Hepatopathy following consumption of a commercially available blue-green algae dietary supplement in a dog

BACKGROUND: Dietary supplement use in both human and animals to augment overall health continues to increase and represents a potential health risk due to the lack of safety regulations imposed on the manufacturers. Because there are no requirements for demonstrating safety and efficacy prior to marketing, dietary supplements may contain potentially toxic contaminants such as hepatotoxic microcystins produced by several species of blue-green algae. CASE PRESENTATION: An 11-year-old female spayed 8.95 kg Pug dog was initially presented for poor appetite, lethargy polyuria, polydipsia, and an inability to get comfortable. Markedly increased liver enzyme activities were detected with no corresponding abnormalities evident on abdominal ultrasound. A few days later the liver enzyme activities were persistently increased and the dog was coagulopathic indicating substantial liver dysfunction. The dog was hospitalized for further care consisting of oral S-adenosylmethionine, silybin, vitamin K, and ursodeoxycholic acid, as well as intravenous ampicillin sodium/sulbactam sodium, dolasetron, N-acetylcysteine, metoclopramide, and intravenous fluids. Improvement of the hepatopathy and the dog’s clinical status was noted over the next three days. Assessment of the dog’s diet revealed the use of a commercially available blue-green algae dietary supplement for three-and-a-half weeks prior to hospitalization. The supplement was submitted for toxicology testing and revealed the presence of hepatotoxic microcystins (MCs), MC-LR and MC-LA. Use of the supplement was discontinued and follow-up evaluation over the next few weeks revealed a complete resolution of the hepatopathy. CONCLUSIONS: To the authors’ knowledge, this is the first case report of microcystin intoxication in a dog after using a commercially available blue-green algae dietary supplement. Veterinarians should recognize the potential harm that these supplements may cause and know that with intervention, recovery is possible. In addition, more prudent oversight of dietary supplement use is recommended for our companion animals to prevent adverse events/intoxications

A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss

The use of megestrol acetate in the treatment of weight loss in gastrointestinal cancer patients has been disappointing. The aim of the present study was to compare the combination of megestrol acetate and placebo with megestrol acetate and ibuprofen in the treatment of weight loss in such patients. At baseline, 4–6 weeks and 12 weeks, patients underwent measurements of anthropometry, concentrations of albumin and C-reactive protein and assessment of appetite, performance status and quality of life using EuroQol-EQ-5D and EORTC QLQ-C30. Thirty-eight and 35 patients (median weight loss 18%) were randomized to megestrol acetate/placebo or megestrol acetate/ibuprofen, respectively, for 12 weeks. Forty-six (63%) of patients failed to complete the 12-week assessment. Of those evaluable at 12 weeks, there was a decrease in weight (median 2.8 kg) in the megestrol acetate/placebo group compared with an increase (median 2.3 kg) in the megestrol acetate/ibuprofen group (P < 0.001). There was also an improvement in the EuroQol-EQ-5D quality of life scores of the latter group (P < 0.05). The combination of megestrol acetate/ibuprofen appeared to reverse weight loss and appeared to improve quality of life in patients with advanced gastrointestinal cancer. Further trials of this novel regimen in weight-losing patients with hormone-insensitive cancers are warranted. © 1999 Cancer Research Campaig

Genetic Factors Influence the Clustering of Depression among Individuals with Lower Socioeconomic Status

Objective: To investigate the extent to which shared genetic factors can explain the clustering of depression among individuals with lower socioeconomic status, and to examine if neuroticism or intelligence are involved in these pathways. Methods: In total 2,383 participants (1,028 men and 1,355 women) of the Erasmus Rucphen Family Study were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) and the Hospital Anxiety and Depression Scale (HADSD). Socioeconomic status was assessed as the highest level of education obtained. The role of shared genetic factors was quantified by estimating genetic correlations (rG) between symptoms of depression and education level, with and without adjustment for premorbid intelligence and neuroticism scores. Results: Higher level of education was associated with lower depression scores (partial correlation coefficient 20.09 for CESD and 20.17 for HADS-D). Significant genetic correlations were found between education and bo

A Review of the Implications of Heterozygosity and Inbreeding on Germplasm Biodiversity and Its Conservation in the Silkworm, Bombyx mori

Silkworm genebanks assume paramount importance as the reservoirs of biodiversity and source of alleles that can be easily retrieved for genetic enhancement of popular breeds. More than 4000 Bombyx mori L (Lepidoptera: Bombycidae) strains are currently available and these strains are maintained through continuous sibling mating. This repeated sibling mating makes the populations of each strain more homozygous, but leads to loss of unique and valuable genes through the process of inbreeding depression. Hence, it is essential to maintain a minimal degree of heterozygosity within the population of each silkworm strain, especially in the traditional geographic strains, to avoid such loss. As a result, accurate estimation of genetic diversity is becoming more important in silkworm genetic resources conservation. Application of molecular markers help estimate genetic diversity much more accurately than that of morphological traits. Since a minimal amount of heterozygosity in each silkworm strain is essential for better conservation by avoiding inbreeding depression, this article overviews both theoretical and practical importance of heterozygosity together with impacts of inbreeding depression and the merits and demerits of neutral molecular markers for measurements of both heterozygosity and inbreeding depression in the silkworm Bombyx mori

Dissecting Genetic Networks Underlying Complex Phenotypes: The Theoretical Framework

Great progress has been made in genetic dissection of quantitative trait variation during the past two decades, but many studies still reveal only a small fraction of quantitative trait loci (QTLs), and epistasis remains elusive. We integrate contemporary knowledge of signal transduction pathways with principles of quantitative and population genetics to characterize genetic networks underlying complex traits, using a model founded upon one-way functional dependency of downstream genes on upstream regulators (the principle of hierarchy) and mutual functional dependency among related genes (functional genetic units, FGU). Both simulated and real data suggest that complementary epistasis contributes greatly to quantitative trait variation, and obscures the phenotypic effects of many ‘downstream’ loci in pathways. The mathematical relationships between the main effects and epistatic effects of genes acting at different levels of signaling pathways were established using the quantitative and population genetic parameters. Both loss of function and “co-adapted” gene complexes formed by multiple alleles with differentiated functions (effects) are predicted to be frequent types of allelic diversity at loci that contribute to the genetic variation of complex traits in populations. Downstream FGUs appear to be more vulnerable to loss of function than their upstream regulators, but this vulnerability is apparently compensated by different FGUs of similar functions. Other predictions from the model may account for puzzling results regarding responses to selection, genotype by environment interaction, and the genetic basis of heterosis

Reduced Amygdala and Ventral Striatal Activity to Happy Faces in PTSD Is Associated with Emotional Numbing

There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1) individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2) that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral) faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing

DNA methylation in diploid inbred lines of potatoes and its possible role in the regulation of heterosis

Self-incompatible diploid potatoes were altered to self-compatible ones by a function of S-locus inhibitor gene and continued selfing generated highly homozygous inbreds. In this study, this process was investigated for the status of DNA methylation by a simple method using genomic DNA digested by methylation-sensitive restriction enzymes prior to RAPD analysis. We detected 31 methylation-sensitive RAPD bands, of which 11 were newly appeared in the selfed progenies, and 6 of them stably inherited to subsequent generations. Aberrant segregations and paternal- or atavism-like transmission were also found. Segregating methylation-sensitive bands in initial populations became fixed in the advanced selfed progenies by 75.0–93.8%, of which 41.7% were fixed to all present and 58.3% to all absent. Because DNA methylation is generally recognized to suppress gene expression as regulatory factors, homozygosity/heterozygosity of methylated DNA may be involved in inbreeding depression/heterosis

MUC2 polymorphisms are associated with endometriosis development and infertility: a case-control study

<p>Abstract</p> <p>Background</p> <p>Mucins are highly glycosylated proteins protecting and lubricating epithelial surface of respiratory, gastrointestinal and reproductive tracts. Members of the mucin protein family have been suggested to play an important role in development of endometriosis and infertility. This study investigates genetic association of mucin2 (<it>MUC2</it>) with the risk of endometriosis and endometriosis-related infertility.</p> <p>Methods</p> <p>This case-control study was conducted at China Medical University Hospital, with 195 endometriosis patients and 196 healthy controls enrolled. Genotyping of six SNPs (rs2856111, rs11245936, rs10794288, rs10902088, rs7103978 and rs11245954) within <it>MUC2 </it>gene were performed by using <it>Taqman </it>genotyping assay; individual SNP and haplotype associations with endometriosis and endometriosis-related infertility were assessed by <it>χ</it>²test.</p> <p>Results</p> <p>Endometriosis patients exhibit significantly lower frequency of the rs10794288 C allele, the rs10902088 T allele and the rs7103978 G allele (<it>P </it>= 0.030, 0.013 and 0.040, respectively). In addition, the rs10794288 C allele and the rs10902088 T allele were also less abundant in patients with infertility versus fertile ones (<it>P </it>= 0.015 and 0.024, respectively). Haplotype analysis of the endometriosis associated SNPs in <it>MUC2 </it>also showed significantly association between the most common haplotypes and endometriosis or endometriosis-related infertility.</p> <p>Conclusions</p> <p><it>MUC2 </it>polymorphisms, especially rs10794288 and rs10902088, are associated with endometriosis as well as endometriosis-related infertility. Our data present MUC2 as a new candidate involved in development of endometriosis and related infertility in Taiwanese Han women.</p

The GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders

Recent evidence suggests that the GABA transporter 1 (GAT-1; SLC6A1) plays a role in the pathophysiology and treatment of anxiety disorders. In order to understand the impact of genetic variation within SLC6A1 on pathological anxiety, we performed a case–control association study with anxiety disorder patients with and without syndromal panic attacks. Using the method of sequential addition of cases, we found that polymorphisms in the 5′ flanking region of SLC6A1 are highly associated with anxiety disorders when considering the severity of syndromal panic attacks as phenotype covariate. Analysing the effect size of the association, we observed a constant increase in the odds ratio for disease susceptibility with an increase in panic severity (OR ~ 2.5 in severely affected patients). Nominally significant association effects were observed considering the entire patient sample. These data indicate a high load of genetic variance within SLC6A1 on pathological anxiety and highlight GAT-1 as a promising target for treatment of anxiety disorders with panic symptoms