Morphological changes induced by prolonged darkness in the retinal pigment epithelium of the turtle (Pseudemys scripta elegans)

The retinal pigment epithelium of Vertebrates was shown to be sensitive to cyclic oscillations of light and darkness. The morphological changes induced by prolonged darkness on the retinal epithelial cells of the freshwater turtle were studied, with particular regard to their localization and to their reversibility if animals are recovered under cyclic light. The eyes were processed for light and electron microscopy and a morphological and morphometric analysis was performed on the specimens. After 7 days of prolonged darkness, the vitreal extremity of some epithelial cells was partially detached; on the basal zone the infoldings were missing and vesicles and tubules, often arranged in rows, were observed. After 30 days of prolonged darkness, partial or complete double layers of epithelial cells were present: the superficial layer was connected, by means of the apical fringes, to the photoreceptors, whilst the deepest layer showed vesicles and tubules on its basal zone. After 7 days of recovery to L:D = 12:12, no cyclic activity was demonstrated and only occasional double layers of cells were present; on the basal surface isolated basal infoldings were present where two adjacent cells were joined together. It could be concluded that the detachment of the apical part of some cells, rapidly covered by the lateral sliding of the adjacent cells, and the substitution of the basal infoldings with vesicles and tubules could represent the morphological response of the retinal epithelium to the functional changes induced by prolonged darkness.     

Calpain inhibitor I reduces the development of acute and chronic inflammation

There is limited evidence that inhibition of the activity of the protease calpain I reduces inflammation. Here we investigate the effects of calpain inhibitor I in animal models of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis). We report here for the first time that calpain inhibitor I (given at 5, 10, or 20 mg/kg i.p. in the pleurisy model or at 5 mg/kg i.p every 48 hours in the arthritis model) exerts potent anti-inflammatory effects (eg, inhibition of pleural exudate formation, mononuclear cell infiltration, delayed the development of the clinical signs and histological injury) in vivo. Furthermore, calpain inhibitor I reduced (1) the staining for nitrotyrosine and poly (ADP-ribose) polymerase (immunohistochemistry) and (2) the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated rats and in joints from collagen-treated rats. Thus, prevention of the activation of calpain I reduces the development of acute and chronic inflammation. Inhibition of calpain I activity may represent a novel therapeutic approach for the therapy of inflammation.     

Beneficial effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimetic, in zymosan-induced shock

1 The therapeutic efficacy of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase mimetic which scavenges peroxynitrite, was investigated in rats subjected to shock induced by peritoneal injection of zymosan. 2 Our data show that MnTBAP (given at 1, 3 and 10 mg kg-1 intraperitoneally, 1 and 6 h after zymosan injection) significantly reduce in dose dependent manner the development of peritonitis (peritoneal exudation, high nitrate/nitrite and peroxynitrite plasma levels, leukocyte infiltration and histological examination). 3 Furthermore, our data suggest that there is a reduction in the lung, small intestine and liver myeloperoxidase (MPO) activity and lipid peroxidation activity from MnTBAP-treated rats. 4 MnTBAP also reduced the appearance of nitrotyrosine immunoreactivity in the inflamed tissues. 5 Furthermore, a significant reduction of suppression of mitochondrial respiration, DNA strand breakage and reduction of cellular levels of NAD+ was observed in ex vivo macrophages harvested from the peritoneal cavity of zymosan-treated rat. 6 In vivo treatment with MnTBAP significantly reduced in a dose-dependent manner peroxynitrite formation and prevented the appearance of DNA damage, the decrease in mitochondrial respiration and the loss of cellular levels of NAD+. 7 In conclusion our results showed that MnTBAP was effective in preventing the development of zymosan-induced shock.     

Is the cold loop hysteroscopic technique a myometrial sparing treatment for placenta accreta residuals in a puerperal uterus?

Placenta accreta is a life-threatening obstetric pathology characterized by an abnormal invasion of chorionic villi into the uterine wall. The management represents a challenge for the gynecologist, especially in patients desiring to preserve their fertility. Several methods have been proposed to avoid hysterectomy. A case of a hysteroscopic conservative management with the cold loop technique in a puerpera with a large mass of placenta accreta residuals is described. The chorionic tissue was safely detached and it was subsequently removed by an electric cutting loop. Even in the absence of a clear cleavage plane, the thermal damage of surrounding healthy myometrium and dreadful complications as uterine perforation due to the electric cutting loop were avoided. The cold-loop hysteroscopic resection seems to be a safe and effective choice for the treatment of retained placenta accreta in patients desiring to preserve fertility. Moreover, it can also be proposed to patients who need to be treated immediately after delivery.     

Combination of dexamethasone and etanercept reduces secondary damage in experimental spinal cord trauma

The aim of our study was to evaluate the therapeutic efficacy of combination therapy with etanercept and dexamethasone (DEX) in vivo in experimental murine model of spinal cord trauma, which was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and cytokine production followed by recruitment of other inflammatory cells, production of inflammation mediators, tissue damage, apoptosis and disease. Treatment of the mice with etanercept (1.25 mg/kg) and DEX (0.025 mg/kg) when administered as a combination therapy but not as a single treatment significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) inducible nitric oxide synthase, nitrotyrosine, and cytokines expression (tumor necrosis factor-alpha and interleukin-1 beta), (4) and apoptosis (Terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, Fas-ligand expression and Bax and Bcl-2 expression). In a separate set of experiments we have also clearly demonstrated that the combination therapy significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate for the first time that strategies targeting multiple proinflammatory pathways may be more effective than a single effector molecule for the treatment of spinal cord trauma.     

Fertility preservation after bilateral severe testicular trauma

Dear Editor, Testicular trauma is a frequent acquired cause o fin fertility; being accidents, work injuries and sport activities that are the most common causes of testicular traumas.1＇2 Strangely, the issue of management of serious testicular trauma and fertility preservation has not been studied extensively before, existing only sporadic reports in international literature. Besides, no guidelines exist on fertility preservation in cases of important scrotal trauma when injury may result in irreparable damage to all testicular tissue （torsion of a solitary testis, bilateral synchronous testicular torsion,     

Modeling and biological evaluation of 3,3'-(1,2-ethanediyl)bis[2-(4-methoxyphenyl)-thiazolidin-4-one], a new synthetic cyclooxygenase-2 inhibitor

Within the series of chiral 3,3'-(1,2-ethanediyl)bis[2-arylthiazolidin-4-ones], the 3,4-dimethoxyphenyl substituted derivative was found in the primary anti-inflammatory screening to be endowed with superior in vivo properties and good safety profile. Such a lead compound was modified by eliminating 3-methoxy group while retaining 4-methoxy group on the aryl rings at 2 and 2' stereogenic carbons. The 2R,2'S-meso isomer (VIG3b) of the resulting bisthiazolidinone has been widely investigated. The inhibitory effects on cyclo-oxygenase-1 and cyclo-oxygenase-2 isoenzymes were measured in a human whole blood assay. VIG3b was almost 50 times more selective on the inducible isoform. The cyclo-oxygenase-2 preferential selectivity has been confirmed by modeling VIG3b into the cyclo-oxygenase-1 and cyclo-oxygenase-2 active sites. Furthermore, VIG3b was assayed in the experimental model of carrageenan-induced lung injury by evaluating its ability to inhibit: (1) fluid accumulation in the pleural cavity, (2) neutrophil infiltration, (3) prostaglandin E(2) production and (4) lung injury. VIG3b exhibited interesting activity in all these tests.