Home About us Contact
|
Home About us Contact | ||
|
|
||
Significant Protection (significant + protection)
Selected AbstractsShort-term dietary restriction and fasting precondition against ischemia reperfusion injury in miceAGING CELL, Issue 1 2010James R. Mitchell Summary Dietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long-term restriction, the kinetics of onset of benefits against acute stress is not known. Here, we show that 2,4 weeks of 30% DR improved survival and kidney function following renal ischemia reperfusion injury in mice. Brief periods of water-only fasting were similarly effective at protecting against ischemic damage. Significant protection occurred within 1 day, persisted for several days beyond the fasting period and extended to another organ, the liver. Protection by both short-term DR and fasting correlated with improved insulin sensitivity, increased expression of markers of antioxidant defense and reduced expression of markers of inflammation and insulin/insulin-like growth factor-1 signaling. Unbiased transcriptional profiling of kidneys from mice subject to short-term DR or fasting revealed a significant enrichment of signature genes of long-term DR. These data demonstrate that brief periods of reduced food intake, including short-term daily restriction and fasting, can increase resistance to ischemia reperfusion injury in rodents and suggest a rapid onset of benefits of DR in mammals. [source] Characterization of serum and mucosal antibody responses and relative per cent survival in rainbow trout, Oncorhynchus mykiss (Walbaum), following immunization and challenge with Flavobacterium psychrophilumJOURNAL OF FISH DISEASES, Issue 12 2002B R LaFrentz Abstract Serum and mucosal antibody responses of juvenile rainbow trout, Oncorhynchus mykiss, were characterized by enzyme-linked immunosorbent assay (ELISA) following immunization with various preparations of formalin-killed Flavobacterium psychrophilum cells. The protective nature of these preparations was then determined by immunizing rainbow trout fry and challenging with the bacterium. Juvenile rainbow trout immunized intraperitoneally (i.p.) with formalin-killed F. psychrophilum emulsified with Freund's complete adjuvant (FCA), and i.p. with formalin-killed F. psychrophilum either with or without culture supernatant generated significant serum antibody responses by 6 and 9 weeks, respectively. Significant mucosal antibody responses were detected by 9 weeks only in fish immunized i.p. with killed F. psychrophilum/FCA. Following immunization and bacterial challenge of rainbow trout fry, protective immunity was conferred in F. psychrophilum/FCA and saline/FCA groups with relative per cent survival values of up to 83 and 51, respectively. Significant protection was not observed in treatment groups immunized by immersion or i.p. without adjuvant at the challenge doses tested. Results suggest that stimulation of non-specific immune factors enhances the ability of fish to mount a protective immune response, but specific antibody appears necessary to provide near complete protection. In this study, an ELISA was developed to monitor anti- F. psychrophilum antibody production in trout. The relationship of such responses to protective immunity suggests that future vaccination strategies against coldwater disease may require stimulation of both the innate and adaptive arms of the immune response. [source] Cross-protection elicited in channel catfish (Ictalurus punctatus Rafinesque) immunized with a low dose of virulent Edwardsiella ictaluri strainsAQUACULTURE RESEARCH, Issue 8 2009Victor S Panangala Abstract Cross-protection of channel catfish (Ictalurus punctatus Rafinesque) immunized with a low dose of virulent Edwardsiella ictaluri and challenged with six E. ictaluri strains was examined in four trials. The relative per cent survival among low-dose immunized and then challenged fish ranged from 27.7% to 100%. Significant protection (P<0.05), with the exception of strain ATCC-33202, was conferred by immunization with a given E. ictaluri strain challenged either with a homologous or a heterologous strain. Antibody titres of pooled serum collected on day 22 from surviving fish examined by enzyme-linked immunosorbent assay (ELISA) ranged from 1:40 to 1:320, but no differences were apparent among different vaccinated groups. The protein profiles of six E. ictaluri strains examined by Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a relatively homogeneous pattern. Immuno-blots probed with pooled serum from immunized and challenged fish showed a pattern similar to LPS-reaction patterns observed with E. ictaluri in other studies. Since the present studies further corroborate that E. ictaluri is a clonal bacterial species with no apparent antigenic differences, it is possible that immunization with a single E. ictaluri field strain should confer protection against any other strain. [source] Two similar enhanced root-colonizing Pseudomonas strains differ largely in their colonization strategies of avocado roots and Rosellinia necatrix hyphaeENVIRONMENTAL MICROBIOLOGY, Issue 12 2008Clara Pliego Summary Pseudomonas alcaligenes AVO73 and Pseudomonas pseudoalcaligenes AVO110 were selected previously as efficient avocado root tip colonizers, displaying in vitro antagonism towards Rosellinia necatrix, causal agent of avocado white root rot. Despite the higher number of antagonistic properties shown in vitro by AVO73, only AVO110 demonstrated significant protection against avocado white root rot. As both strains are enhanced root colonizers, and as colonization is crucial for the most likely biocontrol mechanisms used by these strains, namely production of non-antibiotic antifungal compounds and competition for nutrients and niches, we decided to compare the interactions of the bacterial strains with avocado roots as well as with R. necatrix hyphae. The results indicate that strain AVO110 is superior in biocontrol trait swimming motility and establishes on the root tip of avocado plants faster than AVO73. Visualization studies, using Gfp-labelled derivatives of these strains, showed that AVO110, in contrast to AVO73, colonizes intercellular crevices between neighbouring plant root epidermal cells, a microhabitat of enhanced exudation. Moreover, AVO110, but not AVO73, also colonizes root wounds, described to be preferential penetration sites for R. necatrix infection. This result strongly suggests that AVO110 meets, and can attack, the pathogen on the root. Finally, when co-inoculated with the pathogen, AVO110 utilizes hyphal exudates more efficiently for proliferation than AVO73 does, and colonizes the hyphae more abundantly than AVO73. We conclude that the differences between the strains in colonization levels and strategies are likely to contribute to, and even can explain, the difference in disease-controlling abilities between the strains. This is the first report that shows that two similar bacterial strains, selected by their ability to colonize avocado root, use strongly different root colonization strategies and suggests that in addition to the total bacterial root colonization level, the sites occupied on the root are important for biocontrol. [source] Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in miceENVIRONMENTAL TOXICOLOGY, Issue 5 2007R. Jayaraj Abstract Toxic cyanobacteria (blue-green algae) water blooms have become a serious problem in several industrialized areas of the world. Microcystin-LR (MC-LR) is a cyanobacterial heptapeptide that represents acute and chronic hazards to animal and human health. Identification of suitable chemprotectants against microcystin is essential considering human health hazards. In the present study, we have evaluated the protective efficacy of three flavanoids namely quercetin (200 mg/kg), silybin (400 mg/kg), and morin (400 mg/kg)] pretreatment against microcystin toxicity (0.75 LD50, 57.5 ,g/kg) in mice. Various biochemical variables were measured to study the recovery profile of protected animals at 1- and 3-days post-toxin treatment. The serum alanine amino transferase (ALT) shows 17-fold increase in MC-LR treated animals compared with control group at 1 day. The silybin and quercetin group showed a decrease in level of ALT compared with MC-LR group but still higher than control group. No significant protection was observed with aspartate aminotransaminase (AST) and lactate dehydrogenase (LDH) levels in flavanoid-treated groups at 1-day post-treatment. But at 3 days, the serum levels of AST and ALT were normalized to control values, but the serum LDH levels were still significantly higher than the control group. No significant changes were observed in glutathione peroxidase and reduced glutathione levels at both 1- and 3-day postexposure. The catalase activity shows a significant decrease in quercetin-treated animals at 3-day postexposure. The protein phosphatase was significantly inhibited in MC-LR group compared to control. The silybin pretreated group showed recovery after 1 day. At 3 days, the PPAse activity was reversed to control values in all the flavanoid-treated groups. Immunoblotting analysis showed microcystin-PPAse adduct in liver tissues of toxin-treated as well as flavanoid-treated mice even after 3 days. The results of this study show that flavanoids, quercetin, silybin, and morin could reverse the hepatotoxic effects of MC-LR in vivo. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 472,479, 2007. [source] Efficacy of a live equine herpesvirus-1 (EHV-1) strain C147 vaccine in foals with maternally-derived antibody: protection against EHV-1 infectionEQUINE VETERINARY JOURNAL, Issue 5 2004J. R. PATEL Summary Reasons for performing study: Currently, there is no recommended immunoprophylaxis against febrile respiratory diseases due to equine herpesvirus-1 (EHV-1) and -4 (EHV-4) in horses below age 5,6 months. This is because of interference by maternally-derived antibody (MDA) of vaccines. Objective: Unweaned equine foals are an important reservoir of EHV-1 transmission; therefore, we experimentally assessed the efficacy of a live EHV-1 vaccine in foals age 1.4-3.5 months with MDA. Methods: Following vaccination and challenge, parameters assessed were virus shedding in nasal mucus, leucocyte-associated viraemia, circulating virus neutralising antibody activity and clinical reactions. Results: Controlled challenge showed that a single intranasal dose of the vaccine afforded partial but significant protection against febrile respiratory disease, virus shedding and viraemia due to EHV-1 infection, despite virus-neutralising MDA. Conclusions and potential relevance: The prospective vaccine would be a significant step forward in reducing the incidence of the disease caused by EHV-1 infection. [source] Aminoguanidine prevents arterial stiffening in a new rat model of type 2 diabetesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2006K.-C. Chang Abstract Background, Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats. Materials and methods, The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg,1 nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg,1 streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg,1 AG for 8 weeks were compared with the age-matched, untreated, diabetic controls. Results, After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18·8% reduction of aortic characteristic impedance (P < 0·05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23·7%, P < 0·05) and a decrease in wave reflection factor (,26·6%, P < 0·05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. Conclusions, Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall. [source] Modulation of sarcoplasmic reticulum Ca2+ -ATPase by chronic and acute exposure to peroxynitriteFEBS JOURNAL, Issue 13 2004Yolanda Gutiérrez-Martín The Ca2+ -ATPase of skeletal muscle sarcoplasmic reticulum (SERCA), an integral membrane protein, becomes irreversibly inactivated in vitro by the addition of a single bolus of peroxynitrite with a K0.5 of 200,300 µm, and this results in a large decrease of the ATP-dependent Ca2+ gradient across the sarcoplasmic reticulum (SR) membranes. The inactivation of SERCA is raised by treatment of SR vesicles with repetitive micromolar pulses of peroxynitrite. The inhibition of the SERCA is due to the oxidation of thiol groups and tyrosine nitration. Scavengers that react directly with peroxynitrite, such as cysteine, reduced glutathione, NADH, methionine, ascorbate or Trolox, a water-soluble analog of ,-tocopherol, afforded significant protection. However, dimethyl sulfoxide and mannitol, two hydroxyl radical scavengers, and ,-tocopherol did not protect SERCA from inactivation. Our results showed that the target of peroxynitrite is the cytosolic globular domain of the SERCA and that major skeletal muscle intracellular reductants (ascorbate, NADH and reduced glutathione) protected against inhibition of this ATPase by peroxynitrite. [source] Salmonella enteritidis temperature-sensitive mutants protect mice against challenge with virulent Salmonella strains of different serotypesFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2000M.Magdalena Gherardi Abstract The protection conferred by temperature-sensitive mutants of Salmonella enteritidis against different wild-type Salmonella serotypes was investigated. Oral immunization with the single temperature-sensitive mutant E/1/3 or with a temperature-sensitive thymine-requiring double mutant (E/1/3T) conferred: (i) significant protection against the homologous wild-type Salmonella strains; (ii) significant cross-protection toward high challenge doses of S. typhimurium. Significant antibody levels against homologous lipopolysaccharide and against homologous and heterologous protein antigens were detected in sera from immunized mice. Moreover, a wide range of protein antigens from different Salmonella O serotypes were recognized by sera from immunized animals. Besides, primed lymphocytes from E/1/3 immunized mice recognized Salmonella antigens from different serotypes. Taken together, these results indicate that temperature-sensitive mutants of S. enteritidis are good candidates for the construction of live vaccines against Salmonella. [source] RpoS involvement and requirement for exogenous nutrient for osmotically induced cross protection in Vibrio vulnificusFEMS MICROBIOLOGY ECOLOGY, Issue 3 2005Thomas M. Rosche Abstract Vibrio vulnificus is an opportunistic human pathogen which is the causative agent of food-borne disease and wound infections. V. vulnificus is able to adapt to a variety of potentially stressful environmental changes, such as osmotic, nutrient, and temperature variations in estuarine environments, as well as oxidative, osmotic, and acidity differences following infection of a human host. After exposure to sub-lethal levels of a particular environmental stress, many bacteria become resistant to unrelated stresses, a phenomenon termed cross protection. In this study, we examined the ability of osmotic shock to cross protect V. vulnificus to high temperature as well as oxidative stress. Log phase cells of V. vulnificus strain C7184o were cross protected by prior osmotic shock to both heat and oxidative challenge, but only when exogenous nutrient was present during the osmotic upshift. Further, and unlike other bacteria, nutrient starvation alone did not result in cross protection against either stress. When small amounts of nutrient were present during osmotic shock, cross protection to an otherwise lethal heat challenge developed extremely rapidly, with significant protection seen within 10 min. Cross protection to oxidative stress was slower to develop, requiring several hours. Although stationary phase alone conferred some cross protection to heat and oxidative stress, the alternate sigma factor RpoS was required for complete cross protection of log phase cells to oxidative stress but not for resistance to heat challenge. Together these findings suggest that the cross protective response in V. vulnificus is complex and appears to involve multiple mechanisms. [source] Chlamydia pneumoniae infections prevent the programmed cell death on THP-1 cell lineFEMS MICROBIOLOGY LETTERS, Issue 1 2002C.Romano Carratelli Abstract Chlamydia pneumoniae is an obligate intracellular bacterium which frequently causes airway infection in humans and has been implicated in chronic inflammatory disease and atherosclerosis. Here we show that infection with C. pneumoniae protects THP-1 cells against the apoptosis which spontaneously occurs in macrophages in the absence of an activation signal. Analysis by flow cytometry at different post-infection times revealed that 50±7% of THP-1 cells were apoptotic at 48 h after onset of the experiments, whereas C. pneumoniae -infected cultures (multiplicity of infection, MOI = 30) displayed only 18±4% of cells in apoptosis. At MOI = 20 and MOI = 10 the cells susceptible to apoptosis at 48 h were 28±5% and 35±6% respectively. Moreover, the results show that heat-inactivated bacteria do not give significant protection against apoptosis, even at higher MOI (MOI = 30), while UV-treated Chlamydia did provide a degree of protection against apoptosis. These data suggest that the anti-apoptotic effect of C. pneumoniae requires a heat-labile component released during infection, and that the effect is not lipopolysaccharide-dependent. [source] Mitochondrial protection by the JNK inhibitor leflunomide rescues mice from acetaminophen-induced liver injury,HEPATOLOGY, Issue 2 2007Calivarathan Latchoumycandane Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that is safe at therapeutic doses but which can precipitate liver injury at high doses. We have previously found that the antirheumatic drug leflunomide is a potent inhibitor of APAP toxicity in cultured human hepatocytes, protecting them from mitochondria-mediated cell death by inhibiting the mitochondrial permeability transition. The purpose of this study was to explore whether leflunomide protects against APAP hepatotoxicity in vivo and to define the molecular pathways of cytoprotection. Male C57BL/6 mice were treated with a hepatotoxic dose of APAP (750 mg/kg, ip) followed by a single injection of leflunomide (30 mg/kg, ip). Leflunomide (4 hours after APAP dose) afforded significant protection from liver necrosis as assessed by serum ALT activity and histopathology after 8 and 24 hours. The mechanism of protection by leflunomide was not through inhibition of cytochrome P450 (CYP),catalyzed APAP bioactivation or an apparent suppression of the innate immune system. Instead, leflunomide inhibited APAP-induced activation (phosphorylation) of c-jun NH2 -terminal protein kinase (JNK), thus preventing downstream Bcl-2 and Bcl-XL inactivation and protecting from mitochondrial permeabilization and cytochrome c release. Furthermore, leflunomide inhibited the APAP-mediated increased expression of inducible nitric oxide synthase and prevented the formation of peroxynitrite, as judged from the absence of hepatic nitrotyrosine adducts. Even when given 8 hours after APAP dose, leflunomide still protected from massive liver necrosis. Conclusion: Leflunomide afforded protection against APAP-induced hepatotoxicity in mice through inhibition of JNK-mediated activation of mitochondrial permeabilization. (HEPATOLOGY 2007.) [source] Multiple myeloma biology: lessons from the 5TMM modelsIMMUNOLOGICAL REVIEWS, Issue 1 2003Karin Vanderkerken Summary:, Multiple myeloma (MM) is a B cell neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, the development of osteolytic lesions and the induction of angiogenesis. These different processes require three-dimensional interactions, with both humoral and cellular contacts. The 5TMM models are suitable models to study these interactions. These murine models originate from spontaneously developed myeloma in elderly mice, which are propagated by in vivo transfer of the myeloma cells into young syngeneic mice. In this review we report on studies performed in the 5TMM models with special emphasis on the homing of the myeloma cells, the characterization of the migrating and proliferating clone and the identification of the isotype switch variants. The bone marrow microenvironment was further targeted with osteoprotegerin (OPG) to block the RANK/RANKL/OPG system and with potent bisphosphonates. Both treatments resulted in a significant protection against myeloma-associated bone disease, and they decreased myeloma disease, as evidenced by a lower tumor load and an increased survival of the mice. These different studies demonstrate the strength of these models, not only in unraveling basic biological processes but also in the testing of potentially new therapeutic targets. [source] Comparison of alternatives to in-feed antimicrobials for the prevention of clinical necrotic enteritisJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2010M.S. Geier Abstract Aims:, The capacity for Lactobacillus johnsonii and an organic acid (OA) blend to prevent Clostridium perfringens -induced clinical necrotic enteritis (NE) in chickens was studied. Methods and Results:, Cobb 500 birds were allocated into six groups (n = 25 birds/pen, eight pens/treatment); Unchallenged, Challenged, Antimicrobial (zinc bacitracin (ZnB)/monensin), OA, probiotic Lact. johnsonii and probiotic sham (Phosphate,buffered saline). All birds were challenged with Eimeria spp. and Cl. perfringens except for unchallenged controls. Birds fed antimicrobials were protected from NE development as indicated by maintenance of body weight, low mortality and clostridium levels, and decreased intestinal macroscopic lesion scores compared to challenged controls (P < 0·05). Lactobacillus johnsonii -fed birds had reduced lesion scores, whilst OA-fed birds had decreased Cl. perfringens levels. Both Lact. johnsonii and OA-fed birds had improved feed efficiency between days 0 and 28 compared to challenged controls; however, mortality and body weights were not improved by either treatment. Microbial profiling indicated that the challenge procedure significantly altered the jejunal microbiota. The microbiota of antimicrobial-fed birds was significantly different from all other groups. Conclusions:, Whilst Lact. johnsonii and OA altered specific intestinal parameters, significant protection against NE was not observed. Significance and Impact of the Study:,Lactobacillus johnsonii and OA did not prevent NE; however, some improvements were evident. Other related treatments, or combinations of these two treatments, may provide greater protection. [source] Suppression of Rhizoctonia solani diseases of sugar beet by antagonistic and plant growth-promoting yeastsJOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2004K.A. El-Tarabily Abstract Aims:, Isolates of Candida valida, Rhodotorula glutinis and Trichosporon asahii from the rhizosphere of sugar beet in Egypt were examined for their ability to colonize roots, to promote plant growth and to protect sugar beet from Rhizoctonia solani AG-2-2 diseases, under glasshouse conditions. Methods and Results:, Root colonization abilities of the three yeast species were tested using the root colonization plate assay and the sand-tube method. In the root colonization plate assay, C. valida and T. asahii colonized 95% of roots after 6 days, whilst Rhod. glutinis colonized 90% of roots after 8 days. Root-colonization abilities of the three yeast species tested by the sand-tube method showed that roots and soils attached to roots of sugar beet seedlings were colonized to different degrees. Population densities showed that the three yeast species were found at all depths of the rhizosphere soil adhering to taproots up to 10 cm, but population densities were significantly (P < 0·05) greater in the first 4 cm of the root system compared with other root depths. The three yeast species, applied individually or in combination, significantly (P < 0·05) promoted plant growth and reduced damping off, crown and root rots of sugar beet in glasshouse trials. The combination of the three yeasts (which were not inhibitory to each other) resulted in significantly (P < 0·05) better biocontrol of diseases and plant growth promotion than plants exposed to individual species. Conclusions:, Isolates of C. valida, Rhod. glutinis and T. asahii were capable of colonizing sugar beet roots, promoting growth of sugar beet and protecting the seedlings and mature plants from R. solani diseases. This is the first successful attempt to use yeasts as biocontrol agents against R. solani which causes root diseases. Significance and Impact of the Study:, Yeasts were shown to provide significant protection to sugar beet roots against R. solani, a serious soil-borne root pathogen. Yeasts also have the potential to be used as biological fertilizers. [source] Catechin as an antioxidant in liver mitochondrial toxicity: Inhibition of tamoxifen-Induced protein oxidation and lipid peroxidation,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2007Heena Tabassum Abstract Tamoxifen (TAM) is a nonsteroidal triphenylethylene antiestrogenic drug widely used in the treatment and prevention of breast cancer. TAM brings about a collapse of the mitochondrial membrane potential. It acts both as an uncoupling agent and as a powerful inhibitor of mitochondrial electron transport chain. The effect of catechin pretreatment on the mitochondrial toxicity of TAM was studied in liver mitochondria of Swiss albino mice. TAM treatment caused a significant increase in the mitochondrial lipid peroxidation (LPO) and the protein carbonyls (PCs). It also caused a significant increase in superoxide radical production. Pretreatment of mice with catechin (40 mg/kg) showed significant protection as demonstrated by marked attenuation of increased oxidative stress parameters such LPO, PCs, and superoxide production. It also restored the decreased nonenzymatic and enzymatic antioxidants of mitochondria. The inhibitory effect of catechin on TAM-induced oxidative damage suggests that it may have potential benefits in prevention of human diseases where reactive oxygen species have some role as causative agents. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:110,117, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20167 [source] Long-Term Sensitivity of Uterus and Hypothalamus/Pituitary Axis to 17,-Estradiol Is Higher Than That of Bone in Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2004Reinhold G Erben MD Abstract We examined the long-term sensitivity of uterus and bone to low-dose 17,-estradiol in a 4-month experiment in OVX rats and found that a dose of estradiol that fully protected against uterine atrophy did not protect against bone loss. Our results suggest higher estrogen sensitivity of the uterus compared with bone. Introduction: Estrogen is essential for the function of reproductive tissues and for the normal acquisition and maintenance of bone mass in females. This study was designed to examine the long-term sensitivity of the uterus and bone to low-dose estrogen. Materials and Methods: In preliminary experiments, we determined the lowest subcutaneous dose of 17,-estradiol able to fully protect against uterine atrophy in ovariectomized (OVX) rats. This dose was found to be 1.5 ,g/kg, given five times per week. Subsequently, groups of sham-operated (SHAM) or OVX 6-month-old rats (n = 8 each) were subcutaneously injected with vehicle or 1.5 ,g/kg 17,-estradiol five times per week. All animals were killed 4 months after surgery. Serum osteocalcin and urinary deoxypyridinoline were measured as biochemical markers of bone turnover. Bones were analyzed by bone histomorphometry and pQCT. Results and Conclusions: Our study clearly showed that a dose of estradiol that restores physiological estradiol serum levels, fully maintains uterine weight in OVX rats at the SHAM control level, and suppresses serum follicle-stimulating hormone (FSH) by 67% relative to OVX vehicle controls does not provide significant protection against OVX-induced bone loss at different cancellous and cortical bone sites. We conclude that the long-term sensitivity of the uterus and the hypothalamus/pituitary axis to 17,-estradiol is higher than that of bone in rats. [source] Cell-penetrating peptide TAT-mediated delivery of acidic FGF to retina and protection against ischemia,reperfusion injury in ratsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 7 2010Yi Wang Abstract The development of non-invasive ocular drug delivery systems is of practical importance in the treatment of retinal disease. In this study, we evaluated the efficacy of transactivator of transcription protein transduction domain (TAT-PTD, TAT49,57) as a vehicle to deliver acidic FGF (aFGF) to retina in rats. TAT-conjugated aFGF-His (TAT-aFGF-His) exhibited efficient penetration into the retina following topical administration to the ocular surface. Immunochemical staining with anti-His revealed that TAT-aFGF-His proteins were readily found in the retina (mainly in the ganglion cell layer) at 30 min. and remained detectable for at least 8 hrs after administration. In contrast, His+ proteins were undetectable in the retina after topical administration of aFGF-His, indicating that aFGF-His cannot penetrate the ocular barrier. Furthermore, TAT-aFGF-His, but not aFGF-His, mediated significant protection against retinal ischemia,reperfusion (IR) injury. After IR injury, retina from TAT-aFGF-His-treated rats showed better-maintained inner retinal layer structure, reduced apoptosis of retinal ganglion cells and improved retinal function compared to those treated with aFGF-His or PBS. These results indicate that conjugation of TAT to aFGF-His can markedly improve the ability of aFGF-His to penetrate the ocular barrier without impairing its biological function. Thus, TAT49,57 provides a potential vehicle for efficient drug delivery in the treatment of retinal disease. [source] Amoebic gill disease resistance is not related to the systemic antibody response of Atlantic salmon, Salmo salar L.JOURNAL OF FISH DISEASES, Issue 1 2010R S Taylor Abstract Amoebic gill disease (AGD) is a proliferative gill tissue response caused by Neoparamoeba perurans and is the main disease affecting Australian marine farmed Atlantic salmon. We have previously proposed that macroscopic gill health (,gill score') trajectories and challenge survival provide evidence of a change in the nature of resistance to AGD. In order to examine whether the apparent development of resistance was because of an adaptive response, serum was sequentially sampled from the same individuals over the first three rounds of natural AGD infection and from survivors of a subsequent non-intervention AGD survival challenge. The systemic immune reaction to ,wildtype'Neoparamoeba sp. was characterized by Western blot analysis and differentiated to putative carbohydrate or peptide epitopes by periodate oxidation reactions. The proportion of seropositive fish increased from 46% to 77% with each AGD round. Antibody response to carbohydrate epitope(s) was immunodominant, occurring in 43,64% of samples. Antibodies that bound peptide epitope were identified in 16% of the challenge survivors. A 1:50 (single-dilution) enzyme-linked immunosorbent assay confirmed a measurable immune titre in 13% of the survivors. There was no evidence that antibodies recognizing wildtype Neoparamoeba provided significant protection against AGD. [source] Neuroprotection with caspase-9 inhbition against in vitro and in vivo traumaJOURNAL OF NEUROCHEMISTRY, Issue 2002R. A. Wallis Objective:, To evaluate the neuroprotective efficacy of the cell-permeable caspase-9 inhibitor, LEHD-CHO, against in vitro and in vivo traumatic neuronal injury. Methods:, The neuroprotective potential of LEHD-CHO was assessed in vitro using rat hippocampal slices. CA1 orthodromic and antidromic population spike (PS) amplitude was monitored before and after fluid percussion injury in slices treated with or without LEHD-CHO. Final recovery of PS amplitude was assessed 95 min after trauma. Studies of in vivo neuroprotection with LEHD-CHO utilized a model of controlled cortical impact (CCI). Rats were given either LEHD-CHO (10 nmol icv) or an equal volume of vehicle at 5 min following CCI. Rats were perfused 24 h after CCI and brains were processed for histological examination. Results:, LEHD-CHO provided significant protection against loss of CA1 evoked response after fluid percussion. The EC50 for LEHD-CHO protection of CA1 orthodromic and antidromic PS amplitude against trauma was 2.1 ,m and 2.3 ,m. Protection extended to preservation of LTP after trauma. In vivo treatment with LEHD-CHO significantly decreased the appearance of eosinophilic cells in the CA1 region after CCI from 131 ± 23 cells in vehicle-treated animals to 24 ± 5 in LEHD-CHO treated animals. Extensive labelling with TUNEL staining was seen in vehicle-treated animals, whereas sections from LEHD-CHO treated animals demonstrated little staining. Conclusions:, These findings indicate that the caspase 9 inhibitor LHED-CHO provides concentration-dependent protection against in vitro CA1 neuronal injury, which extends to protection against in vivo CA1 injury from CCI. They further suggest that inhibition of caspase 9 may be a useful treatment strategy for traumatic brain injury. Acknowledgement:, Supported by VA Research and UCLA BIRC. [source] Lipid Alterations in Transient Forebrain IschemiaJOURNAL OF NEUROCHEMISTRY, Issue 6 2000Possible New Mechanisms of CDP-Choline Neuroprotection Abstract: We have previously demonstrated that cytidine5,-diphosphocholine (CDP-choline or citicoline) attenuated arachidonicacid (ArAc) release and provided significant protection for the vulnerablehippocampal CA1 neurons of the cornu ammonis after transientforebrain ischemia of gerbil. ArAc is released by the activation ofphospholipases and the alteration of phosphatidylcholine (PtdCho) synthesis.Released ArAc is metabolized by cyclooxygenases/lipoxygenases to formeicosanoids and reactive oxygen species (ROS). ROS contribute to neurotoxicitythrough generation of lipid peroxides and the cytotoxic byproducts4-hydroxynonenal and acrolein. ArAc can also stimulate sphingomyelinase toproduce ceramide, a potent pro-apoptotic agent. In the present study, weexamined the changes and effect of CDP-choline on ceramide and phospholipidsincluding PtdCho, phosphatidylethanolamine (PtdEtn), phosphatidylinositol(PtdIns), phosphatidylserine (PtdSer), sphingomyelin, and cardiolipin (anexclusive inner mitochondrial membrane lipid essential for electron transport)following ischemia/1-day reperfusion. Our studies indicated significantdecreases in total PtdCho, PtdIns, PtdSer, sphingomyelin, and cardiolipin andloss of ArAc from PtdEtn in gerbil hippocampus after 10-min forebrainischemia/1-day reperfusion. CDP-choline (500 mg/kg i.p. immediately afterischemia and at 3-h reperfusion) significantly restored the PtdCho,sphingomyelin, and cardiolipin levels as well as the ArAc content of PtdChoand PtdEtn but did not affect PtdIns and PtdSer. These data suggest multiplebeneficial effects of CDP-choline: (1) stabilizing the cell membrane byrestoring PtdCho and sphingomyelin (prominent components of outer cellmembrane), (2) attenuating the release of ArAc and limiting its oxidativemetabolism, and (3) restoring cardiolipin levels. [source] p -quinone mediates 6-hydroxydopamine-induced dopaminergic neuronal death and ferrous iron accelerates the conversion of p -quinone into melanin extracellularlyJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Yasuhiko Izumi Abstract Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN). 6-Hydroxydopamine (6-OHDA), a dopaminergic neurotoxin, is detected in human brains and the urine of PD patients. Using SH-SY5Y, a human neuroblastoma cell line, we demonstrated that 6-OHDA toxicity was determined by the amount of p -quinone produced in 6-OHDA auto-oxidation rather than by reactive oxygen species (ROS). Glutathione (GSH), which conjugated with p -quinone, provided significant protection whereas catalase, which detoxified hydrogen peroxide and superoxide anions, failed to block cell death caused by 6-OHDA. Although iron accumulated in the SN of patients with PD can cause dopaminergic neuronal degeneration by enhancing oxidative stress, we found that extracellular ferrous iron promoted the formation of melanin and reduced the amount of p -quinone. The addition of ferrous iron to the culture medium inhibited caspase-3 activation and apoptotic nuclear morphologic changes and blocked 6-OHDA-induced cytotoxicity in SH-SY5Y cells and primary cultured mesencephalic dopaminergic neurons. These data suggested that generation of p -quinone played a pivotal role in 6-OHDA-induced toxicity and extracellular iron in contrast to intracellular iron was protective rather than harmful because it accelerated the conversion of p -quinone into melanin. © 2005 Wiley-Liss, Inc. [source] The pharmacological potential of Sorbus commixta cortex on blood alcohol concentration and hepatic lipid peroxidation in acute alcohol-treated ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2006Syng-Ook Lee The effect of Sorbus commixta cortex, a traditional herbal medicine used for the treatment of bronchitis, gastritis and dropsy, on blood alcohol concentration (BAC) and hepatic lipid peroxidation was examined in acute alcohol-treated rats. A 30-min pretreatment with a methanol extract of S. commixta cortex (SC) at concentrations higher than 200 mg kg,1 resulted in a significant decrease in BAC and the ethyl acetate fraction (SE) of the extract showed the highest potency, with a maximum of a 46% decrease at 150 mg kg,1 2h after alcohol administration (3.0 g kg,1) compared with the control group (P < 0.005). The rapid reduction in BAC did not appear to be due to the protection or activation of hepatic alcohol dehydrogenase (ADH) activity by SE. Hepatic malondialdehyde (MDA) levels were significantly increased by acute alcohol administration within 6h, although pretreatment with the SE caused a significant decrease in MDA levels compared with alcohol treatment alone. Hepatic glutathione (GSH) levels and superoxide dismutase (SOD) activity remained unchanged by alcohol, SE alone or by the combined treatment of alcohol and SE. However, catalase activity was significantly reduced by acute alcohol administration and pretreatment with the SE led to significant protection of its activity. These results suggest that pretreatment with SE reduces hepatic lipid peroxidation by decreasing the bioavailability of alcohol and its oxidative metabolites, such as H2O2, at least partly, through the protection of hepatic catalase in acute alcohol-treated rats. [source] Melatonin protects against cardiac toxicity of doxorubicin in ratJOURNAL OF PINEAL RESEARCH, Issue 4 2001Mei Feng Xu Doxorubicin (DOX) is commonly used for the treatment of hematological and solid tumors. However, there are serious toxic effects on the cardiovascular system, which limits the application of the drug. Recently, melatonin has been reported to have immunomodulatory effect in addition to lowering cholesterol levels as well as inhibiting malignant tumors. In this study, the effect of melatonin against the toxicity of doxorubicin was investigated in rats. Hemodynamic function, pathological and biochemical changes were determined in different treated hearts. Our findings showed that a significant protection by melatonin (6 mg kg,1 for 15 days, cumulative dose of 90 mg kg,1) against the DOX-induced toxicity was observed. Cardiac function was improved and lipid peroxidation decreased after melatonin treatment. It is concluded that melatonin provides protection against doxorubicin toxicity via an attenuation of lipid peroxidation. [source] Photoprotection of bacterial-derived melanin against ultraviolet A,induced cell death and its potential application as an active sunscreenJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 7 2008J Geng Abstract Background, The increase in the incidence of non-melanoma skin tumours, photoaging, and immunosuppression demand for more effective sunscreen on ultraviolet A (UVA) irradiation. Objectives, The aim of the study is to evaluate the photoprotective effects of a bacterial-derived melanin against UVA-induced damages in vitro and in vivo. Methods, Human fibroblasts were used to assess the role of the bacterial-derived melanin on cell viability against UVA. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and nuclear morphology were employed to evaluate the photoprotection at the cellular level. Fluorometric assays were performed to detect the formation of reactive oxygen species (ROS) in the cells. Evaluations of the bacterial-derived melanin as a sunscreen were measured by transmission test and persistent pigment darkening on human skin. Results, Bacterial-derived melanin efficiently scavenged ROS in the fibroblasts after UVA irradiation. The cell viability of xeroderma pigmentosum (XP) fibroblast treated with varied doses of melanin increased dramatically in comparison with untreated control and the treated XP fibroblasts became more resistant to UVA-induced apoptosis than normal fibroblasts. Although the relative transmission didn't change too much with different concentration of bacterial-derived melanin, this melanin could keep UVA-irradiated skin from pigment darkening and act as an active sunscreen on skin. Conclusions, The bacterial-derived melanin provided significant protection to fibroblast cell and human skin against the UVA radiation. It has the potential to be developed as an active sunscreen for the patients with photosensitivity skin to sun exposure. [source] Evaluation of aluminide diffusion coatings for thermal cyclic oxidation protection of a nickel-base superalloyMATERIALS AND CORROSION/WERKSTOFFE UND KORROSION, Issue 10 2005A. Elsawy Abstract Active element modified aluminide diffusion coatings on IN738 substrates were produced by a new route using continuously cast, aluminum alloy wires consisting of Al-Y, Al-Ce, Al-La and Al-Si-Y. The cast wires were used as evaporation sources for ion-vapour deposition followed by diffusion heat treatments to form nickel aluminide coatings. In order to examine the oxidation resistance of these coatings at elevated temperatures, thermal cyclic oxidation experiments were carried out in air at 1050°C. While all coatings were found to provide significant protection, the Al-La modified coatings provided the greatest resistance to cyclic oxidation. On the other hand, with coatings based on Al-Si-Y alloys, while silicon has a strong ability to reduce the outward diffusion of aluminum, the adverse effect of silicon on mechanical properties of the coating, together with the formation of volatile silicon monoxide, led to catastrophic localized oxidation of the protective coatings. [source] Minocycline treatment following hypoxic/ischaemic injury attenuates white matter injury in a rodent model of periventricular leucomalaciaNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2008M. Lechpammer Aims: Periventricular white matter injury in premature infants occurs following hypoxia/ischaemia and systemic infection, and results in hypomyelination, as well as neuromotor and cognitive deficits later in life. Inflammatory infiltrates are seen within human cerebral white matter from periventricular leucomalacia (PVL) cases. Methods: In this study, we examine the time course of CD-68+ microglial cell responses relative to cell death within white matter following hypoxia/ischaemia in a rat model of PVL. We also tested the efficacy of the minocycline, an agent that suppresses microglial activation, in this model when administered as a post-insult treatment. Results: We show that preoligodendrocyte injury in the post-natal day 6 begins within 24 h and continues for 48,96 h after hypoxia/ischaemia, and that microglial responses occur primarily over the first 96 h following hypoxia/ischaemia. Minocycline treatment over this 96 h time window following the insult resulted in significant protection against white matter injury, and this effect was concomitant with a reduction in CD-68+ microglial cell numbers. Conclusions: These results suggest that anti-inflammatory treatments may represent a useful strategy in the treatment of PVL, where clinical conditions would favour a post-insult treatment strategy. [source] Antibodies to surface epitopes of the carbohydrate larval antigen CarLA are associated with passive protection in strongylid nematode challenge infectionsPARASITE IMMUNOLOGY, Issue 11-12 2008G. B. L. HARRISON SUMMARY Sheep were immunized by multiple truncated infections with the gastrointestinal nematodes Trichostrongylus colubriformis, Haemonchus contortus and Teladorsagia circumcincta. Three infections with T. colubriformis of 14 days plus five booster doses of L3 stimulated highly effective protection against challenge (99%). Three infections of 14 days plus three booster doses with H. contortus also resulted in significant protection against challenge infection (87%), but the same procedure was not effective for T. circumcincta. Antibodies derived from gastrointestinal mucus of these immunized sheep were tested for their ability to reduce worm burden following injection of antibody-coated exsheathed larvae into the abomasum (H. contortus and T. circumcincta) or duodenum (T. colubriformis) of nematode-naďve sheep in a passive immunity test. The IgG fraction from the mucus of immunized sheep reduced worm burdens by 62%, 76% and 91% in three tests with T. colubriformis but was not effective for either of the abomasal dwelling nematodes H. contortus and T. circumcincta. Antibodies in immune mucus predominantly recognized two larval surface antigens on immunoblots of L3 extract, a high MW surface glycoprotein and the carbohydrate larval antigen (CarLA). Antibodies raised against purified T. colubriformis glycoprotein Tc-120 and CarLA were tested in the passive immunity model and it was found that only the antibody against CarLA resulted in a significant reduction of infection (87%). The protective anti-CarLA antibodies strongly recognized the surface of living T. colubriformis L3. Antibodies from abomasal mucus of sheep immunized by H. contortus and T. circumcincta infections reacted weakly with CarLA and the larval surface and did not reduce worm counts in a passive immunity test. The results provide further evidence that the larval surface carbohydrate antigen CarLA has potential as a mucosal immunogen for a strongylid nematode vaccine. [source] Protective effects of 3,-deoxy-4-O-methylepisappanol from Caesalpinia sappan against glutamate-induced neurotoxicity in primary cultured rat cortical cellsPHYTOTHERAPY RESEARCH, Issue 3 2010Hyung-In Moon Abstract To examine the neuroprotective effects of Caesalpinia sappan L., we tested its protection against the glutamate-induced neurotoxicity in primary cortical cultured neurons. We found that an aqueous extract of this medicinal plant exhibited significant protection against glutamate-induced toxicity in primary cultured rat cortical cells. In order to clarify the neuroprotective mechanism(s) of this observed effect, isolation was performed to seek and identify active fractions and components. By such fractionation, two known compounds , sappanchalcone and 3,-deoxy-4-O-methylepisappanol , were isolated from the methanol extracts from the air-dried and chipped C. sappan. Among these two compounds, 3,-deoxy-4-O-methylepisappanol exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viability of about 50%, at concentrations ranging from 0.1,,M to 10,,M. Therefore, the neuroprotective effect of C. sappan might be due to the inhibition of glutamate-induced toxicity by the protosappanin derivative it contains. Copyright © 2009 John Wiley & Sons, Ltd. [source] Protective effect of resveratrol on markers of oxidative stress in human erythrocytes subjected to in vitro oxidative insultPHYTOTHERAPY RESEARCH, Issue S1 2010Kanti Bhooshan Pandey Abstract Resveratrol is a natural polyphenolic compound found largely in the skin of red grapes. Growing evidence suggests that resveratrol may play an important role in the prevention of many human diseases. Many of the biological actions of this polyphenol have been attributed to its antioxidant properties. The present study was undertaken to evaluate the effect of resveratrol on intracellular reduced glutathione (GSH) and membrane sulphydryl groups in erythrocytes subjected to oxidative stress in vitro by incubating with t-BHP (10 µm). The study was aimed to test the efficacy of the antioxidant effect of resveratrol on human erythrocytes. Subjecting erythrocytes to oxidative stress (in vitro) by incubating them with t-BHP (10 µm) caused a significant decrease in the intracellular GSH level and membrane ,SH content compared with basal values. Incubation of erythrocytes/membranes with resveratrol (1,100 µm final conc) resulted in significant protection against the t-BHP-induced oxidative stress as evidenced by the increase in GSH level and membrane ,SH content. It was observed that the effect of resveratrol is dose/concentration and time-dependent. Since resveratrol is naturally present in many fruits and vegetables, a diet rich in resveratrol may provide protection against degenerative diseases. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||