Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes

Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies, short-term exposure to tobacco has been evaluated. From a biological perspective, however, long-term (chronic) exposure to tobacco mimics the pathogenesis of oral cancer more closely. We developed a cell line model to investigate the chronic effects of chewing tobacco. Chronic exposure to tobacco resulted in higher cellular proliferation and invasive ability of the normal oral keratinocytes (OKF6/TERT1). We carried out quantitative proteomic analysis of OKF6/TERT1 cells chronically treated with chewing tobacco compared to the untreated cells. We identified a total of 3,636 proteins among which expression of 408 proteins were found to be significantly altered. Among the overexpressed proteins, stearoyl-CoA desaturase (SCD) was found to be 2.6-fold overexpressed in the tobacco treated cells. Silencing/inhibition of SCD using its specific siRNA or inhibitor led to a decrease in cellular proliferation, invasion and colony forming ability of not only the tobacco treated cells but also in a panel of head and neck cancer cell lines. These findings suggest that chronic exposure to chewing tobacco induced carcinogenesis in non-malignant oral epithelial cells and SCD plays an essential role in this process. The current study provides evidence that SCD can act as a potential therapeutic target in head and neck squamous cell carcinoma, especially in patients who are users of tobacco.     

Tinea capitis: still an unsolved problem?

Tinea capitis is a fungal infection specifically involving the scalp and hair. It is the most common dermatophyte infection in children under 12 years of age, with a predominance in those of sub‐Saharan African descent. Common signs include hair loss, scaling, erythema and impetigo‐like plaques. Adults may also be affected, but to a lesser degree. The causative species are from the Microsporum and Trichophyton genera. Limited treatment options and diverse modes of transmission complicate the clinician’s ability to address this disease adequately. Although dermatophytes are ubiquitous in our environment and tinea capitis is common, therapeutic options can be utilised to reduce morbidity.     

Cardiovascular computed tomographic angiography evaluation following unsuccessful invasive angiography: The clinical utility of 3D volume rendering

In an appropriate clinical setting, cardiac CT angiography (CCT) can be used as a safe and effective noninvasive imaging modality for defining coronary arterial anatomy by providing detailed three‐dimensional anatomic information that may be difficult to obtain with invasive coronary angiography (ICA). We present a patient where coronary angiography by ICA was unsuccessful and where the subsequent CCT proved to be very useful in providing us relevant information. © 2009 Wiley‐Liss, Inc.     

A novel DNA intercalator,butylamino-pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline,induces cell cycle arrest and apoptosis in leukemic cells

DNA intercalators are one of the most commonly used chemotherapeutic agents. Novel intercalating compounds of pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline series having a butylamino or piperazino group at fourth position (BPSQ and PPSQ, respectively) are studied. Our results showed that BPSQ induced cytotoxicity whereas PPSQ was cytostatic. The cytotoxicity induced by BPSQ was concentration- and time-dependent. Cell cycle analysis and tritiated thymidine assay revealed that BPSQ affects the cell cycle progression by arresting at S phase. The absence of p-histone H3 and reduction in the levels of PCNA in the cells treated with BPSQ further confirmed the cell cycle arrest. Further, annexin V staining, DNA fragmentation, nuclear condensation and changes in the expression levels of BCL2/BAD confirmed the activation of apoptosis. Activation of caspase 8 and lack of cleavage of caspase 9, caspase 3 and PARP suggest the possibility of BPSQ triggering extrinsic pathway for induction of apoptosis, which is discussed. Hence, we have identified a novel compound which would have clinical relevance in cancer chemotherapeutics.     

Disparities in Obesity and Overweight Prevalence Among US Immigrant Children and Adolescents by Generational Status

We examined the prevalence and socio-behavioral correlates of obesity and overweight among 46,707 immigrant and US-born children and adolescents aged 10–17 years. The 2003 National Survey of Children’s Health was used to estimate obesity and overweight prevalence among children in 12 immigrant groups, stratified by race/ethnicity and generational status. Logistic regression was used to examine immigrant differentials in the prevalence and odds of obesity and overweight. Obesity and overweight prevalence varied from a low of 6 and 18% for second-generation Asian immigrants to a high of 24 and 42% for native-born black children (US-born black children with US-born parents), respectively. After adjusting for age, gender, ethnicity, socioeconomic status, perceived neighborhood safety, television viewing, computer use, and physical activity, first-generation immigrant children, overall, had 26% lower odds of obesity than native-born children. Obesity and overweight prevalence was lower for immigrant black and white children than their native-born counterparts, while obesity and overweight prevalence among Hispanic children did not vary significantly by generational status. Compared with native-born white children, the adjusted odds of obesity were 64% higher for native-born blacks, 55% higher for second-generation Hispanic immigrants, and 63% lower for first-generation Asian immigrants. Adjusted immigrant differentials in overweight risks were also marked. Socioeconomic, demographic, and behavioral factors accounted for 61 and 35% of ethnic-immigrant disparities in obesity and overweight prevalence, respectively. Immigrant patterns in childhood obesity and overweight vary substantially by ethnicity and generational status. To reduce disparities, obesity prevention programs must target at-risk children of both immigrant and US-born parents.