Coexistence of pernicious anemia and prostate cancer - 'an experiment of nature' involving vitamin B12 modulation of prostate cancer growth and metabolism: a case report

<p>Abstract</p> <p>Introduction</p> <p>This report presents the clinical and laboratory course of a patient with prostate cancer and severe vitamin B₁₂deficiency undergoing watchful waiting for prostate cancer. The possible interaction between therapy for B₁₂deficiency and the natural course of prostate cancer is presented.</p> <p>Case presentation</p> <p>We present the case of a 75-year-old Chinese man with prostate cancer and pernicious anemia. His serum vitamin B₁₂level was 32 pg/ml (300-900 pg/ml) and holotranscobalamin was 0 pg/ml (>70 pg/ml). There was an unexpected rapid progression of Gleason's score during 10 months of watchful waiting. After the diagnosis of pernicious anemia was made, therapeutic injections of vitamin B₁₂were started. We observed a significant acceleration in prostate-specific antigen and prostatic acid phosphatase and a shortening of prostate-specific antigen doubling time after initiation of B₁₂therapy.</p> <p>Conclusion</p> <p>We propose that the relatively short period of watchful waiting before histological progression of Gleason's score (GS [3+2] = 5 to GS [3+4] = 7 over 10 months) may have been a result of depleted holotranscobalamin 'active' B₁₂. Replacement of B₁₂was associated with an initial rapid increase in serum prostate-specific antigen and prostatic acid phosphatase followed by stabilization. The patient represents an 'experiment of nature' involving vitamin B₁₂metabolism and raises the question as to whether rapid histological progression of Gleason's score was related to absence of serum holotranscobalamin while prostate-specific antigen and prostatic acid phosphatase, markers of cell growth, were accelerated by vitamin B₁₂replacement. To our knowledge, this is the first report of a possible cellular kinetic interaction between an epithelial malignancy and vitamin B₁₂metabolism.</p

Stringy Stability of Charged Dilaton Black Holes with Flat Event Horizon

Electrically charged black holes with flat event horizon in anti-de Sitter space have received much attention due to various applications in Anti-de Sitter/Conformal Field Theory (AdS/CFT) correspondence, from modeling the behavior of quark-gluon plasma to superconductor. Crucial to the physics on the dual field theory is the fact that when embedded in string theory, black holes in the bulk may become vulnerable to instability caused by brane pair-production. Since dilaton arises naturally in the context of string theory, we study the effect of coupling dilaton to Maxwell field on the stability of flat charged AdS black holes. In particular, we study the stability of Gao-Zhang black holes, which are locally asymptotically anti-de Sitter. We find that for dilaton coupling parameter $\alpha$ > 1, flat black holes are stable against brane pair production, however for 0 < $\alpha$ < 1, the black holes eventually become unstable as the amount of electrical charges is increased. Such instability however, behaves somewhat differently from that of flat Reissner-Nordstr\"om black holes. In addition, we prove that the Seiberg-Witten action of charged dilaton AdS black hole of Gao-Zhang type with flat event horizon (at least in 5-dimension) is always logarithmically divergent at infinity for finite values of $\alpha$, and is finite and positive in the case $\alpha$ tends to infinity . We also comment on the robustness of our result for other charged dilaton black holes that are not of Gao-Zhang type.Comment: Fixed some confusions regarding whether part of the discussions concern electrically charged hole or magnetically charged one. No changes to the result

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

Liquid-gas phase transition in nuclear multifragmentation

The equation of state of nuclear matter suggests that at suitable beam energies the disassembling hot system formed in heavy ion collisions will pass through a liquid-gas coexistence region. Searching for the signatures of the phase transition has been a very important focal point of experimental endeavours in heavy ion collisions, in the last fifteen years. Simultaneously theoretical models have been developed to provide information about the equation of state and reaction mechanisms consistent with the experimental observables. This article is a review of this endeavour.Comment: 63 pages, 27 figures, submitted to Adv. Nucl. Phys. Some typos corrected, minor text change

Exacerbation of Bloody Diarrhea as a Side Effect of Mesalamine Treatment of Active Ulcerative Colitis

Mesalamine has been used as the first-line therapy for the treatment of ulcerative colitis (UC) because of its efficacy and fewer side effects. However, earlier study showed that mesalamine occasionally causes diarrhea. We are presenting a patient with active UC in whom bloody diarrhea accompanied by abdominal pain and fever occurred and the symptoms were aggravated after administration of mesalamine. In order to clarify the reason of symptoms aggravation, drug lymphocyte stimulation test and rechallenge trial with mesalamine were performed. The results indicated the possibility that aggravation was related to allergic reaction and was dose-dependent. Furthermore, we examined colonoscopic views but there was no remarkable change in before and after rechallenge trial. Based on the above result, the patient was diagnosed with mesalamine intolerance. In order to differentiate whether the exacerbation of bloody diarrhea is due to the side effects of the mesalamine or a true relapse of UC, taking careful history before and after increasing mesalamine dosage as well as being aware of side effects of mesalamine are required. Clinicians should be aware of diarrhea as a side effect of mesalamine particularly after onset of mesalamine formulation, change in mesalamine formulation, or change in mesalamine dose

Lessons to be learnt from Leishmania studies

Leishmaniasis is a disease caused by infection with the protozoan parasite Leishmania, which is responsible for three main types of disease: cutaneous leishmaniasis, visceral leishmaniasis and mucocutaneous leishmaniasis based to the site of infection for the particular species. This presents a major challenge to successful drug treatment, as a drug must not only reach antileishmanial concentrations in infected macrophages, the parasites' host cell, but also reach infected cells in locations specific to the type of disease. In this paper we discuss how studies using Leishmania have contributed to our knowledge on how drug delivery systems can be used to improve drug efficacy and delivery

Spatial concordance of DNA methylation classification in diffuse glioma

BACKGROUND: Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence. METHODS: We used neuronavigation to acquire 133 image-guided and spatially separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a 3-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites. RESULTS: Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account. CONCLUSION: Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists

BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.

Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating&nbsp;levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health