Effect of polymeric black tea polyphenols on benzo(a)pyrene [B(a)P]-induced cytochrome P4501A1 and 1A2 in mice

The chemopreventive activity of green tea polyphenols (GTPs) is, in part, due to modulation of cytochrome P450s (CYPs). To investigate the enzyme modulatory properties of major black tea polyphenols, the effect of decaffeinated black tea extract (DBTE) or polymeric black tea polyphenol (PBP) mix was studied on CYP1A1 and CYP1A2 in mouse tissues. Animals receiving 2.5% DBTE or 1% PBP mix or drinking water (15 days) were challenged with single oral benzo(a)pyrene (B(a)P) (1 mg/mouse) treatment on the 14th day. Liver and lung microsomes isolated after 24 h were analysed for CYP1A1 and CYP1A2, using biochemical substrate(s) and Western blot analysis. Treatment with 2.5% DBTE or 1% PBP mix did not significantly alter the basal activity and level of CYP1A1 and CYP1A2, whereas pretreatment with 2.5% DBTE or 1% PBP mix resulted in a significant decrease in both the activity and the level of B(a)P-induced CYP1A1 and CYP1A2 in liver and lungs. The PBP mix possesses enzyme modulatory properties exhibited by monomeric GTPs.     

Histopathologic features of Mycobacterium ulcerans infection

Because of the emergence of Buruli ulcer disease, the World Health Organization launched a Global Buruli Ulcer Initiative in 1998. This indolent skin infection is caused by Mycobacterium ulcerans. During a study of risk factors for the disease in Ghana, adequate excisional skin-biopsy specimens were obtained from 124 clinically suspicious lesions. Buruli ulcer disease was diagnosed in 78 lesions since acid-fast bacilli (AFB) were found by histopathologic examination. Lesions with other diagnoses included filariasis (3 cases), zygomycosis (2 cases), ulcerative squamous cell carcinomas (2 cases), keratin cyst (1 case), and lymph node (1 case). Thirty-seven specimens that did not show AFB were considered suspected Buruli ulcer disease cases. Necrosis of subcutaneous tissues and dermal collagen were found more frequently in AFB-positive specimens compared with specimens from suspected case-patients (p<0.001). Defining histologic criteria for a diagnosis of Buruli ulcer disease is of clinical and public health importance since it would allow earlier treatment, leading to less deforming sequelae.     

Low density lipoprotein particle size and risk of early-onset myocardial infarction in women

Previous studies of middle-aged men have shown a univariate association between low density lipoprotein (LDL) particle diameter (size) and coronary heart disease, but this association has yet to be examined in younger women. Using a subsample from a population-based case-control study of women living in western Washington State, the authors examined the association between LDL particle size and risk of early-onset myocardial infarction (MI) in 1992-1995. Gradient gel electrophoresis was used to characterize LDL subclasses in nonfasting blood samples from 72 MI cases and 159 controls aged 20-44 years. Mean LDL particle size in cases was significantly smaller compared with controls (26.4 vs. 26.9 nm, p < 0.001), with an odds ratio of 2.3 (p < 0.0001) for a 1-nm smaller LDL particle size. These results were independent of age, menopausal status, smoking, diabetes, hypertension, and LDL cholesterol (odds ratios = 1.9-2.3 for a 1-nm smaller LDL particle size, all p < 0.02) but were not independent of body mass index, high density lipoprotein cholesterol, or triglyceride (odds ratios = 1.4, 1.4, and 1.1, respectively; all p > 0.05). Therefore, in age-adjusted analyses, smaller LDL particle size was associated with MI in young women, but the risk was attenuated after adjustments for metabolic factors related to both LDL particle size and MI.     

Audiovestibular dysfunction in alcohol dependence. Are we worried?

PURPOSE: To study the audiovestibular function in patients of long-term alcohol dependence and compare these changes with social users of alcohol and complete abstainers. MATERIAL AND METHODS: This was a prospective study of 20 randomly selected patients of long-term alcohol dependence fulfilling International Statistical Classification of Diseases, 10th Revision criteria of alcohol dependence. Audiovestibular function in this group was compared with social user of alcohol and complete abstainers. RESULTS: Statistically significant elevations of thresholds were found at higher frequencies (4000 and 8000 Hz ) in the alcohol-dependent group (P < .001). Alcohol-dependent patients had elevated thresholds at 4 and 8 kHz. Brainstem-evoked response audiometry showed prolongation of latencies of waves I, III, and V alone with interpeak latencies of I-III and III-V. One third of alcohol-dependent patients had abnormal electronystagmographic (ENG) findings. Abnormal ENG findings were only seen in alcohol-dependent patients with vertigo. There was no significant correlation between duration of alcohol dependence and abnormal ENG. CONCLUSIONS: Elevated thresholds at higher frequencies can be the only abnormality in alcohol-dependent patients. Presence of vertigo in alcohol-dependent patient may be associated with abnormal ENG findings. There is no correlation of duration of dependence and ENG abnormalities.     

Photopatternable and photoactive hydrogel for on-demand generation of hydrogen peroxide in cell culture

Oxidative stress, largely mediated by reactive oxygen species (ROS), is a nearly ubiquitous component in complex biological processes such as aging and disease. Optimal in vitro methods used in elucidating disease mechanisms would deliver of low levels of hydrogen peroxide, emulating the in vivo pathological state, but current methods are limited by kinetic stability or accurate measurement of the dose administered. Here we present an in vitro platform that exploits anthraquinone catalysts for the photocatalytic production of hydrogen peroxide. This system can be dynamically tuned to provide constant generation of hydrogen peroxide at a desired physiologic rate over at least 14 days and is described using a kinetic model. Material characterization and stability is discussed along with a proof-of-concept in vitro study that assessed the viability of cells as they were oxidatively challenged over 24 h at different ROS generation rates.     

Tuning DNA-amphiphile condensate architecture with strongly binding counterions

Electrostatic self-assembly of colloidal and nanoparticles has attracted a lot of attention in recent years, since it offers the possibility of producing novel crystalline structures that have the potential to be used as advanced materials for photonic and other applications. The stoichiometry of these crystals is not constrained by charge neutrality of the two types of particles due to the presence of counterions, and hence a variety of three-dimensional structures have been observed depending on the relative sizes of the particles and their charge. Here we report structural polymorphism of two-dimensional crystals of oppositely charged linear macroions, namely DNA and self-assembled cylindrical micelles of cationic amphiphiles. Our system differs from those studied earlier in terms of the presence of a strongly binding counterion that competes with DNA to bind to the micelle. The presence of these counterions leads to novel structures of these crystals, such as a square lattice and a √3 x √3 superlattice of an underlying hexagonal lattice, determined from a detailed analysis of the small-angle diffraction data. These lower-dimensional equilibrium systems can play an important role in developing a deeper theoretical understanding of the stability of crystals of oppositely charged particles. Further, it should be possible to use the same design principles to fabricate structures on a longer length-scale by an appropriate choice of the two macroions.