Edward Fitzgerald—pioneer, coach driver, shepherd, and rabitter : a very brief reflection

My extended whānau, Edward Fitzgerald’s descendants, know very little about him. We know he was of Irish descent, and his death certificate notes that he was born in Tauranga to Tom Fitzgerald and Elizabeth Blackburn. His death certificate states that he died of chronic myocardial degeneration at Waiōhau at the age of 82. This very brief paper gathers the very few known strands of his history and merely describes what is known of him. This paper is published here in memory of him and to inspire whānau to continue searching for more information.

Toxico-Pathological Studies of the Insecticide Metasystox-R (Oxydemeton-Methyl) in Rabbits

One of the widely used insecticides in agriculture and urban pest control is oxydemeton-methyl, which is an organothiophosphate compound. It has a high bioaccumulation effect due to its increased solubility and mobility. This study was carried out to investigate the effect of oxydemeton-methyl toxicity on the environment, and female New Zealand rabbits were used as a model. The rabbits were given oxydemeton-methyl orally in drinking water at a concentration of 34 ppm for six weeks. The clinical signs were diarrhoea, emesis, salivation, lacrimation, fasciculation, muscle tremors and weakness. The haematological parameters, such as the RBCs count, the Hb concentration and the PCV % were significantly decreased. On the contrary, the WBCs count were significantly increased. In addition, an acetylcholinesterase enzyme was inhibited, and a histopathological examination on the liver showed small areas of oval and bridge necrosis infiltrated with mononuclear cells. In the kidneys, there was a variable degree of nephrosis, and the heart showed foci of myocardial degeneration infiltrated with mononuclear cells. Therefore, it is concluded that oxydemeton-methyl is highly toxic to the environment.

N-acetyl Cysteine Can Blunt Metabolic and Cardiovascular Effects via Down-regulation of Cardiotrophin-1 in Rat Model of Fructose-induced Metabolic Syndrome

Background Chronic fructose consumption is associated with development of obesity, insulin resistance (IR) and metabolic syndrome (MS). Cardiovascular diseases are linked to metabolic deregulation observed in MS. N-acetylcysteine (NAC) is a sulfur containing compound of Allium plants (such as garlic and onion) that increases intracellular reduced glutathione concentrations, which is an endogenous antioxidant. Methods This study investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced MS in male Wistar rats and to examine its protective effect on aortic and cardiac tissues via its influence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose (20% w/v) induced MS animals for twelve weeks. Results Chronic fructose consumption increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), IR and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and fibrosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP and mitigated atherogenic dyslipidaemia and oxidative stress (OS). Additionally, NAC down-regulated CT-1 expression in the heart and aorta. Furthermore, CT-1 expression in the heart and aorta was positively correlated with basal glycemia, final SBP and DBP, total cholesterol, triglycerides, low density lipoproteins and negatively correlated with high density lipoproteins levels. Conclusion The findings reported here demonstrated, for the first time, the protective effect of NAC against aortic and myocardial degeneration and fibrosis through down-regulation of CT-1 in fructose induced MS animal model. Also, our results revealed the infallible role of NAC to blunt the cardiometabolic deregulation observed in MS.

Toxicity effects of Nerium oleander, basic and clinical evidence: A comprehensive review

Introduction: Nerium oleander is a plant that is frequently grown in gardens and public areas. N. oleander is distributed originally in subtropical Asia but is now growing in many parts of the world, such as the United States, Australia, China, and Middle East countries. Pharmacological effects of plant including antinociceptive, anti-inflammatory, and anticancer activity were reported, but the potential toxic effects of all parts of the shrub either fresh or dried on animal and human body were documented. Method: The data of this review article were obtained from Medline/Pubmed, Scopusand Google Scholar databases in English until September 2019. To include all publications in this field, keywords such as N. oleander and toxicity were used. Results: The poisoning effects of plant or their active alkaloids induced infiltration of cells with hemorrhage and sever negative changes in the lung, induce lesions, and infiltration of inflammatory cells into the portal spaces with scattered necrosis of hepatocytes in the liver, cardiac toxicity of the plant in the heart were included, induced varying degrees of hemorrhage, myocardial degeneration, and necrosis. It also induced arrhythmia, sinus bradycardia, and prolonged P-R interval in electrocardiographic records. Conclusions: The toxic effects of N. oleander are mostly related to its inhibitory effects on the Na+-K+ ATPase pump in the cellular membrane. However, the exact molecular mechanism involved in the toxicity of N. oleander is not clear.

Investigating the Histological Changes in Heart, Lung, Liver and Kidney of Male Albino Mice Treated with Ivabradine

The present study aimed to investigate the histological changes of heart, lung, liver and kidney which caused by different concentrations (10, 20 and 40 mg/kg) of Ivabradine. Results of the study revealed some histological changes represented by aggregation of the lymphocytes around respiratory bronchioles of the lung. In the liver, the drug caused hepatocyte necrosis and infiltration of the lymphocytes. In Kidney, there are no histopathological modifications in the tissue after the animals treated with 10 mg\kg of Ivabradine. When the animals treated with Ivabradine drug at 20mg/kg of bw, dose showed vascular congestion between myocardial fibers of heart. Emphysematous changes of the alveoli and infiltration of lymphocytes around respiratory bronchioles of lung. In the liver there were dilated blood sinusoids. Also, there are vascular congestion and congestion of capillaries in the glomerular of kidney. Male mice treated with Ivabradine drug at 40 mg/kg of bw cause increase spaces between myocardial fibers, cardiac atrophy and myocardial degeneration in the heart. In addition, there are infiltration of lymphocytes around respiratory bronchioles, pulmonary congestion and emphysematous changes of the alveoli in lung. In the liver, the drug cause amyloid deposition and degeneration of hepatocytes. Furthermore, the drug caused vascular congestion in the kidney. Conclusion: From the current study, we conclude that the different concentrations of Ivabradine caused tissue changes in the heart, lung, liver and kidneys. The study should continue using different drugs and concentrations.

Effects of Bisphenol A on Incidence and Severity of Cardiac Lesions in the NCTR-Sprague-Dawley Rat: A CLARITY-BPA Study

The goal of this study was to determine whether bisphenol A (BPA) had adverse effects indicative of cardiac toxicity. As part of the “Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA), study dams and offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to 25000 μg/kg/day, 0.05 or 0.5 μg/kg/day 17α-ethinyl-estradiol (EE) or 0.3% carboxymethylcellulose vehicle. Exposure-related effects were analyzed in isolated hearts by quantitative morphometry and histopathology. No dose-related changes in body weight were detected. Across all exposure groups including vehicle controls, body weight of continuously dosed males was reduced compared to males dosed only until PND21. Heart weight was increased only in females exposed to EE, and consistent alterations in LV wall thickness were not observed. Exposure-related changes in collagen accumulation were minor and limited to highest EE exposure groups with increased collagen accumulation in PND21 males. Decreased collagen was observed in hearts of BPA or EE exposed females at PND90 and PND180. In BPA or EE treated females cardiomyopathy incidence and severity was significantly increased compared to control females at PND21 with myocardial degeneration observed in both males and females at PND21 and PND90.

Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories

There is a great need for improved diagnostic and prognostic accuracy of potential cardiac toxicity in drug development. This study reports the evaluation of several commercially available biomarker kits by 3 institutions (SRI, Eli Lilly, and Pfizer) for the discrimination between myocardial degeneration/necrosis and cardiac hypertrophy as well as the assessment of the interlaboratory and interplatform variation in results. Serum concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide [NT-proANP] and N-terminal pro-brain natriuretic peptide [NT-proBNP]), cardiac and skeletal troponins (cTnI, cTnT, and sTnI), myosin light chain 3 (Myl3), and fatty acid binding protein 3 (FABP3) were assessed in rats treated with minoxidil (MNX) and isoproterenol (ISO). MNX caused increased heart-to-body weight ratios and prominent elevations in NT-proANP and NT-proBNP concentrations detected at 24-hr postdose without elevation in troponins, Myl3, or FABP3 and with no abnormal histopathological findings. ISO caused ventricular leukocyte infiltration, myocyte fibrosis, and necrosis with increased concentrations of the natriuretic peptides, cardiac troponins, and Myl3. These results reinforce the advantages of a multimarker strategy in elucidating the underlying cause of cardiac insult and detecting myocardial tissue damage at 24-hr posttreatment. The interlaboratory and interplatform comparison analyses also showed that the data obtained from different laboratories and platforms are highly correlated and reproducible, making these biomarkers widely applicable in preclinical studies.