Cardiomyopathy induced by Adriamycin (ADR) is a cause of congestive heart failure. Recently, it has been suggested that ADR inhibits the carnitine palmitoyltransferase system (CPT I) and consequently the transport of long-chain fatty acids across mitochondrial membranes. This study was devised to ascertain how ADR affects serum lipid and fatty acid metabolism in rats given ADR with and without L-carnitine supplementation. Male Sprague-Dawley rats were divided into four groups. The first group was the control. The second group was given intraperitoneal injections of ADR (5 mg/kg) twice a week over a period of 2 wk. The third group received the same dose of ADR plus L-carnitine (200 mg/kg). The fourth group was injected with L-carnitine only. Serum lipids (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol) and fatty acid levels were determined on the first, eighth, and 15th d after injection of ADR. ADR caused an increase of serum total cholesterol, triglyceride, and LDL cholesterol compared with the control group. HDL cholesterol was similar between two groups. Similarly, total fatty acids, especially C16-C18 fatty acids, were significantly elevated after injection of ADR. Striking reduction in these substances was observed when L-carnitine was added (p Ͻ 0.05). This study is the first report regarding the reversal effect of L-carnitine in connection with FFA profiles (C6-C18) in the serum of ADRinduced cardiomyopathic rats. This study also supports the view that ADR causes cardiomyopathy because it interferes with fatty acid metabolism, and we hypothesize that there is a possible protective effect of L-carnitine. (Pediatr Res 51: 249-255, 2002) Abbreviations ADR, Adriamycin CARN, L-carnitine CPT, carnitine palmitoyltransferase FFA, free fatty acid ADR (doxorubicin) is an anthracycline antibiotic and has major clinical significance because of its broad-spectrum antitumor activity. Several studies show a cumulative dosedependent and irreversible cardiotoxicity that limits its usefulness as a broad-spectrum anticancer drug (1, 2). One major chronic side effect is the development of cardiomyopathy and ultimately congestive heart failure known as ADR cardiomyopathy (3).The precise mechanism of this pathogenesis has not been completely defined (4, 5). A number of different mechanisms have been proposed for the cardiotoxic effect of ADR (6 -13), such as its interaction with nucleic acid and/or with nuclear components, disruption of cardiac-specific effects of gene expression, and low antioxidant defense in tissue such as the heart. An abnormal fatty acid metabolism has been suggested by . Although alteration of fatty acid oxidation has been associated with ADR, the lack of understanding of fatty acid metabolism in this type of cardiotoxicity and other cardiomyopathies has led to conflicting results.Recently, it has been suggested that ADR may exert at least a part of its cardiotoxicity by inhibition of long-chain fatty acid oxidation in the heart (18). Because long-chain fatty acids are the major su...
X-linked hypophosphatemic rickets (XLH) results from mutations in the PHEX gene. Mutational analysis of the PHEX gene in 15 unrelated Korean patients with hypophosphatemic rickets revealed eight mutations, including five novel mutations, in nine patients: two nonsense mutations, two missense mutations, one insertion, and three splicing acceptor/donor site mutations. Of these, c.64G>T, c.1699C>T, c.466_467 insAC, c.1174-1G>A, and c.1768+5G>A were novel mutations. To analyze the correlation between genotype and phenotype, phenotypes were compared between groups with and without a mutation, in terms of mutation location, mutation type, and sex. Skeletal disease tended to be more severe in the group with a mutation in the C-terminal half of the PHEX gene, but no genotype-phenotype correlation was detected in other comparisons. Further extensive studies of the PHEX gene mutations and analyses of the genotype-phenotype relationships are required to understand PHEX function and the pathogenesis of XLH.
Between January 2006 and May 2008, 2624 pregnant S. Korean women between 35-37 weeks gestation were screened for group B streptococcus (GBS). Resistance to antimicrobials was tested by disk diffusion and serotype determined using co-agglutination assays and microarray methods. Overall, 8% of pregnant women were colonized. Serotype III was the predominant serotype (43.8%), followed by serotypes V (20.3%), Ia (12.1%), and Ib (9.5%). GBS was frequently resistant to clindamycin (54.0%) and erythromycin (25.6%); 3.7% were resistant to cefazolin. More than three-quarters of serotype V were resistant to clindamycin or erythromycin or both, and 71% of serotype III were resistant to clindamycin but only 12% were resistant to erythromycin. GBS prevalence exceeded earlier reports by one-third. This is the first report of cefazolin resistance in Korea. These results underscore the need to establish screening measures and chemoprophylaxis guidelines regarding GBS infections in Korea.
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