TNF-α receptor 1 deficiency reduces antigen-presenting capacity of Schwann cells and ameliorates experimental autoimmune neuritis in mice

Tumor necrosis factor-α (TNF-α) is a pleiotropic pro-inflammatory cytokine with potentially neurodestructive effects and plays a pivotal role in autoimmune demyelinating disease. To address the role of TNF-α in the pathogenesis of experimental autoimmune neuritis (EAN), the current study investigated the antigen-presenting capacity of Schwann cells (SCs) in EAN induced by P0 protein peptide 106–125 in TNF-α recepter 1 deficient (TNFR1^−/−) mice. The antigen-presenting capacity of SCs was assessed by the expression of MHC class II (MHCII), CD40, CD80 and CD86 molecules on activated SCs as well as by induction of T cell proliferation in co-cultures of P0 protein peptide 106–125 specific T cells with activated SCs. In addition, the expression of inducible nitric oxide synthase (iNOS) was measured in activated SCs by flow cytometry. TNFR1^−/− EAN mice developed significantly delayed and reduced clinical signs of EAN compared to wild type EAN mice. In parallel, the expression of MHCII, CD80 and iNOS on SCs were decreased in TNFR1^−/− mice compared to wild type mice. Likewise, proliferation of P0 protein peptide 106–125 specific T cells simulated by activated SCs of TNFR1^−/− EAN mice was lower than that of wild type EAN mice. Our data suggest that TNF-α may exert pro-inflammatory effects in EAN via TNFR1 by up-regulating the antigen-presenting function and iNOS production of SCs.     

Transfer of single dose of intravitreal injection of ranibizumab and bevacizumab into milk of sheep

AIM: To investigate whether single-dose intravitreal injections of bevacizumab and ranibizumab transfer into milk. METHODS: This study included lactating 12 sheep and a single 3-month old suckling lamb of each sheep. Two groups consisting of 6 sheep and their lambs were constituted; the ranibizumab group and the bevacizumab group before the administration of intravitreal injections, blood and milk samples were obtained from all sheep and, following the injections, blood and milk samples of all sheep and blood samples of all lambs were collected at regular time points. Serum and milk concentrations of bevacizumab and ranibizumab were measured using an enzyme-linked immunosorbent assay (ELISA) kit. The limit of determination was 0.9 ng/mL for bevacizumab and 0.62 ng/mL for ranibizumab. RESULTS: At 6h after intravitreal injections, bevacizumab concentration was above the limit of determination in the blood of all sheep. At 3wk, when the study was terminated, bevacizumab concentrations were high in 4 sheep. Even though bevacizumab concentrations in milk showed fluctuations, the drug transferred into the milk of all sheep at detectable concentrations. Ranibizumab drug concentrations in the blood and milk of sheep and those in the blood of lambs were below the limit of determination by the ELISA kit. CONCLUSION: This sheep model study demonstrate that intravitreal injection of ranibizumab, which did not transfer into the milk of sheep and suckling lambs, is safer than bevacizumab during lactation period.     

The superior vena cava syndrome caused by malignant disease. Imaging with multi-detector row CT

OBJECTIVE: The superior vena cava (SVC) obstruction by malignant diseases is either by direct invasion and compression or by tumour thrombus of the SVC. Whatever is its cause, obstruction of the SVC causes elevated pressure in the veins draining into the SVC and increased or reversed blood flow through collateral vessels. Severity of the syndrome depends on the collateral vascular system development. Therefore, imaging of the collateral veins with variable location and connection is important in determining the extension and management of the disease. Our aims are to describe collateral vessels of the superior vena cava syndrome (SVCS) related with the malignant diseases and to assess the ability of multi-detector row CT with multiplanar and 3D volume rendering techniques in determining and describing collateral circulations. MATERIALS AND METHODS: We present CT angiography findings of seven patients with small cell carcinoma of the lung (n = 2), squamous cell carcinoma of the lung (n = 3), Hodgkin disease of the thorax (n = 1), and squamous cell carcinoma of the oesophagus (n = 1). The patients received contrast-enhanced CT scans of the chest and abdomen on a multi-detector row CT during breath holding at suspended inspiration. RESULTS: CT images revealed the cause and level of the SVC obstruction in all patients with axial and multiplanar reconstructed images. The SVC showed total obstruction in five patients and partial obstruction in two patients. The most common experienced collateral vessels were azygos vein (6), intercostal veins (6), mediastinal veins (6), paravertebral veins (5), hemiazygos vein (5), thoracoepigastric vein (5), internal mammary vein (5), thoracoacromioclavicular venous plexus (5), and anterior chest wall veins (5). While one case showed the portal-systemic shunt, V. cordis media and sinus coronarius with phrenic veins were enlarged in two cases, and the left adrenal vein was enlarged in a patient. In one case, the azygos vein with reversed blood flow was drained into both inferior vena cava and hemiazygos vein with the left renal vein. CONCLUSION: Multi-detector row CT with multiplanar and 3D imaging is an effective tool in evaluation of the SVCS and has a greater advantage than the other imaging techniques. 3D volume rendering is a useful technique in determining and describing collateral circulations in addition to the primary disease process.     

Lens and cornea lesions of rats fed corn syrup and the protective effects of alpha lipoic acid

Objective: To examine the pathological findings that occurred in the lens and cornea and biochemical findings in the lens of rats fed with corn syrup and the protective effects of alpha lipoic acid (ALA).

Materials and methods: Twenty-four rats were randomly divided into three groups. Group I served as the control group. Group II was used as the study group; the rats were treated with 30% corn sugar solution for 10 weeks. Group III was the treatment group. Corn syrup was given by the oral route to the rats during the study, and ALA (100?mg/kg) was added to the treatment 4 weeks after the study began. At the end of the experiment, central corneal thickness (CCT) was measured in all rats with an ultrasonic pachymeter. Then the right eyes of the rats were enucleated for histopathological examination of the cornea and lens. The left lenses were homogenized for biochemical analyses.

Results: The lenses of the rats treated with corn syrup revealed severe damage; many lens fibers appeared swollen and ruptured with large vacuoles near the lens epithelium. In addition, malondialdehyde (MDA) levels, a parameter of oxidative stress, increased but not significantly in Group II; however. ALA treatment decreased MDA levels significantly. Antioxidant enzyme and catalase (CAT) activities were significantly decreased in Group II, and ALA treatment increased these activities; however, the increase was not significant. Changes were observed in the cornea such as epithelial alterations, subepithelial vacuolizations, collagen fibers loss in the stromal layer, interruptions in the subepithelial basement membrane and central corneal thickening.

Conclusions: Corn syrup can cause severe damage in rat lenses and corneas. However, ALA ameliorates the effect of corn syrup-related lesions on the cornea and lens.     

Allopurinol plus pentoxifilline in hepatic ischaemia/reperfusion injury

OBJECTIVES: Ischaemia/reperfusion injury of the liver is the major cause of liver dysfunction and cellular death in transplantation and in liver resection with hepatic pedicle clamping. Many agents are used to prevent this phenomenon, which occurs following interaction of different mediators during both ischaemia and reperfusion. In this study, we aimed to assess the effects of allopurinol, a xanthine oxidase inhibitor, and pentoxifilline, on liver ischaemia/reperfusion injury when used together and to compare these with the effects of using these agents singly. METHODS: Thirty-two rats were divided into four groups consisting of eight rats: Group C, control; Group P, pentoxifilline; Group A, allopurinol; and Group PA, pentoxifilline + allopurinol. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels were measured before hepatic pedicle clamping, on the 45th minute of ischaemia and 15 and 45 minutes after reperfusion. Group P rats were injected with 50 mg/kg pentoxifilline, Group A rats 50 mg/kg allopurinol and Group PA rats were injected with both agents 15 minutes before hepatic pedicle clamping. RESULTS: Ischaemia/reperfusion injury was produced by hepatic pedicle clamping, as demonstrated by AST, ALT and LDH increase. Injury prevention occurred in Groups P, A and PA. No significantly different (better) prevention was provided by giving allopurinol plus pentoxifilline to the rats. Furthermore, no difference was observed between the allopurinol and pentoxifilline injected groups in terms of preventing ischaemia/reperfusion injury. CONCLUSIONS: Pretreatment with allopurinol or pentoxifilline resulted in significantly lower hepatic enzyme elevation than that in controls in the rat liver ischaemia/reperfusion model. Using both agents does not provide better protection than using either agent alone.