Search

Gentianella acuta (Michx.) Hulten (G. acuta) has been widely used in Mongolian medicines for the treatment of cardiovascular diseases in Ewenki and Oroqen, Inner Mongolia autonomous region, China. The aim of this study was to investigate the effects and related mechanism of G. acuta on isoproterenol (ISO)-induced oxidative stress, fibrosis, and myocardial damage in rats. Male Sprague Dawley rats were randomly divided into the normal control group, ISO induced group and ISO+G. acuta treatment group. Rats were administered with ISO subcutaneously (5 mg/kg/day) for 7 days, and were orally administered simultaneously with aqueous extracts of G. acuta for 21 days. This investigation showed G. acuta treatment ameliorated cardiac structural disorder, excessive collagenous fiber accumulation and cardiac malfunction. Compared with the ISO induced model group, G. acuta treatment increased superoxide dismutase (SOD) activities and glutathione (GSH) level, prevented the rise of malondialdehyde (MDA), and decreased hydroxyproline contents in the heart tissues. Moreover, G. acuta reduced the expression of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF), and inhibited the expression and activation of NF-κB-P65 in myocardial tissues. These results suggested that G. acuta protects against ISO-induced cardiac malfunction probably by preventing oxidative stress, and fibrosis, and the mechanism might be through inhibiting NF-κB pathway.

Myocardial fibrosis (MF) plays a key role in the development and progression of heart failure (HF) with limited effective therapies. Galectin-3 (Gal-3) is a biomarker associated with fibrosis and inflammation in patients with HF. The Gal-3 inhibitor modified citrus pectin (MCP) protects against cardiac dysfunction, though the underlying mechanism remains unclear. The aim of this study was to investigate the effect and mechanism of MCP on MF using an isoproterenol (ISO)-induced rat model of HF. Cardiac function was analyzed by echocardiography and electrocardiography. Histopathological changes in the heart tissue were assessed by hematoxylin-eosin and Masson trichrome staining. The mRNA and protein expression levels of signaling molecules and pro-inflammatory cytokines were monitored by immunohistochemistry, western blot, qRT-PCR and ELISA analyses. The results demonstrated that MCP ameliorated cardiac dysfunction, decreased myocardial injury and reduced collagen deposition. Furthermore, MCP downregulated the expression of Gal-3, TLR4 and MyD88, thereby inhibiting NF-κB-p65 activation. MCP also decreased the expression of IL-1β, IL-18 and TNF-α, which have been implicated in the pathogenesis of HF. These inhibitory effects were observed on day 15 and continued until day 22. Taken together, these results suggest that MCP ameliorates cardiac dysfunction through inhibiting inflammation and MF. These effects may be through downregulating Gal-3 expression and suppressing activation of the TLR4/MyD88/NF-κB signaling pathway. The present study supports the use of Gal-3 as a therapeutic target for the treatment of MF after myocardial infarction.

To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD).From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up.In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c.1484TC, c.394-1GT, c.431TC and c.265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c.1400CG (42.3%), c.760CT (11.5%) and c.51CG (7.7%). During the 8-42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment.The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c.1400CG. Above finding has enriched the spectrum of SLC22A5 gene mutations.

There is discussion concerning the cardiac safety of citalopram in an overdose. The aim of this study was to investigate the toxic effects and toxicokinetic parameters of citalopram in an overdose as a single drug and in combination with other drugs. Cases observed between 1997 and 2006 were evaluated. Patient demographics, ingested doses, serum concentrations of citalopram, coingested drugs, and clinical parameters were acquired. Outcomes were observed symptoms of the gastrointestinal tract, respiratory tract, central nervous system, and cardiovascular system. Poisoning Severity Score was used to evaluate severity of every intoxicated patient. Individual toxicokinetic parameter values were calculated. Twenty-nine cases of citalopram overdose were observed; three cases had incomplete data so that 26 cases were evaluable. The ingested amount ranged from 200 to 4960 mg. Blood concentrations ranged from 0.21 to 7.5 mg/L with 20 minutes to 8 hours between suggested time of ingestion and blood sampling. Most frequently reported symptoms were drowsiness (seven cases), tachycardia (15 cases), QTc prolongation (eight cases), decrease of consciousness (eight cases), and seizures (four cases). Median length of hospital stay was 3 days (range, 1-8 days). Of the 26 evaluated cases, two fatalities occurred, one because of a cardiac arrest and one as a result of a respiratory arrest. According to Poisoning Severity Score, severity of intoxication was minor in three patients (11%), moderate in nine patients (35%), and severe in 14 patients (54%). Severity was mainly caused by neurologic and respiratory effects. Elimination half-life was prolonged but did not correlate with the amount of ingestion. Citalopram intoxications seem to proceed more severely than is known for other selective serotonin reuptake inhibitor intoxications, causing drowsiness, coma, and seizures in overdose. Cardiac toxicity is generally mild. Therefore, we recommend seizure precautions and intensive care unit admission with cardiac monitoring for citalopram-intoxicated patients. Because elimination half-life is prolonged, normal pharmacokinetics do not apply.

Recent studies suggest that oxygen-derived free radicals contribute to the pathogenesis of postischemic myocardial dysfunction (myocardial "stunning"). This concept, however, is predicated exclusively on results obtained in open-chest preparations, which are subject to the confounding influence of many unphysiological conditions. The lack of supporting evidence in more physiological animal models represents a major persisting limitation of the oxy-radical hypothesis of myocardial stunning. The goal of this study was to address two fundamental (and related) questions: 1) Does the open-chest animal model alter the phenomenon of myocardial stunning? 2) If so, how valid are the concepts, derived from such a model, regarding the pathogenetic role of oxy-radicals? In part 1 of the study, myocardial stunning after a 15-minute coronary occlusion was compared in 30 pentobarbital-anesthetized open-chest dogs and in 19 conscious dogs. For any given level of collateral flow during occlusion, the recovery of systolic wall thickening after reperfusion was markedly less in open-chest animals. In an additional group of five open-chest dogs, a close inverse relation was noted between body temperature and postischemic wall thickening, indicating that the recovery of the stunned myocardium in acute experiments may vary markedly depending on how temperature is controlled. Because of these major differences between open-chest and conscious dogs, the oxy-radical hypothesis needs to be tested in the latter model. Thus, in part 2 of the study, conscious unsedated dogs undergoing a 15-minute coronary occlusion were randomized to an intravenous infusion of either saline (19 coronary occlusions) or superoxide dismutase (SOD) plus catalase (CAT) (21 coronary occlusions). Despite the fact that the plasma levels of SOD and CAT declined rapidly after reperfusion, postischemic wall thickening was significantly greater in treated compared with control dogs throughout the first 6 hours of reflow. Thus, a brief (60-minute) infusion of SOD and CAT produced a sustained improvement of recovery of contractility. The magnitude of this beneficial effect was a function of the severity of ischemia: the lower the collateral perfusion, the greater the improvement effected by the enzymes. The accelerated recovery produced by SOD and CAT was not followed by any deterioration of contractility, suggesting that postischemic dysfunction is not a teleologically "protective" phenomenon. In conclusion, the severity of myocardial stunning is greatly exaggerated by the unphysiological conditions present in the barbiturate-anesthetized open-chest dog.(ABSTRACT TRUNCATED AT 400 WORDS)