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Voltage dependent anion channels (VDAC) in the outer mitochondrial membrane regulate the influx of metabolites that sustain mitochondrial metabolism and the efflux of ATP to the cytosol. Free tubulin and NADH close VDAC. The VDAC-binding small molecules X1 and SC18 modulate mitochondrial metabolism. X1 antagonizes the inhibitory effect of tubulin on VDAC. SC18 occupies an NADH-binding pocket in the inner wall of all VDAC isoforms. Here, we hypothesized that X1 and SC18 have a synergistic effect with sorafenib, regorafenib or lenvatinib to arrest proliferation and induce death in hepatocarcinoma cells. We used colony formation assays to determine cell proliferation, and a combination of calcein/propidium iodide, and trypan blue exclusion to assess cell death in the well differentiated Huh7 and the poorly differentiated SNU-449 cells. Synergism was assessed using the Chou-Talalay method. The inhibitory effect of X1, SC18, sorafenib, regorafenib and lenvatinib was concentration and time dependent. IC50s calculated from the inhibition of clonogenic capacity were lower than those determined from cell survival. At IC50s that inhibited cell proliferation, SC18 arrested cells in G0/G1. SC18 at 0.25-2 IC50s had a synergistic effect with sorafenib on clonogenic inhibition in Huh7 and SNU-449 cells, and with regorafenib or lenvatinib in SNU-449 cells. X1 or SC18 also had synergistic effects with sorafenib on promoting cell death at 0.5-2 IC50s for SC18 in Huh7 and SNU-449 cells. These results suggest that small molecules targeting VDAC represent a potential new class of drugs to treat liver cancer.

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Macrocyclic lactones are frequently used dewormers in livestock farms around the world. Due to their wide spectrum of action against nematodes and arthropods and their practicality of application at very low doses, their use has become massive since their discovery. These compounds are eliminated in a large percentage in the feces of animals, causing adverse effects on coprophilic fauna. Several research groups around the world have been devoted to evaluating these effects on this fauna. The aim of this review is to register the adverse effects of the concentrations in which macrocyclic lactones are eliminated in the feces of domestic animals and the importance of the coprophilic and edaphilous fauna on the degradation of the feces of the animals. The documented data shows that the use of macrocyclic lactones has a high toxicological risk for the different species that colonize the dung, thus causing an adverse effect on its disintegration and its subsequent incorporation into the soil. Even so, more studies at the regional level and their standardization are necessary to make the comparison between different areas possible.

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Experience gained in the risk assessment (RA) of genetically engineered (GE) crops since their first experimental introductions in the early nineties, has increased the level of familiarity with these breeding methodologies and has motivated several agencies and expert groups worldwide to revisit the scientific criteria underlying the RA process. Along these lines, the need to engage in a scientific discussion for the case of GE crops transformed with similar constructs was recently identified in Argentina. In response to this need, the Argentine branch of the International Life Sciences Institute (ILSI Argentina) convened a tripartite working group to discuss a science-based evaluation approach for transformation events developed with genetic constructs which are identical or similar to those used in previously evaluated or approved GE crops. This discussion considered new transformation events within the same or different species and covered both environmental and food safety aspects. A construct similarity concept was defined, considering the biological function of the introduced genes. Factors like environmental and dietary exposure, familiarity with both the crop and the trait as well as the crop biology, were identified as key to inform a construct-based RA process.

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La adenomatosis erosiva del pezón es un tumor raro y benigno que se origina a partir de los conductores lactíferos del pezón y afecta principalmente a mujeres de mediana edad. Clínicamente se presenta como eritema, costras, erosiones, ulceraciones o nódulos, con o sin exudación serosa o sanguinolenta, pudiendo ser asintomática o presentar prurito, sensibilidad o dolor. La biopsia de piel es necesaria para llegar al diagnóstico, pues clínicamente puede ser indistinguible de la enfermedad de Paget. Histológicamente, su principal diagnóstico diferencial es el de adenocarcinoma de mama. El tratamiento es usualmente quirúrgico. Presentamos el caso de un paciente de 32 años de edad con una lesión inicialmente eritematosa y luego costrosa en el pezón derecho de 8 años de evolución.

Erosive adenomatosis of the nipple is a rare and benign tumor of the lactiferous ducts of the breast that affects primarily middle-aged women. Erythema, crusts, erosions, ulcerations or nodules, with or without serous or bloody discharge, are common clinical findings; pruritus, tenderness or pain may occur or it can be asymptomatic. Since the lesions are clinically indistinguishable from PagetÆs disease of the breast, a skin biopsy is mandatory for diagnosis. Adenocarcinoma of the breast is the main histologically differential diagnosis. Surgical resection is the treatment of choice. We present such a case in a 32-year-old woman with an 8-year history that begun as an erythematous, crusty lesion on her right nipple.

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Abnormally low(131)I uptakes were noticed in dogs fed with commercial diets at the University Animal Clinic in Buenos Aires, but the total iodine content of eight different commercial diets examined was found to provide an iodine intake above daily requirements. To investigate this anomaly, 18 dogs were distributed into three groups, fed either: (1) a home-prepared diet; (2) a commercial diet; (3) a home-prepared diet supplemented with potassium iodide equivalent to that found in the commercial diet. The(131)I uptake in dogs of groups B and C was significantly decreased, as was basal serum thyroxine (T(4)) and free thyroxine (FT(4)), whereas urinary iodide excretion and serum thyroid stimulating hormone (TSH), were increased. The thyroid releasing hormone (TRH)-TSH test showed an increased response in dogs from group B, while the TRH-T(4)test was inhibited in both groups B and C. The results demonstrate that the excessive amount of iodine present in some commercial diets in Argentina causes a significant impairment of thyroid function and hypothyroidism.

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Ketoconazole is an imidazole derivative used as an antimycotic agent with reported effects on the endocrine system, but very little is known about its possible actions on thyroid function. Our purpose was to study the influence of this substance on the basal and TSH-stimulated iodide uptake in the rat thyroid cell strain FRTL-5. Ketoconazole (1-50 mumol/l) was shown to slightly increase the basal iodide uptake but, at higher concentrations (75-100 mumol/l), it sharply decreased iodide uptake below the basal levels. When the cells were cultured under bTSH stimulation (30 UI/l), the inhibitory effect of ketoconazole was exerted at concentrations as low as 25 mumol/l. This inhibition was observed even if it was added to the culture medium immediately before the Na125I addition. Forskolin, a stimulator of adenylate cyclase activity, was unable to prevent the iodide uptake inhibition. Low doses of ketoconazole increased cAMP concentrations. In the presence of TSH this effect was more evident in an inverse dose-dependent way. Because of its dual action, it can be assumed that ketoconazole could influence the iodide uptake in the FRTL-5 cells through more than one mechanism.

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A 12 year old female with three to four annual episodes of respiratory tract infections since age 2 months, was admitted to the hospital with the chief complaint of acute bronchitis. During her hospital stay, the diagnosis of left pulmonary hypoplasia was considered, which was lately confirmed by means of respiratory function tests, chest X-ray films, simple and perfusion gammagraphy as well as bronchography. During the 3 years follow-up, her body growth although below the third percentile for Mexican standards, has had normal annual increments (4.5-5.0 cm/year) and in the last eight months she has grown at a rate of 10.5 cm/year, simultaneously with the initial development of her secondary sexual characteristics. During the follow-up she has had only four minor episodes of respiratory tract infections which have been treated exclusively with symptomatic drugs. She is now under a program of pulmonary physiotherapy. It is concluded that throughout the years the right lung has satisfactorily compensated the initial deficit in pulmonary function and thus, is not only the degree of malformation, but also the complications secondary to it, with has a prognostic value for these patients, along with the supportive general medical management implanted.

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