Synthesis of Quinazolin-2,4,6-triamine Derivatives as Non-purine Xanthine Oxidase Inhibitors and Exploration of Their Toxicological Potential.

In this work, a new set of quinazolin-2,4,6-triamine derivatives were synthesized to explore their potential biological activity as xanthine oxidase (XO) inhibitors, superoxide scavengers and screening of their toxicological profile. Among all the synthesized compounds, B1 exhibited better inhibitory activity against bovine xanthine oxidase (bXO) than allopurinol (IC50 =1.56 µM and IC50 =6.99 µM, respectively). As superoxide scavengers, B1, B2 and B13 exhibited a better effect than allopurinol (97.3 %, 82.1 %, 87.4 % and 69.4 %, respectively). Regarding the toxicological profile, B1 was less cytotoxic than methotrexate on HCT-15 cancer cells. Apoptosis results obtained in cells of female and male mice, showed that B1 and B2 presented a similar behaviour to CrO3 (positive control) with respect to the average frequency to induce apoptosis; while B13 apoptosis induced effect was similar to DMSO and control group. Finally, B1, B2, B13 did not induce genotoxicity in a micronuclei murine model compared to CrO3 .

Nuanced role for dendritic cell intrinsic IRE1 RNase in the regulation of antitumor adaptive immunity.

In cancer, activation of the IRE1/XBP1s axis of the unfolded protein response (UPR) promotes immunosuppression and tumor growth, by acting in cancer cells and tumor infiltrating immune cells. However, the role of IRE1/XBP1s in dendritic cells (DCs) in tumors, particularly in conventional type 1 DCs (cDC1s) which are cellular targets in immunotherapy, has not been fully elucidated. Here, we studied the role of IRE1/XBP1s in subcutaneous B16/B78 melanoma and MC38 tumors by generating loss-of-function models of IRE1 and/or XBP1s in DCs or in cDC1s. Data show that concomitant deletion of the RNase domain of IRE1 and XBP1s in DCs and cDC1s does not influence the kinetics of B16/B78 and MC38 tumor growth or the effector profile of tumor infiltrating T cells. A modest effect is observed in mice bearing single deletion of XBP1s in DCs, which showed slight acceleration of melanoma tumor growth and dysfunctional T cell responses, however, this effect was not recapitulated in animals lacking XBP1 only in cDC1s. Thus, evidence presented here argues against a general pro-tumorigenic role of the IRE1/XBP1s pathway in tumor associated DC subsets.

Evaluation of Integrative Community Therapy with Domestic Violence Survivors in Quito, Ecuador.

Integrative community therapy (ICT) is a methodology used in the public health arena to deal with problems facing communities such as depression, substance abuse, and stress. This approach is unique as it builds on critical pedagogy, cultural anthropology, communication, resilience, and systems theory. Additionally, creative arts therapies point to the utility of music as a therapeutic tool. This study employed ICT and a music workshop with domestic violence survivors in Quito, Ecuador, via a pre-post comparison group design. A total of 87 women completed the six-week study-49 in the intervention group and 38 in the comparison group. Measures were taken on self-esteem, general health, resilience, dating violence attitudes, and social support. Additionally, the intervention group answered open-ended questions about their experience, and some participated in a focus group (n = 21). The quantitative results indicated that there was improvement in the domains of general health, self-esteem, and social support for the intervention group compared to the comparison group. Themes from the qualitative responses indicated changes in the relationship with the aggressor, psychological and emotional changes, changes in feelings of social support, and changes for the future. The study found promising results for this approach with domestic violence survivors, possibly leading to a community-grounded, non-hierarchical, culturally-responsive intervention for this population.

Dopaminergic Signalling Enhances IL-2 Production and Strengthens Anti-Tumour Response Exerted by Cytotoxic T Lymphocytes in a Melanoma Mouse Model.

Dopamine has emerged as an important regulator of immunity. Recent evidence has shown that signalling through low-affinity dopamine receptors exerts anti-inflammatory effects, whilst stimulation of high-affinity dopamine receptors potentiates immunity in different models. However, the dopaminergic regulation of CD8+ T-cells in anti-tumour immunity remains poorly explored. Here, we studied the role of dopamine receptor D3 (DRD3), which displays the highest affinity for dopamine, in the function of CD8+ T-cells and its consequences in the anti-tumour immune response. We observed that the deficiency of Drd3 (the gene encoding DRD3) in CD8+ T-cells limits their in vivo expansion, leading to an impaired anti-tumour response in a mouse melanoma model. Mechanistic analyses suggest that DRD3 stimulation favours the production of interleukin 2 (IL-2) and the surface expression of CD25, the α-chain IL-2 receptor, which are required for expansion and effector differentiation of CD8+ T-cells. Thus, our results provide genetic and pharmacologic evidence indicating that DRD3 favours the production of IL-2 by CD8+ T-cells, which is associated with higher expansion and acquisition of effector function of these cells, promoting a more potent anti-tumour response in a melanoma mouse model. These findings contribute to understanding how dopaminergic signalling affects the cellular immune response and represent an opportunity to improve melanoma therapy.

Saxitoxin Group Toxins Accumulation Induces Antioxidant Responses in Tissues of Mytilus chilensis, Ameghinomya antiqua, and Concholepas concholepas during a Bloom of Alexandrium pacificum.

Saxitoxin (STX) group toxins consist of a set of analogues which are produced by harmful algal blooms (HABs). During a HAB, filter-feeding marine organisms accumulate the dinoflagellates and concentrate the toxins in the tissues. In this study, we analyze the changes in antioxidant enzymes and oxidative damage in the bivalves Mytilus chilensis and Ameghinomya antiqua, and the gastropod Concholepas concholepas during a bloom of Alexandrium pacificum. The results show that during the exponential phase of the bloom bivalves show an increase in toxicity and activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathinoe reductase, p < 0.05), while in the gastropods, increased activity of antioxidant enzymes was associated with the bioaccumulation of toxins through the diet. At the end of the bloom, decreased activity of antioxidant enzymes in the visceral and non-visceral tissues was detected in the bivalves, with an increase in oxidative damage (p < 0.05), in which the latter is correlated with the detection of the most toxic analogues of the STX-group (r = 0.988). In conclusion, in areas with high incidence of blooms, shellfish show a high activity of antioxidants, however, during the stages involving the distribution and bioconversion of toxins, there is decreased activity of antioxidant enzymes resulting in oxidative damage.

Oxidative Stress Parameters and Morphological Changes in Japanese Medaka (Oryzias latipes) after Acute Exposure to OA-Group Toxins.

Toxins of the OA-group (okadaic acid, OA; dinophysistoxin-1, DTX-1) are the most prevalent in the fjords of southern Chile, and are characterized by their potential harmful effects on aquatic organisms. The present study was carried out to determine the acute toxicity of OA/DTX-1 on oxidative stress parameters in medaka (Oryzias latipes) larvae. Medaka larvae were exposed to different concentrations (1.0-30 µg/mL) of OA/DTX-1 for 96 h to determine the median lethal concentration. The LC50 value after 96 h was 23.5 µg/mL for OA and 16.3 µg/mL for DTX-1 (95% confidence interval, CI was 22.56, 24.43 for OA and 15.42, 17.17 for DTX-1). Subsequently, larvae at 121 hpf were exposed to acute doses (10, 15 and 20 µg/mL OA and 5.0, 7.5 and 11.0 µg/mL DTX-1) for 96 h and every 6 h the corresponding group of larvae was euthanized in order to measure the activity levels of biochemical biomarkers (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPx; and glutathione reductase, GR) as well as the levels of oxidative damage (malondialdehyde, MDA; and carbonyl content). Our results showed that acute doses caused a decrease in SOD (≈25%), CAT (≈55%), and GPx and GR (≈35%) activities, while MDA levels and carbonyl content increased significantly at the same OA/DTX-1 concentrations. This study shows that acute exposure to OA-group toxins tends to simultaneously alter the oxidative parameters that induce sustained morphological damage in medaka larvae. DTX-1 stands out as producing greater inhibition of the antioxidant system, leading to increased oxidative damage in medaka larvae. Considering that DTX-1 is the most prevalent HAB toxin in southern Chile, these findings raise the possibility of an important environmental impact on the larval stages of different fish species present in the southern fjords of the South Pacific.

In Silico Characterization of Masitinib Interaction with SARS-CoV-2 Main Protease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a global health problem. Despite the current implementation of COVID-19 vaccination schedules, identifying effective antiviral drug treatments for this disease continues to be a priority. A recent study showed that masitinib (MST), a tyrosine kinase inhibitor, blocks the proteolytic activity of SARS-CoV-2 main protease (Mpro ). Although MST is a potential candidate for COVID-19 treatment, a comprehensive analysis of its interaction with Mpro has not been done. In this work, we performed molecular dynamics simulations of the MST-Mpro complex crystal structure. The effect of the protonation states of Mpro H163 residue and MST titratable groups were studied. Furthermore, we identified the MST substituents and Mpro mutations that affect the stability of the complex. Our results provide valuable insights into the design of new MST analogs as potential treatments for COVID-19.

Toxicity and differential oxidative stress effects on zebrafish larvae following exposure to toxins from the okadaic acid group.

Okadaic acid-group (OA-group) is a set of lipophilic toxins produced only in seawater by species of the Dinophysis and Prorocentrum genera, and characterized globally by being associated with harmful algal blooms (HABs). The diarrhetic shellfish poisoning toxins okadaic acid (OA) and dinophysistoxin-1 (DTX-1) are the most prevalent toxic analogues making up the OA-group, which jeopardize environmental safety and human health through consumption of hydrobiological organisms contaminated with these toxins that produce diarrhetic shellfish poisoning (DSP) syndrome in humans. Consequently, a regulatory limit of 160 µg of OA-group/kg was established for marine resources (bivalves). The aim of this study was to investigate effects varying concentrations of 1-15 µg/ml OA or DTX-1 on toxicity, development, and oxidative damage in zebrafish larvae (Danio rerio). After determining the lethal concentration 50 (LC50) in zebrafish larvae of 10 and 7 µg/ml (24 h) and effective concentration 50 (EC50) of 8 and 6 µg/ml (24 h), different concentrations (5, 6.5, or 8 µg/ml of OA and 4, 4.5, or 6 µg/ml of DTX-1) were used to examine the effects of these toxins on oxidative damage to larvae at different time points between 24 and 120 hpf. Macroscopic evaluation during the exposure period showed alterations in zebrafish including pericardial edema, cyclopia, shortening in the anteroposterior axis, and developmental delay. The activity levels of biochemical biomarkers superoxide dismutase (SOD) and catalase (CAT) demonstrated a concentration-dependent decrease while glutathione peroxidase (GPx) and glutathione reductase (GR) were markedly elevated. In addition, increased levels of oxidative damage (malondialdehyde and carbonyl content) were detected following toxin exposure. Data demonstrate that high concentrations of OA and DTX-1produced pathological damage in the early stages of development <48 h post-fertilization (hpf) associated with oxidative damage.

In vitro biotransformation of OA-group and PTX-group toxins in visceral and non-visceral tissues of Mytilus chilensis and Ameghinomya antiqua.

Lipophilic marine toxins (LMTs) are made up of multiple groups of toxic analogues, which are characterised by different levels of cellular and toxic action. The most prevalent groups in the southern Pacific zone are: a) okadaic acid group (OA-group) which consists of okadaic acid (OA) and dinophysistoxin-1 (DTX-1); and, b) pectenotoxin-2 (PTX2) group which consists of pectenotoxin-2 (PTX-2). The main objective of our study was to examine in vitro biotransformation of OA-group and PTX-group in the tissues of two endemic species of bivalves from southern Chile; blue mussels (Mytilus chilensis) and clams (Ameghinomya antiqua). The biotransformation processes of both groups were only detected in the digestive glands of both species using LC-MS/MS. The most frequently detected analogues were acyl derivatives (≈2.0 ± 0.1 µg ml-1) for OA-group and PTX-2SA (≈1.4 ± 0.1 µg ml-1) for PTX-group, with a higher percentage of biotransformation for OA-group (p < .001). In addition, simultaneous incubations of the different analogues (OA/PTX-2; DTX-1/PTX-2 and OA/DTX-1/PTX-2) did not show any interaction between the biotransformation processes. These results show that the toxicological variability of endemic species leads to biotransformation of the profile of toxins, so that these new analogues may affect people's health.

Mitochondrial genomes and genetic structure of the Kemp's ridley sea turtle (Lepidochelys kempii).

The Kemp's ridley (Lepidochelys kempii) is the world's most endangered sea turtle species and is primarily distributed in the Gulf of Mexico. In the United States, South Padre Island, Texas serves as a key nesting ground for the species. Genetic studies of the Kemp's ridley have been used to aid in conservation and management practices, with the mitochondrial control region as the most commonly used marker due to its perceived hypervariability and ease of sequencing. However, with the advent of next generation sequencing technology, targeting complete mitochondrial genomes is now feasible. Here, we describe a more complete mitochondrial genome for the Kemp's ridley than has been previously published in literature and demonstrate a cost-effective and efficient method for obtaining complete mitochondrial genomes from sea turtles. We compare the genetic diversity and taxonomic resolution obtained from whole mitochondrial genomes to that obtained from the mitochondrial control region alone. We compare current genetic diversity with previous records. Furthermore, we evaluate the genetic structure between the breeding stock in South Padre Island and that of deceased Kemp's ridleys recovered on the Northern coast of the Gulf of Mexico after the 2010 BP Deepwater Horizon oil spill, and of Kemp's ridleys stranded on the East Coast of the United States. Our results show that complete mitochondrial genomes provide greater resolution than the control region alone. They also show that the genetic diversity of the Kemp's ridley has remained stable, despite large population declines, and that the genetic makeup of deceased turtles stranded after the Deepwater Horizon oil spill is indistinguishable from the breeding stock in South Padre Island, Texas. OPEN DATA BADGE: This article has earned an Open Data Badge for making publicly available the digitally-shareable data necessary to reproduce the reported results. The data is available at https://www.ncbi.nlm.nih.gov/genbank/.

"Hay que tener suerte": Gender-based Violence Service Provision in Quito, Ecuador.

This study utilized the United Nations' Essential Services Package for Women and Girls Subject to Violence, a technical guidebook on quality services in line with human rights declarations, to examine the characteristics of availability, accessibility, adaptability, and appropriateness from the viewpoint of 21 victim service users in Quito, Ecuador. Availability was evidenced by warm service providers willing to aid victims but was hindered by a failure to make available all desired services (such as those related to economic empowerment). Accessibility was aided by service locations that were easily accessible and by referrals, but a lack of information and conflicting schedules thwarted users' help-seeking efforts. Participants shared experiences of services adapted to their specific needs and experiences of violence, but additional services were needed to fully attend to their particular circumstances. Participants shared how service providers empowered them by listening to their experiences and helping them move forward in their lives. Nonetheless, participants shared experiences of victim-blaming and other harmful attitudes from providers. Overall, there was a great amount of variability in participants' service experiences. Areas for consideration include economic empowerment, expansion of services to men and children, increased access to information, and trauma-informed training of staff in order to better respond to gender-based violence.

Aerobic Training Is Better Than Resistance Training on Cardiac Function and Autonomic Modulation in Female ob/ob Mice.

Objective: This study evaluated the effects of aerobic, resistance, and combined exercise training on cardiac function and autonomic modulation in female ob/ob mice. Methods: Four-week-old female wild type and obese (ob/ob) mice were divided into five groups (n = 8): control (WT), obese (OB) obese + aerobic training (OBA), obese + resistance training (OBR), and obese + combined training (OBC). The exercise training was performed on treadmill and/or ladder at 40-60% maximum test during 8 weeks. Cardiac function was measured using echo machine. Heart rate variability (HRV) was evaluated in the time and frequency domain. Results: OB group presented higher body weight gain (~600%), glycemia (~44%) and glucose intolerance (~150%), reduction of cardiac vagal modulation, evidenced by a lower RMMSD (~56%), total power and high frequency band, and a higher isovolumic relaxation time (IVRT) (~24%) in relation to the WT group. Aerobic and combined training led to a lower IVRT (OBA: ~14%; OBC: ~14%) and myocardial global index (OBA: ~37%; OBC: ~44%). The OBA group presented an increased in vagal indexes of HRV than the other ob/ob groups. A negative correlation was observed between the delta of aerobic exercise capacity and MPI (r = 0.45; p = 0.002) and exercise capacity and body weight gain (r = 0.39; p = 0.002). Conclusion: Only the obese females underwent to aerobic exercise training showed improvement in cardiac function and HRV. Moreover, the aerobic exercise capacity as well as a greater responsivity to aerobic exercise training is intimately associated with these improvements, reinforcing the importance of aerobic exercise training to this population.

Tissue-resident memory CD8+ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells.

Tissue-resident memory CD8+ T (Trm) cells mediate potent local innate and adaptive immune responses and play a central role against solid tumors. However, whether Trm cells cross-talk with dendritic cells (DCs) to support anti-tumor immunity remains unclear. Here we show that antigen-specific activation of skin Trm cells leads to maturation and migration to draining lymph nodes of cross-presenting dermal DCs. Tumor rejection mediated by Trm cells triggers the spread of cytotoxic CD8+ T cell responses against tumor-derived neo- and self-antigens via dermal DCs. These responses suppress the growth of intradermal tumors and disseminated melanoma lacking the Trm cell-targeted epitope. Moreover, analysis of RNA sequencing data from human melanoma tumors reveals that enrichment of a Trm cell gene signature associates with DC activation and improved survival. This work unveils the ability of Trm cells to amplify the breath of cytotoxic CD8+ T cell responses through DCs, thereby strengthening anti-tumor immunity.

The complete mitochondrial genome of Tanacetipathes thamnea Warner, 1981 (Antipatharia: Myriopathidae).

Specimens of the black coral Tanacetipathes thamnea were collected from the Northwestern Gulf of Mexico. The complete mitochondrial genome of one of these specimens was obtained from genomic DNA by next-generation sequencing technology on the Illumina HiSeq 2500. Only three species of black corals have a completely sequenced mitochondrial genome. These were used to reconstruct the phylogeny for the order Antipatharia. The mitochondrial genome of T. thamnea is 17,712 base pairs and contains 13 protein-coding genes, 2 ribosomal RNAs, and 2 transfer RNAs in the following order: 16s RNA, COX3, COX1 (with intron), ND4L, COX2, ND4, ND6, ATP8, ATP6, and ND5 (with intron and copies of ND1 and ND3), tRNA-Trp, ND2, 12s RNA, CYTB, tRNA-Met. The gene arrangement is the same as that for Myriopathes japonica with a nearly identical sequence (99.35% identical). These results show that the mitochondrial genome within the family Myriopathidae is highly conserved.

Mitogenomic phylogenetic analyses of Leptogorgia virgulata and Leptogorgia hebes (Anthozoa: Octocorallia) from the Gulf of Mexico provides insight on Gorgoniidae divergence between Pacific and Atlantic lineages.

The use of genetics in recent years has brought to light the need to reevaluate the classification of many gorgonian octocorals. This study focuses on two Leptogorgia species-Leptogorgia virgulata and Leptogorgia hebes-from the northwestern Gulf of Mexico (GOM). We target complete mitochondrial genomes and mtMutS sequences, and integrate this data with previous genetic research of gorgonian corals to resolve phylogenetic relationships and estimate divergence times. This study contributes the first complete mitochondrial genomes for L. ptogorgia virgulata and L. hebes. Our resulting phylogenies stress the need to redefine the taxonomy of the genus Leptogorgia in its entirety. The fossil-calibrated divergence times for Eastern Pacific and Western Atlantic Leptogorgia species based on complete mitochondrial genomes shows that the use of multiple genes results in estimates of more recent speciation events than previous research based on single genes. These more recent divergence times are in agreement with geologic data pertaining to the formation of the Isthmus of Panama.

Erratum: Interval and continuous aerobic exercise training similarly increase cardiac function and autonomic modulation in infarcted mice.

[This corrects the article on p. 257 in vol. 13, PMID: 28702435.].

Interval and continuous aerobic exercise training similarly increase cardiac function and autonomic modulation in infarcted mice.

The present study aimed to compare the effects of moderate-intensity continuous and high-intensity interval exercise training (ET) on exercise tolerance, cardiac morphometry and function, hemodynamic, and cardiac autonomic modulation in myocardial infarcted mice. Wild-type mice (WT) were divided into four groups: sedentary WT (S); WT myocardium infarction sedentary (IS); WT myocardium infarction underwent to moderate-intensity continuous ET (MICT), and WT myocardium infarction underwent to high-intensity interval ET (MIIT). After 60 days of descending coronary artery ligation, moderate-intensity continuous ET consisted of running at 60% of maximum, while the high-intensity interval training consisted of eight sprints of 4 min at 80% of maximum and a 4-min recovery at 40% of maximum. Both exercises were performed 1 hr a day, 5 days a week, during 8 weeks. Results demonstrated that IS showed elevated exercise tolerance, as well as decreased hemodynamic and heart function, and autonomic control. On the other hand, both programs of ET were equally effective to increase all parameters, without further differences between the groups. In conclusion, the results of the present study showed that myocardial infarction leads to damage in both investigated strains and the two types of physical exercise attenuated the major impairments provoked by myocardial infarction in exercise tolerance, cardiac structure, cardiac function, hemodynamic and cardiac autonomic modulation.

Cardiac Arrest after Local Anaesthetic Toxicity in a Paediatric Patient.

We report a case of a paediatric patient undergoing urological procedure in which a possible inadvertent intravascular or intraosseous injection of bupivacaine with adrenaline in usual doses caused subsequent cardiac arrest, completely reversed after administration of 20% intravenous lipid emulsion. Early diagnosis of local anaesthetics toxicity and adequate cardiovascular resuscitation manoeuvres contribute to the favourable outcome.

Inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase induces orofacial defects in zebrafish.

BACKGROUND: Orofacial clefts (OFCs) are common birth defects, which include a range of disorders with a complex etiology affecting formation of craniofacial structures. Some forms of syndromic OFCs are produced by defects in the cholesterol pathway. The principal enzyme of the cholesterol pathway is the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Our aim is to study whether defects of HMGCR function would produce orofacial malformation similar to those found in disorders of cholesterol synthesis. METHODS: We used zebrafish hmgcrb mutants and HMGCR inhibition assay using atorvastatin during early and late stages of orofacial morphogenesis in zebrafish. To describe craniofacial phenotypes, we stained cartilage and bone and performed in situ hybridization using known craniofacial markers. Also, we visualized neural crest cell migration in a transgenic fish. RESULTS: Our results showed that mutants displayed loss of cartilage and diminished orofacial outgrowth, and in some cases palatal cleft. Late treatments with statin show a similar phenotype. Affected-siblings displayed a moderate phenotype, whereas early-treated embryos had a minor cleft. We found reduced expression of the downstream component of Sonic Hedgehog-signaling gli1 in ventral brain, oral ectoderm, and pharyngeal endoderm in mutants and in late atorvastatin-treated embryos. CONCLUSION: Our results suggest that HMGCR loss-of-function primarily affects postmigratory cranial neural crest cells through abnormal Sonic Hedgehog signaling, probably induced by reduction in metabolites of the cholesterol pathway. Malformation severity correlates with the grade of HMGCR inhibition, developmental stage of its disruption, and probably with availability of maternal lipids. Together, our results might help to understand the spectrum of orofacial phenotypes found in cholesterol synthesis disorders. Birth Defects Research (Part A) 106:814-830, 2016. © 2016 Wiley Periodicals, Inc.

Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling.

BACKGROUND: The effects of streptozotocin (STZ)-induced diabetes on heart metabolism and function after myocardial infarction (MI) remodelling were investigated in rats. METHODS: Fifteen days after STZ (50 mg/kg b.w. i.v.) injection, MI was induced by surgical occlusion of the left coronary artery. Two weeks after MI induction, contents of glycogen, ATP, free fatty acids and triacylglycerols (TG) and enzyme activities of glycolysis and Krebs cycle (hexokinase, glucose-6-phosphate dehydrogenase, phosphofructokinase, citrate synthase) and expression of carnitine palmitoyl-CoA transferase I (a key enzyme of mitochondrial fatty acid oxidation) were measured in the left ventricle (LV). Plasma glucose, free fatty acids and triacylglycerol levels were determined. Ejection fraction (EF) and shortening fraction (SF) were also measured by echocardiography. RESULTS: Glycogen and TG contents were increased (p < 0.05) whereas ATP content was decreased in the LV of the non-infarcted diabetic group when compared to the control group (p < 0.05). When compared to infarcted control rats (MI), the diabetic infarcted rats (DI) showed (p < 0.05): increased plasma glucose and TG levels, elevated free fatty acid levels and increased activity of, citrate synthase and decreased ATP levels in the LV. Infarct size was smaller in the DI group when compared to MI rats (p < 0.05), and this was associated with higher EF and SF (p < 0.05). CONCLUSIONS: Systolic function was preserved or recovered more efficiently in the heart from diabetic rats two weeks after MI, possibly due to the high provision of glucose and free fatty acids from both plasma and heart glycogen and triacylglycerol stores.