Neuronal coordination of motile cilia in locomotion and feeding.

Efficient ciliary locomotion and transport require the coordination of motile cilia. Short-range coordination of ciliary beats can occur by biophysical mechanisms. Long-range coordination across large or disjointed ciliated fields often requires nervous system control and innervation of ciliated cells by ciliomotor neurons. The neuronal control of cilia is best understood in invertebrate ciliated microswimmers, but similar mechanisms may operate in the vertebrate body. Here, we review how the study of aquatic invertebrates contributed to our understanding of the neuronal control of cilia. We summarize the anatomy of ciliomotor systems and the physiological mechanisms that can alter ciliary activity. We also discuss the most well-characterized ciliomotor system, that of the larval annelid Platynereis. Here, pacemaker neurons drive the rhythmic activation of cholinergic and serotonergic ciliomotor neurons to induce ciliary arrests and beating. The Platynereis ciliomotor neurons form a distinct part of the larval nervous system. Similar ciliomotor systems likely operate in other ciliated larvae, such as mollusc veligers. We discuss the possible ancestry and conservation of ciliomotor circuits and highlight how comparative experimental approaches could contribute to a better understanding of the evolution and function of ciliary systems. This article is part of the Theo Murphy meeting issue 'Unity and diversity of cilia in locomotion and transport'.

Melatonin protects rat thymus against oxidative stress caused by exposure to microwaves and modulates proliferation/apoptosis of thymocytes.

The aim of the study was to evaluate the effect of melatonin on oxidative stress, DNA fragmentation, apoptsis and proliferation in thymus tissue of rats exposed to microwaves. Wistar rats were divided in four groups: I - treated with saline; II - treated with melatonin; III - microwaves exposed; IV - microwaves exposed and melatonin treated. Melatonin (2 mg/kg i.p.) was administered daily. Animals were sacrificed after 20, 40 and 60 days. A significant increase in malondialdehyde and carbonyl group content, as well as decrease in catalase and increase in xanthine oxidase activity were registered under microwave exposure. Melatonin prevented the increase in malondialdehyde and carbonyl group content, and reversed the effect on catalase and xanthine oxidase activity. Both, alkaline and acid DNase activity were increased due to microwave exposure. Furthermore, microwaves caused increase in apoptosis rate (detected using Annexin V-FITC/PI kit) and reduced proliferative capacity of thymocytes (induced by ConA). However, melatonin caused decrease in alkaline and acid DNase activity, decrease in apoptotic rate and increase in proliferation rate of thymocytes. Melatonin exerts protective effects on rat thymocytes by modulating processes of apoptosis and proliferation, and causes decrease in DNA fragmentation and oxidative stress intensity under exposure to microwaves.

Protective effects of glutathione and lipoic acid against cadmium-induced oxidative stress in rat's kidney.

Cadmium is a widespread, toxic industrial pollutant. The proximal tubule of the mammalian kidney is a major target of Cd-induced toxicity. We analyzed the effects of cadmium exposure on the model system of experimental animals, the thiobarbituric acid (TBA)-reactive substance (TBARS) level, and the activity of xanthine oxidase (XO) and catalase in kidney of rats, with and without glutathione and lipoic acid (LA). The experimental animals were classified into six groups, regarding cadmium, glutathione, and LA intake. The concentration of TBARSs in the homogenate was determined by spectrophotometric method according to Nabavi et al. The specific activity of XO was determined spectrophotometrically by the method of Aygul et al. Catalase activity in tissues was determined by spectrophotometric method according to Nabavi et al. The increased level of TBARS and the increased activity of XO in kidney tissue in cadmium poisoning are statistically significant compared to control (p < 0.001). Glutathione and LA applied along with cadmium lowered TBARS concentration and reduced XO activity (p < 0.001). Catalase activity in the kidney tissue was increased in the group, which was administered cadmium (p < 0.001). In conclusion, glutathione and LA, as physiological antioxidants applied with cadmium, have reduced the level of lipid peroxide and the activity of XO, and can be used as protectors in conditions of cadmium poisoning.

[Association of TNF-alpha polymorphism (-308 A/G) with high activity of rheumatoid arthritis and therapy response to Etanercept].

INTRODUCTION: Genetic markers are significant predictive factors in the assessment of therapeutic response of rheumatoid arthritis (RA) to biological medication. OBJECTIVE: The aim of the study was to determinate the association of TNF-alpha -308 G/A polymorphism with a high RA activity and its predictive value in therapeutic response after 12 months of treatment with Etanercept. METHODS: The study enrolled 132 patients with RA treated with Methotrexate (MTX) and 58 control subjects. The -308 TNF polymorphism was examined using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). The patients were divided into two groups: group A with A/A and A/G genotype and group G with G/G genotype. After 12 months, beside MTX, Etanercept was introduced in 36 patients. We compared clinical activity among the groups at the beginning and after one year of therapy by using DAS28 SE (Disease activity score with sedimentation). RESULTS: There was no significant difference found in the distribution of G and A allele in the RA group compared to the control group. A significantly higher disease activity was noticed in A compared to the G group (DAS28 SE: 6.31 to 5.81; p < 0.05). The patients with A allele kept the majority of the disease activity even after a year of study (DAS28 SE: 5.25 to 3.89). After a year of MTX and Etanercept therapy, a significantly larger proportion of patients in the G group displayed a good clinical response to treatment compared to the A group (81.5% to 25%; p < 0.05). The average change of DAS28 SE in G group was 2.24, while in the A group DAS 28 reduction was significantly lower (1.17; p = 0.005). CONCLUSION: There was no significant difference in the frequency of A in the patients with RA compared to healthy subjects. The presence of A allele is associated with more serious clinical presentation of the disease and lower therapeutic response to Etanercept.

Etanercept reduces matrix metalloproteinase-9 level in children with polyarticular juvenile idiopathic arthritis and TNF-alpha-308GG genotype.

Genetic contribution of tumor necrosis factor polymorphism (TNF-alpha-308G/A) in patients with juvenile idiopathic arthritis (JIA) on response to TNF blocking agents, as well as matrix metalloproteinase-9 (MMP-9) production, is not yet well established. We have investigated whether the TNF-alpha-308G/A polymorphism can influence MMP-9 level and clinical response to etanercept (TNF receptor II-Fc fusion protein) in JIA patients, after 1 year of treatment. A total of 66 patients with polyarticular JIA and 65 healthy children were screened for the polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. JIA patients donated paired blood samples prior to and 12 months after etanercept therapy. Plasma MMP-9 level was determined using an enzyme-linked immunosorbent assay kit. Clinical assessment was performed according to ACR Pedi 50 improvement criteria. The frequency of the A allele was significantly higher in JIA patients compared to controls (39% vs. 26%, P = 0.026). Patients with the -308GG genotype achieved an ACR Pedi 50 response significantly more frequently than those with the -308AA genotype (P = 0.035). MMP-9 level in patients with the genotype -308GG was significantly decreased after 1 year of treatment with etanercept compared to the value from before (P = 0.036). On the other hand, there was a decrease of MMP-9 levels after treatment, but not statistically significant in patients with the genotypes -308GA/AA. We conclude that etanercept reduces MMP-9 level in children with polyarticular JIA and TNF-alpha-308GG genotype. Our results correlate with findings that the -308A allele is associated with a lower response to etanercept treatment.

Etanercept reduces matrix metalloproteinase-9 level in children with polyarticular juvenile idiopathic arthritis and TNF-alpha-308GG genotype

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Genetic contribution of tumor necrosis factor polymorphism (TNF-alpha-308G/A) in patients with juvenile idiopathic arthritis (JIA) on response to TNF blocking agents, as well as matrix metalloproteinase-9 (MMP-9) production, is not yet well established. We have investigated whether the TNF-alpha-308G/A polymorphism can influence MMP-9 level and clinical response to etanercept (TNF receptor II-Fc fusion protein) in JIA patients, after 1 year of treatment. A total of 66 patients with polyarticular JIA and 65 healthy children were screened for the polymorphism using the polymerase chain reaction–restriction fragment length polymorphism method. JIA patients donated paired (..) (AU)