bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of growth of the human gastric pathogen Helicobacter pylori by atmospheric level of oxygen under high carbon dioxide tension
Authors: Park Shin Ae , Ko Ara , Lee Na Gyong
Published: May 2011

Background

Helicobacter pylori (Hp), a human pathogen that is associated with gastritis, peptic ulcer, and gastric cancer, has been considered a microaerophile, but there is no general consensus about its specific O2 requirements. A clear understanding of Hp physiology is needed to elucidate the pathogenic mechanism(s) of Hp infection.

Results

We cultured Hp under a range of O2 levels with or without 10% CO2 and evaluated growth profiles, morphology, intracellular pH, and energy metabolism. We found that, in the presence of 10% CO2, the normal atmospheric level of O2 inhibited Hp growth at low density but stimulated growth at a higher density. Field emission scanning electron microscopy and fluorescence microscopy of Hp cells cultured under 20% O2 tension revealed live spiral-shaped bacteria with outer membrane vesicles on a rugged cell surface, which became smooth during the stationary phase. Fermentation products including acetate, lactate, and succinate were detected in cell culture media grown under microaerobic conditions, but not under the aerobic condition. CO2 deprivation for less than 24 h did not markedly change cytoplasmic or periplasmic pH, suggesting that cellular pH homeostasis alone cannot account for the capnophilic nature of Hp. Further, CO2 deprivation significantly increased intracellular levels of ppGpp and ATP but significantly decreased cellular mRNA levels, suggesting induction of the stringent response.

Conclusions

We conclude, unlike previous reports, that H. pylori may be a capnophilic aerobe whose growth is promoted by atmospheric oxygen levels in the presence of 10% CO2. Our data also suggest that buffering of intracellular pH alone cannot account for the CO2 requirement of H. pylori and that CO2 deprivation initiates the stringent response in H. pylori. Our findings may provide new insight into the physiology of this fastidious human pathogen.
GABAergic synaptic response and its opioidergic modulation in periaqueductal gray neurons of rats with neuropathic pain
Authors: Hahm Eu-Teum , Kim Younghoon , Lee Jong-Ju , Cho Young-Wuk
Published: May 2011

Background

Neuropathic pain is a chronic and intractable symptom associated with nerve injury. The periaqueductal gray (PAG) is important in the endogenous pain control system and is the main site of the opioidergic analgesia. To investigate whether neuropathic pain affects the endogenous pain control system, we examined the effect of neuropathic pain induced by sacral nerve transection on presynaptic GABA release, the kinetics of postsynaptic GABA-activated Cl- currents, and the modulatory effect of μ-opioid receptor (MOR) activation in mechanically isolated PAG neurons with functioning synaptic boutons.

Results

In normal rats, MOR activation inhibited the frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) to 81.3% of the control without any alteration in their amplitude. In neuropathic rats, the inhibition of mIPSC frequency by MOR activation was 82.4%. The frequency of GABAergic mIPSCs in neuropathic rats was 151.8% of normal rats without any difference in the mIPSC amplitude. Analysis of mIPSC kinetics showed that the fast decay time constant and synaptic charge transfer of mIPSCs in neuropathic rats were 76.0% and 73.2% of normal rats, respectively.

Conclusions

These results indicate that although the inhibitory effect of MOR activation on presynaptic GABA release is similar in both neuropathic and normal rats, neuropathic pain may inhibit endogenous analgesia in the PAG through an increase in presynaptic GABA release.
TILLING for allergen reduction and improvement of quality traits in peanut (Arachis hypogaea L.)
Authors: Knoll Joseph E , Ramos M Laura , Zeng Yajuan , Holbrook C Corley , Chow Marjorie , Chen Sixue , Maleki Soheila , Bhattacharya Anjanabha , Ozias-Akins Peggy
Published: May 2011

Background

Allergic reactions to peanuts (Arachis hypogaeaL.) can cause severe symptoms and in some cases can be fatal, but avoidance is difficult due to the prevalence of peanut-derived products in processed foods. One strategy of reducing the allergenicity of peanuts is to alter or eliminate the allergenic proteins through mutagenesis. Other seed quality traits could be improved by altering biosynthetic enzyme activities. Targeting Induced Local Lesions in Genomes (TILLING), a reverse-genetics approach, was used to identify mutations affecting seed traits in peanut.

Results

Two similar copies of a major allergen gene,Ara h 1, have been identified in tetraploid peanut, one in each subgenome. The same situation has been shown for major allergenAra h 2. Due to the challenge of discriminating between homeologous genes in allotetraploid peanut, nested PCR was employed, in which both gene copies were amplified using unlabeled primers. This was followed by a second PCR using gene-specific labeled primers, heteroduplex formation, CEL1 nuclease digestion, and electrophoretic detection of labeled fragments. Using ethyl methanesulfonate (EMS) as a mutagen, a mutation frequency of 1 SNP/967 kb (3,420 M2individuals screened) was observed. The most significant mutations identified were a disrupted start codon inAra h 2.02and a premature stop codon inAra h 1.02. Homozygous individuals were recovered in succeeding generations for each of these mutations, and elimination of Ara h 2.02 protein was confirmed. Several Ara h 1 protein isoforms were eliminated or reduced according to 2D gel analyses. TILLING also was used to identify mutations in fatty acid desaturaseAhFAD2(also present in two copies), a gene which controls the ratio of oleic to linoleic acid in the seed. A frameshift mutation was identified, resulting in truncation and inactivation of AhFAD2B protein. A mutation inAhFAD2Awas predicted to restore function to the normally inactive enzyme.

Conclusions

This work represents the first steps toward the goal of creating a peanut cultivar with reduced allergenicity. TILLING in peanut can be extended to virtually any gene, and could be used to modify other traits such as nutritional properties of the seed, as shown in this study.
Phagocytic ability of neutrophils and monocytes in neonates
Authors: Filias Athanasios , Theodorou Georgios L , Mouzopoulou Sofia , Varvarigou Anastasia A , Mantagos Stephanos , Karakantza Marina
Published: May 2011

Background

Infections by a variety of pathogens are a significant cause of morbidity and mortality during perinatal period. The susceptibility of neonates to bacterial infections has been attributed to immaturity of innate immunity. It is considered that one of the impaired mechanisms is the phagocytic function of neutrophils and monocytes. The purpose of the present study was to investigate the phagocytic ability of neonates at birth.

Methods

The phagocytic ability of neutrophils and monocytes of 42 neonates was determined using the Phagotest flow cytometry method, that assesses the intake of E. Coli by phagocytes, in cord blood and in peripheral blood 3 days after birth. Fifteen healthy adults were included in the study as controls.

Results

The phagocytic ability of neutrophils in the cord blood of neonates was significantly reduced compared to adults. The 3rd postnatal day the reduction of phagocytic ability of neutrophils was no longer significant compared to adults. The phagocytic ability of monocytes did not show any difference from that of adults either at birth or the 3rd postnatal day.

Conclusions

Our findings indicate that the intake of E. Coli by phagocytes is impaired at birth in both preterm and full term neonates compared to adults. This defect is transient, with the phagocytic ability in neonates reaching that of the adults 3 days after birth.
Does improving maternal knowledge of vaccines impact infant immunization rates? A community-based randomized-controlled trial in Karachi, Pakistan
Authors: Owais Aatekah , Hanif Beenish , Siddiqui Amna R , Agha Ajmal , Zaidi Anita KM
Published: May 2011

Background

In Pakistan, only 59-73% of children 12-23 months of age are fully immunized. This randomized, controlled trial was conducted to assess the impact of a low-literacy immunization promotion educational intervention for mothers living in low-income communities of Karachi on infant immunization completion rates.

Methods

Three hundred and sixty-six mother-infant pairs, with infants aged ≤ 6 weeks, were enrolled and randomized into either the intervention or control arm between August - November 2008. The intervention, administered by trained community health workers, consisted of three targeted pictorial messages regarding vaccines. The control group received general health promotion messages based on Pakistan's Lady Health Worker program curriculum. Assessment of DPT/Hepatitis B vaccine completion (3 doses) was conducted 4-months after enrollment. A Poisson regression model was used to estimate effect of the intervention. The multivariable Poisson regression model included maternal education, paternal occupation, ownership of home, cooking fuel used at home, place of residence, the child's immunization status at enrollment, and mother's perception about the impact of immunization on child's health.

Results

Baseline characteristics among the two groups were similar. At 4 month assessment, among 179 mother-infant pairs in the intervention group, 129 (72.1%) had received all 3 doses of DPT/Hepatitis B vaccine, whereas in the control group 92/178 (51.7%) had received all 3 doses. Multivariable analysis revealed a significant improvement of 39% (adjusted RR = 1.39; 95% CI: 1.06-1.81) in DPT-3/Hepatitis B completion rates in the intervention group.

Conclusion

A simple educational intervention designed for low-literate populations, improved DPT-3/Hepatitis B vaccine completion rates by 39%. These findings have important implications for improving routine immunization rates in Pakistan.
Nicotine Dependence among Rural-Urban Migrants in China
Authors: Wu Junqing , Yang Tingzhong , Rockett Ian RH , Xing Rui , Karalic Sejla , Li Yuyan , Zhang Yufeng
Published: May 2011

Background

The complex mechanism of nicotine dependency makes it challenging to evaluate dependence or progress towards dependence. The aim of this study was to estimate nicotine dependence levels and identify determinants of dependence among Chinese rural-urban migrants.

Methods

Multi-stage systematic sampling was used to select 4,198 rural-urban migrants aged 18 years or older from three metropolises in China. A structured questionnaire was administered during face-to-face interviews. Nicotine dependence among participants was assessed by means of the six-item Mandarin Chinese Version of the Fagerström Test for Nicotine Dependence (CFTND). Determinants of dependence were analyzed using multivariate analysis of variance (MANOVA).

Results

Among 4,198 participants, estimated current, daily, and occasional smoking rates were 28.3%, 21.2%, and 7.1%, respectively. The CTFND score for the 894 daily smokers was 3.39(SD: 2.32). MANOVA showed that work type, age at first migration, length of migration, and number of cities ever lived were associated with nicotine dependence.

Conclusion

A migratory lifestyle is associated with nicotine dependence. Results could inform the design of tobacco control programs that target Chinese rural-urban migrant workers as a special at-risk population.
Integrating an ecological approach into an Aboriginal community-based chronic disease prevention program: a longitudinal process evaluation
Authors: Cargo Margaret , Marks Elisabeth , Brimblecombe Julie , Scarlett Maria , Maypilama Elaine , Dhurrkay Joanne Garnggulkpuy , Daniel Mark
Published: May 2011

Background

Public health promotes an ecological approach to chronic disease prevention, however, little research has been conducted to assess the integration of an ecological approach in community-based prevention programs. This study sought to contribute to the evidence base by assessing the extent to which an ecological approach was integrated into an Aboriginal community-based cardiovascular disease (CVD) and type 2 diabetes prevention program, across three-intervention years.

Methods

Activity implementation forms were completed by interview with implementers and participant observation across three intervention years. A standardised ecological coding procedure was applied to assess participant recruitment settings, intervention targets, intervention strategy types, extent of ecologicalness and organisational partnering. Inter-rater reliability for two coders was assessed at Kappa = 0.76 (p < .0.001), 95% CI (0.58, 0.94).

Results

215 activities were implemented across three intervention years by the health program (HP) with some activities implemented in multiple years. Participants were recruited most frequently through organisational settings in years 1 and 2, and organisational and community settings in year 3. The most commonly utilised intervention targets were the individual (IND) as a direct target, and interpersonal (INT) and organisational (ORG) environments as indirect targets; policy (POL), and community (COM) were targeted least. Direct (HP→ IND) and indirect intervention strategies (i.e., HP→ INT→ IND, HP→ POL → IND) were used most often; networking strategies, which link at least two targets (i.e., HP→[ORG-ORG]→IND), were used the least. The program did not become more ecological over time.

Conclusions

The quantity of activities with IND, INT and ORG targets and the proportion of participants recruited through informal cultural networking demonstrate community commitment to prevention. Integration of an ecological approach would have been facilitated by greater inter-organisational collaboration and centralised planning. The upfront time required for community stakeholders to develop their capacity to mobilise around chronic disease is at odds with short-term funding cycles that emphasise organisational accountability.
Evaluation of free-radical quenching properties of standard Ayurvedic formulation Vayasthapana Rasayana
Authors: Mukherjee Sourav , Pawar Nayana , Kulkarni Omkar , Nagarkar Bhagyashri , Thopte Shrikant , Bhujbal Akshay , Pawar Pankaj
Published: May 2011

Background

Cellular damage induced by free-radicals like Reactive Oxygen and Nitrogen Species (ROS and RNS) has been implicated in several disorders and diseases, including ageing. Hence naturally occurring anti-oxidant rich-herbs play a vital role in combating these conditions. The present study was carried out to investigate the in vitro free-radical quenching capacity of a known Ayurvedic poly-herbal formulation called Vayasthapana Rasayana.

Methods

Methanol extracts of Vayasthapana Rasayana formulation (VRF) were studied for in vitro total antioxidant activity along with phenolic content and reducing power. In vitro assays like DPPH, FRAP, ABTS scavenging to evaluate radical quenching potential were performed.

Results

The formulation has shown 94% at 0.1 mg/ml DPPH free-radical scavenging activity as against 84% at 0.1 mg/ml for standard ascorbic acid (IC50 value 5.51 μg/ml for VRF and 39 μg/ml for standard). It has a significant higher ferric reducing potential also (OD 0.87 at 700 nm & 0.21 at 0.1 mg/ml for VRF and standard, respectively). The total phenolic content (gallic acid equivalent) of the VRF is 8.3 mg per g of dry mass. Total antioxidant capacity of the formulation, estimated by FRAP was 1150 ± 5 μM Fe(II)/g dry mass. ABTS radical scavenging activity of VRF was 69.55 ± 0.21% at 100 μg/ml concentration with a IC50 value of 69.87 μg/ml as against 9% and 95% by ascorbic acid and Trolox (at 70.452 μg/ml and 0.250 μg/ml concentrations, respectively).

Conclusion

In Indian traditional Ayurvedic system, use of VRF is in regular practice for mainly combating age-related disorders and diseases as many of the components of the Rasayana are known for their free-radical scavenging activity. This study has validated the potential use of VRF as an anti-oxidant to fight age-related problems.
A hepatoprotective Lindera obtusiloba extract suppresses growth and attenuates insulin like growth factor-1 receptor signaling and NF-kappaB activity in human liver cancer cell lines
Authors: Freise Christian , Ruehl Martin , Erben Ulrike , Neumann Ulf , Seehofer Daniel , Kim Ki Young , Trowitzsch-Kienast Wolfram , Stroh Thorsten , Zeitz Martin , Somasundaram Rajan
Published: May 2011

Background

In traditional Chinese and Korean medicine, an aqueous extract derived from wood and bark of the Japanese spice bush Lindera obtusiloba (L.obtusiloba) is applied to treat inflammations and chronic liver diseases including hepatocellular carcinoma. We previously demonstrated anti-fibrotic effects of L.obtusiloba extract in hepatic stellate cells. Thus, we here consequently examine anti-neoplastic effects of L.obtusiloba extract on human hepatocellular carcinoma (HCC) cell lines and the signaling pathways involved.

Methods

Four human HCC cell lines representing diverse stages of differentiation were treated with L.obtusiloba extract, standardized according to its known suppressive effects on proliferation and TGF-β-expression. Beside measurement of proliferation, invasion and apoptosis, effects on signal transduction and NF-κB-activity were determined.

Results

L.obtusiloba extract inhibited proliferation and induced apoptosis in all HCC cell lines and provoked a reduced basal and IGF-1-induced activation of the IGF-1R signaling cascade and a reduced transcriptional NF-κB-activity, particularly in the poorly differentiated SK-Hep1 cells. Pointing to anti-angiogenic effects, L.obtusiloba extract attenuated the basal and IGF-1-induced expression of hypoxia inducible factor-1α, vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ, cyclooxygenase-2 and inducible nitric oxide synthase.

Conclusions

The traditional application of the extract is confirmed by our experimental data. Due to its potential to inhibit critical receptor tyrosine kinases involved in HCC progression via the IGF-1 signaling pathway and NF-κB, the standardized L.obtusiloba extract should be further analysed for its active compounds and explored as (complementary) treatment option for HCC.
How diverse is the diet of adult South Africans?
Authors: Labadarios Demetre , Steyn Nelia Patricia , Nel Johanna
Published: May 2011

Background

The objective of the current study was to measure dietary diversity in South Africans aged 16 years and older from all population groups as a proxy of food security.

Methods

A cross-sectional study representative of adults from all specified ages, provinces, geographic localities, and socio-economic strata in South Africa was used (n = 3287). Trained interviewers visited participants at their homes during the survey. Dietary data was collected by means of a face validated 24 hour recall which was not quantified. A dietary diversity score (DDS) was calculated by counting each of 9 food groups. A DDS <4 was regarded as reflecting poor dietary diversity and poor food security.

Results

The provinces with the highest prevalence of poor dietary diversity (DDS <4) were Limpopo (61.8%) and the Eastern Cape (59.6%). By contrast, only 15.7% of participants in Western Cape had a low score. Participants in tribal areas (63.9%) and informal urban areas (55.7%) were by far the worst affected. There were significant differences in DDS by Living Standards Mean (LSM) analysis (p < 0.05) with the lowest LSM group having the lowest mean DDS (2.93).The most commonly consumed food groups were cereals/roots; meat/fish; dairy and vegetables other than vitamin A rich. Eggs, legumes, and vitamin A rich fruit and vegetables were the least consumed.

Conclusion

Overall the majority of South Africans consumed a diet low in dietary variety. The tribal areas and informal urban areas were worst affected and eggs, legumes and vitamin A rich fruit and vegetables, were the least consumed.
Does context matter for the relationship between deprivation and all-cause mortality? The West vs. the rest of Scotland
Authors: Sridharan Sanjeev , Koschinsky Julia , Walker Jeremy J
Published: May 2011

Background

A growing body of research emphasizes the importance of contextual factors on health outcomes. Using postcode sector data for Scotland (UK), this study tests the hypothesis of spatial heterogeneity in the relationship between area-level deprivation and mortality to determine if contextual differences in the West vs. the rest of Scotland influence this relationship. Research into health inequalities frequently fails to recognise spatial heterogeneity in the deprivation-health relationship, assuming that global relationships apply uniformly across geographical areas. In this study, exploratory spatial data analysis methods are used to assess local patterns in deprivation and mortality. Spatial regression models are then implemented to examine the relationship between deprivation and mortality more formally.

Results

The initial exploratory spatial data analysis reveals concentrations of high standardized mortality ratios (SMR) and deprivation (hotspots) in the West of Scotland and concentrations of low values (coldspots) for both variables in the rest of the country. The main spatial regression result is that deprivation is the only variable that is highly significantly correlated with all-cause mortality in all models. However, in contrast to the expected spatial heterogeneity in the deprivation-mortality relationship, this relation does not vary between regions in any of the models. This result is robust to a number of specifications, including weighting for population size, controlling for spatial autocorrelation and heteroskedasticity, assuming a non-linear relationship between mortality and socio-economic deprivation, separating the dependent variable into male and female SMRs, and distinguishing between West, North and Southeast regions. The rejection of the hypothesis of spatial heterogeneity in the relationship between socio-economic deprivation and mortality complements prior research on the stability of the deprivation-mortality relationship over time.

Conclusions

The homogeneity we found in the deprivation-mortality relationship across the regions of Scotland and the absence of a contextualized effect of region highlights the importance of taking a broader strategic policy that can combat the toxic impacts of socio-economic deprivation on health. Focusing on a few specific places (e.g. 15% of the poorest areas) to concentrate resources might be a good start but the impact of socio-economic deprivation on mortality is not restricted to a few places. A comprehensive strategy that can be sustained over time might be needed to interrupt the linkages between poverty and mortality.
Lipid phosphate phosphatase-3 regulates tumor growth via β-catenin and Cyclin-D1 signaling
Authors: Chatterjee Ishita , Humtsoe Joseph O , Kohler Erin E , Sorio Claudio , Wary Kishore K
Published: May 2011

Background

The acquisition of proliferative and invasive phenotypes is considered a hallmark of neoplastic transformation; however, the underlying mechanisms are less well known. Lipid phosphate phosphatase-3 (LPP3) not only catalyzes the dephosphorylation of the bioactive lipid sphingosine-1-phosphate (S1P) to generate sphingosine but also may regulate embryonic development and angiogenesis via the Wnt pathway. The goal of this study was to determine the role of LPP3 in tumor cells.

Results

We observed increased expression of LPP3 in glioblastoma primary tumors and in U87 and U118 glioblastoma cell lines. We demonstrate that LPP3-knockdown inhibited both U87 and U118 glioblastoma cell proliferation in culture and tumor growth in xenograft assays. Biochemical experiments provided evidence that LPP3-knockdown reduced β-catenin, CYCLIN-D1, and CD133 expression, with a concomitant increase in phosphorylated β-catenin. In a converse experiment, the forced expression of LPP3 in human colon tumor (SW480) cells potentiated tumor growth via increased β-catenin stability and CYCLIN-D1 synthesis. In contrast, elevated expression of LPP3 had no tumorigenic effects on primary cells.

Conclusions

These results demonstrate for the first time an unexpected role of LPP3 in regulating glioblastoma progression by amplifying β-catenin and CYCLIN-D1 activities.
Fish oil consumption prevents glucose intolerance and hypercorticosteronemy in footshock-stressed rats
Authors: Eguchi Ricardo , Scarmagnani Flavia R , Cunha Claudio A , Souza Gabriel IH , Pisani Luciana P , Ribeiro Eliane B , Oller do Nascimento Claudia M , Spadari-Bratfisch Regina C , Oyama Lila M
Published: May 2011

Background

Environmental stress plays an important role in the development of glucose intolerance influencing lipid and glucose metabolism through sympathetic nervous system, cytokines and hormones such as glucocorticoids, catecholamines and glucagon. Otherwise, fish oil prevents glucose intolerance and insulin resistance. Although the mechanisms involved are not fully understood, it is known that sympathetic and HPA responses are blunted and catecholamines and glucocorticoids concentrations can be modulated by fish consumption. The aim of the present study was to evaluate whether fish oil, on a normal lipidic diet: 1) could prevent the effect of footshock-stress on the development of glucose intolerance; 2) modified adiponectin receptor and serum concentration; and 3) also modified TNF-α, IL-6 and interleukin-10 (IL-10) levels in adipose tissue and liver. The study was performed in thirty day-old male Wistar randomly assigned into four groups: no stressed (C) and stressed (CS) rats fed with control diet, and no stressed (F) and stressed (FS) rats fed with a fish oil rich diet. The stress was performed as a three daily footshock stress sessions.

Results

Body weight, carcass fat and protein content were not different among groups. FS presented a reduction on the relative weight of RET. Basal serum glucose levels were higher in CS and FS but 15 min after glucose load just CS remained with higher levels than other groups. Serum corticosterone concentration was increased in CS, this effect was inhibited in FS. However, 15 min after footshock-stress, corticosterone levels were similar among groups. IL-6 was increased in EPI of CS but fish oil consumption prevented IL-6 increase in FS. Similar levels of TNF-α and IL-10 in RET, EPI, and liver were observed among groups. Adipo R1 protein concentration was not different among groups. Footshock-stress did not modify AdipoR2 concentration, but fish oil diet increases AdipoR2 protein concentration.

Conclusions

Footshock-stress promotes glucose intolerance associated to corticosterone serum level and epididymal white adipose tissue IL-6 concentration increase. The fish oil consumption by stressed rats normalized the stress responses. These results suggested that fish oil intake could be useful to minimize or prevent the development of diseases associated to the stress.
Determination of the volume-specific surface area by using transmission electron tomography for characterization and definition of nanomaterials
Authors: Van Doren Elke AF , De Temmerman Pieter-Jan RH , Francisco Michel Abi Daoud , Mast Jan
Published: May 2011

Background

Transmission electron microscopy (TEM) remains an important technique to investigate the size, shape and surface characteristics of particles at the nanometer scale. Resulting micrographs are two dimensional projections of objects and their interpretation can be difficult. Recently, electron tomography (ET) is increasingly used to reveal the morphology of nanomaterials (NM) in 3D. In this study, we examined the feasibility to visualize and measure silica and gold NM in suspension using conventional bright field electron tomography.

Results

The general morphology of gold and silica NM was visualized in 3D by conventional TEM in bright field mode. In orthoslices of the examined NM the surface features of a NM could be seen and measured without interference of higher or lower lying structures inherent to conventional TEM. Segmentation by isosurface rendering allowed visualizing the 3D information of an electron tomographic reconstruction in greater detail than digital slicing. From the 3D reconstructions, the surface area and the volume of the examined NM could be estimated directly and the volume-specific surface area (VSSA) was calculated. The mean VSSA of all examined NM was significantly larger than the threshold of 60 m2/cm3.

The high correlation between the measured values of area and volume gold nanoparticles with a known spherical morphology and the areas and volumes calculated from the equivalent circle diameter (ECD) of projected nanoparticles (NP) indicates that the values measured from electron tomographic reconstructions are valid for these gold particles.

Conclusion

The characterization and definition of the examined gold and silica NM can benefit from application of conventional bright field electron tomography: the NM can be visualized in 3D, while surface features and the VSSA can be measured.
Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke
Authors: Rodríguez-González Raquel , Sobrino Tomás , Rodríguez-Yáñez Manuel , Millán Mónica , Brea David , Miranda Elena , Moldes Octavio , Pérez Juan , Lomas David A , Leira Rogelio , Dávalos Antoni , Castillo José
Published: May 2011

Background

Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption.

Methods

We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years) not treated with tPA within 12 hours (h) of symptoms onset (mean time, 4.7 ± 2.1 h). Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6), Intercellular adhesion molecule-1 (ICAM-1), active Matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (cFn) (determined by ELISA) and glutamate (determined by HPLC) were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity.

Results

The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), MMP-9 (r = -0.554) and cFn (r = -0.703) (all P < 0.0001). In the multivariate analysis, serum levels of glutamate (OR, 1.04; CI95%, 1.01-1.06, p = 0.001); IL-6 (OR, 1.4; CI95%, 1.1-1.7, p = 0.001); and cFn (OR, 1.3; CI95%, 1.1-1.6, p = 0.002) were independently associated with a decrease of neuroserpin levels <70 ng/mL at 24 h after adjusting for confounding factors.

Conclusions

These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke.
Human papillomavirus vaccine introduction in low-income and middle-income countries: guidance on the use of cost-effectiveness models
Authors: Jit Mark , Demarteau Nadia , Elbasha Elamin , Ginsberg Gary , Kim Jane , Praditsitthikorn Naiyana , Sinanovic Edina , Hutubessy Raymond
Published: May 2011

Background

The World Health Organization (WHO) recommends that the cost effectiveness of introducing human papillomavirus (HPV) vaccination is considered before such a strategy is implemented. However, developing countries often lack the technical capacity to perform and interpret results of economic appraisals of vaccines. To provide information about the feasibility of using such models in a developing country setting, we evaluated models of HPV vaccination in terms of their capacity, requirements, limitations and comparability.

Methods

A literature review identified six HPV vaccination models suitable for low-income and middle-income country use and representative of the literature in terms of provenance and model structure. Each model was adapted by its developers using standardised data sets representative of two hypothetical developing countries (a low-income country with no screening and a middle-income country with limited screening). Model predictions before and after vaccination of adolescent girls were compared in terms of HPV prevalence and cervical cancer incidence, as was the incremental cost-effectiveness ratio of vaccination under different scenarios.

Results

None of the models perfectly reproduced the standardised data set provided to the model developers. However, they agreed that large decreases in type 16/18 HPV prevalence and cervical cancer incidence are likely to occur following vaccination. Apart from the Thai model (in which vaccine and non-vaccine HPV types were combined), vaccine-type HPV prevalence dropped by 75% to 100%, and vaccine-type cervical cancer incidence dropped by 80% to 100% across the models (averaging over age groups). The most influential factors affecting cost effectiveness were the discount rate, duration of vaccine protection, vaccine price and HPV prevalence. Demographic change, access to treatment and data resolution were found to be key issues to consider for models in developing countries.

Conclusions

The results indicated the usefulness of considering results from several models and sets of modelling assumptions in decision making. Modelling groups were prepared to share their models and expertise to work with stakeholders in developing countries.

Please see related article: http://www.biomedcentral.com/1741-7007/9/55
Minocycline fails to modulate cerebrospinal fluid HIV infection or immune activation in chronic untreated HIV-1 infection: results of a pilot study
Authors: Ho Emily L , Spudich Serena S , Lee Evelyn , Fuchs Dietmar , Sinclair Elizabeth , Price Richard W
Published: May 2011

Background

Minocycline is a tetracycline antibiotic that has been shown to attenuate central nervous system (CNS) lentivirus infection, immune activation, and brain injury in model systems. To initiate assessment of minocycline as an adjuvant therapy in human CNS HIV infection, we conducted an open-labelled pilot study of its effects on cerebrospinal fluid (CSF) and blood biomarkers of infection and immune responses in 7 viremic subjects not taking antiretroviral therapy.

Results

There were no discernable effects of minocycline on CSF or blood HIV-1 RNA, or biomarkers of immune activation and inflammation including: CSF and blood neopterin, CSF CCL2, CSF white blood cell count, and expression of cell-surface activation markers on CSF and blood T lymphocytes and monocytes.

Conclusions

This pilot study of biological responses to minocycline suggests little potential for its use as adjunctive antiviral or immunomodulating therapy in chronic untreated HIV infection.
Human Immunodeficiency Virus Type 1 Vif causes dysfunction of Cdk1 and CyclinB1: implications for cell cycle arrest
Authors: Sakai Keiko , Barnitz R Anthony , Chaigne-Delalande Benjamin , Bidère Nicolas , Lenardo Michael J
Published: May 2011

The two major cytopathic factors in human immunodeficiency virus type 1 (HIV-1), the accessory proteins viral infectivity factor (Vif) and viral protein R (Vpr), inhibit cell-cycle progression at the G2 phase of the cell cycle. Although Vpr-induced blockade and the associated T-cell death have been well studied, the molecular mechanism of G2 arrest by Vif remains undefined. To elucidate how Vif induces arrest, we infected synchronized Jurkat T-cells and examined the effect of Vif on the activation of Cdk1 and CyclinB1, the chief cell-cycle factors for the G2 to M phase transition. We found that the characteristic dephosphorylation of an inhibitory phosphate on Cdk1 did not occur in infected cells expressing Vif. In addition, the nuclear translocation of Cdk1 and CyclinB1 was disregulated. Finally, Vif-induced cell cycle arrest was correlated with proviral expression of Vif. Taken together, our results suggest that Vif impairs mitotic entry by interfering with Cdk1-CyclinB1 activation.
Antiviral activity of Acacia nilotica against Hepatitis C Virus in liver infected cells
Authors: Rehman Sidra , Ashfaq Usman A , Riaz Sana , Javed Tariq , Riazuddin Sheikh
Published: May 2011

Hepatitis C virus (HCV) belonging to the family Flaviviridae has infected 3% of the population worldwide and 6% of the population in Pakistan. The only recommended standard treatment is pegylated INF-α plus ribavirin. Due to less compatibility of the standard treatment, thirteen medicinal plants were collected from different areas of Pakistan on the basis of undocumented antiviral reports against different viral infections. Medicinal plants were air dried, extracted and screened out against HCV by infecting HCV inoculums of 3a genotype in liver cells. RT-PCR results demonstrate that acetonic and methanolic extract of Acacia nilotica (AN) showed more than 50% reduction at non toxic concentration. From the above results, it can be concluded that by selecting different molecular targets, specific structure-activity relationship can be achieved by doing mechanistic analysis. So, additional studies are required for the isolation and recognition of antiviral compound in AN to establish its importance as antiviral drug against HCV. For further research, we will scrutinize the synergistic effect of active antiviral compound in combination with standard PEG INF-α and ribavirin which may be helpful in exploring further gateways for antiviral therapy against HCV.
Successful surgical resection of infected left atrial myxoma in a case complicated with disseminated intravascular coagulation and multiple cerebral infarctions: case report
Authors: Yoshioka Daisuke , Takahashi Toshiki , Ishizaka Toru , Higuchi Takuya
Published: May 2011

Cardiac myxoma is the most common primary cardiac tumour, but infected cardiac myxoma is relatively rare. Infected cardiac myxoma is very fragile, and has a potential to lead to catastrophic disorder with systemic bacteremia, systemic mycotic embolism, and disseminated intravascular coagulation (DIC).

We present here the successful surgical treatment of a case of infected left atrial myxoma with septic shock, DIC and cerebral infarction without hemorrahage. Collective review of 58 reported cases with infected cardiac myxoma revealed that surgical treatment for it were still challenging and its result was poor. Until date, only one successful surgical treatment for a case complicated by DIC and cerebral infarctions has been reported, and our report describes second such case of successful resection. Even though this report is limited to a case, only aggressive and prompt surgical intervention could relieve the intractable conditions in such a patient with extremely high risk.
Rapamycin-loaded nanoparticles for inhibition of neointimal hyperplasia in experimental vein grafts
Authors: Zou Junjie , Zhang Xiwei , Yang Hongyu , Zhu Yi , Ma Hao , Wang Shui
Published: May 2011

Background

Nanoparticles possess several advantages as a carrier system for intracellular delivery of therapeutic agents. Rapamycin is an immunosuppressive agent which also exhibits marked antiproliferative properties. We investigated whether rapamycin-loaded nanoparticles(NPs) can reduce neointima formation in a rat model of vein graft disease.

Methods

Poly(lactic-co-glycolic acid) (PLGA) NPs containing rapamycin was prepared using an oil/water solvent evaporation technique. Nanoparticle size and morphology were determined by dynamic light scattering methodology and electron microscopy. In vitro cytotoxicity of blank, rapamycin-loaded PLGA (RPLGA) NPs was studied using MTT Assay. Excised rat jugular vein was treated ex vivo with blank-NPs, or rapamycin-loaded NPs, then interposed back into the carotid artery position using a cuff technique. Grafts were harvested at 21 days and underwent morphometric analysis as well as immunohistochemical analysis.

Results

Rapamycin was efficiently loaded in PLGA nanoparticles with an encapsulation efficiency was 87.6%. The average diameter of NPs was 180.3 nm. The NPs-containing rapamycin at 1 ng/ml significantly inhibited vascular smooth muscular cells proliferation. Measurement of rapamycin levels in vein grafts shown that the concentration of rapamycin in vein grafts at 3 weeks after grafting were 0.9 ± 0.1 μg/g. In grafted veins without treatment intima-media thickness was 300.4 ±181.5 μm after grafting 21 days. Whereas, Veins treated with rapamycin-loaded NPs showed a reduction of intimal-media thickness of 150.2 ± 62.5 μm (p = 0.001). CD-31 staining was used to measure luminal endothelial coverage in grafts and indicated a high level of endothelialization in 21 days vein grafts with no significant effect of blank or rapamycin-loaded NPs group.

Conclusions

We conclude that sustained-release rapamycin from rapymycin loaded NPs inhibits vein graft thickening without affecting the reendothelialization in rat carotid vein-to-artery interposition grafts and this may be a promising therapy for the treatment of vein graft disease.
Viral load testing in a resource‐limited setting: quality control is critical
Authors: Greig Jane , du Cros Philipp , Klarkowski Derryck , Mills Clair , Jørgensen Steffen , Harrigan P Richard , O'Brien Daniel P
Published: May 2011

Background

World Health Organization guidelines now recommend routine use of viral load testing, where available, for patients receiving antiretroviral treatment (ART). However, its use has not been routinely implemented in many resource‐limited settings due to cost, availability and accessibility. Viral load testing is complex, making its application in resource‐limited settings challenging. We describe the issues encountered by Médecins Sans Frontières (MSF) when using routine viral load testing in a large HIV programme in sub‐Saharan Africa.

Methods

Between October 2005 and August 2006, more than 1200 patients on ART had viral load tests at baseline and at three‐month intervals performed by a local reference laboratory that was quality assured by an experienced international institution. Concerns with reliability of results halted testing. The quality control measures instituted with a second laboratory and outcomes of these were documented.

Results

In 2005 and 2006, only 178 of 334 (53%) previously ART‐naïve patients tested after six to 12 months of treatment had viral loads of less than 1000 copies/mL. Similar MSF programmes elsewhere demonstrated virological suppression rates of more than 85%, and duplicate testing showed unacceptable discordance. Laboratory problems encountered included: disregarded quality control; time delays; requirement for retesting; and duplicate sample variations. Potentially harmful clinical outcomes of inaccurate viral load results include: unnecessary ART regimen changes; unnecessary enhanced adherence counselling after “false failures”; and undetected virological failure.

Conclusions

Viral load testing performed without rigorous quality control carries the risk of erroneous and potentially damaging results. Viral load testing should be utilized only if robust quality assurance has been implemented. Our experience in this and other settings led to the development of a guide for assessing the suitability of a laboratory for viral load testing that can be used to help achieve reliable results.
A child with hyperferritinemia: Case report
Authors: Serra Melania , Longo Filomena , Roetto Antonella , Sandri Alessandro , Piga Antonio
Published: May 2011

Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare condition caused by mutations in the gene coding for the light chain of ferritin; it does not lead to iron overload, but it is associated with the risk of developing a bilateral nuclear cataract also in childhood. On the contrary, a raise of serum ferritin levels is a common finding in pediatrics. We describe here a case of HHCS that offers some interesting clues for the daily practice. Our patient is a 6 year old Italian boy who came to our attention after some time of diagnostic uncertainties because of persistently high levels of ferritin with no apparent cause. We were guided to the suspect of this syndrome by the family history (5 members with various degrees of cataract developed in first infancy). High levels of serum ferritin and specific genetic testing (mutation A37C) confirmed the diagnosis. This case underlines the need of considering rare genetic syndromes, including hereditary hyperferritinemia cataract syndrome, in the differential diagnosis of raised serum ferritin in children and the importance of paying attention to family history in considering a patient with isolated raised levels of serum ferritin.
Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats
Authors: Gloy Viktoria , Langhans Wolfgang , Hillebrand Jacquelien JG , Geary Nori , Asarian Lori
Published: May 2011

Background

Menopause is associated with increased adiposity, especially increased deposition of intra-abdominal (IA) adipose tissue (AT). This differs from common or 'dietary' obesity, i.e., obesity apparently due to environmentally stimulated overeating, in which IAAT and subcutaneous (S) AT increase in similar proportions. The effect of menopause on adiposity is thought to be due to the decreased secretion of ovarian estrogens. Ovariectomy in rats and other animals is a commonly used model of menopause. It is well known that ovariectomy increases adiposity and that this can be reversed by estradiol treatment, but whether ovariectomy selectively increases IAAT has not been measured directly. Therefore, we used micro-computed tomography (microCT) to investigate this question in both chow-fed and dietary-obese rats.

Methods

Ovariectomized, ovariectomized and estradiol treated, and sham-operated (intact) rats were fed chow or chow plus Ensure (Abbott Nutrition; n = 7/group). Total (T) AT, IAAT and SAT were measured periodically by microCT. Regional distribution of AT was expressed as IAAT as a percentage of TAT (%IAAT). Excesses in these measures were calculated with respect to chow-fed intact rats to control for normal maturational changes. Chemical analysis of fat was done in chow-fed intact and ovariectomized rats at study end. Data were analyzed by t-tests and planned comparisons.

Results

Body mass, TAT, total fat mass, fat-free body mass, and %IAAT all increased in chow-fed intact rats during the 41 d study. In chow-fed rats, ovariectomy increased excess body mass, TAT, fat mass, fat-free body mass, and SAT, but had little effect on IAAT, in chow-fed rats, leading to a decrease in %IAAT. Ensure feeding markedly increased SAT, IAAT and TAT and did not significantly affect %IAAT. Ovariectomy had similar effects in Ensure-fed rats as in chow-fed rats, although less statistically reliable. Estradiol treatment prevented all the effects of ovariectomy.

Conclusions

Both ovariectomy in rats and menopause are associated with increased TAT. After ovariectomy, fat is preferentially deposited as SAT and lean body mass increases, whereas after menopause fat is preferentially deposited as IAAT and lean body mass decreases. These opposite effects of ovariectomy and menopause on regional AT distribution and lean body mass indicate that ovariectomy in rats is not a homologous model of menopause-associated changes in body composition that should be used with great caution in investigations of adiposity-related diseases.