Interaction of Lactoferrin with Unsaturated Fatty Acids: In Vitro and In Vivo Study of Human Lactoferrin/Oleic Acid Complex Cytotoxicity

As shown recently, oleic acid (OA) in complex with lactoferrin (LF) causes the death of cancer cells, but no mechanism(s) of that toxicity have been disclosed. In this study, constitutive parameters of the antitumor effect of LF/OA complex were explored. Complex LF/OA was prepared by titrating recombinant human LF with OA. Spectral analysis was used to assess possible structural changes of LF within its complex with OA. Structural features of apo-LF did not change within the complex LF:OA = 1:8, which was toxic for hepatoma 22a cells. Cytotoxicity of the complex LF:OA = 1:8 was tested in cultured hepatoma 22a cells and in fresh erythrocytes. Its anticancer activity was tested in mice carrying hepatoma 22a. In mice injected daily with LF-8OA, the same tumor grew significantly slower. In 20% of animals, the tumors completely resolved. LF alone was less efficient, i.e., the tumor growth index was 0.14 for LF-8OA and 0.63 for LF as compared with 1.0 in the control animals. The results of testing from 48 days after the tumor inoculation showed that the survival rate among LF-8OA-treated animals was 70%, contrary to 0% rate in the control group and among the LF-treated mice. Our data allow us to regard the complex of LF and OA as a promising tool for cancer treatment.     

Relationship between Root Apices and the Mandibular Canal: A Cone-beam Computed Tomographic Comparison of 3 Populations

Introduction

This study aimed to investigate the difference in the location of the inferior alveolar nerve (IAN) in relation to the apices of mandibular molars in 3 different populations using cone-beam computed tomographic (CBCT) imaging and to assess the proportion of teeth in close proximity (a distance of 1 mm or less) to the IAN.

Considerations Before Establishing an Environmental Health Registry

Public health registries can provide valuable information when health consequences of environmental exposures are uncertain or will likely take long to develop. They can also aid research on diseases that may have environmental causes that are not completely well defined.We discuss factors to consider when deciding whether to create an environmental health registry. Those factors include public health significance, purpose and outcomes, duration and scope of data collection and availability of alternative data sources, timeliness, availability of funding and administrative capabilities, and whether the establishment of a registry can adequately address specific health concerns.We also discuss difficulties, limitations, and benefits of exposure and disease registries, based on the experience of the Agency for Toxic Substances and Disease Registry.The use of public health registries has become increasingly common in the past 2 decades.1,2 Although they are widespread in the context of immunizations, cancer epidemiology, and drug development research,3 the field of environmental health has also benefited from the establishment of a number of disease and exposure registries.A registry is generally defined as a set of records containing systematically collected, standardized data about individual people.4 These data are typically acquired, maintained, and updated over a prolonged period, usually years. Registries range from only a listing of exposed individuals with associated contact information to a research repository of information that includes demographics, exposure data, and health information. A public health registry is set up to accomplish a public health goal or activity. It might be used to obtain information on people who have a particular disease, a condition or a risk factor that predisposes them to illness from a health-related event, or previous exposure to substances or circumstances known or suspected to cause adverse health effects. The particular data assembled are a function of the purpose of the registry. The variables might be chosen to help study or detect specific health problems or to study treatments in specific individuals or disorders. In the context of environmental health, registries include information regarding individual exposures to chemical or physical environmental agents or the known or potential consequences of such exposures.The central purpose of a registry is to facilitate epidemiological research or provide information to registrants about a certain disease, exposure, or event. Registries are also used to generate relevant statistics about the group of registered people. We discuss the main factors to consider when deciding whether to create an environmental health registry. We also discuss some of the difficulties, limitations, and benefits of registries, based on the experience of their use by the Agency for Toxic Substances and Disease Registry (ATSDR) in the United States.     

Rasch Analysis of the Edmonton Symptom Assessment System

Context

The Edmonton Symptom Assessment System (ESAS) is a widely used multisymptom assessment tool in cancer and palliative care settings, but its psychometric properties have not been widely tested using modern psychometric methods such as Rasch analysis.

Isoform-specific antagonists of exchange proteins directly activated by cAMP

The major physiological effects of cAMP in mammalian cells are transduced by two ubiquitously expressed intracellular cAMP receptors, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC), as well as cyclic nucleotide-gated ion channels in certain tissues. Although a large number of PKA inhibitors are available, there are no reported EPAC-specific antagonists, despite extensive research efforts. Here we report the identification and characterization of noncyclic nucleotide EPAC antagonists that are exclusively specific for the EPAC2 isoform. These EAPC2-specific antagonists, designated as ESI-05 and ESI-07, inhibit Rap1 activation mediated by EAPC2, but not EPAC1, with high potency in vitro. Moreover, ESI-05 and ESI-07 are capable of suppressing the cAMP-mediated activation of EPAC2, but not EPAC1 and PKA, as monitored in living cells through the use of EPAC- and PKA-based FRET reporters, or by the use of Rap1-GTP pull-down assays. Deuterium exchange mass spectroscopy analysis further reveals that EPAC2-specific inhibitors exert their isoform selectivity through a unique mechanism by binding to a previously undescribed allosteric site: the interface of the two cAMP binding domains, which is not present in the EPAC1 isoform. Isoform-specific EPAC pharmacological probes are highly desired and will be valuable tools for dissecting the biological functions of EPAC proteins and their roles in various disease states.     

No Association between Hyponatremia and Rhabdomyolysis in Rats

Background

Rhabdomyolysis is an uncommon complication of hyponatremia, reported previously only in case reports and small retrospective studies, and its underlying mechanism is controversial. Some studies support the hypothesis that the rapid correction of hyponatremia is responsible for rhabdomyolysis, whereas others emphasize the severity of the hyponatremia as a predisposing factor for rhabdomyolysis.

Objectives

To test the association between hyponatremia and rhabdomyolysis and to demonstrate a causal association.

Methods

Hyponatremia was induced by administration of water and desmopressin acetate in rats during 3 days, followed by its rapid correction, using animal models established for the evaluation of central pontine myelinolysis. The plasma creatine phosphokinase levels, a marker for rhabdomyolysis, were monitored, and hematoxylin and eosin sections of the quadriceps and gastrocnemius muscles were evaluated for signs of rhabdomyolysis.

Results

The induction of hyponatremia and its correction were accompanied by the previously reported neurological sequelae, including signs of central pontine myelinolysis. However, no increase in plasma creatine phosphokinase levels was found, and histopathological examination of the quadriceps and gastrocnemius muscles revealed no sign of rhabdomyolysis.

Conclusions

The present study, which is the first to test the association between hyponatremia and rhabdomyolysis in an animal model, does not support any causal association between hyponatremia and rhabdomyolysis. Thus, other factors might be necessary for an association between hyponatremia and rhabdomyolysis, such as genetic factors or convulsions that are known to be associated with both hyponatremia and rhabdomyolysis. Further research in this important physiologic and clinical question is needed.