No abstract

HoloTC has a better diagnostic accuracy than vitamin B(12) and can replace the existing vitamin B(12) assay as a primary screening test in patients suspected of vitamin B(12) deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B(12) deficiency (defined by MMA > 0.45μmol/L) in a mixed patient population.

Background: Smokeless tobacco is often referred to as a major contributor to oral cancer. In some regions, especially Southeast Asia, the risk is difficult to quantify due to the variety of products, compositions (including non-tobacco ingredients) and usage practices involved. In Western populations, the evidence of an increased risk in smokeless tobacco users seems unclear, previous reviews having reached somewhat differing conclusions. We report a detailed quantitative review of the evidence in American and European smokeless tobacco users, and compare our findings with previous reviews and meta-analyses.

The sorption phenomena that nicotine undergoes in indoor environments are generally recognized as a limitation in its use as a marker for environmental tobacco smoke (ETS). An empirical description of these phenomena is proposed, and they are compared to those exhibited by a well-accepted ETS gas-phase marker, ethenylpyridine. The sorption of both compounds onto different surfaces (glass, cotton, and nylon fabrics) was investigated through dynamic experiments in a 1-m3 glass chamber. The combined influence of the nature of the sink and of relative humidity on the sorption of each compound is outlined. These results can be used to predict the dynamics and the magnitude of these processes. As much as 1 mg of nicotine can be adsorbed and re-emitted from 1 m2 of cotton cloth over a few hours, and consequently the significant biases likely to be caused if nicotine is used to assess low-level ETS exposures need to be addressed. These could arise from re-emission of adsorbed nicotine from indoor surfaces after the air would have been cleared of ETS, or from its transport on clothing and subsequent re-emission.

Altered metabolism of cancer first highlighted by Otto Warburg has a long history. Although ignored for a considerable amount of time, it is now receiving substantial attention. We recently published results obtained with a combination of two drugs, lipoic acid and hydroxycitrate, targeting metabolic enzymes particularly affected in cancer: ATP citrate lyase and pyruvate dehydrogenase kinase. This treatment was as efficient as chemotherapy in the three mouse cancer models that were tested. In this work, we asked if our drug combination could be used in conjunction with standard cytotoxic chemotherapy, in particular cisplatin, to improve basic protocol efficacy. A combination of lipoic acid and hydroxycitrate was administered to mice implanted with syngeneic cancer cells, LL/2 lung carcinoma and MBT-2 bladder carcinoma, concommitantly with classical chemotherapy (cisplatin or methotrexate). We demonstrate that the triple combination lipoic acid + hydroxycitrate + cisplatin or methotrexate is more efficient than cisplatin or methotrexate used individually or the combination of lipoic acid and hydroxycitrate administered alone. Of particular note are the results obtained in the treatment of an 80 year-old female who presented with ductal adenocarcinoma of the pancreas accompanied by liver metastases. A treatment course using gemcitabine plus α-lipoic acid and hydroxycitrate gave highly promising results. The in vivo data, coupled with the case study results, suggest a possible advantage in using a treatment targeted at cancer metabolism in association with classical chemotherapy.

Isomyosin expression patterns in embryonic chicken atria during the first two weeks of development were analyzed immunohistochemically. In the 3-days embryonic chicken heart (HH19-20), strong coexpression of both isomyosins can be found as band-like zones at the lateral sides of the sinoatrial junction. The zones converge on the bottom of the atrium and continue as a band around the atrioventricular canal. In the 5-days heart (HH27-28) the coexpression area encompasses the entire sinoatrial junction and extends into parts of the sinus venosus and into the dorsocaudal atrial wall. In the 7-days heart (HH 32-33) the relative extension of coexpression areas reaches its maximum. Coexpression is also found in a ring-like band in the ventral (bottom) wall of the atria peripheral to the ring-like band in the atrioventricular junction. The latter band has now become continuous with the coexpression area in the bottom of the interatrial septum. Caudally coexpression extends behind the atrioventricular cushions towards the interventricular septum and cranially coexpression of the atrioventricular junction has become continuous with that of the ring around the outflow tract (cf Sanders et al. 1986). In the second week of incubation a decrease of coexpression is observed. The isomyosin expression pattern described in this study has put forward additional arguments that the conductive tissue originates from areas that continue to express both isomyosins relatively late in development.

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The hypothesis that elevated levels of ammonia-releasing compounds in tobacco and ammonia in mainstream (MS) smoke increase the rate and amount of nicotine evaporation from the particles of MS smoke aerosol was examined by kinetic modeling and experiments with MS cigarette smoke. Computational simulation of a kinetic mechanism describing volatile loss of nicotine, ammonia, and acetic acid from an aqueous solution was used to compute the time-dependent concentration of all species in the model. Because of the high volatility of ammonia relative to that of nicotine, variation over a wide range of initial ammonia concentration had no significant effect upon the rate of loss of nicotine from the model system. The effects of a variation in the volatile loss rate constant for ammonia and for the acid were examined. The simulations show that ammonia is lost from the model solution at a greater rate than nicotine and acid, and the loss of volatile acid has a significant role in the rate and amount of nicotine loss. Simulations with a model system undergoing a continuous steady addition of ammonia showed that high rates of ammonia addition could significantly increase the rate of nicotine volatile loss from the model solution. A series of smoking experiments was performed using blended cigarettes connected to a denuder tube. Deposition of smoke constituents can occur directly from the gas phase and by the deposition of smoke aerosol particles themselves. As nicotine exists >99% in the particle phase of MS smoke, in the absence of particle deposition, denuder tube deposition of nicotine occurs via the evaporation-deposition pathway. Solanesol, a nonvolatile tobacco and smoke terpene, was used to quantify the amount of particle deposition onto the denuder tube. The amount of ammonia deposited on the denuder tube was an order of magnitude greater than that of nicotine, showing that ammonia evaporates from the MS smoke particles much faster than does nicotine. The experimental results were supported and explained by the aqueous model simulations. Included in these experiments are cigarettes that differ in their MS smoke ammonia content by a factor of ca. five. However, an increased amount of MS smoke ammonia does not increase the rate of nicotine loss from the particles. The combined results support the conclusion that ammonia in mainstream smoke has little effect, if any, upon the rate and amount of nicotine evaporation from MS smoke particles.