphorylation of emerin
Authors: Yip Shu-Chin , Cotteret Sophie , Chernoff Jonathan
Published: January 2012

Protein tyrosine phosphatase (PTP)1B is an abundant non-transmembrane enzyme that plays a major role in regulating insulin and leptin signaling. Recently, we reported that PTP1B is inhibited by sumoylation, and that sumoylated PTP1B accumulates in a perinuclear distribution, consistent with its known localization in the endoplasmic reticulum (ER) and the contiguous outer nuclear membrane. Here, we report that, in addition to its localization at the ER, PTP1B also is found at the inner nuclear membrane, where it is heavily sumoylated. We also find that PTP1B interacts with emerin, an inner nuclear membrane protein that is known to be tyrosine phosphorylated, and that PTP1B expression levels are inversely correlated with tyrosine phosphorylation levels of emerin. PTP1B sumoylation greatly increases as cells approach mitosis, corresponding to the stage where tyrosine phosphorylation of emerin is maximal. In addition, expression of a non-sumoylatable mutant of PTP1B greatly reduced levels of emerin tyrosine phosphorylation. These results suggest that PTP1B regulates the tyrosine phosphorylation of a key inner nuclear membrane protein in a sumoylation- and cell-cycle-dependent manner.
Annexin A5 stimulates autophagy and inhibits endocytosis
Authors: Ghislat Ghita , Aguado Carmen , Knecht Erwin
Published: January 2012

Macroautophagy is a major lysosomal catabolic process activated particularly under starvation in eukaryotic cells. A new organelle, the autophagosome, engulfs cytoplasmic substrates, which are degraded after fusion with endosomes and/or lysosomes. During a shotgun proteome analysis of purified lysosomal membranes from mouse fibroblasts, a Ca2+-dependent phospholipid-binding protein, annexin A5, was found to increase on lysosomal membranes under starvation. This suggests a role for this protein, an abundant annexin with a still unknown intracellular function, in starvation-induced lysosomal degradation. Transient overexpression and silencing experiments showed that annexin A5 increased lysosomal protein degradation, and colocalisation experiments, based on GFP sensitivity to lysosomal acidic pH, indicated that this was mainly the result of inducing autophagosome–lysosome fusion. Annexin A5 also inhibited the endocytosis of a fluid-phase marker and cholera toxin, but not receptor-mediated endocytosis. Therefore, we propose a double and opposite role of annexin A5 in regulating the endocytic and autophagic pathways and the fusion of autophagosomes with lysosomes and endosomes.
Liprin-α controls stress fiber formation by binding to mDia and regulating its membrane localization
Authors: Sakamoto Satoko , Ishizaki Toshimasa , Okawa Katsuya , Watanabe Sadanori , Arakawa Takatoshi , Watanabe Naoki , Narumiya Shuh
Published: January 2012

Regulation of the actin cytoskeleton is crucial for cell morphology and migration. mDia is an actin nucleator that produces unbranched actin filaments downstream of Rho. However, the mechanisms by which mDia activity is regulated in the cell remain unknown. We pulled down Liprin-α as an mDia-binding protein. The binding is mediated through the central region of Liprin-α and through the N-terminal Dia-inhibitory domain (DID) and dimerization domain (DD) of mDia. Liprin-α competes with Dia autoregulatory domain (DAD) for binding to DID, and binds preferably to the open form of mDia. Overexpression of a Liprin-α fragment containing the mDia-binding region decreases localization of mDia to the plasma membrane and attenuates the Rho–mDia-mediated formation of stress fibers in cultured cells. Conversely, depletion of Liprin-α by RNA interference (RNAi) increases the amount of mDia in the membrane fraction and enhances formation of actin stress fibers. Thus, Liprin-α negatively regulates the activity of mDia in the cell by displacing it from the plasma membrane through binding to the DID-DD region.
Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair
Authors: Elliott Christopher G. , Wang Jian , Guo Xiaolei , Xu Shi-wen , Eastwood Mark , Guan Jianjun , Leask Andrew , Conway Simon J. , Hamilton Douglas W.
Published: January 2012

The matricellular protein periostin is expressed in the skin. Although periostin has been hypothesized to contribute to dermal homeostasis and repair, this has not been directly tested. To assess the contribution of periostin to dermal healing, 6 mm full-thickness excisional wounds were created in the skin of periostin-knockout and wild-type, sex-matched control mice. In wild-type mice, periostin was potently induced 5–7 days after wounding. In the absence of periostin, day 7 wounds showed a significant reduction in myofibroblasts, as visualized by expression of α-smooth muscle actin (α-SMA) within the granulation tissue. Delivery of recombinant human periostin by electrospun collagen scaffolds restored α-SMA expression. Isolated wild-type and knockout dermal fibroblasts did not differ in in vitro assays of adhesion or migration; however, in 3D culture, periostin-knockout fibroblasts showed a significantly reduced ability to contract a collagen matrix, and adopted a dendritic phenotype. Recombinant periostin restored the defects in cell morphology and matrix contraction displayed by periostin-deficient fibroblasts in a manner that was sensitive to a neutralizing anti-β1-integrin and to the FAK and Src inhibitor PP2. We propose that periostin promotes wound contraction by facilitating myofibroblast differentiation and contraction.
The ESCRT machinery mediates polarization of fibroblasts through regulation of myosin light chain
Authors: Lobert Viola Hélène , Stenmark Harald
Published: January 2012

Recent evidence implicates the endosomal sorting complex required for transport (ESCRT) in the regulation of epithelial polarity in Drosophila melanogaster, but the mechanisms responsible for this action remain unclear. Here we show that ESCRTs determine cell orientation during directed migration in human fibroblasts. We find that endosomal retention of α5β1 integrin and its downstream signaling effector Src in ESCRT-depleted cells is accompanied by the failure to activate myosin light chain kinase (MLCK), which thereby cannot phosphorylate myosin regulatory light chain (MRLC). Using this mechanism, ESCRT-depleted fibroblasts fail to orient their Golgi complex to undergo directional migration and show impaired focal adhesion turnover and increased spreading on fibronectin. Consistent with these findings, expression of a phosphomimetic mutant of MRLC in ESCRT-depleted cells restores normal phenotypes during cell spreading and orientation of the Golgi. These results suggest that, through their role in regulating integrin trafficking, ESCRTs regulate phosphorylation of MRLC and, subsequently, Golgi orientation and cell spreading.
Keratinocyte-associated protein 2 is a bona fide subunit of the mammalian oligosaccharyltransferase
Authors: Roboti Peristera , High Stephen
Published: January 2012

The oligosaccharyltransferase (OST) complex catalyses the N-glycosylation of polypeptides entering the endoplasmic reticulum, a process essential for the productive folding and trafficking of many secretory and membrane proteins. In eukaryotes, the OST typically comprises a homologous catalytic STT3 subunit complexed with several additional components that are usually conserved, and that often function to modulate N-glycosylation efficiency. By these criteria, the status of keratinocyte-associated protein 2 (KCP2) was unclear: it was found to co-purify with the canine OST suggesting it is part of the complex but, unlike most other subunits, no potential homologues are apparent in Saccharomyces cerevisiae. In this study we have characterised human KCP2 and show that the predominant species results from an alternative initiation of translation to form an integral membrane protein with three transmembrane spans. KCP2 localises to the endoplasmic reticulum, consistent with a role in protein biosynthesis, and has a functional KKxx retrieval signal at its cytosolic C-terminus. Native gel analysis suggests that the majority of KCP2 assembles into a distinct ~500 kDa complex that also contains several bona fide OST subunits, most notably the catalytic STT3A isoform. Co-immunoprecipitation studies confirmed a robust and specific physical interaction between KCP2 and STT3A, and revealed weaker associations with both STT3B and OST48. Taken together, these data strongly support the proposal that KCP2 is a newly identified subunit of the N-glycosylation machinery present in a subset of eukaryotes.
Mutational analysis supports a core role forDrosophilaα-Catenin in adherens junction function
Authors: Sarpal Ritu , Pellikka Milena , Patel Ridhdhi R. , Hui Felix Yan Wai , Godt Dorothea , Tepass Ulrich
Published: January 2012

α-catenin associates the cadherin–catenin complex with the actin cytoskeleton. α-catenin binds to β-catenin, which links it to the cadherin cytoplasmic tail, and F-actin, but also to a multitude of actin-associated proteins. These interactions suggest a highly complex cadherin–actin interface. Moreover, mammalian αE-catenin has been implicated in a cadherin-independent cytoplasmic function in Arp2/3-dependent actin regulation, and in cell signaling. The function and regulation of individual molecular interactions of α-catenin, in particular during development, are not well understood. We have generated mutations in Drosophila α-Catenin (α-Cat) to investigate α-Catenin function in this model, and to establish a setup for testing α-Catenin-related constructs in α-Cat-null mutant cells in vivo. Our analysis of α-Cat mutants in embryogenesis, imaginal discs and oogenesis reveals defects consistent with a loss of cadherin function. Compromising components of the Arp2/3 complex or its regulator SCAR ameliorate the α-Cat loss-of-function phenotype in embryos but not in ovaries, suggesting negative regulatory interactions between α-Catenin and the Arp2/3 complex in some tissues. We also show that the α-Cat mutant phenotype can be rescued by the expression of a DE-cadherin::α-Catenin fusion protein, which argues against an essential cytosolic, cadherin-independent role of Drosophila α-Catenin.