Search

Cloacal exstrophy presents as a complex abdominal wall defect thought to result from a mesodermal abnormality. Anatomically, its main components are Omphalocele, bladder Exstrophy and Imperforate anus. Other associated malformations include renal malformations and Spine defects (OEIS complex). Historically, the prevalence ranges from 1 in 200,000 to 400,000 births, with higher rates in females. Cloacal exstrophy is likely etiologically heterogeneous as suggested by its recurrence in families and occurrence in monozygotic twins. The defect has been described in infants with limb-body wall, with trisomy 18, and in one pregnancy exposed to Dilantin and diazepam. Due to its rarity, the use of a nonspecific diagnostic code for case identification, and lack of validation of the clinical findings, cloacal exstrophy remains an epidemiologic challenge. The purpose of this study was to describe the prevalence, associated anomalies and maternal characteristics among infants born with cloacal exstrophy. We used data from the International Clearinghouse for Birth Defects Surveillance and Research submitted from 18 birth defect surveillance programs representing 24 countries. Cases were clinically evaluated locally and reviewed centrally by two authors. Cases of persistent cloaca were excluded. A total of 186 cases of cloacal exstrophy were identified. Overall prevalence was 1 in 131,579 births: ranging from 1 in 44,444 births in Wales to 1 in 269,464 births in South America. Live birth prevalence was 1 in 184,195 births. Prevalence ratios did not vary by maternal age. Forty-two (22.6%) cases met the criteria for the OEIS complex, whereas 60 (32.3%) were classified as OEI and 18 (9.7%) as EIS (one with suspected VATER (0.5%)). Other findings included two cases with trisomy 13 (one without a karyotype confirmation), one with mosaic trisomy 12 (0.5%), one with mosaic 45,X (0.5%) and one classified as having amnion band sequence (0.5%). Twenty-seven (14.5%) infants had other anomalies unrelated to cloacal exstrophy. Cloacal exstrophy is a rare anomaly with variability in prevalence by geographic location. The proportion of cases classified as OEIS complex was lower in this study than previously reported. Among all cases, 54.8% were reported to have an omphalocele., (Copyright © 2011 Wiley Periodicals, Inc.)

Epidemiologic data on phocomelia are scarce. This study presents an epidemiologic analysis of the largest series of phocomelia cases known to date. Data were provided by 19 birth defect surveillance programs, all members of the International Clearinghouse for Birth Defects Surveillance and Research. Depending on the program, data corresponded to a period from 1968 through 2006. A total of 22,740,933 live births, stillbirths and, for some programs, elective terminations of pregnancy for fetal anomaly (ETOPFA) were monitored. After a detailed review of clinical data, only true phocomelia cases were included. Descriptive data are presented and additional analyses compared isolated cases with those with multiple congenital anomalies (MCA), excluding syndromes. We also briefly compared congenital anomalies associated with nonsyndromic phocomelia with those presented with amelia, another rare severe congenital limb defect. A total of 141 phocomelia cases registered gave an overall total prevalence of 0.62 per 100,000 births (95% confidence interval: 0.52-0.73). Three programs (Australia Victoria, South America ECLAMC, Italy North East) had significantly different prevalence estimates. Most cases (53.2%) had isolated phocomelia, while 9.9% had syndromes. Most nonsyndromic cases were monomelic (55.9%), with an excess of left (64.9%) and upper limb (64.9%) involvement. Most nonsyndromic cases (66.9%) were live births; most isolated cases (57.9%) weighed more than 2,499 g; most MCA (60.7%) weighed less than 2,500 g, and were more likely stillbirths (30.8%) or ETOPFA (15.4%) than isolated cases. The most common associated defects were musculoskeletal, cardiac, and intestinal. Epidemiological differences between phocomelia and amelia highlighted possible differences in their causes., (Copyright © 2011 Wiley Periodicals, Inc.)

Cyclopia is characterized by the presence of a single eye, with varying degrees of doubling of the intrinsic ocular structures, located in the middle of the face. It is the severest facial expression of the holoprosencephaly (HPE) spectrum. This study describes the prevalence, associated malformations, and maternal characteristics among cases with cyclopia. Data originated in 20 Clearinghouse (ICBDSR) affiliated birth defect surveillance systems, reported according to a single pre-established protocol. A total of 257 infants with cyclopia were identified. Overall prevalence was 1 in 100,000 births (95%CI: 0.89-1.14), with only one program being out of range. Across sites, there was no correlation between cyclopia prevalence and number of births (r = 0.08; P = 0.75) or proportion of elective termination of pregnancy (r = -0.01; P = 0.97). The higher prevalence of cyclopia among older mothers (older than 34) was not statistically significant. The majority of cases were liveborn (122/200; 61%) and females predominated (male/total: 42%). A substantial proportion of cyclopias (31%) were caused by chromosomal anomalies, mainly trisomy 13. Another 31% of the cases of cyclopias were associated with defects not typically related to HPE, with more hydrocephalus, heterotaxia defects, neural tube defects, and preaxial reduction defects than the chromosomal group, suggesting the presence of ciliopathies or other unrecognized syndromes. Cyclopia is a very rare defect without much variability in prevalence by geographic location. The heterogeneous etiology with a high prevalence of chromosomal abnormalities, and female predominance in HPE, were confirmed, but no effect of increased maternal age or association with twinning was observed., (Copyright © 2011 Wiley Periodicals, Inc.)

The isothiocyanate sulforaphane (SF), abundant in Cruciferous vegetables, is known to induce antioxidant/detoxification enzymes in many cancer cell lines, but studies focused on its cytoprotective action in nontransformed cells are just at the beginning. Since we previously demonstrated that SF elicits cardioprotection through an indirect antioxidative mechanism, the aim of this study was to analyze the signaling pathways through which SF exerts its protective effects. Using cultured rat cardiomyocytes, we investigated the ability of SF to activate Akt/protein kinase B (PKB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathways, which are implicated in cardiac cell survival, and to increase the phosphorylation of Nuclear factor E2-related factor 2 (Nrf2) and its binding to the antioxidant response element. By means of specific inhibitors, we demonstrated that the Phosphatidylinositol 3-kinase (PI3K)/Akt pathway represents a mechanism through which SF influences both expression and activity of glutathione reductase, glutathione-S-transferase, thioredoxin reductase, and NAD(P)H:quinone oxidoreductase-1, analyzed by western immunoblotting and spectrophotometric assay, respectively, and modulates Nrf2 binding and phosphorylation resulting in a cytoprotective action against oxidative damage. Results of this study confirm the importance of phase II enzymes modulation as cytoprotective mechanism and support the nutritional assumption of Cruciferous vegetables as source of nutraceutical cardioprotective agents., (© 2011 Institute of Food Technologists®)

Background: There are few published studies on microtia-anotia frequency., Methods: Using data from birth defects surveillance programs around the world, we conducted a systematic review on the frequency of microtia-anotia to further explore the differences in prevalence across countries. Ninety-two birth defects surveillance programs were evaluated with a total of 8917 cases of microtia-anotia. We computed the prevalence per 10,000 births for each surveillance program for total cases of microtia-anotia (microtia types I to IV), microtia (types I to III), and anotia (type IV). Prevalence ratios were calculated by large geographic areas, race/ethnicity, and by surveillance methodologies., Results: The overall prevalences were: microtia-anotia, 2.06 (confidence interval [CI], 2.02-2.10); microtia, 1.55 (CI, 1.50-1.60); and anotia 0.36 (CI, 0.34-0.38). Higher prevalences were observed for the Americas, Northern Europe and Asia, among Hispanics and Asians, and among active ascertainment and hospital-based surveillance programs., Conclusions: We observed marked variation in the prevalence of microtia-anotia across surveillance programs and within countries. These results must be interpreted cautiously as this variability may be explained mainly by differences in surveillance methods. However, given the magnitude of some of the differences, other factors may also be involved. This study contributes to the knowledge of the prevalence of microtia-anotia by providing a critical analysis of the existing data. In addition, it supports the need for a coding system that allows complete phenotype characterization of microtia-anotia, including severity and laterality, as well as for further studies on the variation of its frequency related to race and ethnicity., (Copyright © 2011 Wiley-Liss, Inc.)

In recent years, a number of studies have been performed to evaluate the possible health benefits of an increased intake of folic acid (FA) on human health. However, the only well-documented benefit emerging from randomized controlled trials, nonrandomized interventions trials, and observational studies is the risk reduction of neural tube defects (NTDs). NTDs are congenital malformations that include anencephaly, encephalocele, and spina bifida caused by the failure of fusion of the neural tube that normally closes between 22nd and 28th day since conception (on an average 40-42th day after the first day of last menstrual period). The occurrence of NTDs varies among population between 0.8 and 3 per 1,000, and it is estimated that 324,000 pregnancies are affected every year worldwide. More FA can decrease the NTDs risk up to 0.6 per 1,000 births. Other malformations as congenital heart defects, cleft lip, and limb deficiencies can be most probably also reduced. To decrease the NTDs risk, it is recommended that all women capable of becoming pregnant should have more FA. The goal is that every woman could start her pregnancy with an optimal folate status, estimated today to be as more than 906 nmol/L of red blood cell folate concentration. More FA can be obtained through a strict Mediterranean pattern of nutrition and healthy life style, fortified food, supplements. Women and health authorities can choose the most appropriate strategy. Monitoring folate status of women during the periconceptional period is an essential way to evaluate the success of the preferred strategy., (Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.)

Ischemic preconditioning is a complex cardioprotective phenomenon that involves adaptive changes in cells and molecules and occurs in a biphasic pattern: an early phase after 1-2 h and a late phase after 12-24 h. While it is widely accepted that reactive oxygen species are strongly involved in triggering ischemic preconditiong, it is not clear if they play a major role in the early or late phase of preconditioning and which are the mechanisms involved. The present study was designed to investigate the mechanisms behind H(2)O(2)-induced cardioprotection in rat neonatal cardiomyocytes. We focused on antioxidant and phase II enzymes and their modulation by protein kinase signaling pathways and nuclear-factor-E(2)-related factor-1 (Nrf1) and Nrf2. H(2)O(2) preconditioning was able to counteract oxidative stress more effectively in the late than in the early phase of adaptation. In particular, H(2)O(2) preconditioning counteracted oxidative stress-induced apoptosis by decreasing caspase-3 activity, increasing Bcl2 expression and selectively increasing the expression and activity of antioxidant and phase II enzymes through Nrf1 and Nrf2 translocation to the nucleus. The downregulation of Nrf1 and Nrf2 by small interfering RNA reduced the expression level of phase II enzymes. Specific inhibitors of phosphatidylinositol 3-kinase/Akt and p38 MAPK activation partially reduced the cardioprotection elicited by H(2)O(2) preconditioning and the induction and activity of phase II enzymes. These findings demonstrate, for the first time, a key role for Nrf1, and not only for Nrf2, in the induction of phase II enzymes triggered by H(2)O(2) preconditioning.

Context: Clinical hyperthyroidism is not uncommon in pregnancy, with a reported prevalence of 0.1 to 0.4%. The available antithyroid drugs are propylthiouracil and methimazole/carbimazole., Objectives: In this report we examined the association of both drugs with congenital malformations using data from the International Clearinghouse for Birth Defects Surveillance and Research., Design: The study used a case-affected control analysis and included 18,131 cases with malformations and reported first-trimester exposure to medication. A total of 127 subjects were born to mothers with known first-trimester antithyroid drug exposure., Results: Among the 52 groups of malformations that were analyzed, situs inversus ± dextrocardia, isolated unilateral kidney a/dysgenesis, and cardiac outflow tract defects were associated with prenatal exposure to propylthiouracil based on three, two, and five cases, respectively. Prenatal exposure to methimazole/carbimazole was significantly associated with choanal atresia, omphalocele, and total situs inversus ± dextrocardia (P < 0.01)., Conclusions: Further studies are required to exhaustively evaluate the associations between propylthiouracil and birth defects because of the low number, the lack of biological plausibility, and the possibility of underdiagnosis. Association between methimazole/carbimazole exposure and omphalocele and choanal atresia is consistent with previous reports and definitely suggests that these malformations could be part of a specific, even if rare, embryopathy.

Rates of Down syndrome (DS) show considerable international variation, but a systematic assessment of this variation is lacking. The goal of this study was to develop and test a method to assess the validity of DS rates in surveillance programs, as an indicator of quality of ascertainment. The proposed method compares the observed number of cases with DS (livebirths plus elective pregnancy terminations, adjusted for spontaneous fetal losses that would have occurred if the pregnancy had been allowed to continue) in each single year of maternal age, with the expected number of cases based on the best-published data on rates by year of maternal age. To test this method we used data from birth years 2000 to 2005 from 32 surveillance programs of the International Clearinghouse for Birth Defects Surveillance and Research. We computed the adjusted observed versus expected ratio (aOE) of DS birth prevalence among women 25-44 years old. The aOE ratio was close to unity in 13 programs (the 95% confidence interval included 1), above 1 in 2 programs and below 1 in 18 programs (P < 0.05). These findings suggest that DS rates internationally can be evaluated simply and systematically, and underscores how adjusting for spontaneous fetal loss is crucial and feasible. The aOE ratio can help better interpret and compare the reported rates, measure the degree of under- or over-registration, and promote quality improvement in surveillance programs that will ultimately provide better data for research, service planning, and public health programs., ((c) 2010 Wiley-Liss, Inc.)

Sulforaphane (SF), one of the most important isothiocyanates in the human diet, present in cruciferous vegetables, is known to have chemopreventive activities in different tissues. No data are available on its effects in the prevention of skeletal muscle damage. In this study, we investigated the potential protective effects of SF treatment on muscle damage and oxidative stress induced by an acute bout of exhaustive exercise in rats. Male Wistar rats were treated with SF (25 mg/kg body wt ip) for 3 days before undergoing an acute exhaustive exercise protocol in a treadmill (+7% slope and 24 m/min). Acute exercise resulted in a significant increase in plasma lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities. It also resulted in a significant increase in thiobarbituric acid-reactive substances, in a significant decrease in tissue total antioxidant capacity, and in a significant decrease in NAD(P)H:quinone oxidoreductase 1 (NQO1) expression and activity in vastus lateralis muscle. SF treatment significantly increased muscle NQO1, glutathione-S-transferase, and glutathione reductase expression and activity, with no effect on glutathione peroxidase and thioredoxin reductase. The observed SF-induced upregulation of phase II enzymes was accompanied by a significant increase in nuclear erythroid 2 p45-related factor 2 expression and correlated with a significant increase in total antioxidant capacity and a decrease in plasma LDH and CPK activities. Our data demonstrate that SF acts as an indirect antioxidant in skeletal muscle and could play a critical role in the modulation of the muscle redox environment, leading to the prevention of exhaustive exercise-induced muscle damage.

This study investigated potential cardiotoxicity as exerted by Erbicin-derived-immunoagents (EDIAs), novel human anti-ErbB2 immunoagents engineered by fusion of a human anti-ErbB2 scFv, Erbicin, with either a human RNase or the Fc region of a human IgG1. EDIAs are strongly cytotoxic on ErbB2-positive cells in vitro and in vivo and bind to an epitope different from that of Herceptin, a humanized anti-ErbB2 mAb effective in the therapy of breast carcinoma, but cardiotoxic in a high percentage of cases. Toxicity and apoptosis were tested in vitro by 3-(4,5-dimethyl-2-thizolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), DNA fragmentation, and immunoblotting analyses. Echocardiography was measured in mice after treatment with each immunoagent. Cardiac fibrosis and detection of apoptosis were examined by Sirius red staining of collagen and TUNEL assay, respectively. EDIAs were found in vitro to have no adverse effects on cardiac cells for which Herceptin is severely toxic. In vivo studies on a mouse model showed that the EDIAs did not alter cardiac function, whereas Herceptin and doxorubicin, used as positive controls, significantly reduced the fractional shortening parameter. Cardiac fibrosis and apoptosis were not significantly affected in mice treated with EDIAs. Thus, EDIAs could fulfill the therapeutic need of patients ineligible for Herceptin treatment due to cardiac dysfunction.

Oxidative stress plays a major role in the pathophysiology of cardiac disorders, but the experimental data on the protective effects of exogenous antioxidants are controversial. A promising cardioprotective strategy may be through the induction of the endogenous antioxidants and phase II enzymes by chemical inducers. Sulforaphane is an isothiocyanate derived from cruciferous vegetables, and it has gained attention mainly as a potential chemopreventive agent in part through the induction of detoxifying enzymes. Accordingly, this study was undertaken to investigate the time-dependent induction of gene transcription, protein expression, and enzyme activity of antioxidant and phase II enzymes [glutathione reductase, glutathione-S-transferase, glutathione peroxidase, NAD(P)H:quinone oxidoreductase-1, thioredoxin reductase] by sulforaphane in cultured rat neonatal cardiomyocytes. The potential cardioprotective action of sulforaphane was confirmed by the decrease in intracellular reactive oxygen species production, the increase in cell viability, and the decrease in DNA fragmentation after long-term treatment accompanied by the induction of antioxidants and phase II enzymes in cardiomyocytes.

Background: Holoprosencephaly (HPE) is a developmental field defect of the brain that results in incomplete separation of the cerebral hemispheres that includes less severe phenotypes, such as arhinencephaly and single median maxillary central incisor. Information on the epidemiology of HPE is limited, both because few population-based studies have been reported, and because small studies must observe a greater number of years in order to accumulate sufficient numbers of births for a reliable estimate., Methods: We collected data from 2000 through 2004 from 24 of the 46 Birth Defects Registry Members of the International Clearinghouse for Birth Defects Surveillance and Research. This study is based on more than 7 million births in various areas from North and South America, Europe, and Australia., Results: A total of 963 HPE cases were registered, yielding an overall prevalence of 1.31 per 10,000 births. Because the estimate was heterogeneous, possible causes of variations among populations were analyzed: random variation, under-reporting and over-reporting bias, variation in proportion of termination of pregnancies among all registered cases and real differences among populations., Conclusions: The data do not suggest large differences in total prevalence of HPE among the studied populations that would be useful to generate etiological hypotheses., (Copyright 2008 Wiley-Liss, Inc.)

Aim: To prospectively investigate a new high resolution MRI technique for dynamic evaluation of the enhancement kinetics of bowel parietal layers and to correlate it with CDAI, CRP, endoscopic activity and histologic features., Methods: About 16 consecutive patients with proven diagnosis of CD underwent ileocolonoscopy with biopsy and serial bowel dynamic contrasted-MRI (D-CE-MRI) evaluated in blind fashion. Quantitative analysis of bowel wall enhancement kinetics was performed basing on signal to noise ratio (SNR) of inner parietal layers (Mucosa-Submucosa, M-SM) and outer parietal layers (Muscular-Serosa, Ms-S). Disease activity was defined by CDAI > 150, serum CRP > 5 mg/dL and histologic results., Results: About 9 patients showed a layered enhancement of bowel wall (8 active, 1 inactive), whereas inactive (7 cases) group presented a homogeneous pattern. In active patients we found a significant difference in parietal layered enhancement curves (M-SM vs. Ms-S, P < 0.03) not observed in inactive disease and controls (intra-group analysis). M-SM and Ms-S enhanced curves in clinically active patients were significantly different respect to those of patients with inactive CD (P < 0.001) (inter-group analysis). Parietal D-CE-MRI pattern well correlated with histologic features (r = 0.8; P < 0.001, Spearman test)., Conclusions: D-CE-MRI can be a useful tool for clinical follow-up and in the treatment strategies in CD patients.

Objective: The objective was to prospectively determine CT density changes in bone metastases, before and after intravenous zoledronic acid for a maximum period of 12 months., Patients and Methods: Twenty-three consecutive patients presented with bone metastases and underwent therapy with zoledronic acid from December 2004. All patients underwent CT of the chest, abdomen, and pelvis. Bone density, measured in Hounsfield units (HU), was determined by segmenting lesions in the same anatomical area of the metastasis sites on the axial images of the sequential series of CT examinations. The effects of zoledronic acid were evaluated by calculating absolute and relative increases in bone density., Results: The patients presented with multiple metastases in 65% of the cases. When compared with the baseline, all groups demonstrated a significant increase in bone density, which significantly (p < 0.01) correlated with the number of zoledronic acid administrations. There was increased bone density of at least 100% in 57%, and an increase of at least 50% in 87% of the patients. This increase was significant in both lytic and sclerotic metastases after 3 months of therapy. No significant bone density difference was found in normal-appearing bone., Conclusion: Bone density measured by CT increases at metastatic sites after zoledronic acid treatment, regardless of the type of metastasis, in contrast to apparently normal bone.

alpha1-Adrenergic stimulation triggers glucose transport in the heart through the translocation of glucose transporter (GLUT) 1 and GLUT4 to plasma membranes, mediated by protein kinase C (PKC) isoforms. Evidence is emerging that dietary polyphenolic compounds may act not only as antioxidants but also by modulating PKC-mediated signaling. This study evaluated the ability of a green tea extract (GTE) to modulate alpha1-adrenoceptor-mediated glucose transport in rat cardiomyocytes. GTE supplementation decreased phenylephrine (PhE)-stimulated glucose uptake and GLUT4 recruitment. PhE stimulation activated PKC alpha, beta, delta, and epsilon, while GTE supplementation decreased the translocation of beta and delta isoforms, but not alpha and epsilon, supporting the notion that GTE directly affects PKC activation and is a beta and delta isoform-selective PKC inhibitor. Due to reactive oxygen species (ROS) involvement in pathological heart alterations, the observation that GTE is able to both inhibit effects originated by some PKC isoforms and counteract ROS deleterious effects could be important in the prevention/counteraction of these diseases.

Background and Aims: Peroxidation of membrane lipids, altering cell integrity and function, plays an important part in the onset and development of cardiac damage following ischemia and reperfusion. Cells maintain their membrane lipid homeostasis by substituting peroxidized lipids with new polyunsaturated fatty acids. The microsomal enzymatic system converting essential fatty acids to highly unsaturated fatty acids (HUFAs) contributes to this repairing mechanism. The membrane of the endoplasmic reticulum could be one of the potential targets of free radicals generated in ischemia/reperfusion, thus causing a reduced efficacy of the system required for HUFA biosynthesis. To verify this hypothesis, and the consequent modification in fatty acid composition, we exposed cultured rat cardiomyocytes to different periods of hypoxia (H), eventually followed by reoxygenation (R). Furthermore, the effectiveness of antioxidants like alpha-tocopherol and a green tea extract in counteracting H/R damage towards HUFA biosynthesis was tested., Methods and Results: Linoleic (LA) and alpha-linolenic acid (ALA) conversion was measured by pre-labelling cells with [1-14C]LA or [1-14C]ALA for 1 h; total lipid fatty acid composition was determined by gas chromatographic analysis. H profoundly affected HUFA biosynthesis, and this effect was much more evident on LA than on ALA. Conversion of both substrates was partially restored during R due to the readmission of the final acceptor of the desaturating complex. Fatty acid composition data were in agreement with the modifications observed in essential fatty acid conversion. Antioxidant protection appeared to be related to the duration of H, and to be more effective during H than during R., Conclusion: This study points out the importance of possessing good antioxidant defenses not only after, but mainly prior to the onset of H.

Since in the aged heart an increased basal production of reactive oxygen species (ROS) has been demonstrated, and the resistance to ROS attack could be ameliorated by antioxidant supplementation, we verified the protective effect of selenium, as sodium selenite (SS) or seleno methionine (SM), in cultured rat cardiomyocytes aged in vitro. In normoxia, glutathione peroxidase (GPx) activity and total antioxidant activity were higher in old than in young cardiomyocytes, suggesting the existence of a compensatory increase of antioxidant defenses. When aged cells were submitted to hypoxia/reoxygenation, GPx activity was not modified; while total antioxidant activity decreased, conjugated diene level increased. Selenium supplementation, particularly as SM, was able to increase GPx, and consequently total antioxidant activity, and to decrease conjugated diene production. The observed ability of selenium supplementation to protect aged cardiomyocytes from hypoxia/reoxygenation damage underlines the importance of an optimal selenium dietary intake, particularly in the elderly.

Preventing oxidative damage in the heart is subject of considerable investigation and studies developing nutritional intervention methods to attenuate or prevent the resulting pathological state of free radical damage are now emerging. In this light, a dietary intervention directed to increase the daily intake of antioxidant molecules represents a fundamental step to achieve a beneficial result. In this minireview the attention is focused on the damage induced in cultured cardiac cells by the antitumoral doxorubicin, known for its cardiotoxicity, and by hypoxia/reoxygenation that occur in a wide variety of important clinical conditions. The identification of antioxidant molecules having specific effectiveness in a particular cell type may be useful for the development of a prevention strategy specific for free radical induced-diseases related to that cell type. Although the connection between consumption of foods rich in polyphenolic compounds and the decreased risk of cardiovascular disease has been reported, the role of different antioxidant molecules contained in foods is still to be elucidated. The protective effect of the polyphenolic components of green tea in the prevention/counteraction of cell damage induced in the heart by doxorubicin or hypoxia/reoxygenation has been discussed.

Ten benzimidazole-4,7-diones were synthesized and tested in vitro on two tumor cell lines. Several compounds showed a significant antiproliferative activity on K562 cells, although to a different extent, whereas compound 1i showed a highly significant activity on SW620 cells, comparable to that of doxorubicin. Both the substituents in the quinone ring and the position of the nitrogen atom in the pyridine moiety play a crucial role for the biological activity.

The possibility of enhancing glutathione peroxidase (GPx) activity and cytosolic total antioxidant activity (TAA) in normoxia and hypoxia/reoxygenation (H/R) by the supplementation of different concentrations of sodium selenite (SS) or selenomethionine (SM) was investigated in cultured rat cardiomyocytes. To assess the entity of oxidative stress due to H/R, levels of conjugated dienes containing lipids were determined. In normoxia, GPx activity and TAA increased in parallel with the increase in SS and SM supplementation. H/R did not influence GPx activity but lowered TAA; both SS and SM supplementations were effective in increasing GPx activity, the most effective concentration being 1 microM. At this SS and SM concentration, TAA returned to a normoxic value. Conjugated diene production, increased by H/R, was reduced by SS and SM supplementation, the 1 microM concentration appearing to be the most effective one. According to these data Se supplementation represents another possibility to counteract oxidative damage in the myocardium.

Some thiazolylbenzimidazole-4,7-diones were synthesized and tested in vitro on two tumor cell lines. Compounds 2d and 2e show a very good activity on K562 cells, whereas compounds 2a and 2b are active on SW620 cells. The importance of the methoxy group on the quinone moiety is confirmed and the function at 4-position of the thiazole ring plays a determining role for the activity.