Entire hemithorax irradiation for Masaoka stage IVa thymomas

Thymomas are rare neoplasms that have an indolent growth with a preferentially intra-thoracic dissemination pattern. Surgery is currently the standard treatment of thymomas; however radiotherapy is often used in an adjuvant setting due to a high sensitivity of these tumors to such treatment. Postoperative entire hemithoracic irradiation has been used in selected Masaoka stage IVa cases after complete surgical excision of metastatic lesions.In the present article, the authors report three cases of Masaoka stage IVa thymoma that underwent entire hemithorax irradiation after surgical excision of metastatic lesions. The first two patients presented as stage IVa thymomas. The third case consisted of a pleural recurrence of a thymoma.Hemithoracic irradiation with low doses has been used by different authors; the available data shows that it is a well-tolerated treatment that could potentially lead to better loco-regional control and increased overall survival.     

Combining molecular dynamics and docking simulations of the cytidine deaminase from Mycobacterium tuberculosis H37Rv

Cytidine Deaminase (CD) is an evolutionarily conserved enzyme that participates in the pyrimidine salvage pathway recycling cytidine and deoxycytidine into uridine and deoxyuridine, respectively. Here, our goal is to apply computational techniques in the pursuit of potential inhibitors of Mycobacterium tuberculosis CD (MtCDA) enzyme activity. Molecular docking simulation was applied to find the possible hit compounds. Molecular dynamics simulations were also carried out to investigate the physically relevant motions involved in the protein-ligand recognition process, aiming at providing estimates for free energy of binding. The proposed approach was capable of identifying a potential inhibitor, which was experimentally confirmed by IC₅₀ evaluation. Our findings open up the possibility to extend this protocol to different databases in order to find new potential inhibitors for promising targets based on a rational drug design process.     

Insights into the toxicity mechanism of and cell response to the herbicide 2,4-D in plants

Although structurally similar to the natural plant hormone indol-3- acetic acid, auxin herbicides were developed for purposes other than growth, and have been successfully used in agriculture for the last 60 years. Concerted efforts are being made to understand and decipher the precise mechanism of action of IAA and synthetic auxins. Innumerable results need to be interconnected to resolve the puzzle of auxin biology and action mode of auxin herbicides. To date, different breakthroughs are providing more insights into the process of plant-herbicide interactions. Here we highlight some of the latest findings on how the 2,4-dichlorophenoxyacetic acid damages susceptible broadleaf plants, emphasizing the role of ROS as a downstream component of the auxin signal transduction under herbicide treatment.     

Somatostatin action on insulin secretion induced by chicken and porcine vasoactive intestinal peptide in the perfused rat pancreas

The isolated perfused rat pancreas with duodenal exclusion was used to study the stimulation of glucose-induced insulin release in response to chicken and porcine vasoactive intestinal peptide (VIP). The insulin response to 5.5 or 16.7 mM glucose was markedly enhanced by 750 pM porcine VIP and a concentration of 250 pM was still effective. At 250 pM, chicken VIp exhibited a slightly higher potency than porcine VIP at both glucose concentrations. The main difference between the two peptides was that the effect of porcine VIP disappeared immediately after the peptide suppression but tha of chicken VIP persisted for an additional period of 8-10 min. Somatostatin (10 ng/ml) blocked the stimulatory effect of both VIP molecules on glucose-induced insulin secretion. After suppression of VIP and somatostatin from the perfusion medium, insulin release increased to levels higher than those with glucose alone in the case of the avian peptide, but not in that porcine VIP. The data are consistent with previous results in the literature on stimulation of exocrine pancreas secretion and interaction with intestinal epithelium.     

Stimulation of the hydrolytic activity of Na+,K+-ATPase in the erythrocytes by arginine vasopressin

The effects of arginine vasopressin (AVP) on Na+,K+-ATPase activity in human erythrocytes have been studied. AVP stimulates enzymatic activity with no effect on transport activity. Since the enzymatic reaction with AVP can proceed in the absence of ion transport, it may explain the discrepancies between the in vivo and in vitro effects observed with the hormone on Na+ processing by the kidney.     

Renal cortical intermediary metabolism in the recovery phase of postischemic acute renal failure in the dog.

Renal metabolism has been studied in eight dogs before and 48 hr after a 60-min period of renal ischemia induced by clamping the left renal artery with the simultaneous removal of the right kidney, and in 12 sham-operated animals. The study involved the measurement of renal uptake and production of lactate, glutamine, glutamate, alanine, ammonium, and oxygen, and the measurement of the tissue concentrations of ATP, glutamine, lactate, alpha-ketoglutarate, aspartate, and alanine in the renal cortex. Two days after a temporary renal ischemia, the remaining kidney showed a 22% decrease in glomerular filtration rate (GFR) and a 25% decrease in renal plasma flow. Fractional sodium and potassium excretions were similar to those of control dogs. Renal production or extraction of glutamine, glutamate, alanine, ammonium, and oxygen (all expressed by 100 ml of GFR) was not significantly different in basal conditions or 2 days after ischemia, but lactate extraction was reduced in postischemic kidneys (-101 +/- 29 vs -204 +/- 38 mumol/100 ml GFR in control dogs). The cortical concentrations of glutamine and glutamate were lower in postischemic than in control kidneys. No differences were found in cortical concentration of alpha-ketoglutarate, aspartate, lactate, pyruvate, or ATP, but total nucleotides and inorganic phosphate were decreased in postischemic kidneys. It is concluded that in the recovery phase of the ischemia, a decreased lactate uptake is the main metabolic change, and total ATP production is adapted to the decrease of GFR and sodium reabsorption.     

Differences in prolyl-leucyl-glycinamide metabolism by hypothalamus,pituitary and cerebral cortex of male and female rats

l-Prolyl-l-leucyl-glycinamide is rapidly hydrolyzed by hypothalamic, hypophyseal and cortical homogenates from male or female rats. The peptidase activity is higher in the pituitary followed in decreasing order by the hypothalamus and the cerebral cortex. It is mostly localized in the supernatant fraction of a 100,000 g centrifugation and is inhibited by bacitracin.Tissues from female rats are half as active as those from male rats and show variations during the estrous cycle, with very low PLG metabolism at diestrus 1 in pituitary and hypothalamus. In contrast, the cerebral cortex at proestrus and estrus has significant lower hydrolyzing activity than at diestrus. No change of the peptidase activity is observed in tissues from ovariectomized animals after treatment with estrogen or progesterone.The results obtained suggest the existence of a correlation between peptidasic activity and melanotropin secretion.     

Effect of the removal of different endocrine glands upon insulin secretion and B-cell ultrastructure

Glucose-induced insulin secretion and B-cell ultrastructure were studied in islets obtained from normal, adrenalectomized, radiothyroidectomized, ovariectomized and orchidectomized rats. Both parameters were also studied in the same experimental groups submitted to specific substitutive therapy. Insulin secretion in response to high glucose was significantly diminished in adrenalectomized, hypothyroid and male castrated rats. Conversely, this secretion was enhanced in ovariectomized rats. These abnormal insulin responses were restored to normal range by specific substitutive therapy. B-cell ultrastructure was markedly altered in hypothyroid and in female and male castrated rats. No significant changes were observed in the adrenalectomized rats. No conspicuous alterations were depicted in the other islet cell populations. The features of the morphological alterations were mainly related to changes in the B-granules and the rough endoplasmic reticulum. Modifications of the other B-cell organelles were less frequent. In the castrated rats, a distinctive feature was the appearance of a finely granulated colloid material. These B-cell alterations, consecutive to changes in the circulating levels of a given hormone, seemed to depend on the chemical structure of the hormone itself rather than on the changes induced in the B-cell secretory function. The ultrastructural changes described were reversed, as in the case of insulin release, by specific substitutive therapy. It is concluded that changes in the circulating levels of the hormones studied are followed by specific alterations in both B-cell secretion and ultrastructure.