Gastroesophageal infection caused by cytomegalovirus in immunodepressed patients. Presentation of 3 cases]

We report three cases of upper gastrointestinal infection by Cytomegalovirus in immunocompromised patients. Two patients suffered from AIDS and the other one had a recent heart transplantation and was on immunodepressant drugs for an episode of rejection. The stomach in two cases and the esophagus in the other were the affected organs. In all cases there were upper gastrointestinal symptoms and the diagnosis was established by biopsy of endoscopically suspicious lesions. Antiviral therapy was effective in all three cases. This diagnosis has to be considered whenever immunocompromised patients present with unusual clinical and endoscopic findings.     

Protection against selenite cataract in rat lens by drevogenin D, a triterpenoid aglycone from Dregea volubilis

Dregea volubilis is a woody climbing plant commonly found in the hotter parts of India. The leaves are edible and used as a green vegetable, while the plant extract has been used traditionally to treat several diseases including eye ailments. Drevogenin D is a triterpenoid aglycone that has been isolated, purified, and characterized as an active component from the leaves of D. volubilis. In this study, drevogenin D was evaluated for antioxidant and potential anticataractogenic activity in an in vitro model. 1,1-Diphenyl-2-picrylhydrazyl radical and superoxide radical scavenging activities of drevogenin D were studied and found to exhibit a 50% inhibitory concentration of 43 microg/mL and 200.6 microg/mL, respectively. Normal rat lenses cultured in 0.1 mM sodium selenite-supplemented medium were used as the experimental model for this study. Selenite-induced models are excellent mimics of oxidative stress induced cataract. Treatment with drevogenin D at a concentration of 50 microg/mL medium was found to reverse the level of activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, elevate the level of reduced glutathione and protein sulfhydryl, and lower the level of lipid peroxidation as indicated by the concentration of thiobarbituric acid-reacting substances. These results indicate good antioxidant activity and potential anticataractogenic activity for drevogenin D against selenite-induced cataractous changes, which have been reported for the first time.     

Changes in homologous and heterologous gap junction contacts during maturation-inducing hormone-dependent meiotic resumption in ovarian follicles of Atlantic croaker

Homologous (granulosa cell-granulosa cell) gap junction (GJ) contacts increase in ovarian follicles of Atlantic croaker (Micropogonias undulatus) during the early (first) stage of maturation, but their profile during the second stage [i.e., during maturation-inducing hormone (MIH)-mediated meiotic resumption] is unknown. The profile of homologous GJ contacts during the second stage of maturation in croaker follicles was examined in this study and compared to that of heterologous (granulosa cell-oocyte) GJ, for which changes have been previously documented. Follicles were incubated with human chorionic gonadotropin to induce maturational competence (first stage), and then with MIH to induce meiotic resumption. The follicles were collected for examination immediately before and after different durations of MIH exposure until the oocyte had reached the stage of germinal vesicle breakdown (GVBD; index of meiotic resumption). Ultrathin sections were observed by transmission electron microscopy, and homologous and heterologous GJ contacts were quantified along a 100-microm segment of granulosa cell-zona radiata complex per follicle (three follicles/time/fish, n=3 fish). Relatively high numbers of both types of GJ were observed before and after the first few hours of MIH exposure (up to the stage of oil droplet coalescence). GJ numbers declined during partial yolk globule coalescence (at or near GVBD) and were just under 50% of starting values after the completion of GVBD (P<0.05). These results confirm earlier observations that GVBD temporally correlates with declining heterologous GJ contacts, and for the first time in teleosts show that there is a parallel decline in homologous GJ. The significance of the changes in homologous and heterologous GJ is uncertain and deserves further study.     

Disulfiram (DSF) acts as a copper ionophore to induce copper‐dependent oxidative stress and mediate anti‐tumor efficacy in inflammatory breast cancer

Cancer cells often have increased levels of reactive oxygen species (ROS); however, acquisition of redox adaptive mechanisms allows for evasion of ROS‐mediated death. Inflammatory breast cancer (IBC) is a distinct, advanced BC subtype characterized by high rates of residual disease and recurrence despite advances in multimodality treatment. Using a cellular model of IBC, we identified an oxidative stress response (OSR) signature in surviving IBC cells after administration of an acute dose of an ROS inducer. Metagene analysis of patient samples revealed significantly higher OSR scores in IBC tumor samples compared to normal or non‐IBC tissues, which may contribute to the poor response of IBC tumors to common treatment strategies, which often rely heavily on ROS induction. To combat this adaptation, we utilized a potent redox modulator, the FDA‐approved small molecule Disulfiram (DSF), alone and in combination with copper. DSF forms a complex with copper (DSF‐Cu) increasing intracellular copper concentration both in vitro and in vivo, bypassing the need for membrane transporters. DSF‐Cu antagonized NFκB signaling, aldehyde dehydrogenase activity and antioxidant levels, inducing oxidative stress‐mediated apoptosis in multiple IBC cellular models. In vivo, DSF‐Cu significantly inhibited tumor growth without significant toxicity, causing apoptosis only in tumor cells. These results indicate that IBC tumors are highly redox adapted, which may render them resistant to ROS‐inducing therapies. DSF, through redox modulation, may be a useful approach to enhance chemo‐ and/or radio‐sensitivity for advanced BC subtypes where therapeutic resistance is an impediment to durable responses to current standard of care.