Risk factors of thyroid abnormalities in bipolar patients receiving lithium: a case control study

Background

Lithium-induced thyroid abnormalities have been documented in many studies. They may occur despite normal plasma lithium levels. The objectives of this study were: 1) to determine possible relationship between lithium ratio, defined as erythrocyte lithium concentrations divided by plasma lithium concentrations, and thyroid abnormalities in bipolar patients receiving lithium and 2) to find other possible risk factors for developing thyroid abnormalities in the subjects.

Methods

Sixty-eight bipolar patients receiving lithium therapy were enrolled in a cross-sectional evaluation of thyroid function test and thyroid size. Patients were divided into two groups based on their thyroid function tests and thyroid sizes. Erythrocyte and plasma lithium concentrations were determined by atomic absorption spectrometry for each patient. Lithium ratio was then calculated.

Results

No significant differences were found between age, positive family history of affective disorder, plasma lithium concentration, erythrocyte lithium concentration, and lithium ratio comparing the two groups. Thyroid abnormalities was significantly higher in women than in men (p < 0.05).

Conclusions

Lithium ratio does not appear to have a predictive role for thyroidal side effects of lithium therapy. Female gender was the main risk factor. We suggest more frequent thyroid evaluation of bipolar women who are treated with lithium.

     

Primary pleural lymphomas

Two patients are presented with primary low grade pleural B cell lymphomas with no history of a pyothorax.     

Inhibition of ultraviolet B-mediated activation of nuclear factor kappaB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate

Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, possesses significant anti-inflammatory and cancer chemopreventive properties. Studies have shown the photochemopreventive effects of green tea and EGCG in cell culture, animal models, and human skin. The molecular mechanism(s) of photochemopreventive effects of EGCG are incompletely understood. We recently showed that EGCG treatment of the normal human epidermal keratinocytes (NHEK) inhibits ultraviolet (UV)B-mediated activation of the mitogen-activated protein kinase (MAPK) pathway. In this study, we evaluated the effect of EGCG on UVB-mediated modulation of the nuclear factor kappa B (NF-kappaB) pathway, which is known to play a critical role in a variety of physiological functions and is involved in inflammation and development of cancer. Immunoblot analysis demonstrated that the treatment of NHEK with EGCG (10-40 microM) for 24 h resulted in a significant inhibition of UVB (40 mJ/cm(2))-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha, in a dose-dependent manner. UVB-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha was also observed in a time-dependent protocol (15 and 30 min, 1, 2, 3, 6, 12 h post-UVB exposure). Employing immunoblot analysis, enzyme-linked immunosorbent assay, and gel shift assay, we demonstrate that EGCG treatment of the cells resulted in a significant dose- and time-dependent inhibition of UVB-mediated activation and nuclear translocation of a NF-kappaB/p65. Our data suggest that EGCG protects against the adverse effects of UV radiation via modulations in NF-kappaB pathway, and provide a molecular basis for the photochemopreventive effect of EGCG.     

Base excision repair deficiency caused by polymerase beta haploinsufficiency: accelerated DNA damage and increased mutational response to carcinogens

The base excision repair pathway (BER) is believed to maintain genomic integrity by repairing DNA damage arising spontaneously or induced by oxidizing and alkylating agents. To establish the role of DNA polymerase beta (beta-pol) in BER and beta-pol-dependent BER in maintaining genomic stability, we have measured the impact of a gene-targeted disruption in the beta-pol gene on DNA repair capacity and on in vivo sensitivity to carcinogens. We have extensively phenotyped the DNA beta-pol heterozygous (beta-pol(+/-)) mouse as expressing approximately 50% less beta-pol mRNA and protein and as exhibiting an equivalent reduction in the specific activity of beta-pol. We measured BER activity by in vitro G:U mismatch and (8-OH)G:C repair and find that there is a significant reduction in the ability of extracts from beta-pol(+/-) mice to repair these types of DNA damage. In vivo, the beta-pol(+/-) mice sustain higher levels of DNA single-strand breaks as well as increased chromosomal aberrations as compared with beta-pol(+/+) littermates. Additionally, we show that reduction in beta-pol expression and BER activity results in increased mutagenicity of dimethyl sulfate as evidenced by a 2-fold increase in LacI mutation frequency. Importantly, the beta-pol(+/-) mice do not exhibit increased sensitivity to DNA damage induced by N-nitroso-N-ethylurea, ionizing radiation, or UV radiation, which induce damage processed by alternative repair pathways, demonstrating that this model is specifically a BER-deficient model.     

Enhancement of the mutagenicity of benzo(a)pyrene diol epoxide by a nonmutagenic dose of ultraviolet A radiation

We investigated the effects of single and combined exposures to two ubiquitous environmental carcinogens, polycyclic aromatic hydrocarbons and UVA radiation, in Big Blue mouse embryonic fibroblasts. We quantified the cytotoxicity, DNA adduct formation, and induction of mutations in the cII transgene in cells treated with a single agent or combinations of agents in both direct and reverse order. Mapping of DNA adducts by terminal transferase-dependent PCR showed the preferential formation of bulky adducts at identical nucleotide positions along the cII gene after treatment with the prototype polycyclic aromatic hydrocarbon, benzo(a)pyrene diol epoxide [B(a)PDE], or B(a)PDE plus UVA radiation treatments but not after UVA irradiation alone. The cII mutant frequency determined by a lambda phage-based mutation detection system was not increased significantly by UVA irradiation (1.7-fold over background; P < 0.3); however, B(a)PDE alone or in combinations with UVA radiation significantly increased the cII mutant frequency (P < 0.001). The highest cII mutant frequency was induced by the treatment with B(a)PDE followed by UVA irradiation, which was more than the added mutant frequencies of the two agents individually (>12.2-fold versus <7.6-fold over background; P < 0.01). In support of these findings, DNA sequencing analyses showed that the mutational spectra induced by B(a)PDE alone or combined with UVA radiation were significantly different from those derived spontaneously (P < 0.0001) or by UVA irradiation (P < 0.0005). The signature of mutations produced by B(a)PDE i.e., "G-->T + C-->A" transversions, was significantly enhanced when the B(a)PDE treatment was followed by UVA irradiation (47% versus 65%; P < 0.01). Also, the methylated CpG dinucleotide-targeted overall mutations specifically induced by B(a)PDE were increased after the subsequent UVA irradiation (43% versus 51%, respectively). Such enhancements in the mutational signature of B(a)PDE were most pronounced within the preferential DNA adduction sites along the cII gene after the treatment with B(a)PDE plus UVA radiation, which suggests that the primary B(a)PDE adducts are converted to more mutagenic species on UVA irradiation. We conclude that UVA radiation at a nonmutagenic dose has an enhancing effect on the mechanism by which B(a)PDE induces mutations.     

Infrastructural considerations for supporting POC devices. Healthcare executives must focus on creating integration-friendly environments for the most effective use of mobile devices

Creating an integration-friendly infrastructure is the best way to prepare for current as well as next-generation POC devices. Fortunately, hassle-free system integration is needed throughout healthcare today for reasons beyond the domain of POC devices, so integration progress already made in other areas helps pave the way for POC devices. Healthcare IT professionals, as much or more than any other IT group, have had to deal with the challenges of integrating disparate systems. When considering deployment of POC devices, you will want to make sure they adhere to open industry standards. In this way, these important devices won't add to the problem of disparate systems, but will contribute to the solution. We see XML and Web services as being especially important to the future of healthcare delivery and administration. XML and Web services, along with powerful orchestrators, can provide an ever-richer collection of clinical data to be delivered to, and received from, the POC devices that will become an ever more important addition to the physician armamentarium.     

Evaluation of endomorphin-1 on the activity of Na(+),K(+)-ATPase using in vitro and in vivo studies

The goal of this study was to investigate the effects of endomorphin-1 on Na(+),K(+)-ATPase activity in mouse brain synaptosome in vitro, and its antinociceptive interaction with the Na(+),K(+)-ATPase inhibitor ouabain. Endomorphin-1 (0.1 nM-10 microM) produced a concentration-dependent (EC(50): 43.19 nM, CI: 23.38-65.71 nM, E(max): 25.86%, CI: 24.53-27.20%), naloxone-reversible increase of the synaptosomal Na(+),K(+)-ATPase activity. The intrathecally (i.t.) administered endomorphin-1 (2-20 microg) produced a dose-dependent short-lasting increase in the tail-flick latency. Ouabain itself (1-1000 ng, i.t.) did not cause antinociception. Treatment with 10 ng ouabain significantly decreased the antinociceptive effect of 2 microg endomorphin-1, but none of the other combinations did significantly differ from the endomorhin-1-treated groups. These data indicate that endomorphin-1 increases the activity of Na(+),K(+)-ATPase in vitro but this effect may play a weak role in the antinociception induced by intrathecal endomorphin-1.     

Oxidative stress as a possible mode of action for arsenic carcinogenesis

Many modes of action for arsenic carcinogenesis have been proposed, but few theories have a substantial mass of supporting data. Three stronger theories of arsenic carcinogenesis are production of chromosomal abnormalities, promotion of carcinogenesis and oxidative stress. This article presents the oxidative stress theory along with some supporting experimental data. In the area of which arsenic species is causually active, recent data have suggested that trivalent methylated arsenic metabolites, particularly monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), have a great deal of biological activity. Some evidence now indicates that these trivalent, methylated, and relatively less ionizable arsenic metabolites may be unusually capable of interacting with cellular targets such as proteins and even DNA. Thus for inorganic arsenic, oxidative methylation followed by reduction to trivalency may be a activation, rather than a detoxification pathway. This would be particularly true for arsenate. In forming toxic and carcinogenic arsenic species, reduction from the pentavalent state to the trivalent state may be as or more important than methylation of arsenic.