Search NEL Online

Journal Article 2010; 31(Suppl 2): 79-83 PubMed PMID: 21187828 Citation  Keywords:  Animals, Antioxidants:pharmacology, Antirheumatic Agents:therapeutic use, Arthritis, Experimental:drug therapy, Cell Line, Disease Models, Animal, Drug Therapy, Combination, Macrophages:cytology, Male, Methotrexate:therapeutic use, Neutrophils:drug effect.   

OBJECTIVE: Formation of reactive oxygen species in neutrophils of rats with adjuvant arthritis and generation of nitric oxide in RAW 264.7 macrophages were analysed in the presence of pinosylvin.

METHODS AND RESULTS: The method of chemiluminescence was used for the detection of reactive oxygen species in blood of rats with adjuvant arthritis. Pinosylvin (50 mg/kg, daily, p.o.) and methotrexate (0.4 mg/kg, twice a week, p.o.) were applied separately or in a combination over a period of 28 days from the day of immunisation. Adjuvant arthritis was accompanied by a significantly increased number of neutrophils, by elevated concentration of oxidants in blood and by excessive responsiveness of neutrophils to stimulation with PMA. In rats treated with methotrexate, all these changes were significantly reduced and the inhibition became more pronounced when methotrexate was applied in the combination with pinosylvin; the monotherapy with pinosylvin did not induce any detectable changes in the parameters tested. Under in vitro conditions, pinosylvin inhibited formation of nitric oxide (NO) in macrophages, as demonstrated by the decreased concentration of nitrite - the end-product of NO metabolism (assessed by Griess' method), by the reduced expression of inducible NO synthase (detected by Western blot), and by the failure of pinosylvin to scavenge nitric oxide (measured amperometrically in cell-free system).

CONCLUSION: The observed ability of pinosylvin to decrease concentration of reactive oxygen and nitrogen species, along with its capacity to enhance the efficacy of methotrexate in arthritis treatment may shed more light into the pharmacological potential of this prospective natural substance....

Read abstract  Full text PDF

Journal Article 2010; 31(Suppl 2): 91-95 PubMed PMID: 21187826 Citation  Keywords:  Animals, Anti-Inflammatory Agents:pharmacology, Antioxidants:pharmacology, Arthritis, Experimental:drug therapy, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Therapy, Combination, Male, Oxidative Stress:drug effects, Peroxidase:metabolis.   

OBJECTIVE: The aim of this study was to evaluate the effects of pinosylvin (PIN) and pterostilbene (PTE), natural substances from the stilbenoid group, on the development of adjuvant arthritis in rats.

METHODS: Adjuvant arthritis (AA) was induced by a single intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant in male Lewis rats. Our experiments included healthy intact animals as reference controls, arthritic animals without any drug administration, and arthritic animals with administration of PIN and PTE in the oral daily dose of 30 mg/kg b.w. The treatment involved administration of the substances tested from day 0, i.e. the day of immunization, to the experimental day 28. The following parameters were monitored: change of the hind paw volume (HPV) on day 14, 21 and 28, luminol-enhanced chemiluminescence (CL) of the joint and myeloperoxidase (MPO) activity in hind paw joint homogenates (day 28).

RESULTS: Arthritic animals treated with PIN showed a decrease in HPV, significantly on days 14 and 28. PIN decreased CL of the joint as well as MPO activity of the joint homogenate, in comparison with untreated animals. PTE had no effect on HPV and MPO activity in hind paw joint homogenates and exerted only a partial effect on luminol-enhanced CL.

CONCLUSIONS: On the basis of our results we conclude that the effect of PTE on CL was only partial. PIN, on the other hand, had a beneficial anti-inflammatory and antioxidant effect on oxidative stress induced biochemical changes occurring in AA, as determined by all three functional parameters....

Read abstract  Full text PDF

Journal Article 2010; 31(5): 609-615 PubMed PMID: 21173750 Citation  Keywords:  Animals, Disease Models, Animal, Immunohistochemistry, Injections, Intraperitoneal, Injections, Intraventricular, Interleukin-1beta, Lipopolysaccharides, Male, Neuronal Plasticity, Neuropeptides:biosynthesis, Paraventricular Hypothalamic Nucleus:immunolog.   

OBJECTIVES AND METHODS: Neuropeptides, as the main neuroendocrine system effectors, regulate notably the response to different stressors via a secretory plasticity within their respective hypothalamic neuronal populations. The aim of the present study was to explore by immunocytochemistry the occurrence and the potential expression plasticity of the novel neuropeptide EM66 in the CRH neurones of stressed rats.

RESULTS: The secretogranin II (SgII)-derived peptide EM66 is strongly expressed within hypothalamic neuroendocrine areas such as the parvocellular aspect of the paraventricular nucleus (pPVN) as well as the median eminence, suggesting a probable hypophysiotropic effect of this peptide. As a first approach to investigate such a role, we evaluated by immunohistochemistry EM66 expression within the pPVN following acute immune stress induced by lipopolysaccharide (LPS) or interleukin-1β (IL-1β) injection in rat. This study showed that EM66 is present in the pPVN but the number of EM66 immunolabeled cells did not fluctuate in this structure following LPS peripheral injection. In line with this observation, an intracerebroventricular injection of IL-1β did not provoke any significant variation of the number of intraparaventricular EM66 neurones.

CONCLUSION: The present data revealed for the first time that EM66 expression would be insensitive to the central and peripheral cytokines within the neurosecretory hypothalamic pPVN. This result indicates that EM66 does not participate to the phenotypic plasticity of hypothalamic parvicellular neurones in response to acute inflammatory stress....

Read abstract  Full text PDF

Journal Article 2010; 31(2): 181-186 PubMed PMID: 20424592 Citation  Keywords:  Animals, Animals, Newborn, Brain:physiopathology, Disease Models, Animal, Electroencephalography, Hypoxia:physiopathology, Hypoxia, Brain:physiopathology, Recovery of Function, Severity of Illness Index, Swine, Time Factors,.   

OBJECTIVE: To evaluate the frequency content of the electroencephalogram (EEG) during recovery after a severe hypoxic insult in newborn piglets.

METHODS: EEG was continuously monitored in nine newborn piglets exposed to a severe hypoxic period. Power spectra in five frequency bands were calculated using Fourier transformation. Spectral edge frequency 90 (SEF90) was defined as the frequency below which 90% of the power in the EEG was located. The piglets were divided into two groups; Group 1 represented piglets with some EEG recovery and Group 2 represented piglets without any EEG recovery.

RESULTS: The recovery of the EEG in Group 1 had the same time course in all frequency bands. SEF90 indicates recovery earlier than the value of total power. But SEF90 also signals activity in the EEGs that were almost completely suppressed. When SEF90 was calculated during periods of periodic EEG activity during the very early phase of recovery, the values fell within the same range as during the control period.

CONCLUSION: Spectral analysis of continuous EEG in newborn piglets exposed to very severe hypoxia showed that no specific frequency band of the EEG preceded the other ones during recovery. The results of the SEF90 measure, demonstrates the need for critical analysis of the raw EEG before any reliable estimation of cerebral function can be made....

Read abstract  Full text PDF

Journal Article 2009; 30(6): 761-768 PubMed PMID: 20038927 Citation  Keywords:  Acoustic Stimulation, Age Factors, Animals, Animals, Newborn, Anxiety, Separation:immunology, Apoptosis:immunology, Body Weight, Cells, Cultured, Corticosterone:blood, Disease Models, Animal, Female, Immune Tolerance:physiology, Lymphocytes:cytology, Male.   

OBJECTIVES: Different inbred mouse strains but also each animal of the same strain show an individually different stress response which is influenced by genetic and environmental factors such as early life experiences. In this study, we investigated consequences of mild postnatal stress exposure on the stress coping style of adult BALB/c mice.

METHODS: We used a model of mild early life stress where neonatal mice were repeatedly separated from the dam staying with their siblings for 1-h each day during the first two postnatal weeks. The environment during maternal separation was adapted to the nest (bedding, 37 degrees C warm).

RESULTS: Adult female BALB/s mice that underwent the maternal separation protocol or were not isolated from the dam in early life were exposed to combined acoustic and restraint stress in adulthood. Repeated maternal separation which was performed under ambient conditions increased the stress coping ability of mice at the age of 12 weeks when exposed to this psychological stressors. By acoustic and restraint stress-induced alterations such as high corticosterone levels, an anti-inflammatory immune conditioning with an ex vivo hyperinducibility of interleukin-10 of splenocytes and a massive loss of body weight were significantly reduced in the maternally separated group compared with conventionally bred control mice.

CONCLUSIONS: Mild maternal separation in early life modifies the stress coping style of adult female BALB/c mice to a more stress-resistant phenotype which shows reduced repeated stress-induced immune suppression and weight loss and is linked to reduced release of glucocorticoids after stress exposure....

Read abstract  Full text PDF

Journal Article 2009; 30(4): 429-436 PubMed PMID: 20010491 Citation  Keywords:  Animals, Autistic Disorder:pathology, Cell Adhesion Molecules, Neuronal:physiology, Cell Movement:physiology, Disease Models, Animal, Extracellular Matrix Proteins:physiology, Humans, Nerve Tissue Proteins:physiology, Neuronal Plasticity:physiology, Neuro.   

: Autism is the most genetically influenced neuropsychiatric disorder with heritability of approximately 90%. Since genetic factors seem to play a crucial role in autism etiology, enormous attention is focused on genetic analyses of the disorder. Reelin, one of the autism candidates, is necessary in regulation of neuronal migration during brain development and also in maintaining synaptic plasticity during postnatal life period. Reduced reelin levels were observed in sera and brain cortices of autistic patients. In this review, abnormalities in reelin signaling and the relationship between reelin deficiency and principal neuroendocrine pathways are discussed....

Read abstract  Full text PDF

Comparative Study 2008; 29(6): 953-957 PubMed PMID: 19112399 Citation  Keywords:  Analgesics:administration & dosage, Analysis of Variance, Animals, Anticonvulsants:administration & dosage, Disease Models, Animal, Dose-Response Relationship, Drug, Male, Morphine:administration & dosage, Pain, Postoperative:prevention & control, Piracet.   

OBJECTIVES: Preemptive versus therapeutic effects of levetiracetam were investigated in a model of postoperative incisional pain in rats.

METHODS: Levetiracetam (250, 500, and 1000 mg/kg intraperitoneal (i.p.) or morphine (5 mg/kg i.p.) was administered either 1 h before (preemptive administration) or 1 h after (therapeutic administration) incisional surgery to the hind paw of rats. The effects of levetiracetam were evaluated based on thermal hyperalgesia measured by the plantar test.

RESULTS: All preoperatively treated levetiracetam groups showed a significant, dose dependent, increase in paw withdrawal latency. However, post-incisional administration of levetiracetam produced no antihyperalgesic effect at any dose or at any time. In contrast, post-incisional administration of morphine reduced thermal hyperalgesia, while preemptive administration of morphine did not produce any significant antihyperalgesic effects.

CONCLUSION: The present results suggest that levetiracetam might possess preemptive analgesic activity....

Read abstract  Full text PDF

Journal Article 2008; 29(1): 91-99 PubMed PMID: 18283264 Citation  Keywords:  Aging:genetics, Animals, Antioxidants:adverse effects, Disease Models, Animal, Heredodegenerative Disorders, Nervous System:pathology, Hippocampus:drug effects, Injections, Subcutaneous, Male, Maze Learning:drug effects, Melatonin:administration & dosage,.   

OBJECTIVES: A purpose of this study is to compare the differential effects of melatonin on hippocampal neurodegeneration in accelerated senescence prone mouse-8 (SAMP8) which is initiated treatment at different age.

METHODS: The 4-months old SAMP8 mice were injected subcutaneously with melatonin (1 mg/kg/day) for 4 months. Similar treatments were performed in the 7-months old mice. When the animals were complete 11-months old, a series of tests were performed. Y maze test and Eight-arm radial maze task were used to assess cognitive performance. Hippocampal pyramidal cells were estimated by Nissl's staining. By using Gomori's methenamine silver methods, the methenamine silver staining granules (MSSG) were observed in area CA1 of hippocampus. A computer-assisted morphometric study was carried out on the ultrastructure of perikaryal CA1 pyramidal cell mitochondria. The volume density (Vv), surface density (Sv), numerical density (Nv) and mean volume (V) of the mitochondria were calculated.

RESULTS: Melatonin treatment obviously reduced the deposition of MSSG and elevated hippocampal pyramidal cell number while improving the learning and memory deficits of SAMP8. The mice initiated treatment from 4-months old exhibited a greater response to melatonin supplementation than 7-months old mice. It also decreased mean volume (V) and significantly elevated the Sv and Nv of the mitochondria in hippocampal CA1 region. However, 7-months old mice showed little effects on it.

CONCLUSIONS: Our results indicate that the protective effects of melatonin on hippocampal neurodegeneration of SAMP8 are age dependent....

Read abstract  Full text PDF