Hui-Chin Lai

Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes

AIMS The objective of this study was to investigate whether a cytoprotective herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial effect on doxorubicin-induced cardiac toxicity in vitro and in vivo. METHODS AND RESULTS Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 microM), EGb761 (25 microg/mL), or EGb761 plus doxorubicin. After 24 h, doxorubicin upregulated p53 mRNA expression, disturbed Bcl-2 family protein balance, disrupted mitochondrial membrane potential, precipitated mitochondrion-dependent apoptotic signalling, induced apoptotic cell death, and reduced viability of cardiomyocytes, whereas EGb761 pretreatment suppressed all the actions of doxorubicin. Similarly, rats treated with doxorubicin [3 mg/kg intraperitoneally (i.p.) three doses every other day] displayed retarded growth of body and heart as well as elevated apoptotic indexes in heart tissue at both 7 and 28 days after exposure, whereas EGb761 pretreatment (5 mg/kg i.p. 1 day before each dose of doxorubicin) effectively neutralized the aforementioned gross and cellular adverse effects of doxorubicin. CONCLUSION Doxorubicin impairs viability of cardiomyocytes at least partially by activating the p53-mediated, mitochondrion-dependent apoptotic signalling. EGb761 can effectively and extensively counteract this action of doxorubicin, and may potentially protect the heart from the severe toxicity of doxorubicin.

Doxycycline suppresses doxorubicin-induced oxidative stress and cellular apoptosis in mouse hearts

Cardiac toxicity remains a serious yet unsolved complication of doxorubicin. This study was designed to examine whether doxycycline, a tetracycline-derived synthetic antibiotic with potential cytoprotective properties, could ameliorate this complication of doxorubicin. Male mice at 4-week of age were administrated with vehicle, doxorubicin (3mg/kg intraperitoneally every other day at 3 doses), doxycycline (2.5mg/kg intraperitoneally every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1day post doxycycline). After 28days, left ventricular geometric and systolic parameters were measured by transthoracic echocardiography, and hearts were harvested for extensive analyses regarding oxidative stress and cellular apoptosis. At 28days, hearts of doxorubicin-treated mice were characterized by less weight compared with controls, also with remodeling and depressed systolic function of the left ventricle. Biochemical analyses disclosed that content of malondialdehyde was increased and activity of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, was decreased in these hearts. Both mitochondrion-dependent and endoplasmic reticulum stress-induced apoptotic pathways were also activated in the hearts of doxorubicin-treated mice as reflected by decreased Bcl-2/Bcl-(XL) and elevated Bax/Bad, p53/Apaf-1, endoplasmic reticulum glucose-related protein 78, C/EBP homologous protein, cytochrome c release from mitochondria, caspases-9/-3 cleavage, and cardiomyocyte apoptosis. In contrast, all the above left ventricular remodeling, systolic depressing, oxidative and pro-apoptotic actions of doxorubicin could be significantly alleviated by doxycycline pretreatment. Thus, doxycycline extensively counteracts multiple oxidative and apoptotic actions of doxorubicin in heart, hence may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.

Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes

BACKGROUND Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. METHODS Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1μM), propofol (1μM), or propofol plus doxorubicin (given 1h post propofol). After 24h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. RESULTS Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-δ was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. CONCLUSIONS Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.

Impact of chronic advanced aortic regurgitation on the perioperative outcome of noncardiac surgery.

Background: Whether and how chronic advanced aortic regurgitation (AR) impacts the perioperative outcome of noncardiac surgery remains unclear.

Shikonin Induces Apoptosis, Necrosis, and Premature Senescence of Human A549 Lung Cancer Cells through Upregulation of p53 Expression

Shikonin, a natural naphthoquinone pigment isolated from Lithospermum erythrorhizon, has been reported to suppress growth of various cancer cells. This study was aimed to investigate whether this chemical could also inhibit cell growth of lung cancer cells and, if so, works via what molecular mechanism. To fulfill this, A549 lung cancer cells were treated with shikonin and then subjected to microscopic, biochemical, flow cytometric, and molecular analyses. Compared with the controls, shikonin significantly induced cell apoptosis and reduced proliferation in a dose-dependent manner. Specially, lower concentrations of shikonin (1–2.5 μg/mL) cause viability reduction; apoptosis and cellular senescence induction is associated with upregulated expressions of cell cycle- and apoptotic signaling-regulatory proteins, while higher concentrations (5–10 μg/mL) precipitate both apoptosis and necrosis. Treatment of cells with pifithrin-α, a specific inhibitor of p53, suppressed shikonin-induced apoptosis and premature senescence, suggesting the role of p53 in mediating the actions of shikonin on regulation of lung cancer cell proliferation. These results indicate the potential and dose-related cytotoxic actions of shikonin on A549 lung cancer cells via p53-mediated cell fate pathways and raise shikonin a promising adjuvant chemotherapeutic agent for treatment of lung cancer in clinical practice.

True Lumen Stenting for a Spontaneously Dissected Superior Mesenteric Artery May Compromise Major Intestinal Branches and Aggravate Bowel Ischemia

Optimal endovascular therapy for isolated superior mesenteric artery (SMA) dissection remains undetermined. Here, we report a 56-year-old male with ischemic bowel syndrome caused by such a serious vascular disease. He was treated with endovascular true lumen stenting yet got aggravated in bowel ischemia from unexpected jail of major intestinal branches perfused by the false lumen, requiring subsequent complex rewiring and dilatation procedures to resolve at the cost of excessive fluoroscopic and contrast medium exposure. Thus, when treating patients with isolated SMA dissection with a functioning false lumen, true lumen stenting may inadvertently compromise crucial intestinal branches and should not be indiscriminately considered as the prime therapeutic option.

Axillofemoral Bypass Relieves Visceral Malperfusion in Type B Aortic Dissection

A 58-year-old man with acute type B aortic dissection presented with right lower limb cyanosis, mesenteric ischemia, and acute renal failure. He was treated with extraanatomic right axillofemoral bypass surgery alone, recovered completely from renal, mesenteric, and lower extremity malperfusion shortly thereafter, and lived free of symptoms for the following year. Follow-up computed tomography angiograms documented adequate expansion of the true aortic lumen and good perfusion of visceral organs. Thus, managing such patients with coexisting visceral and extremity malperfusion may be accomplished with axillofemoral bypass exclusively, which can relieve ischemia of upstream abdominal organs and downstream lower extremities effectively and durably.

Atrial fibrillation increases medical cost and complicates hospital outcome of traffic accident-related physical trauma--a nationwide population-based study.

BACKGROUND Traffic accidents account substantially for premature disability and deaths in the modern world. Whether atrial fibrillation complicates the outcome of traffic injury remains under-investigated. METHODS From 1998 to 2010, all inpatient records stored in the Taiwan National Health Insurance database were screened. Those related with traffic accidents were aggregated to individuals and enrolled. The medical expenses and hospital outcomes were compared between patients with atrial fibrillation (AF group) and either the rest patients (No-AF group) or the propensity-matched patients without atrial fibrillation (No-AF-matched group). Prognostic predictive variables for adverse in-hospital events were further identified by multivariate regression analysis. RESULTS Within the 13-year time span, of the 776,620 individuals ever admitted for traffic accidents, there were 1233 patients with AF. Compared with No-AF and No-AF-matched groups respectively, AF patients stayed longer in hospital (10.9 ± 10.6 vs. 6.8 ± 7.2 and vs. 8.2 ± 8.7 days, both p < 0.001), more often required surgical operations (73.2% vs. 69.5%, p = 0.006 and vs. 68.9%, p = 0.021), and consumed larger medical expenses (US

A secure and rapid method for orotracheal intubation of laboratory rats utilising handy instruments.

2384 ± 3174 vs. 1246 ± 2024, or 91.3% higher; and vs. 1406 ± 2172, or 69.6% higher, both p < 0.001), yet developed more postoperative complications (8.8% vs. 1.2% and vs. 3.2%, both p<0.001) and deaths (2.5% vs. 0.9%, p < 0.001 and vs. 1.6%, p = 0.015). Identified by regression analysis, CHA2DS2-VASC score and representative demographic/injury-related variables predict in-hospital adverse events in these AF group patients. CONCLUSIONS For patients suffering traffic accidents, those with AF consume more surgical resources and medical expenses yet end up with poorer hospital outcome, especially those with higher CHA2DS2-VASC scores and other relevant variables.

Left Circumflex Coronary-to-Pulmonary Artery Fistula as the Exclusive Collateral to the Occluded Left Anterior Descending Artery

Context Tracheal intubation of anaesthetised rats for laboratory experiments remains an essential yet challenging procedure. Objective We aimed to investigate whether tracheal intubation can be safely and securely accomplished in laboratory rats employing only handy instruments and with minimal experience. Design The feasibility and safety of a modified orotracheal intubation method was evaluated in rats undergoing open-chest surgery as part of another research protocol, and compared with an existing technique. Setting The study was carried out in a tertiary medical centre-affiliated animal laboratory. Animals Eighty-five rats weighing 250 to 350 g anaesthetised with intraperitoneal pentobarbital (60 mg kg−1). Interventions Orotracheal intubation was performed on 35 animals (group Jou) using a previously reported technique and then on another 50 rats (group New) using the modified method employing a 3-ml syringe-derived intubation wedge, a 0.025-inch guidewire and a 16-gauge 45-mm-long intravenous catheter. Main outcome measures The time for completion, the number of attempts and the incidence of difficulties and complications were recorded. The intubated tracheas were subsequently examined macroscopically and microscopically to determine position of the intubation catheter and the integrity of epithelial lining. Results Compared with the previous technique, the new method was completed more rapidly (1 ± 0.2 vs. 5 ± 2.4 min; P < 0.001), more smoothly (difficulties encountered in 8 vs. 74%; P < 0.001), with greater overall success (100 vs. 86%; P=0.022) and with fewer attempts [1 (1 to 1) vs. 2 (2 to 4); P < 0.001) for the new and Jou techniques, respectively, and with a lower incidence of procedure-related complications. Postmortem analysis confirmed there was no microscopic injury to the tracheal epithelial lining with the new technique in contrast to 57% in those using the Jou technique (P < 0.001). Conclusion Tracheal intubation for laboratory rats can be securely and safely completed with the modified method employing a short learning curve and easily available devices.