Structure of the adriamycin-cardiolipin complex. Role in mitochondrial toxicity

Adriamycin and its derivatives are among the most efficient antimitotics used in clinical therapy. A specific cardiotoxicity places a limit on the total dose of adriamycin that may be administered. The mechanism of cardiac toxicity is complex. Data accumulated from in vitro and in vivo studies indicate a possible common cause for the inhibition of numerous enzymes and tissue degradation by a free radical mechanism: the binding of adriamycin to the inner mitochondrial membrane cardiolipin. The structure of the adriamycin-cardiolipin complex has been investigated by using physico-chemical techniques and via conformational analysis. The results open a rational way to design new structures that are less cardiotoxic.     

Contrasting effects of PACAP and carbachol on [Ca]i and inositol phosphates in human neuroblastoma NB-OK-1 cells

The effects of PACAPs on [Ca²⁺]_i were compared to those of carbachol in human neuroblastoma NB-OK-1 cells. PACAP(1–27) and PACAP(1–38) increased [Ca²⁺]_i in a biphasic manner: a transient rise and a secondary plateau. The transient phase reflected the mobilization of [Ca²⁺]_i pool(s) via the inositol phosphate pathway. The modest sustained plateau required extracellular Ca²⁺. Carbachol also increased [Ca²⁺]_i in a biphasic manner, but it mobilized intracellular Ca²⁺ pool(s) with a higher efficacy than PACAPs, then greatly increased Ca²⁺ entry, this being accompanied by a more marked and prolonged elevation of IP₃ and IP₄ than with PACAPs. It is likely that cAMP-mediated phosphorylations due to PACAPs facilitated desensitization at the PACAP receptor-phospholipase C level, so that there was less Ca²⁺ handling through PACAP receptors than with muscarinic M₁ receptors.     

World Health Organization Estimates of the Global and Regional Disease Burden of 11 Foodborne Parasitic Diseases, 2010: A Data Synthesis

Background

Foodborne diseases are globally important, resulting in considerable morbidity and mortality. Parasitic diseases often result in high burdens of disease in low and middle income countries and are frequently transmitted to humans via contaminated food. This study presents the first estimates of the global and regional human disease burden of 10 helminth diseases and toxoplasmosis that may be attributed to contaminated food.

Methods and Findings

Data were abstracted from 16 systematic reviews or similar studies published between 2010 and 2015; from 5 disease data bases accessed in 2015; and from 79 reports, 73 of which have been published since 2000, 4 published between 1995 and 2000 and 2 published in 1986 and 1981. These included reports from national surveillance systems, journal articles, and national estimates of foodborne diseases. These data were used to estimate the number of infections, sequelae, deaths, and Disability Adjusted Life Years (DALYs), by age and region for 2010. These parasitic diseases, resulted in 48.4 million cases (95% Uncertainty intervals [UI] of 43.4–79.0 million) and 59,724 (95% UI 48,017–83,616) deaths annually resulting in 8.78 million (95% UI 7.62–12.51 million) DALYs. We estimated that 48% (95% UI 38%-56%) of cases of these parasitic diseases were foodborne, resulting in 76% (95% UI 65%-81%) of the DALYs attributable to these diseases. Overall, foodborne parasitic disease, excluding enteric protozoa, caused an estimated 23.2 million (95% UI 18.2–38.1 million) cases and 45,927 (95% UI 34,763–59,933) deaths annually resulting in an estimated 6.64 million (95% UI 5.61–8.41 million) DALYs. Foodborne Ascaris infection (12.3 million cases, 95% UI 8.29–22.0 million) and foodborne toxoplasmosis (10.3 million cases, 95% UI 7.40–14.9 million) were the most common foodborne parasitic diseases. Human cysticercosis with 2.78 million DALYs (95% UI 2.14–3.61 million), foodborne trematodosis with 2.02 million DALYs (95% UI 1.65–2.48 million) and foodborne toxoplasmosis with 825,000 DALYs (95% UI 561,000–1.26 million) resulted in the highest burdens in terms of DALYs, mainly due to years lived with disability. Foodborne enteric protozoa, reported elsewhere, resulted in an additional 67.2 million illnesses or 492,000 DALYs. Major limitations of our study include often substantial data gaps that had to be filled by imputation and suffer from the uncertainties that surround such models. Due to resource limitations it was also not possible to consider all potentially foodborne parasites (for example Trypanosoma cruzi).

Conclusions

Parasites are frequently transmitted to humans through contaminated food. These estimates represent an important step forward in understanding the impact of foodborne diseases globally and regionally. The disease burden due to most foodborne parasites is highly focal and results in significant morbidity and mortality among vulnerable populations.     

Methodological Framework for World Health Organization Estimates of the Global Burden of Foodborne Disease

Background

The Foodborne Disease Burden Epidemiology Reference Group (FERG) was established in 2007 by the World Health Organization to estimate the global burden of foodborne diseases (FBDs). This paper describes the methodological framework developed by FERG''s Computational Task Force to transform epidemiological information into FBD burden estimates.

Methods and Findings

The global and regional burden of 31 FBDs was quantified, along with limited estimates for 5 other FBDs, using Disability-Adjusted Life Years in a hazard- and incidence-based approach. To accomplish this task, the following workflow was defined: outline of disease models and collection of epidemiological data; design and completion of a database template; development of an imputation model; identification of disability weights; probabilistic burden assessment; and estimating the proportion of the disease burden by each hazard that is attributable to exposure by food (i.e., source attribution). All computations were performed in R and the different functions were compiled in the R package ''FERG''. Traceability and transparency were ensured by sharing results and methods in an interactive way with all FERG members throughout the process.

Conclusions

We developed a comprehensive framework for estimating the global burden of FBDs, in which methodological simplicity and transparency were key elements. All the tools developed have been made available and can be translated into a user-friendly national toolkit for studying and monitoring food safety at the local level.     

Prevalence of Neurocysticercosis in People with Epilepsy in the Eastern Province of Zambia

Zambia is endemic for Taenia solium taeniosis and cysticercosis. In this single-centered, cross-sectional, community-based study, the role of neurocysticercosis (NCC) as a cause of epilepsy was examined. People with epilepsy (PWE, n = 56) were identified in an endemic area using a screening questionnaire followed by in-depth interviews and neurological examination. Computed tomography (CT) was performed on 49 people with active epilepsy (PWAE) and their sera (specific antibody and antigen detection, n = 56) and stools (copro-antigen detection, n = 54) were analyzed. The CT scan findings were compared to a group of 40 CT scan controls. Of the PWE, 39.3% and 23.2% were positive for cysticercal antibodies and antigens, respectively, and 14.8% for coproantigens (taeniosis). Lesions highly suggestive of NCC were detected in 24.5% and definite NCC lesions in 4.1% of CT scans of PWAE. This compares to 2.5% and 0%, respectively, in the control CT scans. Using the Del Brutto diagnostic criteria, 51.8% of the PWAE were diagnosed with probable or definitive NCC and this rose to 57.1% when the adapted criteria, as proposed by Gabriël et al. (adding the sero-antigen ELISA test as a major criterion), were used. There was no statistically significant relationship between NCC, current age, age at first seizure and gender. This study suggests that NCC is the single most important cause of epilepsy in the study area. Additional large-scale studies, combining a community based prevalence study for epilepsy with neuroimaging and serological analysis in different areas are needed to estimate the true impact of neurocysticercosis in endemic regions and efforts should be instituted to the control of T. solium.     

Taenia solium Human Cysticercosis: A Systematic Review of Sero-epidemiological Data from Endemic Zones around the World

Background

Taenia solium cysticercosis is a zoonotic neglected disease responsible for severe health disorders such as seizures and death. Understanding the epidemiology of human cysticercosis (HCC) in endemic regions will help to expose critical information about the transmission of the disease, which could be used to design efficient control programs. This review gathered serological data on apparent prevalence of T. solium circulating antigens and/or seroprevalence of T. solium antibodies, apparent prevalence of human taeniasis and risk factors for HCC from endemic communities in order to understand the differences in exposure to the parasite and active infections with T. solium metacestodes in endemic areas around the world.

Methods

Three databases were used to search sero-epidemiological data from community-based studies conducted between 1989 and 2014 in cysticercosis endemic communities worldwide. The search focused on data obtained from T. solium circulating antigen detection by monoclonal antibody-based sandwich ELISA and/or T. solium antibody seroprevalence determined by Enzyme-linked Immunoelectrotransfer Blot (EITB). A meta-analysis was performed per continent.

Principal Findings

A total of 39,271 participants from 19 countries, described in 37 articles were studied. The estimates for the prevalence of circulating T. solium antigens for Africa, Latin America and Asia were: 7.30% (95% CI [4.23–12.31]), 4.08% (95% CI [2.77–5.95]) and 3.98% (95% CI [2.81–5.61]), respectively. Seroprevalence estimates of T. solium antibodies were 17.37% (95% CI [3.33–56.20]), 13.03% (95% CI [9.95–16.88]) and 15.68% (95% CI [10.25–23.24]) respectively. Taeniasis reported prevalences ranged from 0 (95% CI [0.00–1.62]) to 17.25% (95% CI [14.55–20.23]).

Significance

A significant variation in the sero-epidemiological data was observed within each continent, with African countries reporting the highest apparent prevalences of active infections. Intrinsic factors in the human host such as age and immunity were main determinants for the occurrence of infections, while exposure was mostly related to environmental factors which varied from community to community.     

Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study

Introduction  

The aims of the present study were to identify histopathological parameters which are linked to local clinical skin disease at two distinct anatomical sites in systemic sclerosis (SSc) patients with skin involvement (limited cutaneous systemic sclerosis (lcSSc) or diffuse cutaneous systemic sclerosis (dcSSc)) and to determine the sensitivity of SSc specific histological alterations, focusing on SSc patients without clinical skin involvement (limited SSc (lSSc)).     

Toward a Carbon Dioxide Neutral Industrial Park

The industrial park of Herdersbrug (Brugge, Flanders, Belgium) comprises 92 small and medium‐sized enterprises, a waste‐to‐energy incinerator, and a power plant (not included in the study) on its site. To study the carbon dioxide (CO₂) neutrality of the park, we made a park‐wide inventory for 2007 of the CO₂ emissions due to energy consumption (electricity and fossil fuel) and waste incineration, as well as an inventory of the existing renewable electricity and heat generation. The definition of CO₂ neutrality in Flanders only considers CO₂ released as a consequence of consumption or generation of electricity, not the CO₂ emitted when fossil fuel is consumed for heat generation. To further decrease or avoid CO₂ emissions, we project and evaluate measures to increase renewable energy generation. The 21 kilotons (kt) of CO₂ emitted due to electricity consumption are more than compensated by the 25 kt of CO₂ avoided by generation of renewable electricity. Herdersbrug Industrial Park is thus CO₂ neutral, according to the definition of the Flemish government. Only a small fraction (6.6%) of the CO₂ emitted as a consequence of fossil fuel consumption (heat generation) and waste incineration is compensated by existing and projected measures for renewable heat generation. Of the total CO₂ emission (149 kt) due to energy consumption (electricity + heat generation) and waste incineration on the Herdersbrug Industrial Park in 2007, 70.5% is compensated by existing and projected renewable energy generated in the park. Forty‐seven percent of the yearly avoided CO₂ corresponds to renewable energy generated from waste incineration and biomass fermentation.     

Effects of inhaled corticosteroids on sputum cell counts in stable chronic obstructive pulmonary disease: a systematic review and a meta-analysis

Background

Whether inhaled corticosteroids suppress airway inflammation in chronic obstructive pulmonary disease (COPD) remains controversial. We sought to determine the effects of inhaled corticosteroids on sputum indices of inflammation in stable COPD.

Methods

We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Databases for randomized, controlled clinical trials that used induced sputum to evaluate the effect of inhaled corticosteroids in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of sputum cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across original studies. If significant heterogeneity was present (p < 0.10), then a random effects model was used to pool the original data. In the absence of significant heterogeneity, a fixed effects model was used.

Results

We identified six original studies that met the inclusion criteria (N = 162 participants). In studies with higher cumulative dose (≥ 60 mg) or longer duration of therapy (≥ 6 weeks), inhaled corticosteroids were uniformly effective in reducing the total cell, neutrophil, and lymphocyte counts. In contrast, studies with lower cumulative dose (< 60 mg) or shorter duration of therapy (< 6 weeks) did not demonstrate a favorable effect of inhaled corticosteroids on these sputum indices.

Conclusions

Our study suggests that prolonged therapy with inhaled corticosteroids is effective in reducing airway inflammation in stable COPD.