Role of TNFα in pulmonary pathophysiology

Tumor necrosis factor alpha (TNFα) is the most widely studied pleiotropic cytokine of the TNF superfamily. In pathophysiological conditions, generation of TNFα at high levels leads to the development of inflammatory responses that are hallmarks of many diseases. Of the various pulmonary diseases, TNFα is implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In addition to its underlying role in the inflammatory events, there is increasing evidence for involvement of TNFα in the cytotoxicity. Thus, pharmacological agents that can either suppress the production of TNFα or block its biological actions may have potential therapeutic value against a wide variety of diseases. Despite some immunological side effects, anti-TNFα therapeutic strategies represent an important breakthrough in the treatment of inflammatory diseases and may have a role in pulmonary diseases characterized by inflammation and cell death

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Effect of mild hyperglycemia +/- meta-iodo-benzylguanidine on the radiation response of R3230 Ac tumors.

The effects of glucose or meta-iodo-benzylguanidine (MIBG) on oxygen utilization (QO2) of several tumor cell lines were studied using a Clark-type electrode chamber. For in vivo studies, rats bearing R3230 Ac rat mammary adenocarcinomas were utilized. To evaluate changes in tumor oxygenation induced by glucose or MIBG, intratumoral pO2 and skeletal muscle pO2 were measured using Eppendorf Histography. To find the effect of mild hyperglycemia (i.p., 1 g/kg) +/- MIBG (i.p., 20 mg/kg) on the radiation response, a growth delay assay was used. Glucose alone produced a approximately 20% inhibition of QO2 in several tumor cells we tested except Q7 tumor cells. MIBG inhibited QO2 in R3230 Ac tumors. The median tumor pO2 for glucose + MIBG was increased from 5.3 mm Hg to 13.8 mm Hg. We hypothesized that combined treatment with glucose + MIBG significantly enhanced radiation-induced tumoricidal effects on R3230 Ac tumors, mainly due to reduction in QO2 and increase in tumor pO2

To treat or not to treat: puberty suppression in childhood-onset gender dysphoria

Puberty suppression using gonadotropin-releasing-hormone analogues (GnRHa) has become increasingly accepted as an intervention during the early stages of puberty (Tanner stage 2-3) in individuals with clear signs of childhood-onset gender dysphoria. However, lowering the age threshold for using medical intervention for children with gender dysphoria is still a matter of contention, and is more controversial than treating the condition in adolescents and adults, as children with gender dysphoria are more likely to express an unstable pattern of gender variance. Furthermore, concerns have been expressed regarding the risks of puberty suppression, which are poorly understood, and the child's ability to make decisions and provide informed consent. However, even if the limited data available mean that it is not possible to make a conclusive treatment recommendation, some safety criteria for puberty suppression can be identified and applied