Prevention of sclerosis around cannulated screw after treatment of femoral neck fractures with bioceramic nails: a finite element analysis.

PURPOSE: Conventional cannulated screws (CS) are the main treatment method for femoral neck fractures (FNF). However, the rate of femoral head necrosis remains high after FNF treatment. The study aimed to compare the biomechanical features of different internal fixation materials for the treatment of Pauwel type III FNF to explore new strategies for clinical management. METHODS: A new material was prepared by applying casting, freeze drying and sintering process. The independently developed calcium magnesium silicate ceramic powder and hydrogel solution were evenly mixed to obtain a high-viscosity bio-ink, and a bioceramic nail (BN) with high mechanical strength and high fracture toughness was successfully prepared. Four internal fixations were developed to establish the Pauwel type III FNF and healed fracture finite element models: A, three CSs; B, three BNs; C, two BNs and one CS; D, one BN and two CSs. Von Mises stress and displacement of the implants and femur were observed. RESULTS: The measured Mg content in ceramic powder was 2.08 wt%. The spectral data confirmed that the ceramic powder has high crystallinity, which coincides with the wollastonite-2 M (PDF# 27-0088). The maximum von Mises stresses for the four models were concentrated in the lower part of the fracture surface, at 318.42 Mpa, 103.52 MPa, 121.16 MPa, and 144.06 MPa in models A, B, C, and D, respectively. Moreover, the maximum Von-mises stresses of the implants of the four models were concentrated near the fracture end at 243.65 MPa (A) and 58.02 MPa (B), 102.18 MPa (C), and 144.06 MPa (D). The maximum displacements of the four models were 5.36 mm (A), 3.41 mm (B), 3.60 mm (C), and 3.71 mm (D). The displacements of the three models with BNs were similar and smaller than that of the triple CS fracture model. In the fracture healing models with and without three CSs, the greatest stress concentration was scattered among the lowest screw tail, femoral calcar region, and lateral femur shaft. The displacement and stress distributions in both models are generally consistent. The stress distribution and displacement of the three healed femoral models with BNs were essentially identical to the healing models with three CSs. The maximum von Mises stresses were 65.94 MPa (B), 64.61 MPa (C), and 66.99 MPa (D) while the maximum displacements of the three healed femoral models were 2.49 mm (B), 2.56 mm (C), and 2.49 mm (D), respectively. CONCLUSIONS: Bioceramic nails offer greater advantages than conventional canulated screws after femoral neck fractures. However, the combination of bioceramic nails and CSs is more clinically realistic; replacing all internal fixations with bioceramic nails after the healing of femoral neck fractures can solve the problem of sclerosis formation around CSs and improve bone reconstruction by their bioactivity.

Rac1 GTPase Inhibition Blocked Podocyte Injury and Glomerular Sclerosis during Hyperhomocysteinemia via Suppression of Nucleotide-Binding Oligomerization Domain-Like Receptor Containing Pyrin Domain 3 Inflammasome Activation.

Elevated homocysteine (Hcy) levels have been shown to activate nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome leading to podocyte dysfunction and glomerular injury. However, it remains unclear how this inflammasome activation in podocytes is a therapeutic target for reversal of glomerular injury and ultimate sclerosis. The present study tested whether inhibition of Rac1 GTPase activity suppresses NLRP3 inflammation activation and thereby blocks podocyte injury induced by elevated Hcy. In cultured podocytes, we found that L-Hcy (the active Hcy form) stimulated the NLRP3 inflammasome formation, as shown by increased colocalization of NLRP3 with apoptosis-associated speck-like protein (ASC) or caspase-1, which was accompanied by increased interleukin-1ß production and caspase-1 activity, indicating NLRP3 inflammasome activation. Rac1 activator, uridine triphosphate (UTP), mimicked L-Hcy-induced NLRP3 inflammasome activation, while Rac1 inhibitor NSC23766 blocked it. This Rac1 inhibition also prevented L-Hcy-induced podocyte dysfunction. All these effects were shown to be mediated via lipid raft redox signaling platforms with nicotinamide adenine dinucleotide phosphate oxidase subunits and consequent O2- production. In animal studies, hyperhomocysteinemia (hHcy) induced by folate-free diet was shown to induce NLRP3 inflammasome formation and activation in glomeruli, which was also mimicked by UTP and inhibited by NSC23766 to a comparable level seen in Nlrp3 gene knockout mice. These results together suggest that Rac1 inhibition protects the kidney from hHcy-induced podocyte injury and glomerular sclerosis due to its action to suppress NLRP3 inflammasome activation in podocytes.

IL-33-Mediated Expansion of Type 2 Innate Lymphoid Cells Protects from Progressive Glomerulosclerosis.

Innate lymphoid cells (ILCs) have an important role in the immune system's response to different forms of infectious and noninfectious pathologies. In particular, IL-5- and IL-13-producing type 2 ILCs (ILC2s) have been implicated in repair mechanisms that restore tissue integrity after injury. However, the presence of renal ILCs in humans has not been reported. In this study, we show that ILC populations are present in the healthy human kidney. A detailed characterization of kidney-residing ILC populations revealed that IL-33 receptor-positive ILC2s are a major ILC subtype in the kidney of humans and mice. Short-term IL-33 treatment in mice led to sustained expansion of IL-33 receptor-positive kidney ILC2s and ameliorated adriamycin-induced glomerulosclerosis. Furthermore, the expansion of ILC2s modulated the inflammatory response in the diseased kidney in favor of an anti-inflammatory milieu with a reduction of pathogenic myeloid cell infiltration and a marked accumulation of eosinophils that was required for tissue protection. In summary, kidney-residing ILC2s can be effectively expanded in the mouse kidney by IL-33 treatment and are central regulators of renal repair mechanisms. The presence of ILC2s in the human kidney tissue identifies these cells as attractive therapeutic targets for CKD in humans.

Hippocampal Sclerosis: Causes and Prevention.

Hippocampal sclerosis is the commonest cause of drug-resistant epilepsy in adults, and is associated with alterations to structures and networks beyond the hippocampus.In addition to being a cause of epilepsy, the hippocampus is vulnerable to damage from seizure activity. In particular, prolonged seizures (status epilepticus) can result in hippocampal sclerosis. The hippocampus is also vulnerable to other insults including traumatic brain injury, and inflammation. Hippocampal sclerosis can occur in association with other brain lesions; the prevailing view is that it is probably a secondary consequence. In such instances, successful surgical treatment usually involves the resection of both the lesion and the involved hippocampus. Experimental data have pointed to numerous neuroprotective strategies to prevent hippocampal sclerosis. Initial neuroprotective strategies aimed at glutamate receptors may be effective, but later, metabolic pathways, apoptosis, reactive oxygen species, and inflammation are involved, perhaps necessitating the use of interventions aimed at multiple targets. Some of the therapies that we use to treat status epilepticus may neuroprotect. However, prevention of neuronal death does not necessarily prevent the later development of epilepsy or cognitive deficits. Perhaps, the most important intervention is the early, aggressive treatment of seizure activity, and the prevention of prolonged seizures.

[An experimental study of the effectiveness of the drug afalaza in chronic aseptic prostatitis].

A pilot study evaluated the efficacy of the drug afalaza (mixture of affinity purified antibodies to PSA and endothelial NO-synthase) compared with the Serenoa repens extract in a model of chronic abacterial prostatitis in Wistar rats caused by suturing of prostate tissue by silk thread. Except for the animals of intact group, rats (n = 13 in each group) underwent intraperitoneal injection of distilled water (10 ml/kg), afalaza (at a doses of 5, 7.5 and 10 ml/kg) or an Serenoa repens extract (50 mg/kg) 1 month after surgery for 45 days. After infusion, the mass, volume, and prostate weighting factor were evaluated, and prostate tissue was examined histologically. 2.5 months after surgery, development of chronic abacterial prostatitis was observed in the control group. Compared with intact group, significant increase in weight, weighting factor, and volume of prostate were detected in control group. Against the background of administration of Serenoa repens extract and afalaza, these parameters were not significantly different from control values. The use of Serenoa repens extract prevented the development of atrophic processes and slowed the development of sclerotic processes. Administration of afalaza at all studied doses prevented the development of sclerotic changes, and a dose of 7.5 ml/kg prevented the development of atrophic processes with the effectiveness matching to Serenoa repens extract. Taking into account the high safety of afalaza, this drug is a promising treatment for chronic prostatitis.

Radiofrequency ablation as a possible method for preparing pathologically altered myocardium for intramyocardial cell transplantation.

We studied the effects of radiofrequency ablation on the results of intramyocardial transplantation of bone marrow NSC into the myocardium of rats with postinfarction cardiosclerosis. It was shown that exposure of the pathologically changed myocardium to radiofrequency radiation led to destruction of formed connective tissue. Transplantation of MSC into sites exposed to radiofrequency radiation promoted the development of regenerative processes (abundant infiltration with mononuclear cells, presence of granulation tissue, and numerous newly formed blood vessels). We concluded that preliminary radiofrequency irradiation of the myocardial areas promotes realization of the regenerative potential of cell transplantation.

Review of the literature and description of a case of sclerosing encapsulating peritonitis requiring home parenteral nutrition.

We present a case of a 48 year old HIV patient, who had recurrent episodes of ascites since 2007. His history includes ischaemic heart disease, for which he was treated with atenolol from 2005 to 2007, and Type 2 diabetes; he was later started on propranolol 40  mg twice a day from 2007 for Didanosine-induced portal hypertension. Because of negative cultures and neutrophil count < 250 cells/µL, spontaneous bacterial peritonitis was excluded. However, some low grade-peritoneal irritation cannot be ruled out because his CRP varied from 24 to 258, during 2007 - 2009, without any other obvious inflammatory cause. He was finally diagnosed in July 2009 with sclerosing encapsulating peritonitis (SEP) based on clinical features of intestinal obstruction, histology and imaging, including computed tomography and magnetic resonance imaging. Propranolol was stopped in November 2009.  Because of the patient's severe intestinal obstruction, he was started on parenteral nutrition 2  L/day. Since then, his CRP has returned to normal levels and there is a great improvement of his clinical features. This case demonstrates beta-blockers as a potential cause of SEP, while the presence of some low-grade peritoneal inflammation leading to SEP is also very likely.

A low-protein diet supplemented with ketoacids plays a more protective role against oxidative stress of rat kidney tissue with 5/6 nephrectomy than a low-protein diet alone.

Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids have been evaluated in CKD patients during restricted-protein diets. The objective of the present study was to compare the efficacy of a low-protein diet supplemented with ketoacids (LPD+KA) and a low-protein diet alone (LPD) in halting the development of renal lesions in CKD. 5/6 Nephrectomy Sprague-Dawley rats were randomly divided into three groups, and fed with either 22 % protein (normal-protein diet; NPD), 6 % protein (LPD) or 5 % protein plus 1 % ketoacids (LPD+KA) for 24 weeks. Sham-operated rats were used as controls. Each 5/6 nephrectomy group included fifteen rats and the control group included twelve rats. Proteinuria, decreased renal function, glomerular sclerosis and tubulointerstitial fibrosis were found in the remnant kidneys of the NPD group. Protein restriction ameliorated these changes, and the effect was more obvious in the LPD+KA group after 5/6 nephrectomy. Lower body weight and serum albumin levels were found in the LPD group, indicating protein malnutrition. Lipid and protein oxidative products were significantly increased in the LPD group compared with the LPD+KA group. These findings indicate that a LPD supplemented with ketoacids is more effective than a LPD alone in protecting the function of remnant kidneys from progressive injury, which may be mediated by ketoacids ameliorating protein malnutrition and oxidative stress injury in remnant kidney tissue.

Neuroprotective effects and improvement of learning and memory elicited by erythravine and 11α-hydroxy-erythravine against the pilocarpine model of epilepsy.

Deficits in cognitive functions are often observed in epileptic patients, particularly in temporal lobe epilepsy (TLE). Evidence suggests that this cognitive decline can be associated with the occurrence of focal brain lesions, especially on hippocampus and cortex regions. We previously demonstrated that the erythrinian alkaloids, (+)-erythravine and (+)-11α-hydroxy-erythravine, inhibit seizures evoked in rats by different chemoconvulsants. AIMS: The current study evaluated if these alkaloids would be acting in a neuroprotective way, reducing hippocampal sclerosis, and consequently, improving learning/memory performance. MAIN METHODS: Here we confirmed the anticonvulsant effect of both alkaloids by means of the pilocarpine seizure-induced model and also showed that they enhanced spatial learning of rats submitted to the Morris Water Maze test reverting the cognition deficit. Additionally, immunohistochemistry assays showed that neuronal death and glial activation were prevented by the alkaloids in the hippocampus CA1, CA3 and dentate gyrus regions at both hemispheres indistinctly 15 days after status epilepticus induction. KEY FINDINGS: Our results show, for the first-time, the improvement on memory/learning elicited by these erythrinian alkaloids. Furthermore, data presented herein explain, at least partially, the cellular mechanism of action of these alkaloids. Together, (+)-erythravine and (+)-11α-hydroxy-erythravine seem to be a promising protective strategy against TLE, comprising three main aspects: neuroprotection, control of epileptic seizures and cognitive improvement. SIGNIFICANCE: Moreover, our findings on neuroprotection corroborate the view that seizure frequency and severity, hippocampal lesions and memory deficits are interconnected events.

Rapamycin inhibits PAI-1 expression and reduces interstitial fibrosis and glomerulosclerosis in chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is characterized by deposition of extracellular matrix (ECM) in all renal compartments. PAI-1 seems to play a pivotal role in ECM turnover in CAN. Rapamycin has been shown to improve long-term graft survival in patients with CAN. The aim of the study was to evaluate the molecular mechanisms underlying the beneficial effects of rapamycin on CAN progression at glomerular and tubulointerstitial level. METHODS: After a biopsy-proven CAN diagnosis (T0), 18 patients on calcineurin inhibitors (CNI) were randomly assigned in a 2:1 ratio to continue CNI (6 patients) or to receive rapamycin (RAPA; 12 patients). After 2 years of treatment (T24), all patients underwent a second renal biopsy. Morphometric analysis was conducted at T0 and at T24. PAI-1 expression was evaluated at T0 and T24 by immunohistochemistry. We evaluated the effect of rapamycin on PAI-1 gene expression in cultured proximal tubular cells incubated with CD40L or thrombin, two potential CAN pathogenic mediators. RESULTS: The RAPA group showed a significant regression of glomerulosclerotic lesions and only a 26% increase in interstitial fibrosis after 2 years compared to baseline, whereas the CNI group showed progression of glomerulosclerosis and 112% increase in fibrosis. Glomerular and tubulointerstitial PAI-1 expression was reduced compared to the baseline in the RAPA group, while they were unchanged in the CNI group. In vitro data showed that rapamycin significantly reduced PAI-1 gene expression induced by both CD40L and thrombin in proximal tubular epithelial cells. CONCLUSIONS: These data suggest that rapamycin may modulate ECM deposition in CAN reducing PAI-1 expression.

Porphyrin-Based SOD Mimic MnTnBu OE -2-PyP5+ Inhibits Mechanisms of Aortic Valve Remodeling in Human and Murine Models of Aortic Valve Sclerosis.

Background Aortic valve sclerosis ( AVS c), the early asymptomatic presentation of calcific aortic valve (AV) disease, affects 25% to 30% of patients aged >65 years. In vitro and ex vivo experiments with antioxidant strategies and antagonists of osteogenic differentiation revealed that AVS c is reversible. In this study, we characterized the underlying changes in the extracellular matrix architecture and valve interstitial cell activation in AVSc and tested in vitro and in vivo the activity of a clinically approved SOD (superoxide dismutase) mimic and redox-active drug MnTnBu OE -2-PyP5+ ( BMX -001). Methods and Results After receiving informed consent, samples from patients with AVS c, AV stenosis, and controls were collected. Uniaxial mechanical stimulation and in vitro studies on human valve interstitial cells were performed. An angiotensin II chronic infusion model was used to impose AV thickening and remodeling. We characterized extracellular matrix structures by small-angle light scattering, scanning electron microscopy, histology, and mass spectrometry. Diseased human valves showed altered collagen fiber alignment and ultrastructural changes in AVS c, accumulation of oxidized cross-linking products in AV stenosis, and reversible expression of extracellular matrix regulators ex vivo. We demonstrated that MnTnBu OE -2-PyP5+ inhibits human valve interstitial cell activation and extracellular matrix remodeling in a murine model (C57 BL /6J) of AVS c by electron microscopy and histology. Conclusions AVS c is associated with architectural remodeling despite marginal effects on the mechanical properties in both human and mice. MnTnBu OE -2-PyP5+ controls AV thickening in a murine model of AVS c. Because this compound has been approved recently for clinical use, this work could shift the focus for the treatment of calcific AV disease, moving from AV stenosis to an earlier presentation ( AVS c) that could be more responsive to medical therapies.

The effect of caffeic acid phenethyl ester on the prevention of experimentally induced myringosclerosis.

OBJECTIVES: Myringosclerosis is a common sequela of ventilation tube insertion for the treatment of the otitis media with effusion. Several antioxidants have been identified to prevent myringosclerosis. The objective of this study was to investigate the effect of caffeic acid phenethyl ester (CAPE) on the prevention of experimentally induced myringosclerosis. METHODS: Thirty-five Sprague-Dawley rats were unilaterally myringotomized. The rats were divided into four groups randomly: group 1 received no treatment, group 2 received intraperitoneally administered saline and group 3 received intraperitoneally administered CAPE. The tympanic membranes were examined by otomicroscopy on the 15th day after treatment. The membranes were then harvested and evaluated histologically by light microscopy. RESULTS: The tympanic membranes from group 1 showed extensive myringosclerosis; those from group 2 showed a similar occurrence of myringosclerosis. However, group 3 had a reduced occurrence of myringosclerosis by otomicroscopic evaluation. Under light microscopic examination, the lamina propria of the pars tensa was found to be thicker and more sclerotic in groups 1 and 2 when compared with group 3. CONCLUSIONS: Systemic treatment with CAPE was found to be effective in the prevention of sclerotic lesions in myringotomized rat tympanic membranes.

Calorie restriction protects against age-related rat aorta sclerosis.

Many theories have been advanced to account for the ageing process, among which the free radical theory deserves much attention. Numerous studies have also shown an association between tissue fibrosis and oxidative stress. Of note, fibrosis may be considered a significant index of tissue ageing. Calorie restriction (CR) has been demonstrated to maintain many physiological processes in a youthful state until a very advanced age. However the anti-ageing mechanisms of CR are still not fully understood. We thus evaluated the effect of CR on oxidative damage and its relationship with fibrosis during ageing. We found a significant increase of both oxidative stress and fibrosis parameters in the aortae from aged vs. young rats. CR reversed both phenomena. CR also protected against the age-associated increase of Jun-N-terminal kinase and p-38 activities, involved in TGFbeta1 expression and signaling. On the contrary, extracellular regulated kinases did not show any age-related change. CR similarly reversed the age-related increase of AP-1 DNA binding activity and the AP-1-dependent increase of vimentin gene expression. In parallel, CR reversed the age-related morphological alterations of the aorta wall cell composition. These data further support the relationship between oxidative stress and fibrosis in different diseases and during ageing. The protection exerted by CR against fibrosclerosis might be due to a decrease of oxidative stress, with consequent decreased MAPK activity and down-regulation of AP-1 activation and of TGFbeta1 expression and signaling.

Vitamin e-coated tympanostomy tube insertion decreases the quantity of free radicals in tympanic membrane.

OBJECTIVE: Tympanosclerosis is a common sequela of ventilation tube treatment of otitis media with effusion causing hearing disability. It is associated with an increased production of free radicals (also known as reactive oxygen species) after myringotomy. Vitamin E is a scavenger of different free radicals by working as an antioxidant. The aim of the present study was to evaluate the effect of vitamin E-coated tympanostomy tube insertion at quantity of free radicals in rat tympanic membrane. METHODS: This prospective, controlled animal study consisted of male Sprague-Dawley rats divided into two groups of 10 animals each. Ordinary silcone tubes were applied to the right ears of the first group and vitamin E-coated silcone tubes were applied to the right ears of the second group. The left ears were used as controls. Then, the animals were killed and chemiluminescence measurements were made for tympanic membranes. RESULTS: Reactive oxygen species levels (ROS) were significantly increased in right ears of the first group when compared with the control ears (P < .0001), and the levels were statistically significant decreased in right ears of the second group as compared with the operated ears of the first group (P < .0001). The free radical levels of right and left ears in the second group were similar. CONCLUSIONS: Our results indicate that vitamin E-coated tube insertion decreases the quantity of reactive oxygen species in tympanic membrane after myringotomy and tympanostomy tube insertion.

The anti-oxidant effect of alpha-tocopherol in the prevention of experimentally induced myringosclerosis.

HYPOTHESIS: The objective of this study was to investigate the possible effect of alpha-tocopherol on the prevention of experimentally induced myringosclerosis. BACKGROUND: Myringosclerosis is a common sequela of ventilation tube treatment of otitis media with effusion. The relationship between oxygen-derived free radicals and occurrence of myringosclerosis has been proven in experimental models, and it was also shown that the formation of myringosclerosis after experimental myringotomy could be reduced by application of various free radical scavengers. METHODS: Eighteen Wistar albino rats were myringotomized on the left side and randomly separated into two groups: group A consisted of rats which received intramuscular alpha-tocopherol injections 100 mg/kg daily and group B which were injected with physiological serum only. The occurrence of myringosclerotic plaques in the tympanic membranes of the two groups was compared by otomicroscopy, histopathology, and tympanometry, which is a novel method of quantification. Blood samples were collected for biochemical evaluation, and the tympanic membranes were harvested on the 15th day of the experiment. RESULTS: In otomicroscopic evaluation, tympanic membranes in group B revealed varying degrees of myringosclerotic plaques; on the other hand, tympanic membranes in group A showed faint or no existence of myringosclerosis. The mean malondialdehyde levels were 1.33 +/- 0.11 micromol/L in group A and 7.49 +/- 1.37 micromol/L in group B (Z = -1.906, p = 0.057). In all ears from group B, the magnitude of the maximum admittance measured by tympanometry reduced to approximately 40% of the values obtained from group A (Z = -2,160, p = 0.031). The mean magnitude of the maximum admittance from group A was very close to the standardization values of Wistar albino rats, which predicts a functional outcome. CONCLUSION: The formation of myringosclerosis after experimental myringotomy can be diminished by intramuscular alpha-tocopherol injections.

Nonvitrectomizing vitreous surgery for epiretinal membrane long-term follow-up.

PURPOSE: To report the long-term follow-up results of nonvitrectomizing vitreous surgery for idiopathic epiretinal membrane (ERM). DESIGN: Nonrandomized comparative case series. PARTICIPANTS: Thirty patients were followed up for at least 5 years after nonvitrectomizing vitreous surgery. INTERVENTION: Epiretinal membranes were peeled without infusion of balanced salt solution and removal of the vitreous. The data from the fellow eye was the control data. MAIN OUTCOME MEASURES: We examined the visual acuities (VAs), objective refractions, and slit-lamp and Scheimpflug photographs from the preoperative and the final examinations of both eyes. Quantitative assessment of the progression of nuclear sclerosis was performed by densitometry analysis using Scheimpflug photography. The recurrence rate of ERM was determined. RESULTS: The follow-up periods ranged from 60 to 102 months (mean+/-standard deviation, 72.2+/-11.0 months). The patient ages ranged from 52 to 76 years (68.8+/-6.3 years). The final VA improved or stabilized within 2 lines in 29 of 30 eyes (96.7%). No unilateral progression of nuclear sclerosis occurred in any cases. The mean preoperative and postoperative refractions without additional surgery were -0.4+/-2.9 diopters (D) and -0.2+/-3.0 D in the operated eyes, respectively, and -0.2+/-2.5 D and 0.1+/-2.4 D, respectively, in the unoperated fellow eyes. The mean differences in the refractive error between both eyes (operated eye data minus fellow eye data) were -0.2+/-0.7 D before surgery and -0.3+/-0.8 D after surgery (P = 0.319, paired t test). The mean preoperative and postoperative nuclear densities in 16 patients were 69+/-14 nuclear density units (NDUs) and 76+/-12 NDUs in the operated eyes and 71+/-14 NDUs and 78+/-14 NDUs in the fellow eyes, respectively. The mean preoperative and postoperative differences in nuclear densities in both eyes were -2+/-2 NDUs and -2+/-5 NDUs, respectively (P = 0.836, paired t test). The ERM recurred in 10 eyes (33%), and 3 eyes underwent conventional vitrectomy combined with cataract surgery. CONCLUSIONS: Unilateral nuclear sclerosis did not progress for at least 5 years after nonvitrectomizing vitreous surgery. The recurrence rate of ERM appeared to be higher than that after conventional vitreous surgery.

Anti-fibrosclerotic effects of shock wave therapy in lipedema and cellulite.

In vivo measurements in 26 female patients with lipedema and cellulite parameters were carried out before and after therapy by means of complex physical decongestive therapy (CPDT) including manual lymph drainage and compression as main components and/or shock wave therapy (SWT). Oxidative stress parameters of blood serum and biomechanic skin properties/smoothening of dermis and hypodermis surface were evaluated. Oxidative stress in lipedema and cellulite was demonstrated by increased serum concentrations of malondialdehyde (MDA) and plasma protein carbonyls compared with healthy control persons. Both MDA and protein carbonyls in blood plasma decreased after serial shock wave application and CPDT. The SWT itself and CPDT itself lead to MDA release from edematous tissue into the plasma. Obviously both therapy types, SWT and CPDT, mitigate oxidative stress in lipedema and cellulite. In parallel SWT improved significantly the biomechanic skin properties leading to smoothening of dermis and hypodermis surface. Significant correlation between MDA depletion of edematous and lipid enriched dermis and improvement of mechanic skin properties was demonstrated. From these findings it is concluded, that a release of lipid peroxidation (LPO) products from edematous dermis is an important sclerosis-preventing effect of SWT and/or CPDT in lipedema and cellulite. Expression of factors stimulating angiogenesis and lymphangiogenesis such as VEGF was not induced by SWT and/or CPDT and, therefore, not involved in beneficial effects by SWT and/or CPDT.

[From the Mailing List SIN: Therapy and prevention of peritoneal sclerosis]. / Dalla Mailing-List soci SIN (ML-SIN). La sclerosi peritoneale: terapia e prevenzione.

Recently, in the Mailing List of the Italian Society of Nephrology (ML-SIN), a message asking for opinions on the diagnosis and treatment of peritoneal sclerosis gave rise to an extensive debate on this interesting clinical topic. The discussion evidenced significant differences both in the reported onset of clinical manifestations, emphasizing the difficulty in obtaining a definite early diagnosis, and in therapy approaches. Occasionally, this is limited to medical treatment, but surgery, although burdened with elevated complexity and high mortality rates due to post-operative complications, is usually advocated for intestinal obstruction. This is the second issue reserved for the review of the ML-SIN concerning this topic, following that dedicated to definition, etiology, pathology and clinical characteristics. In this section, two expert colleagues complete the analysis of the different aspects of peritoneal sclerosis, discussing the therapy and the prevention of this serious complication of peritoneal dialysis.

Tolerance induced by bone marrow chimerism prevents transplant vascular sclerosis in a rat model of small bowel transplant chronic rejection.

BACKGROUND: The major impediment to success in solid organ transplantation is chronic rejection (CR). The characteristic lesion of CR is transplant vascular sclerosis (TVS). Although the mechanism of TVS is thought to have an immunologic basis, in humans immunosuppression does not prevent or reverse it. One possible therapy to prevent TVS is induction of donor-specific tolerance. Bone marrow chimerism has been successful in inducing tolerance in acute and chronic rejection heart and kidney transplant models. The highly immunogenic small bowel (SB) allograft provides a rigorous test of the efficacy of this tolerance regimen. We examined whether induction of tolerance by bone marrow chimerism could prevent TVS in a model of Fisher 344 (F344) to Lewis (LEW) rat SB transplantation. METHODS: Bone marrow chimeras (BMC) were created by transplantation of T-cell-depleted F344 bone marrow into irradiated LEW rats. Chimerism was assessed by flow cytometric method. F344 SB, heterotopically transplanted into the chimeras, was clinically and histologically assessed for CR. F344 SB grafts, transplanted into cyclosporine-A-treated LEW recipients, served as control grafts for CR. RESULTS: Cyclosporine-A-treated LEW rats chronically rejected F344 SB grafts. By contrast, the BMC group demonstrated tolerance and had long-term SB graft survival (>120 days) without TVS. The BMC demonstrated immunocompetence by prompt rejection of third party ACI (RT1av1) SB allografts. CONCLUSIONS: Bone marrow chimerism prevents chronic graft failure secondary to TVS in a model of chronic SB rejection. TVS fails to develop when tolerance is established, suggesting that the mechanisms involved in TVS are, in part, immunologically mediated.

Marked inhibition of transplant vascular sclerosis by in vivo-mobilized donor dendritic cells and anti-CD154 mAb.

BACKGROUND: Combination of donor dendritic cells (DC) and anti-CD40 Ligand (L) (CD154) monoclonal antibody (mAb) markedly prolongs heart or skin allograft survival, but the influence of this strategy in models of chronic rejection is unknown. Our aim was to ascertain the influence of in vivo-mobilized immature donor DC plus anti-CD40L mAb on vascular sclerosis in functional murine aortic allografts. METHODS: C3H He/J (C3H;H2k) mice received 2 x 106 freshly isolated, immunobead-purified (>90%) fms-like tyrosine kinase 3 ligand-mobilized C57BL/10 (B10;H2b) CD11c+ DC intravenously (IV), together with 500 microg of anti-CD40L mAb (MR1) intraperitoneally (IP) on days -7, 0, 4, and 10. Controls received either no donor cells, no mAb, or were untreated. B10 aortic grafts were transplanted in the abdominal aorta on day 0. At day 30, antidonor T-cell proliferative and cytotoxic responses and both complement fixing and immunoglobulin (Ig)G alloantibody levels were determined. Grafts were harvested on days 30 and 60 and examined by histology and immunohistochemistry. RESULTS: DC infusion alone enhanced ex vivo antidonor proliferative and cytotoxic T-cell activity. By contrast, complement-fixing alloantibody levels were reduced. Anti-CD40L mAb alone strongly suppressed each of these responses. Graft inflammatory cell infiltration, intimal smooth muscle cell proliferation, fibrosis, and elastic lamina disruption observed in untreated animals were reduced in response to anti-CD40L mAb or donor DC alone. Antidonor immune reactivity, including IgG levels, and intimal proliferation were all markedly suppressed to an overall greater extent in mice given both treatments. CONCLUSION: Whereas blockade of the CD40-CD40L pathway ameliorated transplant vasculopathy, preservation of near-normal vessel architecture was achieved by simultaneous administration of donor DC. This strategy represents a novel application of DC for suppression of chronic rejection.