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.

The first organic-templated vanadyl(IV) gallophosphates with ambient (51)V hyperfine structure, {V(2)Ga(2)O(14)} cluster or heterometal 12-ring channels.

Three new vanadyl gallium phosphates, (H(2)dap)(3)[(VO)(2)(GaO)(2)(PO(4))(4)].H(2)O (1), (H(2)dap)(1.5)[(VO)(2)(GaO)(2)(PO(4))(3)].3H(2)O (2), and (H(2)dap)[(VO)(2)Ga(4)(PO(4))(6)(H(2)O)(4)].2H(2)O (3) (dap = 1,3-diaminopropane), have been prepared under mild solvothermal conditions and characterized by single-crystal X-ray diffraction, thermogravimetric analysis, magnetic susceptibility, and EPR spectroscopy. They are the first examples of an organic/V(4+)/Ga/P/O system that displays three different dimensional structures with a common template. The 1D chain structure of 1 and the 2D layered 2 are both built up with a PO(4) and {V(2)Ga(2)O(14)} cluster which contains a syn-square pyramidal {V(2)O(8)} dimer and two GaO(4) tetrahedra. The tetrameric cluster and V-O-Ga therein are observed in a metal phosphate system. Compound 3 is composed of VO(5)(H(2)O) octahedra, GaO(4)(H(2)O) trigonal bipyramids, and GaO(4) and PO(4) tetrahedra from which a unique 3D structure containing one-dimensional 12-ring channels is constructed. The channel aperture uncommonly comprises heterometal (V, Ga) polyhedra. Magnetic susceptibility data for 1-3 are consistent with V(4+) and show a T(N) of 12 K for 3. The unusual syn-{V(2)O(8)} dimers in 1 and 2 induce superexchange interactions, while isolated VO(5)(H(2)O) octahedra in 3 display super-super-exchange interaction. Electron paramagnetic resonance spectra with (51)V hyperfine structures were distinctly observed at 300 K for 1, while they started emerging at 30 K for 2 and 7 K for 3. The average hyperfine constant, 85.56 Gauss, was obtained via spectral simulations and nonlinear least-squares fittings for 1 and 2. Crystal data for 1 are triclinic, P1, a = 9.1754(4) A, b = 10.7853(5) A, c = 15.6519(7) A, alpha = 93.251(1) degrees , beta = 92.530(1) degrees , gamma = 95.106(1) degrees , V = 1538.4(1) A(3), and Z = 2; for 2, monoclinic, P2(1)/n, a = 8.9195(3) A, b = 14.6374(5) A, c = 17.8608(6) A, beta = 97.272(1) degrees , V = 2313.1(1) A(3), and Z = 4; and for 3, monoclinic, P2(1)/c, a = 9.0970(5) A, b = 16.9940(9) A, c = 9.6441(5) A, beta = 103.456(3) degrees , V = 1450.0(1) A(3), and Z = 4.

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.

Percutaneous balloon commissurotomy reduces incidence of ischemic cerebral stroke in patients with symptomatic rheumatic mitral stenosis.

Whether percutaneous balloon commissurotomy reduces cerebral stroke in patients with symptomatic rheumatic mitral stenosis remains obscure. This study enrolled 170 such patients undergoing either medical therapy alone (n=71) or balloon commissurotomy (n=99). In the short term, balloon commissurotomy was successfully accomplished in 99% patients without embolic complications. At follow-up (mean 4.2+/-3.2 years), patients undergoing commissurotomy encountered significantly rarer ischemic stroke than the medicine group (2% vs. 13%, p=0.043). Multivariate Cox regression analysis further confirmed balloon commissurotomy as a negative predictor for ischemic stroke (hazard ratio 0.135, p=0.011). These results lead to the conclusion that percutaneous balloon commissurotomy could substantially decrease the long-term incidence of ischemic cerebral stroke in eligible patients with symptomatic rheumatic mitral stenosis.

Protection by doxycycline against doxorubicin-induced oxidative stress and apoptosis in mouse testes.

Spermatogenic cells constitute one of the body tissues that are susceptible to doxorubicin-induced oxidative stress and apoptosis. To explore whether doxorubicin toxicity to these male germ cells could be prevented by adjuvant medication, this study was designed to examine the possible ameliorating action of doxycycline, an antibiotic with anti-oxidant property, on doxorubicin-induced oxidative and apoptotic effects in mouse testes. Male mice at 5-week of age were treated with vehicles, doxorubicin alone (3 mg/kg, i.p. every other day for 3 doses), doxycycline alone (2.5 mg/kg, i.p. every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1 day post-doxycycline). After 28 days, mice treated with doxorubicin alone displayed smaller body and testicular weights, reduced sperm counts, impaired spermatogenic capability (scarcer spermatids and spermatocytes), increased oxidative stress (malondialdehyde levels), decreased anti-oxidant activity (superoxide dismutase and glutathione peroxidase), and elevated apoptotic indexes (upregulation of Bax and Bad, downregulation of Bcl-2 and Bcl-xL, release of cytochrome c from mitochondria to cytosol, activation of caspase-3, and increase of cleaved caspase-3 abundance and TUNEL positive cells), while doxycycline pretreatment could effectively prevent nearly all of these abnormalities. These results provide firm evidence that doxycycline pretreatment would offset the oxidative and apoptotic impact imposed by doxorubicin, and imply doxycycline to be a promising adjuvant agent that may attenuate the toxicity of doxorubicin on testicular tissues in clinical practice.

Functional visual disturbance due to hysteria.

A 23-year-old male complained of loss of peripheral visual field and everything having purple shadows in the afternoon. This had lasted for 3 years but he had paid little attention to the symptoms. Investigations, including visual acuity, intra-ocular pressure, pupil reflex, and anterior and posterior segment of the eyes, were normal. He denied ocular pain, history of head injury, epilepsy or related family history. The Goldmann perimeter and tangent screen examinations showed a bilateral constricted tubular visual field defect within the central 10 degrees and steep margins. Tracing his past social history, he had been in jail for 3 months. He also complained his work was hard and caused him tension. The visual symptoms were a functional disturbance, not an organic disorder. We diagnosed him with hysterical functional visual disturbance. Hysteria, or conversion disorder, has long been a puzzling and fascinating problem in psychology and ophthalmology. The mechanism and reasons for hysteria are still not clear. The tangent screen is useful in diagnosis. The constricted tubular, spiral or star-shaped visual fields with steep slopes are specific findings in hysteria. We suggest that ophthalmologists should treat patients with psychogenic symptoms, using suggestion, patience and reassurance.

Mitral regurgitation complicates postoperative outcome of noncardiac surgery.

BACKGROUND: Whether and how mitral regurgitation impacts perioperative outcome of noncardiac surgery remains unclear. METHODS: From November 1999 to August 2004, all patients undergoing noncardiac operations and ever examined by echocardiography within prior 12 months were screened. Those with moderate-severe or severe mitral regurgitation were enrolled provided they were not already trachea-intubated and the surgery was not performed under local anesthesia. The perioperative outcomes of these patients were analyzed, and related prognostic predictors were investigated by multivariate logistic regression analysis. RESULTS: A total of 84 patients (43 men, mean age of 66 years, low surgical risk in 28 and intermediate in 56) complying with the inclusion criteria were included. Their surgery was complicated by frequent (31%) yet minor intraoperative adverse events of controllable hypotension and bradycardia. In contrast, the postoperative outcomes were seriously complicated with high morbidity (27.4%, mostly pulmonary edema and prolonged tracheal intubation) and mortality (11.9%). Atrial fibrillation was identified by multivariate logistic regression analysis as the predictor of inhospital death (OD 11.579, P = .003), whereas surgical risk level (OD 5.118, P = .021), left ventricular ejection fraction (OD 0.958, P = .026), and atrial fibrillation (OD 3.058, P = .045), as independent predictors of postoperative morbidity. CONCLUSIONS: Under current anesthetic management, patients with advanced mitral regurgitation could go through fairly safe intraoperative course of noncardiac surgery despite minor complications. Their postoperative outcome was, however, complicated by extraordinarily high morbidity and mortality, especially in those with preexisting atrial fibrillation, higher surgical risk level, and lower left ventricular ejection fraction.

Left atrial infective endocarditis with giant vegetation without involvement of the mitral valve--a case report of transesophageal echocardiography in diagnosis.

Cardiac valves are the most commonly victimized sites of infective endocarditis. The vegetations migrating outside the valves are quite rare. Echocardiography is a sensitive method for detecting these lesions. We report a case of unusual echocardiographic presentation of infective endocarditis. Transesophageal echocardiography showed a giant tonguelike echogenic mass, which attached to the posterior wall of left atrium without involving the mitral valve. Also, we discuss the differential diagnosis of infective endocarditis and myxoma, as well as the considerations of anesthetic management of intracardiac mass.

Real-time detection of migratory thrombi by transesophageal echocardiography in a patient undergoing thrombectomy.

We report a 44-year-old male patient who sustained a right atrial (RA) thrombosis with evolvement into right pulmonary artery embolism in consequence of placement of a temporary pacing lead and was successfully treated with surgical thrombectomy under the guidance of perioperative transesophageal echocardiography (TEE). Because of intermittent complete atrioventricular block he therefore underwent implantation of a transvenous temporary pacing. On the ensuing day a large mass was incidentally found echographically in the RA suggestive of a large thrombus. Immediate surgical removal of the mass was indicated. During the emergent open-heart surgery the mass in RA dehiscenced with fragments migrating to the right main pulmonary artery, and exploration of both the RA and right pulmonary artery was done. This migratory mass, which proved to be a fresh thrombus, was surgically removed. The cardiopulmonary bypass was then terminated and the spontaneous contraction of heart was resumed. However, another mass lesion was found in RA on the TEE screen just following the removal of the problematic transvenous pacing wire. The right atrium was thus re-opened immediately and the second thrombus was cleared. Over the on-going surgical course no further abnormal echogenic objects were visible in the cardiac chambers. It is perceivable that transvenous pacing might cause thrombois or dislodgement and dehiscence of thrombi already in existence in the cardiac chamber. Careful and continuous intraoperative surveillance with echocardiography over a patient who is undergoing cardiac embolectomy is quite important in detecting thrombus escape and residual thrombi during surgery.

Early predict the outcomes of refractive accommodative esotropia by initial presentations.

BACKGROUND: The differential diagnosis between fully and partially refractive accommodative esotropia (Ac-ET) depends on outcomes after intervention with refraction correction. Whether the differences exist in terms of initial clinical features between these two variants has not been fully explored. METHODS: Children between the ages of 6 months and 8 years with esotropia and spherical equivalent greater than +3.00 (D) were included in this study. After wearing diopters glasses for at least 2 years, children were classified according to the indexed criteria into the fully Ac-ET group (group A, N=28) partially Ac-ET (group or the B, N=17). Six clinical parameters, including age at onset, age at first visit, visual acuity, refractive error, angle of esodeviation, and presence or absence of inferior oblique overaction at initial presentation were compared between these two groups. RESULTS: The angle of esodeviation (31.4+/-11.6 PD vs. 42.6+/-12.6 PD, p = 0.004) was significantly different between the fully and partially Ac-ET groups, while refraction (+5.79+/-1.84 D vs. +4.79+/-1.40 D, p = 0.062) had borderline significance. On the contrary, the age at onset (2.35+/-1.74 yrs vs. 2.01+/-1.96 yrs, p=0.539), age at first visit (3.51+/-1.36 yrs vs. 3.01+/-1.70 yrs, p =0.285), inferior oblique overaction (32% vs. 47%, p =0.317), and visual acuity before (LogMAR: 0.40+/-0.25 vs. LogMAR: 0.34+/-0.25, p =0.544) and after treatment (LogMAR: 0.057+/-0.079 vs. LogMAR: 0.051+/-0.19, p = 0.088) were similar in the two groups. CONCLUSIONS: Children with a smaller angle of esodeviation and higher hyperopia were more likely belonging to fully Ac-ET, which can be treated with glasses without the need of surgical intervention. Early detection and early treatment of accommodative esotropia are needed to prevent strabismus and amblyopia.