Structure and evolution of neuronal wiring receptors and ligands

One of the fundamental properties of a neuronal circuit is the map of its connections. The cellular and developmental processes that allow for the growth of axons and dendrites, selection of synaptic targets, and formation of functional synapses use neuronal surface receptors and their interactions with other surface receptors, secreted ligands, and matrix molecules. Spatiotemporal regulation of the expression of these receptors and cues allows for specificity in the developmental pathways that wire stereotyped circuits. The families of molecules controlling axon guidance and synapse formation are generally conserved across animals, with some important exceptions, which have consequences for neuronal connectivity. Here, we summarize the distribution of such molecules across multiple taxa, with a focus on model organisms, evolutionary processes that led to the multitude of such molecules, and functional consequences for the diversification or loss of these receptors.     

CT findings of pulmonary artery aneurysms during treatment for Behçet's disease

OBJECTIVE: The purpose of this study was to evaluate the CT findings of pulmonary artery aneurysms in patients being treated for Beh?et's disease. MATERIALS AND METHODS: Thirteen patients with Beh?et's disease who had a total of 46 aneurysms were included in the study. All patients underwent helical CT before and after treatment. Both initial and follow-up CT scans were evaluated for location, number, and size of aneurysms and for thrombosis and pulmonary parenchyma changes. RESULTS: Thirty-five (76%) of the 46 aneurysms completely disappeared during the 3-42 months of treatment (mean, 21 months), and the remaining 11 aneurysms (24%) became smaller. Both disappearance and regression of aneurysms were preceded by thrombus formation. In 15 initially thrombosed aneurysms (33%), the thrombus increased in size during treatment. After treatment, the thrombus regressed and the pulmonary artery aneurysms disappeared. Thirty-one initially nonthrombosed aneurysms (67%) first became thrombosed during treatment; later, the thrombus regressed and the aneurysm decreased in size. Perianeurysmal consolidation and air-space nodules detected in seven patients disappeared in the early stages of treatment. Mosaic attenuation areas were seen in eight patients and disappeared in seven (88%) after treatment. CONCLUSION: Pulmonary artery aneurysms in Beh?et's disease may become smaller or disappear with medical treatment. Mural thrombotic changes may be observed during the regression of pulmonary artery aneurysms. Helical CT is helpful in the diagnosis and follow-up of aneurysms and thrombosis in Beh?et's disease.     

Human and rat liver UDP-glucuronosyltransferases are targets of ketoprofen acylglucuronide.

Acylglucuronides formed from carboxylic acids by UDP-glucuronosyltransferases (UGTs) are electrophilic metabolites able to covalently bind proteins. In this study, we demonstrate the reactivity of the acylglucuronide from the nonsteroidal anti-inflammatory drug, ketoprofen, toward human and rat liver UGTs. Ketoprofen acylglucuronide irreversibly inhibited the glucuronidation of 1-naphthol and 2-naphthol catalyzed by human liver microsomes or by the recombinant rat liver isoform, UGT2B1, which is the main isoform involved in the glucuronidation of the drug. A decrease of about 35% in the glucuronidation of 2-naphthol was observed when ketoprofen acylglucuronide was produced in situ in cultured V79 cells expressing UGT2B1. Inhibition was always associated with the formation of microsomal protein-ketoprofen adducts. The presence of these covalent adducts within the endoplasmic reticulum of cells expressing UGT2B1 was demonstrated following addition of ketoprofen to culture medium by immunofluorescence microscopy with antiketoprofen antibodies. Immunoblots of liver microsomes incubated with ketoprofen acylglucuronide and probed with antiketoprofen antibodies revealed the presence of several protein adducts; among those was a major immunoreactive protein at 56 kDa, in the range of the apparent molecular mass of UGTs. The adduct formation partially prevented the photoincorporation of the UDP-glucuronic acid (UDP-GlcUA) analog, [beta-32P]5N3UDP-GlcUA, on the UGTs, suggesting that ketoprofen glucuronide covalently reacted with the UDP-GlcUA binding domain. Finally, UGT purification from rat liver microsomes incubated with ketoprofen glucuronide led to the isolation of UGT adducts recognized by both anti-UGT and antiketoprofen antibodies, providing strong evidence that UGTs are targets of this metabolite.     

Effect of water extract of Turkish propolis on tuberculosis infection in guinea-pigs.

Mycobacterium tuberculosis (H(37)R(v))-infected guinea-pig model was used to investigate the effect of water extract of propolis (WEP). After subcutaneous inoculation of tubercle bacilli, each animal received oral WEP (n=9), isoniazid (n=5) or saline (n=6) as placebo and were sacrificed 30 days later. Formation of necrosis was less prominent in the group treated with WEP, but was not statistically significant (P>0.05). The granuloma formation in the same group was more prominent than the placebo and isoniazid groups; however, this finding failed to reach statistical significance by the Kruskal-Wallis test (P>0.05). These findings suggest that Turkish WEP may have a limited effect on the development of tuberculosis infection in this guinea-pig model.     

Agmatine co‐treatment attenuates allodynia and structural abnormalities in cisplatin‐induced neuropathy in rats

Cisplatin is a widely used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well‐known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator that has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin‐induced neurotoxicity. Primary cultures of dorsal root ganglia (DRG) which are the primary target of drug injury were prepared. DRG cells were incubated with cisplatin (100, 200, 500 μm ). Then, agmatine (10, 100, 500 μm ) was administered with the submaximal concentration of cisplatin. Cisplatin caused concentration‐dependent neurotoxicity, and agmatine did not alter this effect. The second aim was to investigate the effects of agmatine on cisplatin‐induced peripheral neuropathy in rats and the influence of nitric oxide synthase (NOS) inhibitor, L‐NAME, in this effect. Female Sprague Dawley rats received intraperitoneal saline (control), cisplatin (3 mg/kg), cisplatin+agmatine (100 mg/kg), or cisplatin+agmatine+L‐NAME (10 mg/kg) once a week for 5 weeks. The mechanical allodynia, hot plate, and tail clip tests were performed, and DRG cells and sciatic nerves were analyzed. Agmatine and agmatine+L‐NAME combination attenuated CIS‐induced mechanical allodynia and degeneration in DRG cells and sciatic nerves. However, L‐NAME did not potentiate the antiallodynic or neuroprotective effect of agmatine. These findings indicate that agmatine co‐administration ameliorates cisplatin‐induced neuropathy and may be a therapeutic alternative.     

【In Press】 Protective effect of pomegranate juice on retinal oxidative stress in streptozotocin-induced diabetic rats

AIM: To investigate the effect of pomegranate juice (PJ) intake on overall oxidation status in retinas of diabetic rats. METHODS: Twenty-seven rats were divided into four groups as control (CO), diabetic (DM), control treated with PC (CO-PJ), and diabetic treated with PJ (DM-PJ).The retina tissues were used to determine 8-Hydroxy-2’-deoxyguanosine (8OHdG), malondialdehyde (MDA), reduced glutathione (GSH) levels, and the enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). RESULTS: The levels of 8OHdG and MDA were significantly increased in the retina of DM group compared to CO group (p=0.001, p<0.001 respectively). Both 8OHdG and MDA levels were decreased in PJ-DM group compared to DM group (p=0.004, p<0.001 respectively). The activities of antioxidant enzymes GSH, SOD, and GDH-Px were significantly decreased in the retina of DM group compared to CO group (p≤0.01). GSH and GSH-Px activities were higher in PJ-DM group compared with DM group (p=0.010, p=0.042, respectively) but SOD activity was not statistically different (p=0.938). CONCLUSION: PJ intake was found to be effective in decreasing oxidative end products, and in increasing the activities of antioxidant enzymes in diabetic retinas of rats, which suggests it may be effective against oxidative stress in diabetic retinas.