Reduction of a vascular endothelial growth factor receptor, fetal liver kinase-1, by antisense oligonucleotides induces motor neuron death in rat spinal cord exposed to hypoxia

Vascular endothelial growth factor (VEGF) is reported to play a neuroprotective role through a VEGF receptor, fetal liver kinase-1 (Flk-1) in vitro. We investigated whether reduction of Flk-1 could induce motor neuron loss in rat spinal cord by inhibiting the expression of Flk-1 in rat spinal cord using antisense oligodeoxynucleotides (ODNs) against the Flk-1 receptor. Rat spinal cord was repetitively exposed to 12% hypoxia, and the change of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway and the mitogen-activated protein kinase kinase (MEK)/extracellular-signal-regulated kinase (ERK) pathway was examined. Intrathecal infusion of Flk-1 antisense ODNs for 7 days suppressed almost completely Flk-1 expression in the lumbar segment of the spinal cord and was followed by a hypoxic challenge with 12% oxygen for 1 h that was repeated for 7 more days. In the lumbar segment, we observed that reduced Flk-1 expression and hypoxic challenge for 7 days resulted in approximately 50% loss of motor neurons, in which the activation of Akt and ERK, that is, increased levels of phosphorylated-Akt and of phosphorylated-ERK by hypoxia, was markedly inhibited. In contrast, the reduction of Flk-1 expression alone did not induce motor neuron loss. These results suggest that VEGF exerts its protective effect on motor neurons against hypoxia-induced toxicity by the Flk-1 receptor through the PI3-K/Akt and the MEK/ERK signaling pathways.     

Spatial and temporal differences in the blood parasite fauna of passerine birds during the spring migration in Bulgaria

Species composition and prevalence of the blood parasites of three migratory Acrocephalus species of warblers (Acrocephalus arundinaceus, Acrocephalus scirpaceus and Acrocephalus schoenobaenus) were studied during spring period in Bulgaria. For each of the studied species, we compared the parasite fauna during their spring migration at three study sites in search of infection patterns in time and space. Spatial differences were registered in the blood parasites and their prevalence for two of the studied species—A. arundinaceus and A. scirpaceus, whereas for the third one—A. schoenobaenus, there were no significant differences. The parasite species Haemoproteus belopolskyi was present in migrating A. arundinaceus only at Kalimok station, but not at the other two sampling locations. Plasmodium prevalence in A. arundinaceus migrating through Kalimok was also different between years. A decrease of H. belopolskyi prevalence was detected for A. schoenobaenus at Petarch during the spring of 2006. On the contrary, Plasmodium (Haemamoeba) sp. infections of the same bird species increased during the spring period. The differences found between sites could be explained with the different origin of the migrants at different migration stopover points. Climatic conditions and vector abundance in the zones of origin are probable reasons for the observed differences between years.     

Adaptation of eye and hand movements to target displacements of different size

Previous work has documented that the direction of eye and hand movements can be adaptively modified using the double-step paradigm. Here we report that both motor systems adapt not only to small direction steps (5° gaze angle) but also to large ones (28° gaze angle). However, the magnitude of adaptation did not increase with step size, and the relative magnitude of adaptation therefore decreased from 67% with small steps to 15% with large steps. This decreasing efficiency of adaptation may reflect the participation of directionally selective neural circuits in double-step adaptation.     

Age-related changes in peroxisomal membrane protein 70 and superoxide dismutase 1 in transgenic G93A mice

Peroxisomal membrane protein 70 (PMP70) and Cu/Zn superoxide dismutase (SOD1) were examined in the spinal cords of transgenic (Tg) mice expressing a human mutant SOD1 protein (G93A) and their age-matched controls at 8, 20 and 32 weeks by immunohistochemistry. At pre-symptomatic 20 weeks and symptomatic 32 weeks, PMP70 was reduced in the cytoplasm of motor neurons in Tg animals and increased in glial cells in anterior horn at late age. SOD1 showed a progressive increase of dot-like deposits in the neuropil of anterior horn of Tg mice, and a late decrease of signal intensity in the white matter and motor neurons at 32 weeks. It is conceivable that reduction of PMP70 might underlie decrease in peroxisomal functions and increase in oxidative stress that is well documented in this animal model.     

Effect of human cationic antimicrobial protein 18 Peptide on endotoxin-induced uveitis in rats

PURPOSE. Human cationic antimicrobial protein 18 (hCAP18, 18 kDa) was originally identified in leukocytes on the basis of its antimicrobial activity. The peptide composed of the 27 C-terminal amino acids of hCAP18 (hCAP18(109-135)) binds lipopolysaccharide (LPS). The purpose of the present study was to investigate the effects of hCAP18 peptide on endotoxin-induced uveitis (EIU) in rats. METHODS. EIU was induced by footpad injection of LPS. Each rat was injected intravenously with 1, 10, or 100 micro g hCAP18 peptide in 0.1 mL of PBS immediately after LPS injection in male Lewis rats. At 24 hours after LPS injection, enzyme-linked immunosorbent assay was performed to evaluate concentrations of protein, nitric oxide (NO), tumor necrosis factor (TNF)-alpha, prostaglandin (PG)-E2, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 in aqueous humor. Also, EIU was evaluated by counting inflammatory cells in aqueous humor. RESULTS. hCAP18 peptide at 10 and 100 micro g significantly suppressed an LPS-induced increase in the number of inflammatory cells and the levels of protein, NO, TNF-alpha, PGE2, MCP-1, and MIP-2. The anti-inflammatory effect of 10 micro g hCAP18 peptide was as strong as that of 100 micro g hCAP18 peptide. Treatment with 1 micro g hCAP18 peptide did not suppress EIU, compared with the LPS group. CONCLUSIONS. The present results indicate that hCAP18 peptide suppresses development of EIU. A possible mechanism for the ocular anti-inflammatory effect of hCAP18 peptide is that it suppresses onset of LPS-triggered inflammatory reactions by binding directly to LPS.     

The holistic approach to rehabilitation of patients after total hip joint replacement

AIM: The objective of the present study was to present the principles of a program used jointly by the Clinic of Orthopaedics and Traumatology and the Clinic of Physical Medicine and Early Rehabilitation at St. George University Hospital, Plovdiv for rehabilitation of patients with total hip replacement surgery. MATERIALS AND METHODS: We reviewed 486 cases of endoprostheses implanted by two surgical teams in the Clinic of Orthopaedics and Traumatology over a period of 6 years. We lay the stress on the fact that early mobilization of patients (3 to 5 days after operation) results in better functional results. We particularly emphasize the necessity of using a comprehensive approach that can have an effect on the psychoemotional status and the motivation of patients. RESULTS: The treatment results we evaluated by taking into account not only all functional parameters of restoring the range of hip joint motion but also the psychoemotional aspects of the recovery of patients after surgery. We took into consideration the range of motion of both the operated and the unoperated hip joints, the muscle strength, the walking distance, the type of gait, and the subjective evaluation of the patients (satisfied, not very satisfied, unsatisfied of operation). Particular attention was paid to the psychoemotional status of patients stimulating the positive feedback and their willingness to put in serious efforts toward improvement of their quality of life. CONCLUSION: The new approach to rehabilitation of patients with total hip replacement focuses not only on the collaboration between orthopedists, traumatologists and physical therapeutists, but also on the integral effect both on the physical state of patients and on their psychoemotional status with the aim of improving their quality of life.     

Two mucosal-parenteral schedules to coadminister a multiantigenic formulation against HIV-1 in Balb/c mice

Previous studies showed that simultaneous immunization through the nasal (IN) and subcutaneous (SC) route of a multiantigenic formulation induced a Th1 anti-HIV humoral and cellular immune responses. The formulation was comprised of a recombinant protein of HIV-1 (named CR3; Cellular Response number 3) and the surface and nucleocapsid antigens of hepatitis B virus. This study asks whether four times simultaneous administration through the IN and SC routes (SC+IN) of the multiantigenic formulation induces a similar systemic and mucosal immune responses than two sequential IN priming and two SC boosting (2IN&2SC) inoculations in mice. To answer this question, we tested the same total dose of each antigen per animal in both schedules of inoculation. We found that SC+IN and 2IN&2SC coadministration induced comparable levels of CR3(HIV)-specific IFN-γ-secreting cells and CD8+ cells proliferation in the systemic compartment of animals. Consistent with these findings, a similar Th1 profile considering anti-CR3 IgG1:IGg2a ratio was observed. Additionally, the level of IgG antibodies and the frequency of seroconverting animals in vagina were not different. However, in the case of IgA antibodies the same parameters were significantly higher in the SC+IN group. We also found important level of HBsAg-specific antibodies in serum and vaginal washes.     

Access to antiepileptic drug therapy in children in Camagüey Province,Cuba

Objective To describe access to antiepileptic drug therapy and estimate the prevalence of epilepsy in children in Camagüey Province, Cuba. Methods All the community pharmacies in the province were visited and information collected about the number of children receiving antiepileptic drugs in 2009. Availability and cost of each antiepileptic drug were determined. The prevalence of epilepsy was estimated by determining the number of children receiving antiepileptic drugs. Results There were 923 children who received a total of 977 antiepileptic drugs in Camagüey Province. The estimated prevalence of epilepsy was 5.18 per thousand children which is lower than previously reported rates in other low and lower‐middle income countries. Most of the children (871, 94%) received a single antiepileptic drug. Carbamazepine and valproate were the two most frequently prescribed antiepileptic drugs. Antiepileptic drugs were available from the local pharmacy on 76% of occasions. If the antiepileptic drug was not available from the local pharmacy, the parent had to travel to another pharmacy to obtain the medicine. Conclusions The estimated prevalence of epilepsy in children in Cuba is lower than that estimated in other lower‐middle income countries. Access to drug therapy in children with epilepsy can be achieved in lower‐middle income countries.