Detection of Adriamycin-induced cardiotoxicity in cultured heart cells with technetium 99m-SESTAMIBI

Adriamycin, a broad-spectrum cytotoxic agent useful in cancer chemotherapy, is limited by a dose-dependent cardiomyopathy mediated in part by disruption of mitochondrial energetics. Hexakis(2-methoxyisobutyl isonitrile)technetium(I)(^99mTc-SESTAMIBI) is a gammaemitting radiopharmaceutical with myocellular accumulation properties dependent on mitochondrial membrane potential. To test the hypothesis that^99mTc-SESTAMIBI could monitor Adriamycin-induced alterations in cardiac energetics, cultured chick heart cells were treated with Adriamycin and^99mTc-SESTAMIBI tracer kinetics were determined. Concentration- and time-dependent depression of^99mTc-SESTAMIBI accumulation was evident within 60 min of treatment. The apparentK _i for acute Adriamycin inhibition of tracer accumulation was 82 M. After 24 h of treatment, Adriamycin concentrations as low as 0.1 M demonstrated detectable inhibitory effects. The apparentK _i for this subchronic Adriamycin inhibition of^99mTc-SESTAMIBI accumulation was 18 M. Subchronic concentration-dependent increases in adriamycin-induced myocellular injury as reflected by lactate dehydrogenase (LDH) release correlated inversely with decreases in^99mTc-SESTAMIBI accumulation. These data further support a contribution from altered mitochondrial energetics to Adriamycin-induced injury and establish a pharmacological foundation for pursuing the possibility of noninvasive imaging of chronic Adriamycin cardiotoxicity in cancer patients using^99mTc-SESTAMIBI.     

The pharmacological and pathological studies on Taiwan folk medicine (IV): The effects of echinops grijisii and e. Latifolius

The protective effect of "San-fang-feng" derived from the root of Echinops grijsii Hance on CCl4-induced hepatotoxicity has been studied. This crude drug was found to possess a marked hepatoprotective effect. A comparison of the protective effect with "Lou-lu" derived from the root of E. latifolius Tausch and "Pei-chai-hu" original Bupleurum chinense showed that E. grijisii and E. latifolius were more effective than B. chinense as reported previously. The results suggested that both E. grijisii and E. latifolius could correct the hepatocyte necrosis and functional disorder induced by the CCl4 treatment.     

Rectal cancer mortality and total hardness levels in Taiwan's drinking water.

The possible association between the risk of rectal cancer and hardness levels in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible rectal cancer deaths (986 cases) of Taiwan residents from 1990 through 1994 were compared with deaths from other causes (986 controls), and the hardness levels of the drinking water used by these residents were determined. Data on water hardness throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes and the controls were pair matched to the cases by sex, year of birth, and year of death. The results show a significant negative relationship between drinking water hardness and rectal cancer mortality. Odds ratio and 95% confidence intervals were 1.24 (1.01-1. 55) and 1.38 (1.10-1.73), respectively, for exposure to moderately hard water and soft water compared with the use of hard water. Trend analyses showed an increasing odds ratio for rectal cancer with decreasing levels of hardness in drinking water. This is an important finding for the Taiwan water industry and human health.     

Effect of magnolol on in vitro mitochondrial lipid peroxidation and isolated cold-preserved warm-reperfused rat livers

BACKGROUND/AIM: A mechanism suggested to cause injury to preserved organs is the generation of oxygen free radicals. Lipid peroxidation is one of the biological damages caused by oxygen free radicals. It is our aim to investigate whether magnolol, a strong antioxidant, suppresses the generation of oxygen free radicals and improves the viability of cold-preserved warm-reperfused rat livers. MATERIALS AND METHODS: In vitro lipid peroxidation was induced in rat hepatic mitochondria with ADP and FeSO4. The inhibitory effect of magnolol on lipid peroxidation was measured with oxygen consumption and malondialdehyde (MDA) formation. Subsequently, we preserved and reperfused rat livers in preservation solutions that contained magnolol. The hepatic enzymes and liver MDA were measured to assess the protective effect of magnolol on isolated rat livers. RESULTS: In rat hepatic mitochondria, magnolol was 470 times more potent than alpha-tocopherol in inhibiting oxygen consumption and 340 times more potent than alpha-tocopherol in inhibiting MDA formation. Addition of magnolol to Ringer's lactate solution had a protective effect, in terms of MDA formation and leakage of hepatic enzymes, on warm-reperfused but not cold-stored liver tissue. Addition of magnolol to University of Wisconsin (UW) solution, a widely used preservation solution, did not modify the effect of this solution on isolated liver tissues. CONCLUSIONS: We conclude that magnolol is an effective antioxidant and suppresses lipid peroxidation in rat liver mitochondria and can be used as a rinsing solution in protecting transplanted organs from lipid peroxidation during reperfusion, especially for those organs not preserved with UW solution.     

An open study of sertraline in patients with major depression who failed to respond to moclobemide

OBJECTIVES: The aim of this study is to evaluate the efficacy and tolerability of sertraline in patients with major depression who have failed to respond to an adequate trial of moclobemide. METHOD: Sixty-three patients with major depression who had discontinued moclobemide within the last 6 weeks due to lack of efficacy were recruited from multiple psychiatric services in Victoria and Queensland. After a wash-out period, patients were treated with sertraline 50 mg once daily for 4 weeks. If there was an insufficient response, the dose was titrated upwards to a maximum of 200 mg/day, with 2 weeks at each dosage level. By the end of the study, patients had received a fixed dose of sertraline for 8 weeks. The main outcome measures were the 17-item Hamilton Rating Scale for Depression (HAMD) and Clinical Global Impression (CGI) scales. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI). RESULTS: Of the 62 intention-to-treat patients enrolled, 48 (77%) responded to sertraline (i.e. experienced > or =50% reduction in HAMD total score from baseline and had a final HAMD score of < or =17). Fifty-four (87%) patients were at least 'minimally improved' on the CGI scale. There were also significant improvements in mean total MADRS and BDI scores. Sertraline was well tolerated. Adverse events were reported by 84% of patients, but only 5% withdrew due to adverse events. CONCLUSIONS: This study shows that patients with major depression who have failed to respond to moclobemide can generally be treated successfully with sertraline.     

No association between an intronic presenilin-1 gene polymorphism and schizophrenia in a Chinese population

We investigated the association between schizophrenic psychosis and an intronic polymorphism of the presenilin-1 (PS1) gene in a Chinese population. Schizophrenic and control groups had similar PS1 genotype distributions and allele frequencies, indicating that this polymorphism may not be involved in the development of schizophrenia.     

A simple splinting method for correction of supple congenital clasped thumbs in infants

A splint has been designed to correct the congenital clasped thumb. It is like a short opponens splint that can keep the thumb in a position of abduction and extension without limiting wrist movement. The application of the splint was easy and adjustment for fit could be made at each visit if necessary. The device has been used in 11 infant patients (17 thumbs) with congenital clasped thumb of the supple type. The functional results were excellent in 15 of 17 thumbs, and the other two were good according to the grading system of Weckesser et al. (1968).     

Autogenous venous nerve conduits. A review

Autogenous venous nerve conduit (AVNC) has evolved from an experimental idea to a clinical reality over the last two decades. The effectiveness of AVNC for reconstruction of a peripheral nerve with a nerve gap of less than 3 cm has been established and confirmed. An exciting application of this technique in the near future is to use the conduit as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration.