Mutagenicity and Genotoxicity in Gill Erythrocyte Cells of Poecilia reticulata Exposed to a Glyphosate Formulation

Poecilia reticulata were exposed to herbicide Roundup Transorb^® for micronucleus test, nuclear abnormalities and comet assay. The exposure-concentrations were based on CL_50–96 h following 0, 1.41, 2.83, 4.24 and 5.65 μL L^?1 for 24 h. Micronucleus and comets were significantly increased in the gill erythrocyte cells after herbicide exposure compared with the non-exposed group. Results showed a gradual increase in the number of damaged cells, indicating a concentration-dependent effect and that this herbicide was mutagenic and genotoxic to P. reticulata and this effect could be attributed to a combination of compounds contained in the formulation with the active ingredient glyphosate.     

Coordination of hypothalamic and pituitary T3 production regulates TSH expression

Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3′-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback loop, we developed 2 mouse strains with pituitary- and astrocyte-specific D2 knockdown (pit-D2 KO and astro-D2 KO mice, respectively). The pit-D2 KO mice had normal serum T3 and were systemically euthyroid, but exhibited an approximately 3-fold elevation in serum TSH levels and a 40% reduction in biological activity. This was the result of elevated serum T4 that increased D2-mediated T3 production in the MBH, thus decreasing Trh mRNA. That tanycytes, not astrocytes, are the cells within the MBH that mediate T4-to-T3 conversion was defined by studies using the astro-D2 KO mice. Despite near-complete loss of brain D2, tanycyte D2 was preserved in astro-D2 KO mice at levels that were sufficient to maintain both the T4-dependent negative feedback loop and thyroid economy. Taken together, these data demonstrated that the hypothalamic-thyroid axis is wired to maintain normal plasma T3 levels, which is achieved through coordination of T4-to-T3 conversion between thyrotrophs and tanycytes.     

Amphiphilic Antimony(V) Complexes for Oral Treatment of Visceral Leishmaniasis

The need for daily parenteral administration is an important limitation in the clinical use of pentavalent antimonial drugs against leishmaniasis. In this study, amphiphilic antimony(V) complexes were prepared from alkylmethylglucamides (L8 and L10, with carbon chain lengths of 8 and 10, respectively), and their potential for the oral treatment of visceral leishmaniasis (VL) was evaluated. Complexes of Sb and ligand at 1:3 (SbL8 and SbL10) were obtained from the reaction of antimony(V) with L8 and L10, as evidenced by elemental and electrospray ionization-tandem mass spectrometry (ESI-MS) analyses. Fluorescence probing of hydrophobic environment and negative-staining transmission electron microscopy showed that SbL8 forms kinetically stabilized nanoassemblies in water. Pharmacokinetic studies with mice in which the compound was administered by the oral route at 200 mg of Sb/kg of body weight indicated that the SbL8 complex promoted greater and more sustained Sb levels in serum and liver than the levels obtained for the conventional antimonial drug meglumine antimoniate (Glucantime [Glu]). The efficacy of SbL8 and SbL10 administered by the oral route was evaluated in BALB/c mice infected with Leishmania infantum after a daily dose of 200 mg of Sb/kg for 20 days. Both complexes promoted significant reduction in the liver and spleen parasite burdens in relation to those in the saline-treated control group. The extent of parasite suppression (>99.96%) was similar to that achieved after Glu given intraperitoneally at 80 mg of Sb/kg/day. As expected, there was no significant reduction in the parasitic load in the group treated orally with Glu at 200 mg of Sb/(kg day). In conclusion, amphiphilic antimony(V) complexes emerge as an innovative and promising strategy for the oral treatment of VL.     

Thymectomy by partial sternotomy for the treatment of myasthenia gravis

BACKGROUND: Myasthenia gravis is an autoimmune disease characterized by weakness and fatigue of voluntary muscles. Surgical treatment of choice for myasthenia gravis has been thymectomy. However, thymectomy indications and surgical approach are still controversial. The purpose of this study is to evaluate the efficacy of partial median sternotomy approach to the thymus. METHODS: From 1973 to 1999, 478 patients with myasthenia gravis underwent thymectomy through a partial median sternotomy. RESULTS: Sixty-one patients (12.7%) had complete remission of symptoms, 299 (62.5%) had a significant improvement, and 83 (17.4%), a mild improvement; whereas 35 patients (7.4%) had no improvement of clinical symptoms. CONCLUSIONS: Partial median sternotomy has shown to be a useful surgical approach to the thymus, as demonstrated by the good functional and aesthetic results, associated with low morbidity and no mortality.     

Comparison of the photodynamic fungicidal efficacy of methylene blue, toluidine blue, malachite green and low-power laser irradiation alone against Candida albicans

This study was to evaluate specific effects of photodynamic therapy (energy density 15.8 J/cm², 26.3 J/cm² and 39.5 J/cm²) using methylene blue, toluidine blue and malachite green as photosensitizers and low-power laser irradiation on the viability of Candida albicans. Suspensions of C. albicans containing 10⁶ cells/ml were standardized in a spectrophotometer. For each dye, 120 assays, divided into four groups according to the following experimental conditions, were carried out: laser irradiation in the presence of the photosensitizer; laser irradiation only; treatment with the photosensitizer only; no exposure to laser light or photosensitizer. Next, serial dilutions were prepared and seeded onto Sabouraud dextrose agar for the determination of the number of colony-forming units per milliliter (CFU/ml). The results were subjected to analysis of variance and the Tukey test (P < 0.05). Photodynamic therapy using the photosensitizers tested was effective in reducing the number of C. albicans.. The number of CFU/ml was reduced by between 0.54 log₁₀ and 3.07 log₁₀ and depended on the laser energy density used. Toluidine blue, methylene blue and malachite green were effective photosensitizers in antimicrobial photodynamic therapy against C. albicans, as was low-power laser irradiation alone.     

Nitric oxide synthase in retina and optic nerve head of rat with increased intraocular pressure and effect of timolol

We investigated the expression of nitric oxide synthase (NOS) isoforms -1, -2 and -3 in the retina and optic nerve head (ONH) in an experimental rat model of elevated intraocular pressure (IOP) before and after treatment with timolol, to assess whether its neuroprotective action is associated with the activity of these enzymes. Episcleral vein cauterization in unilateral eyes of Wistar rats was performed to produce elevated IOP. Histological sections of retina and ONH from animals with normal IOP, with elevated IOP, and elevated IOP treated with timolol, were studied by immunohistochemistry with antibodies to NOS-1, NOS-2, and NOS-3. In the control rats, NOS-1 was localized to photoreceptor inner segments, amacrine cells and bipolar cells in the retina, and in astrocytes, pericytes and vascular nitrergic terminals in the ONH. NOS-3 immunostaining localized to the endothelial cells. The rats with elevated IOP showed increased expression of NOS-1 in the plexiform layers of the retina and reactive astrocytes in the ONH. These cells also showed NOS-2 positivity. The rats treated with timolol showed reduced expression of NOS-1 in the retina and ONH. NOS-2 was only detected in a few groups of astrocytes in the ONH. NOS-3 was unchanged in both elevated IOP and timolol-treated groups. These results show that excessive levels of NO synthesized by the NOS-1 and -2 isoforms, considered neurotoxic, might contribute to the progressive lesions of retinal ganglion cell axons. Their reduction after treatment suggests a possible neuroprotective effect of timolol in neurons exposed to excessive amounts of NO.     

Prognostic value of 1H-MRS in neonatal encephalopathy

The aim of this study was to determine the prognostic value of proton magnetic resonance spectroscopy in neonatal encephalopathy. Studies were carried out in 11 consecutive term newborns with encephalopathy probably caused by hypoxic-ischemic injury. The clinical evaluation included pregnancy data, labor conditions, encephalopathy grade, presence of seizures, and necessity of antiepileptic drug therapy. Polygraphic recordings were obtained in all cases. Interest areas evaluated by spectroscopy were the basal ganglia and thalami. Among the cases, N-acetylaspartate/creatine, choline/creatine, and lactate/creatine ratios were calculated and related to the clinical variables, polygraphic recordings, and 6-month neurodevelopmental outcome. Abnormal follow-up occurred in 5 of 11 patients (45.4%) and was clearly related to an Apgar score <5 at 5 minutes (P = 0.003), encephalopathy grade (P = 0.02), early neonatal seizures (P = 0.02), and antiepileptic therapy (P = 0.01). No relationship was observed between spectroscopy results and polygraphic recordings profile. The lowest mean N-acetylaspartate/creatine ratio was observed in four of five patients with an adverse outcome and, although not statistically significant, demonstrated a clear trend to unfavorable follow-up (t test = 0.06). The choline/creatine ratios could not be related to follow-up in our sample. The most consistently observed abnormality on the spectra was the presence of the lactate peak in four of five patients with unfavorable outcome, with a high relative risk to determine evolution in the sample, relative risk 7.0 (chi2 = 0.01, 95% confidence interval = 1.1-42.9).     

Anoxic encephalopathy after ultraviolet radiation session: follow-up and results

Anoxic encephalopathy is the consequence of acute cerebral oxygen deprivation usually generated by cardiac arrest and/or respiratory failure. Recently an interesting case of one patient with cerebral anoxia after ultraviolet radiation session has been published. This paper shows the clinical evolution of this patient after inclusion in a multidisciplinary rehabilitation program, which included treatment of the psychopathological, neuropsychological and functional impairments that this pathology often generates. Over successive decades cerebral anoxia has come to be identified principally as one of the most significant causes of an isolated amnesia syndrome. Our patient presented at baseline intense difficulties in every verbal and visual memory processes associated with moderate impairments in sustained, selective and shifting attention as well as temporal disorientation. Compensation of memory deficit was the main rehabilitation strategy used in this case. This rehabilitation approach was possible thanks to the high degree of self-awareness of memory deficits shown by the patient and the selective impairment of memory with partial preservation of the rest of cognitive functions. This particular case gives us the opportunity to show the multidisciplinary approach of cognitive rehabilitation and the process of reintegration to social activities and to productive work even when deficits persist.     

Results of liver transplantation from donors over 75 years: case control study

Introduction

The use of elderly donors can increase the pool of organs available for transplant. The aim of this study was to analyze the outcomes of grafts from donors older than 75 years.

Patients and methods

We selected 29 patients transplanted from January 2003 to January 2010 with livers from donors older than 75 years for comparison with a control group (58 patients), selected among patients transplanted immediately before or after each study case. Data analyzed using SPSS 15.0 were considered statistically significant at P < .05.

Results

Statistically significant differences were evident in the mean age of donors (78.3 ± 2.9 vs 50.4 ± 17.8 years, P < .001), levels of aspartate aminotransferase alanine aminotransferase (30.8 ± 18.13/24.9 ± 14.4 vs 53.81 ± 68.4/39.37 ± 39.94 U/L, P < .05), and waiting list time of (122.4 ± 94.3 vs 169.2 ± 135.5 days, P = .034) of elderly donor versus control graft cohorts. The median follow-up was 32 months (range: 4-88.0) No differences were observed at 1 and 3 years after transplantation: graft survival was 78% and 61% in the older donor group and 83% and 71% in the younger donor group, respectively.

Conclusion

The use of expanded donors from elderly subjects can increase the donor pool with good results.