Histological assessment of intermediate - and long-term creatine monohydrate supplementation in mice and rats

Creatine monohydrate (CrM) supplementation appears to be relatively safe based on data from short-term and intermediate-term human studies and results from several therapeutic trials. The purpose of the current study was to characterize pathological changes after intermediate-term and long-term CrM supplementation in mice [healthy control and SOD1 (G93A) transgenic] and rats (prednisolone and nonprednisolone treated). Histological assessment (18-20 organs/tissues) was performed on G93A mice after 159 days, and in Sprague-Dawley rats after 365 days, of CrM supplementation (2% wt/wt) compared with control feed. Liver histology was also evaluated in CD-1 mice after 300 days of low-dose CrM supplementation (0.025 and 0.05 g · kg^-1 · day^-1) and in Sprague-Dawley rats after 52 days of CrM supplementation (2% wt/wt) with and without prednisolone. Areas of hepatitis were observed in the livers of the CrM-supplemented G93A mice (P < 0.05), with no significant inflammatory lesions in any of the other 18-20 tissues/organs that were evaluated. The CD-1 mice also showed significant hepatic inflammatory lesions (P < 0.05), yet there was no negative effect of CrM on liver histology in the Sprague-Dawley rats after intermediate-term or long-term supplementation nor was inflammation seen in any other tissues/organs (P = not significant). Dietary CrM supplementation can induce inflammatory changes in the liver of mice, but not rats. The observed inflammatory changes in the murine liver must be considered in the evaluation of hepatic metabolism in CrM-supplemented mice. Species differences must be considered in the evaluation of toxicological and physiological studies.

Histological alterations in the Antarctic cod, Trematomus bernacchii from Davis Station, East Antarctica

During the summer season 2009/10, a comprehensive environmental impact assessment of the sewage discharge was conducted at Davis Station in the Vestfold Hills region of East Antarctica. As part of this project, a survey of the histology of liver, gill, gonad and muscle tissues in the Antarctic rock cod Trematomus bernacchii from nearshore sites in the receiving environment close to Davis Station in was completed. Fish from 4 sites were examined; 1 site adjacent to the Davis Station sewage outfall (within 500 m of the point of discharge), 2 sites approximately 2 km from the outfall (Anchorage Island and Antennae farm), and 1 site approximately 10 km away from the outfall and adjacent to an Adelie penguin population (Kazak Island). All fish sampled from the sewage outfall site exhibited significant histological alterations in all major tissues. Fish from the other 3 sites showed some alterations in either gill and/or liver tissues. Pathological abnormalities present in all fish collected near the sewage outfall included: extensive multifocal cysts of unknown etiology with necrotic liquification; multifocal granuloma with associated inflammation; coagulative necrosis in the liver; and lamellar hyperplasia with associated proliferation and lamella fusion of the gills. Results of this work form part of a weight of evidence approach alongside ecological monitoring, chemical analysis, ecotoxicological testing and dispersal modelling of the discharge plume which is being used to inform and direct upgrades to the Australian Antarctic Divisions operations and current sewage discharge practises at Davis Station.

An examination of a proposed DSM-IV pathological gambling hierarchy in a treatment seeking population: similarities with substance dependence and evidence for three classification systems

Toce-Gerstein et al. (Addiction 98:1661–1672, 2003) investigated the distribution of Diagnostic and Statistical Manual for Mental Disorders, 4th edition (DSM-IV) pathological gambling criteria endorsement in a U.S. community sample for those people endorsing a least one of the DSM-IV criteria (n = 399). They proposed a hierarchy of gambling disorders where endorsement of 1–2 criteria were deemed ‘At-Risk’, 3–4 ‘Problem gamblers’, 5–7 ‘Low Pathological&rsquo;, and 8–10 ‘High Pathological&rsquo; gamblers. This article examines these claims in a larger Australian treatment seeking population. Data from 4,349 clients attending specialist problem gambling services were assessed for meeting the ten DSM-IV pathological gambling criteria. Results found higher overall criteria endorsement frequencies, three components, a direct relationship between criteria endorsement and gambling severity, clustering of criteria similar to the Toce-Gerstein et al. taxonomy, high accuracy scores for numerical and criteria specific taxonomies, and also high accuracy scores for dichotomous pathological gambling diagnoses. These results suggest significant complexities in the frequencies of criteria reports and relationships between criteria.

Metabolic remodelling in obesity and type 2 diabetes: pathological or protective mechanisms in response to nutrient excess?

Altered metabolism in tissues such as the liver, skeletal muscle and adipose tissue is observed in metabolic diseases characterized by nutrient excess and energy imbalance, such as obesity and type 2 diabetes. These alterations in metabolism can include resistance to the hormone insulin, lipid accumulation, mitochondrial dysfunction and transcriptional remodelling of major metabolic pathways. The underlying assumption has been that these same alterations in metabolism are fundamental to the pathogenesis of metabolic diseases. An alternative view is that these alterations in metabolism occur to protect cell and tissue viability in the face of constant positive energy balance. This speculative review presents evidence that many of the metabolic adaptations that occur in metabolic diseases characterized by nutrient excess can be viewed as protective in nature, rather than pathogenic per se for disease progression. Finally, we also briefly discuss the usefulness and potential pitfalls of therapeutic approaches that attempt to correct these same metabolic defects when energy balance is not altered, and the potential links between metabolic survival responses and other chronic diseases such as cancer.