Thioredoxin Interacting Protein (TXNIP) mediates retinal inflammation, gliosis, and apoptosis in experimental diabetes. Here, we investigate the temporal response of Muller glia to high glucose (HG) and TXNIP expression using a rat Muller cell line (rMC1) in culture. We examined if HG-induced TXNIP expression evokes host defense mechanisms in rMC1 in response to metabolic abnormalities. HG causes sustained up-regulation of TXNIP (2 h to 5 days), ROS generation, ATP depletion, ER stress, and inflammation. Various cellular defense mechanisms are activated by HG: (i) NLRP3 inflammasome, (ii) ER stress response (sXBP1), (iii) hypoxic-like HIF-1α induction, (iv) autophagy/mitophagy, and (v) apoptosis. We also found in vivo that streptozocin-induced diabetic rats have higher retinal TXNIP and innate immune response gene expression than normal rats. Knock down of TXNIP by intravitreal siRNA reduces inflammation (IL-1β) and gliosis (GFAP) in the diabetic retina. TXNIP ablation in vitro prevents ROS generation, restores ATP level and autophagic LC3B induction in rMC1. Thus, our results show that HG sustains TXNIP up-regulation in Muller glia and evokes a program of cellular defense/survival mechanisms that ultimately lead to oxidative stress, ER stress/inflammation, autophagy and apoptosis. TXNIP is a potential target to ameliorate blinding ocular complications of diabetic retinopathy.

Previous studies have shown that latent respiratory pathways can be activated by as phyxia or systemic theophylline administration to restore function to a hemidiaphragm paralyzed by C2 spinal cord hemisection in adult female rats. Based on this premise, electrophysiologic recording techniques were employed in the present investigation to first determine qualitatively whether latent respiratory pathways are activated spon taneously following prolonged post hemisection periods (4-16 weeks) without any therapeutic intervention. Our second objective in a separate group of hemisected an imals was to quantitate any documented functional recovery under the following stan dardized recording conditions: bilateral vagotomy, paralysis with pancuronium bro mide, artificial ventilation, and constant PCO 2 (maintained at 25 mmHg).

Summary: Spinal cord injury (SCI) often leads to an impairment of the respiratory system. The more rostral the level of injury, the more likely the injury will affect ventilation. In fact, respiratory insufficiency is the number one cause of mortality and morbidity after SCI. This review highlights the progress that has been made in basic and clinical research, while noting the gaps in our knowledge. Basic research has focused on a hemisection injury model to examine methods aimed at improving respiratory function after SCI, but contusion injury models have also been used. Increasing synaptic plasticity, strengthening spared axonal pathways, and the disinhibition of phrenic motor neurons all result in the activation of a latent respiratory motor pathway that restores function to a previously paralyzed hemidiaphragm in animal models. Human clinical studies have revealed that respiratory function is negatively impacted by SCI. Respiratory muscle training regimens may improve inspiratory function after SCI, but more thorough and carefully designed studies are needed to adequately address this issue. Phrenic nerve and diaphragm pacing are options available to wean patients from standard mechanical ventilation. The techniques aimed at improving respiratory function in humans with SCI have both pros and cons, but having more options available to the clinician allows for more individualized treatment, resulting in better patient care. Despite significant progress in both basic and clinical research, there is still a significant gap in our understanding of the effect of SCI on the respiratory system.

Abstract. We have examined transport, sites of photosensitization, and plasma protein binding by sulfonated derivatives of tetraphenylporphine in vitro and tumor localization of these products in vivo. Studies carried out in culture indicate that the mono‐sulfonated porphyrin sensitized mainly at intracellular loci while drugs with 2 or 3 sulfonates caused photodamage at membrane sites. But the number and distribution of sulfonates were majors factor in both accumulation and efficiency of photodamage. The product with 2 adjacent sulfonates was the most potent photosensitizer; the presence of more or fewer sulfonate residues led to reduced uptake and sensitization. Steady‐state accumulation of drugs with one, two (opposite), three or four sulfonates was rapid, while uptake of the disulfonated (on adjacent rings) porphine was slower. Products bearing one to four sulfonates localized equally well in vivo, but sites of localization varied considerably. Drugs with one sulfonate, or two sulfonates on adjacent rings partitioned into neoplastic cells, analogs with two (opposite), three or four sulfonates partitioned to tumor stroma. Plasma binding studies show that drugs with one or two (adjacent) sulfonates bound to VLDL, LDL and HDL components of plasma, while the tri and tetra‐sulfonated analogs bound progressively more to albumin. These results suggest that tumor localization can occur via two pathways: one mediated by lipoprotein binding and leading to dye accumulation in neoplastic cells, another associated with albumin binding and leading to dye accumulation in stromal elements of neoplastic tissues.