Involvement of rat cytochrome 1A1 in the biotransformation of kaempferol to quercetin: relevance to the genotoxicity of kaempferol

Kaempferol is a flavonoid widely distributed in edible plantsand has been shown to be genotoxic to V79 cells in the absenceof external metabolizing systems. The presence of an externalmetabolizing system, such as rat liver homogenates (S9 mix),leads to an increase in its genotoxicity, which is attributedto its biotransformation to the more genotoxic flavonoid quercetin,via the cytochrome P450 (CYP) mono-oxygenase system. In thepresent work we investigated the mechanisms of the genotoxicityof kaempferol further. Special attention has been given to therole of CYP in the genotoxicity of this flavonoid. We studiedthe induction of mutations in Salmonella typhimurium TA98 inthe presence and in the absence of S9 mix and the inductionof chromosomal aberrations (CAs) and micronuclei (MN) by kaempferolin V79 cells in the presence and in the absence of S9 mix. Toevaluate the role of different CYP in the biotransformationof kaempferol we studied the induction of CAs and MN in V79cells genetically engineered for the expression of rat CYP 1A1,1A2 and 2B1. In addition we performed CYP inhibition studiesusing the above-mentioned indicators and high performance liquidchromatography (HPLC) analysis. The results obtained in thiswork suggest that rat CYP 1A1 is, among the cytochromes studied,the one that plays the major role in the transformation of kaempferolinto quercetin. The relevance of these findings to the humansituation is discussed. ⁴To whom correspondence should be addressed     

B-1 cells are pivotal for in vivo inflammatory giant cell formation

The mechanisms that govern giant cell (GC) formation in inflammatory, neoplastic and physiologic conditions are far from being understood. Here, we demonstrate that B-1 cells are essential for foreign-body GC formation in the mouse. GCs were analysed on the surface of glass cover slips implanted into the subcutaneous tissue of the animals. It was demonstrated that GCs are almost absent on cover slips implanted into the subcutaneous tissue of BALB/c or CBA/N X-linked immunodeficient mice. As these animals do not have B-1 cells in the peritoneal cavity, they were reconstituted with B-1 cells obtained from cultures of adherent mouse peritoneal cells. Results showed that in B-1-reconstituted animals, the number of GCs on the implant surface surpassed the values obtained with preparations from wild animals. In animals selectively irradiated (pleural and peritoneal cavities) to deplete these cavities of B-1 cells, GCs were also not formed. Enriched suspensions of B-1 cells grown in culture were labelled with [(3)H]-tymidine and injected into the peritoneal cavity of naive mice before implantation of glass cover slips. After 4 days, about 17% of mononuclear cells had their nuclei labelled, and almost 70% of GCs had one or more of their nuclei labelled when analysed by histoautoradiographic technique. A few GCs expressed an immunoglobulin M when analysed by immunostaining and confocal microscopy. Overall, these data demonstrate that B-1 cells are pivotal in the mechanisms of foreign-body GC formation in the mouse.     

Personality, manual preference and neuroendocrine reactivity in hirsute subjects

Behavioral and neuroendocrine differences may be postulated in hirsute subjects since central effects of gonadal steroids are well established. We conducted a controlled clinical study with 25 consecutive young hirsute participants compared with 20 consecutive controls. Neuropsychological evaluation included the Minnesota Multiphasic Personality Inventory (MMPI) and the Edinburgh Inventory of Manual Preference (EIMP). Neuroendocrine reactivity was assessed by the adrenocorticotropic hormone (ACTH) and cortisol responses to corticotropin releasing hormone (CRH). Hirsute participants presented a flattened personality profile with lower neurotic triad scores--146 +/- 20 versus 166 +/- 28. Left-hand preference was more common in hirsute participants--4/21 versus 0/20. Decreased ACTH [area under the curve (AUC)--36 +/-2 8 vs. 72 +/- 63 pg/ml h] and cortisol (AUC--18 +/- 4 vs. 25 +/- 10 microg/dl h) responses to CRH were found in the hirsute group. In the hirsute group, higher manual preference scores were associated with lower ACTH responses to CRH, while the opposite association was found in the control group. In the hirsute group, the hyporeactive hypothalamic-pituitary-adrenal (HPA) axis was associated with lower behavior-deviant scores, while in the control group, the hyporeactive HPA axis was associated with more psychopathology. We conclude that personality and HPA axis reactivity are different in hirsute female participants when compared with controls, with a trend for differences regarding handedness. Personality and handedness are differently associated with HPA reactivity. Distinctive features in hirsute participants are probably established very early during ontogenic development.     

Design and development of a digital stethoscope encapsulation for simultaneous acquisition of phonocardiography and electrocardiography signals: the SmartHeart case study

Abstract

The stethoscope is a major symbol of modern medicine. It is used for diagnosis of different conditions and enables physicians to listen to internal body sounds. Electrocardiography was only introduced in medicine in the beginning of the twentieth century. Today measuring heart’s electrical activity is also fundamental cardiac diseases diagnosis. Although performed with independent devices, requiring physician and patient presence in the same physical space, in combination they enhance cardiovascular assessment. In this paper, a digital stethoscope encapsulation was designed, adding new functionality to this advanced medical device. Today wired and wireless communications enable different medical devices to share data and information, over long distances. Using low-cost hardware technologies, the encapsulation will add the ability to acquire and transmit via Bluetooth the Electrocardiographic activity, determined in the same cardiac focus and synchronised with the Phonocardiographic sound recordings. Several encapsulation concepts were developed and prototyped using 3D printing. They were easily fitted to the digital stethoscope and tested in a hospital environment for ergonomics, acoustic and electric signals acquisition. The best concept was chosen with the help of a physician’s opinion and the final prototype performance was very satisfactory.     

Cutaneous mucormycosis in a young, immunocompetent girl.

We report a case of cutaneous mucormycosis in a healthy, immunocompetent young girl (age 14 years). The patient had a 5-year history of a slowly enlarging, erythematous plaque with slight elevated, scaling, circinate borders on the right thigh. Histopathology showed a granulomatous infiltrate with broad, pale, non-septate hyphae. Mycological study identified Mucor hiemalis (Wehmer).     

Vicker's hardness and Raman spectroscopy evaluation of a dental composite cured by an argon laser and a halogen lamp

We present the results of the Vicker's hardness test and the use of near-infrared Raman spectroscopy (RS) to measure in vitro the degree of conversion (DC) of a bis(phenol)-A-glycidyl-dimethacrylate-based composite resin, photoactivated by both a halogen lamp (power density=478 mW/cm(2); 8-mm diameter spot) and an argon laser (power density=625 mW/cm(2); 7-mm diameter spot). The degree of conversion was estimated by analyzing the relative intensities between the aromatic C=C stretching Raman mode at 1610 cm(-1) and the methacrylate C=C stretching Raman mode (1640 cm(-1)) on top and bottom surfaces. For the hardness evaluation, the samples were embedded in polyester resin and three indentations with a 50-g load for 10 s were made on the top surface. The higher relative DC values achieved by the photoactivation of a composite resin by the argon laser suggest a better biocompatibility in the bottom surface. The correlation test showed that the higher Vicker's hardness number (VHN) values were associated with higher DC values. The derivative analysis showed a greater curing rate from 5 to 20 s of exposure. The comparison of VHN and DC values with both light sources at each curing time showed that a small change in conversion is related to a large change in hardness. Raman spectroscopy is more sensitive to changes in the first stages of curing reaction than later ones, and the Vicker's hardness assay is more sensitive to changes in the last stages.