Effects of Lanthanum on Human Lymphocytes Viability and DNA Strand Break

Lanthanum (La) is a rare-earth metal with applications in agriculture, industry, and medicine. Since lanthanides show a broad spectrum of applications there is an increased risk of contamination for humans. We examined the effects of lanthanum in Jurkat cells and human peripheral lymphocytes (HPL), and we found that it was cytotoxic and genotoxic on both cell lines. Additionally, HPL were more sensitive to La treatment than Jurkat cells and necrosis was the pathway by which La induced cytotoxicity. Vitamin E was able to diminish the DNA strand breaks induced suggesting that oxidative stress may be involved in the genotoxic process.     

Inhibitors of strand transfer that prevent integration and inhibit human T-cell leukemia virus type 1 early replication

The replication of the retrovirus human T-cell leukemia virus type 1 (HTLV-1) is linked to the development of lymphoid malignancies and inflammatory diseases. Data from in vitro, ex vivo, and in vivo studies have revealed that no specific treatment can prevent or block HTLV-1 replication and therefore that there is no therapy for the prevention and/or treatment of HTLV-1-associated diseases in infected individuals. HTLV-1 and human immunodeficiency virus type 1 (HIV-1) integrases, the enzymes that specifically catalyze the integration of these retroviruses in host cell DNA, share important structural properties, suggesting that compounds that inhibit HIV-1 integration could also inhibit HTLV-1 integration. We developed quantitative assays to test, in vitro and ex vivo, the efficiencies of styrylquinolines and diketo acids, the two main classes of HIV-1 integrase inhibitors. The compounds were tested in vitro in an HTLV-1 strand-transfer reaction and ex vivo by infection of fresh peripheral blood lymphocytes with lethally irradiated HTLV-1-positive cells. In vitro, four styrylquinoline compounds and two diketo acid compounds significantly inhibited HTLV-1 integration in a dose-dependent manner. All compounds active in vitro decreased cell proliferation ex vivo, although at low concentrations; they also dramatically decreased both normalized proviral loads and the number of integration events during experimental ex vivo primary infection. Accordingly, diketo acids and styrylquinolines are the first drugs that produce a specific negative effect on HTLV-1 replication in vitro and ex vivo, suggesting their potential efficiency for the prevention and treatment of HTLV-1-associated diseases.     

Effects of lithium and valproate on serum and hippocampal neurotrophin-3 levels in an animal model of mania

It has been demonstrated that lithium (Li) and valproate (VPT), first line mood stabilizers, increase BDNF content in rat hippocampus and frontal cortex, which suggests that the regulation of neurotrophic factors might be associated with their pharmacological effects. In sight of the scarcity of studies with other neurotrophins, and the possible relevance of multiple neurotrophic signaling systems in bipolar disorder we investigated the effects of Li and VPT on NT-3 levels in rat serum and hippocampus, using an animal model of mania induced by amphetamine (AMPH). In the reversal model, adult male Wistar rats received AMPH or saline for 14 days, and between the 8th and 14th days, animals were treated with Li, VPT or saline. In the prevention model, rats were pretreated with Li, VPT or saline, and between the 8th and 14th days, the animals received AMPH or saline. Li increased serum and hippocampal NT-3 levels in all conditions, whereas VPT increased hippocampal NT-3 in the prevention model only. Li reversed AMPH changes in NT-3 in the reversal model, and VPT prevented AMPH changes in NT-3 in the prevention model. These results suggest that both Li and VPT modulate serum and central (hippocampal) NT-3 levels, and further support that the regulation of neurotrophic signaling systems may be related to the mechanisms of action of mood stabilizers.     

Water movements in the brain: role of aquaporins

About 80% of the brain is water. This review discusses the importance of the three brain water-channel proteins (AQP1, AQP4, AQP9) in brain physiology. AQP1 is expressed in the choroid plexus and participates in forming cerebrospinal fluid. AQP4, found in astrocyte foot processes, glia limitans and ependyma, facilitates water movement into and out of the brain, accelerates astrocyte migration and alters neuronal activity. Recently, AQP4 autoantibodies were discovered in patients with neuromyelitis optica, a demyelinating disease, and are now being used to diagnose this condition. AQP9 is present in some glia and neurons, but its function is unclear. Finally, we discuss how the discovery of AQP activators and inhibitors will be the next major step in this field.     

Methylene blue dye--a safe and effective alternative for sentinel lymph node localization

Abstract:  Sentinel lymph node (SLN) biopsy has emerged as an effective diagnostic tool in axillary staging in breast cancer. The commonly used technique employs isosulfan blue/patent blue V combined with radioactive colloid tracer. Methylene blue (MB) is a less expensive and readily available alternative dye. The study evaluated the safety and efficacy of MB in SLN localization. A retrospective study of 329 patients with early breast cancer who had SLN localization as part of an ethically approved prospective evaluation study of SLN localization technique was carried out. Lymph node positive, tumors >2 cm on clinical and radiological evaluation, those with previous breast and axillary surgery, neo-adjuvant chemotherapy were excluded from the study. One hundred seventy three patients underwent SLN localization using 1 mL of 1% MB, and a combined MB-radio colloid tracer technique was used in the other 156 patients. Allocation to the groups was by simple randomization. Injection of the dye and radioisotope was into the subdermal plane in the sub-areolar region. Patients underwent breast conservation surgery or mastectomy with SLN directed four node axillary sampling ± axillary clearance. The lymph node was examined by standard microscopy. There were no reported complications with the use of MB aside from temporary tattooing. The technique failed in eight patients giving an identification rate of 97.6%. Ten of the 258 (3.9%) patients had false-negative SLN, with negative predictive value of 96.1%, sensitivity of predicting further axillary disease of 73%, specificity of 87.3%, and overall accuracy of 85.7%. Reported adverse reaction to isosulfan blue/patent blue V varied from minor to severe anaphylactic reactions (1–3%) requiring vigorous resuscitation. Subdermal sub-areolar injection of MB is safe and effective readily available dye for SLN localization in axillary staging of breast cancer with no major adverse reaction.     

Rabies virus in insectivorous bats: Implications of the diversity of the nucleoprotein and glycoprotein genes for molecular epidemiology

Insectivorous bats are the main reservoirs of rabies virus (RABV) in various regions of the world. The aims of this study were to (a) establish genealogies for RABV strains from different species of Brazilian insectivorous bats based on the nucleoprotein (N) and glycoprotein (G) genes, (b) investigate specific RABV lineages associated with certain genera of bats and (c) identify molecular markers that can distinguish between these lineages. The genealogic analysis of N and G from 57 RABV strains revealed seven genus-specific clusters related to the insectivorous bats Myotis, Eptesicus, Nyctinomops, Molossus, Tadarida, Histiotus and Lasiurus. Molecular markers in the amino acid sequences were identified which were specific to the seven clusters. These results, which constitute a novel finding for this pathogen, show that there are at least seven independent epidemiological rabies cycles maintained by seven genera of insectivorous bats in Brazil.