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Comparative Study 2007; 28(2): 166-169 PubMed PMID: 17435668 Citation  Keywords:  Adiponectin:blood, Animals, Inflammation:chemically induced, Injections, Intraperitoneal, Lipopolysaccharides, Male, Pituitary Adenylate Cyclase-Activating Polypeptide:administration & dosage, Rats, Rats, Inbred WKY,.   

BACKGROUND: Pituitary adenylate cyclase activating peptide (PACAP 38) is a neuropeptide with anti-inflammatory activity. Vasoactive intestinal peptide (VIP)/PACAP receptors are found in immune cells, endocrine glands and also in adipose tissue. Adiponectin is an adipocyte-derived protein hormone which possesses anti-inflammatory, antidiabetic and antiatherogenic properties. The aim of this study was to examine the influence of PACAP 38 on adiponectin release in basal conditions and during lipopolysaccharide (LPS)-induced acute inflammation.

METHODS: Male Wistar-Kyoto rats were divided into four groups which received intraperitoneal injections of 0.9% NaCl, LPS, PACAP 38 or LPS+PACAP 38, respectively. Serum adiponectin concentrations were measured using an ELISA test.

RESULTS: LPS administration did not change adiponectin concentration; however, PACAP 38 administered alone decreased serum adiponectin concentration after 2 h (p<0.05) and 4 h (p<0.01). In the group that received LPS+PACAP38, compared with LPS alone, no difference in adiponectin concentration was observed.

CONCLUSIONS: We conclude that PACAP 38 may directly modulate adiponectin secretion by adipocytes in basal conditions....

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Journal Article 2006; 27(Suppl 2): 172-175 PubMed PMID: 17159808 Citation  Keywords:  Animals, Arthritis, Experimental:enzymology, Biomarkers:analysis, Body Weight:drug effects, Joints:enzymology, Male, Mannans:pharmacology, Rats, Rats, Inbred Lew, Spleen:enzymology, gamma-Glutamyltransferase:metabolism,.   

OBJECTIVES: To assess glucomannan and pyridoindole derivatives for possible antioxidant therapy of rheumatoid arthritis (RA) by using the model of adjuvant arthritis (AA). We evaluated the association between clinical markers of the adjuvant arthritis model used - increase of hind paw volume (HPV), changes of body mass (CBM), and tissue gamma-glutamyl transferase (GGT) activity assessed in the spleen and the joint.

METHODS: AA was induced in Lewis rats by a single intradermal injection of Mycobacterium butyricum. The two independent experiments included healthy animals as reference, arthritic animals without any drug administration and arthritic animals with pyridoindole administration in one dose tested or glucomannan administration in two different doses. The pyridoindoles (PI) studied were stobadine dipalmitate and its derivatives SMe1.2HCl and SMe1EC2.HCl. We monitored CBM and HPV twice a week. Parameter of inflammation - GGT in the spleen and the joint from the hind paw (cartilage and soft tissue without bone) was determined on day 28. The correlation coefficient of GGT activity with CBM and with HPV was calculated.

RESULTS: The antioxidants tested were effective in slowing down the progress of adjuvant arhritis. The association between tissue GGT activity and the clinical marker of adjuvant arthritis - CBM was higher in the spleen than in the joint. The other clinical marker assessed - HPV, gave a better association with GGT activity measured in the joint than in the spleen.

CONCLUSIONS: It may be concluded that GGT activity in tissues as the spleen and the joint could provide a simple and inexpensive marker for AA and RA development at systemic as well as local level; all the antioxidants studied were effective in slowing down the progress of adjuvant arhritis....

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Comparative Study 2006; 27(Suppl 2): 96-99 PubMed PMID: 17159789 Citation  Keywords:  Animals, Drug Compounding, Female, Magnetics, Metal Nanoparticles:analysis, Mice, Mice, Inbred ICR, Polyesters:chemistry, Toxicity Tests,.   

OBJECTIVES: The acute toxicity of magnetic nanoparticles was effectively lowered by their encapsulation with poly(D,L lactide). In relation to the idea to use magnetic nanoparticles in development of new delivery systems suitable for targeted drug administration, the toxicological profile of five types of magnetic fluids was assessed in mice.

METHODS: The nanoprecipitation method was used to prepare magnetic fluids containing nanoparticles of Fe(3)O(4) encapsulated with biodegradable substances. The acute toxicity testing was performed according to OECD Test Guideline 425. In the pilot distribution study a special staining method was examined for the detection of Fe ions in body tissues of mice after intravenous administration of magnetic fluids.

RESULTS: The p.o. LD(50) values were greater than 2,000.0 mg/kg of body weight and i.v. LD(50) values were in the range of 231.7-558.9 mg/kg of body weight.

CONCLUSIONS: Of the magnetic nanoparticles tested, those encapsulated with poly(D,L lactide) were the most prospective for further in vivo testing....

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Comparative Study 2006; 27(Suppl 2): 48-52 PubMed PMID: 17159778 Citation  Keywords:  Animals, Antineoplastic Agents:pharmacology, Apoptosis:drug effects, Cell Cycle:drug effects, Cell Proliferation:drug effects, Female, Guinea Pigs, HeLa Cells, Humans, Mice, Mice, Inbred ICR, Rabbits, Salivary Glands:chemistry, Ticks:chemistry, Tissue Ext.   

OBJECTIVES: The anti-proliferative and apoptotic potential of salivary gland extracts (SGE) of unfed and partially fed adult ixodid ticks were screened using human HeLa cells.

METHODS: Cell growth inhibition activity of SGE was measured by the MTT assay. Cell cycle analysis and quantification of DNA fragmentation was performed by DNA staining with propidium iodide. Annexin V-FITC was used to detect apoptotic cells.

RESULTS: SGE of all ticks examined suppressed HeLa cell proliferation in a dose dependent manner. Extracts from 2-day fed R. appendiculatus females (IC(50) 0.22 mg/ml SGE soluble protein) and 9-day fed A. variegatum females (IC(50) 0.30 mg/ml) were most potent. Species-specific differences in the anti-proliferative effects of SGE were revealed, suggesting that the amount of active compounds in tick salivary glands change during feeding. Total apoptosis (about 12%) and no significant alteration in cell cycle were confirmed for SGE of A. variegatum and R. appendiculatus, and additionally SGE of 5-day fed I. ricinus females (IC(50) 0.64 mg/ml).

CONCLUSIONS: The study shows that tumour cell growth suppressant(s) and/or apoptotic triggers are present in tick salivary glands, however, further research into the characteristics and mode of action of such natural substances is necessary....

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Comparative Study 2006; 27(5): 623-630 PubMed PMID: 17159820 Citation  Keywords:  Adenine Nucleotides:analysis, Adenosine Triphosphatases:metabolism, Adenosine Triphosphate:biosynthesis, Animals, Diaphragm:drug effects, Melatonin:pharmacology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Muscle:chemistry, Muscle, Skeletal:ch.   

OBJECTIVES: To evaluate the changes in the mitochondrial ATP production during sepsis and the participation of iNOS in these changes. We also assessed the effect of melatonin administration in this experimental paradigm.

METHODS: The activity of ATPase, the level of adenine nucleotides, and the ATP production were measured in mitochondria of diaphragm and hind leg skeletal muscle of wild type (iNOS+/+) and knockout iNOS (iNOS-/-) mice. Three experimental groups were done: control group; group of septic mice induced by cecal ligation and puncture (CLP), and group of septic mice treated with melatonin. Mice were killed 24 hours after CLP. Melatonin was administrated in four doses (30 mg/kg b.w.) as follows: 30 min before CLP (i.p.) and 30 min, 4 h and 8 h after CLP (s.c.).

RESULTS: Mitochondrial production of ATP decreased in iNOS+/+ but not in iNOS-/- mice after sepsis. No changes in the ATPase activity were found in any group. Melatonin treatment normalized the production of ATP in iNOS+/+ mice, without affecting iNOS-/- animals.

CONCLUSIONS: The reduction of the ATP production in iNOS+/+ but not in iNOS-/- mice suggest the participation of iNOS in the impairment of mitochondrial function in the former. Because ATPase was unaffected by sepsis, it is suggested the ATP deficit depended on the sepsis-induced respiratory chain damage. The normalization of the production of ATP with melatonin may explain the reduction of the mortality reported elsewhere in experimental and clinical sepsis after treatment with the indoleamine....

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Journal Article 2006; 27(1-2): 177-182 PubMed PMID: 16670672 Citation  Keywords:  Animals, Antigens:genetics, Cell Count, Cerebral Cortex:cytology, Female, Immunohistochemistry, Leptin:pharmacology, Mice, Mice, Inbred ICR, Oligodendroglia:drug effects, Pregnancy, Proteoglycans:genetics, Receptor, Platelet-Derived Growth Factor alpha:bi.   

OBJECTIVE: Leptin, which is an obese gene product, decreases appetite and increases energy expenditure in adults. In our previous study, leptin was found to maintain neural stem cells and/or progenitor cells, preferentially astrocyte/oligodendrocyte progenitor cells, whereas it reduces the proportion of oligodendrocyte lineage-restricted precursor cells. It has been reported that leptin-deficient (ob/ob) mice have lower levels of glial proteins than wild-type mice. These findings suggest that leptin affects the development of glial cells. In this study, therefore, we investigated oligodendrocyte development in the cerebral cortex of ob/ob and wild-type mouse embryos by histochemistry.

METHODS: We obtained ob/ob or wild-type (C57BL/6J) embryos on embryonic day (E) 18. We performed immunohistochemistry in the embryonic cerebrum with antibodies against NG2, platelet-derived growth factor receptor-alpha (PDGFR-alpha) and leptin receptor (Ob-R). In the cerebral cortex, we compared the number of the oligodendrocyte precursor cells (OPCs), which are immunopositive for NG2 and/or PDGFR-alpha, between ob/ob and wild-type embryos.

RESULTS: We revealed that ob/ob embryos had significantly more OPCs than wild-type embryos on E18. PDGFR-alpha-positive OPCs did not coexpress leptin receptor in the cerebral cortex.

CONCLUSION: These findings suggest that leptin inhibits differentiation of multipotent and/or glial progenitor cells into OPCs in the mouse embryonic cerebral cortex, but it does not directly act on OPCs....

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Journal Article 2006; 27(1-2): 257-259 PubMed PMID: 16648808 Citation  Keywords:  Animals, Bombesin:pharmacology, Estradiol:pharmacology, Estrogens:pharmacology, Female, Injections, Intraventricular, Luteinizing Hormone:antagonists & inhibitors, Ovariectomy, Rats, Rats, Inbred WKY,.   

OBJECTIVE: Bombesin, 14-amino acid peptide, discovered in the gastrointestinal tract, is widely distributed in the central nervous system (CNS). The specific receptors of bombesin in the pituitary have been characterized. Bombesin plays an important role in the gastric and pancreatic secretion, in the mechanism of food intake, thermoregulation and in pituitary hormone secretion. There are contentious opinions about the effect of bombesin on hormone secretion.

THE AIM: The aim of this study was to evaluate the effect of estrogens in the modulation of bombesin action on LH release.

RESEARCH METHODS: Female Wistar-Kyoto rats, two weeks after ovariectomy (OVX), were implanted with a cannula being located in the third cerebroventricle. Thereafter, the rats were primed with 17beta estradiol in a dose of 25microg/0.2ml s.c. for three consecutive days. On the day of the experiment, bombesin at a concentration of 0.5 microg in 5microl vehicle (artificial cerebrospinal fluid) or equal volume of the vehicle was infused into the third ventricle with an automatic pump. At 60 or 120 min after the infusion the animals were decapitated, and the trunk blood was collected. Rat serum LH was measured by RIA kit supplied by Dr A.F. Parlow from NIDDK Baltimore, MD.

RESULTS: Bombesin inhibited LH release at 120 min and it did not change LH release at 60 min after icv administration.

CONCLUSIONS: The response of LH release after central injection of bombesin is modified by estrogens....

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Journal Article 2006; 27(1-2): 153-156 PubMed PMID: 16648801 Citation  Keywords:  Animals, Cells, Cultured, Dose-Response Relationship, Drug, Growth Hormone:metabolism, Male, Neuropeptides:pharmacology, Pituitary Gland:cytology, Radioimmunoassay, Rats, Rats, Inbred WKY,.   

OBJECTIVE: Cortistatin (CST) is a 17-amino acid neuropeptide expressed mainly in the cortex and hippocampus. It is also found in the peripheral tissues such as the stomach, kidney, pancreas and the immune system. Two forms of cortistatin CST-17, CST-29 bind with high affinity all somatostatin (SS) receptor subtypes. It has been reported that a receptor called MrgX(2) is able to selectively bind both CST-17 and CST-14 rather than SS. In human tissues CST-17 and CST-29, rather than SS, also bind ghrelin receptor GHS-r1a. In in vivo experiments CST inhibited GH and insulin secretion.

THE AIM: The aim of this study was to evaluate the effect of cortistatin on GH release in in vitro experiments.

RESEARCH METHODS: CST-14 and SS-14 in doses of 1nMol, 10nMol, and 100nMol were added after 48 hrs of pituitary cell culture, and the medium was collected 30, 60, 120, 240 min thereafter. rGH was measured with RIA kits provided by Linco.

RESULTS: CST-14 stimulated GH release from cultured pituitary cells in a dose dependent manner. The maximum effect of CST-14 was observed after 60 min of incubation. However, SS-14 in doses of 10 nMol and 100 nMol inhibited GH release.

CONCLUSION: A direct stimulating effect of Cortistatin-14 on GH release from cultured pituitary cells was found....

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