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Protective effect of prostaglandin E1 against ischemia of spinal cord during aortic cross clamping.

PURPOSE: The purpose of this study was to investigate whether or not 5-minute segmental intraaortic perfusion of prostaglandin E1 (PGE1) in the preischemic period has a protective effect against spinal cord ischemia during aortic cross clamping. METHODS: The rabbits were divided into two groups. In group A (n = 6), the infrarenal aorta was segmentally cross clamped and the segment was perfused for 5 minutes with blood and saline solution at first. The aorta was kept cross clamped without perfusion for a subsequent 20 minutes. In group B (n = 6), the infrarenal aorta was segmentally cross clamped and the segment was perfused for 5 minutes with blood and saline solution containing PGE1 of 100 ng/kg/min at first. The aorta was kept cross clamped without perfusion for a subsequent 20 minutes. After the aorta was declamped, the experimental animals recovered from the anesthesia. Twenty-four and 48 hours after the operation, the hind limb function was estimated with Tarlov's grade. Then, the animals were killed for pathologic study. RESULTS: The systolic arterial pressures measured at the left common carotid artery through the experiment were not significantly different between the two groups. The perfusion of the aortic segment between the proximal and distal clamp was nonpulsatile. The perfusion pressures of the aortic segments at 5 minutes after aortic cross clamping were 29 +/- 6 mm Hg and 33 +/- 6 mm Hg in groups A and B, respectively. No significant differences were seen between the two groups. In group A, the hind limb functions evaluated with Tarlov's grade after 24 hours and 48 hours were 0 to 3 (1.5 +/- 1.4) and 0 to 3 (1.3 +/- 1.4), respectively. In group B, these were 3 to 4 (3.5 +/- 0.5) and 3 to 4 (3.7 +/- 0.5), respectively. A significant difference was seen between the two groups (P <.05). In the ventral horn of the L5, L6, and L7 segments, large motor neurons that seemed viable were more preserved in group B than in group A. CONCLUSION: Segmental intraaortic perfusion of PGE1 in the preischemic period reduced neurologic damage of spinal cord ischemia.

Alprostadil↗

Bulky trialkylsilyl acetylenes in the Cadiot-Chodkiewicz cross-coupling reaction.

Bulky trialkylsilyl-protected alkynes such as triethylsilyl (TES), tert-butyldimethylsilyl (TBS), and triisopropylsilyl (TIPS) acetylenes underwent the Cadiot-Chodkiewicz cross-coupling reaction with different bromoalkynes to form a variety of synthetically useful unsymmetrical diynes in good yields. The diyne alcohol 10 was transformed regio- and stereoselectively into enynes by hydrotelluration, carbometalation, and reduction reactions.

Journal Article↗

Protection against mucosal SIVsm challenge in macaques infected with a chimeric SIV that expresses HIV type 1 envelope.

In a monkey model we used a chimeric SIV expressing the HIV-1 envelope gene (SHIV-4) as a live attenuated vaccine and a virulent SIVsm as a mucosal challenge. Four cynomolgus monkeys were inoculated intravenously with SHIV-4. Virus was repeatedly isolated from blood mononuclear cells of all four animals for 2 to 7 months after the inoculation of SHIV. All monkeys developed neutralizing antibodies to HIV-1 and high antibody titers to HIV-1 envelope glycoproteins. In contrast, no neutralizing antibodies to SIVsm were detected and cross-reacting antibodies to SIV envelope glycoproteins were demonstrable in low titers. Nine to 12 months after the SHIV inoculation the four monkeys and six naive control monkeys were challenged intrarectally with 10 monkey infectious doses of macaque cell-grown SIVsm. After a follow-up period of 1 year, two of four SHIV-infected monkeys were completely protected against SIVsm infection as shown by repeated negative virus isolations and negative polymerase chain reaction for SIV envelope DNA. One naive monkey that received blood from the two protected monkeys showed no signs of infection. The remaining two SHIV-infected monkeys showed an initial infection on challenge with SIVsm, but viral replication was thereafter suppressed. Cytotoxic T lymphocytes to SIV Nef and RT were demonstrable in one of four SHIV-infected monkeys before SIVsm challenge, but this monkey was not protected against SIV infection. All six control animals yielded virus repeatedly after SIVsm challenge and three of them showed declining CD4 cell counts. Thus, infection with SHIV expressing HIV-1 envelope could induce cross-protection against mucosal SIVsm challenge.

Acquired Immunodeficiency Syndrome↗

A facile and efficient synthesis of (Purin-6-yl)alanines.

(Purin-6-yl)alanines, a new class of amino acid-nucleobase conjugates, were synthesized by palladium-catalyzed cross-coupling reactions of protected iodozincalanines with 6-iodopurines (9-Bn-6-iodopurine and 9-THP-6-iodopurine as well as acyl-protected 6-iodopurine ribonucleoside and 2-deoxyribonucleoside). Free purine base and nucleosides bearing alanine in position 6 were obtained after complete deprotection of the products of cross-coupling reactions.

Alanine↗

The efficacy of a protective cream in a real-world apprentice hairdresser environment.

The object of this study was to compare the protective action of a new barrier cream (Excipial Protect, Spirig Pharma AG, Egerkingen, Switzerland) to its vehicle in the context of hand irritation of apprentice hairdressers caused by repeated shampooing and exposure to hair-care products. This was a double-blind cross-over comparing Excipial Protect (containing aluminium chlorohydrate 5% as active ingredient) against its vehicle alone. The efficacy of the creams was evaluated taking into account: (1) clinical scores by researchers, (2) biometric measurements, (3) subjective opinions of the subjects. An analysis of variance was performed considering order of application, degree of atopy, and reported number of shampoos. We observed very little difference in efficacy between the protective cream and its vehicle. The presence, however, of aluminium chlorhydrate in the protective cream was shown to have a positive effect against work-related irritation. The cosmetic qualities of the creams seemed, to the participants, to be as important as their real protective and hydrating properties, an important factor in compliance issues.

Cross-Over Studies↗

[Correlation between major histocompatibility complex (MHC)-class II and type 1 diabetes].

The autoimmune disease type 1 diabetes (T1D) results from a T lymphocyte-dependent, selective destruction of the insulin-producing pancreatic beta-cells and subsequent irreversible insulin deficiency. The disease is caused by a combination of genetic and environmental factors. Numerous genetic, structural and biological studies have provided a convincing case that in human T1D and in its murine model, the non obese diabetes (NOD) mouse, the major histocompatibility complex (MHC) class II molecules, HLA-DQB1 and -DRB1 and their murine orthologues, IA and IE, are the major genetic determinants. The two loci act as a complex superlocus, with both haplotype- and genotype-specific effects. In humans the HLA class II molecule-association with the disease is constituted by a two-sided gradient from positively associated-high risk to negatively associated-low risk molecules. Very low risk corresponds to dominant protection from the disease. The protein structure of DQ/IA and DR/IE molecules have been established. Molecular modeling work revealed that there are marked similarities both within, and cross species between T1D protective class II molecules. Likewise, the T1D predisposing molecules show conserved similarities that differ with the shared structural patterns observed between the protective molecules. The available data provide evidence for a joint action of the class II peptide-binding pockets P1, P4 and P9 in disease susceptibility and resistance with a main role for P9 in DQ/IA and for P1 and P4 in DR/IE. Overall these observations suggest shared pathways in human and murine T1D.

Diabetes Mellitus, Type 1↗

Cross-reactivity of Schistosoma mansoni cytosolic superoxide dismutase, a protective vaccine candidate, with host superoxide dismutase and identification of parasite-specific B epitopes.

Schistosoma mansoni, an intravascular parasite, has evolved a number of immune evasion mechanisms to establish itself in the host, such as antioxidant enzymes. Our laboratory has demonstrated that the highest levels of certain antioxidant enzymes are found in adult worms, which are the least susceptible to immune killing. Vaccination of mice with naked DNA constructs containing the gene encoding Cu/Zn cytosolic superoxide dismutase (SmCT-SOD) showed significant levels of protection compared to a control group, and our data demonstrate that the adult worms are a target of the immune response that confers resistance in SmCT-SOD DNA-vaccinated mice. Because SmCT-SOD shows significant identity with the human homologue, we evaluated the reactivity of anti-SmCT-SOD antibodies derived from SmCT-SOD-immunized mice and rabbits and from S. mansoni-infected individuals to human superoxide dismutase (hSOD) and SmCT-SOD parasite-specific peptides to assess the potential for autoimmune responses from immunization with the recombinant molecule. In addition, we evaluated the ability of various SmCT-SOD adjuvant-delivered immunizations to induce cross-reactive antibodies. Both mouse and rabbit antibodies generated against SmCT-SOD recognized the denatured form of hSOD. The same antibodies did not recognize nondenatured hSOD. Sera from infected individuals with different clinical forms of schistosomiasis recognized SmCT-SOD but not hSOD. Antibodies from mice immunized with different SmCT-SOD-containing formulations of both DNA and protein were able to recognize SmCT-SOD-derived peptides but not soluble hSOD. All together, these findings serve as a basis for developing a subunit vaccine against schistosomiasis.

Amino Acid Sequence↗

[UV-induced formation of DNA-protein cross-links in chromatin in the presence of chemical agents].

Hindered phenols, quinones, and SH-compounds have been studied as possible protectors and sensitizers of DNA-protein cross-linking in chromatin. Efficacy of cross-linking was estimated by the quantity of protein linked to DNA after UV irradiation at 254 um in the presence of chemical agents. Phenols and quinones exert protective influence on cross-linking whereas DNA-protein cross-links are sensibilized by cysteine hydrochloride.

Animals↗

'Original antigenic sin', T cell memory, and malaria sporozoite immunity: an hypothesis for immune evasion.

Prior to any exposure to malaria, most adults have T cells specific for malaria parasites and various malaria proteins. The protein for which this has been shown more than any other is the circumsporozoite protein (CSP) of Plasmodium falciparum. These T cells can be present in high frequency and appear to have arisen through exposure to other (non-malaria) organisms. Although T cells are thought to provide protection against sporozoites, these T cells specific for cross-reactive organisms are clearly unable to protect against malaria, and may be preferentially expanded following exposure to malaria sporozoites. Thus, cross-reactive organisms have the potential to skew the repertoire of sporozoite-induced T cells and affect the induction of protective immunity. This is analogous to the concept of 'original antigenic sin' whereby prior exposure to one strain of influenza virus was shown to be able to divert the antibody response to a second challenging strain to focus on the shared (cross-reactive) epitopes.

Animals↗

Myocardial protective effect of deep hypothermic cardiac arrest without aortic cross clamp in neonatal hearts: comparison with cardioplegic arrest in a rabbit model.

Using an isolated perfusion model of neonatal rabbit hearts aged 3 to 6 days, cardioplegic arrest (CPA) using crystalloid cold cardioplegia with aortic cross clamp (AXC: 60 min, n = 15) and continuous deep hypothermic perfusion (DHP) at 15 degrees C without AXC (n = 15) were compared. The hearts were divided into two subgroups: intact hearts (n = 18) and with preceding 40 min warm ischemia (stressed hearts, n = 22). In the intact hearts, there were no significant differences between the CPA and DHP groups in left ventricular function, myocardial water content, and myocardial mitochondrial score after reperfusion. In the stressed hearts, recovery of cardiac output and left ventricular work was significantly higher in the DHP group than in the CPA group. The post-reperfusion myocardial mitochondrial score was significantly better in the DHP group than in the CPA group. These results suggest that non-AXC DHP may be advantageous in the setting of stressed hearts with preceding ischemic injury where conventional CPA cannot provide adequate myocardial protection.

Animals↗

Synthesis of enantiomerically pure (purin-6-yl)phenylalanines and their nucleosides, a novel type of purine-amino acid conjugates.

[Chemical reaction: See text] Enantiomerically or diastereomerically pure 4-(purin-6-yl)phenylalanines, a novel type of stable amino acid-purine conjugates, were synthesized by palladium-catalyzed cross-coupling reactions of protected 4-boronophenylalanines or 4-(trimethylstanyl)phenylalanines with diverse 6-halopurines (9-benzyl-6-halopurines and 9-(tetrahydropyran-2-yl)-6-halopurines as well as acyl- and silyl-protected 6-halopurine ribonucleosides and 2-deoxyribonucleosides). Free purine bases and nucleosides bearing (S)- or (R)-phenylalanine in position 6 were obtained after complete deprotection of the products of cross-coupling reactions. Reactivity trends for both of these cross-coupling and deprotection protocols have been compared in terms of practicability, efficiency, and stereoselectivity.

Amino Acids↗

Development of a questionnaire to assess worker knowledge, attitudes and perceptions underlying dermal exposure.

OBJECTIVES: Workers' behavior is identified as an important determinant of dermal exposure and is influenced by knowledge, attitudes, and risk perceptions. Because behavior may be a significant predictor of exposure, its assessment provides a means for examining exposure and designing strategies and incentives that encourage worker protective behavior. Currently, there are no psychosocial instruments examining worker knowledge, attitudes, and perceptions with respect to dermal hazards. Accordingly, a questionnaire was developed and tested to provide an instrument for measuring worker knowledge, attitudes, and perceptions. METHODS: The questionnaire was developed on the basis of a literature review and expert consultation. Scales were constructed based on standard methods. Two worker focus groups were used to evaluate worker understanding and content validity of the KAP (knowledge, attitudes, perceptions) questionnaire. The resulting 115-item questionnaire that included scales for knowledge (N=13), attitudes (N=27), perceptions (N=15), behavior (N=8), behavioral intentions (N=15), barriers (N=13), and facilitators (N=5) was tested on 89 workers from 19 facilities. RESULTS: The concepts identified in the focus groups included worker perception of higher risk due to a poor fit and replacement frequency for personal protective equipment and cross-contamination by workers moving into work zones. Field testing of the questionnaire (N=89) yielded Cronbach's alpha reliability scores ranging from 0.87 for the self-efficacy personal protective equipment scale to 0.92 for the overall belief scale, indicating high internal reliability. CONCLUSIONS: Although further testing and refinement is needed, this survey instrument provides an initial and conceptually unique means for evaluating behavioral determinants of worker dermal exposure.

Focus Groups↗

Antigen profiles of Anaplasma ovis and A. mesaeterum and cross infection trials with them and A. marginale.

Antigen profiles of Anaplasma ovis and A. mesaeterum were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting, and cross infection trials were performed by A. ovis challenge to A. mesaeterum- or A. marginale-inoculated goats and A. marginale challenge to an A. ovis-inoculated calf. Antigen analysis showed unique and common proteins of A. ovis and A. mesaeterum and identified a major 38 kDa protein to be a dominant immunogen bearing two epitopes common to Anaplasma species. An epitope specific to A. ovis and A. marginale, absent from A. mesaeterum, was recognised on the major protein of A. ovis. Pre-inoculation of goats with A. mesaeterum induced continuous antibody response with low parasitemia and partial protection against A. ovis challenge, as demonstrated by lower peak parasitemia and normal body temperature compared with values for goats inoculated with A. ovis alone. Pre-inoculation of goats with A. marginale and a calf with A. ovis induced weak or no antibody response without parasitemia, and was of no effect for preventing anaplasmosis by heterologous challenge. These results suggest that the development of parasitemia is essential for inducing continuous antibody by which cross protection would be possible.

Anaplasma↗

Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy.

We previously reported damage and elevated biogenesis in cardiac mitochondria of a type 1 diabetic mouse model and proposed that mitochondria are one of the major targets of oxidative stress. In this study, we targeted overexpression of the mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) to the heart to protect cardiac mitochondria from oxidative damage. Transgenic hearts had a 10- to 20-fold increase in superoxide dismutase (SOD) activity, and the transgenic SOD was located in mitochondria. The transgene caused a twofold increase in cardiac catalase activity. MnSOD transgenic mice demonstrated normal cardiac morphology, contractility, and mitochondria, and their cardiomyocytes were protected from exogenous oxidants. Crossing MnSOD transgenic mice with our type 1 model tested the benefit of eliminating mitochondrial reactive oxygen species. Overexpression of MnSOD improved respiration and normalized mass in diabetic mitochondria. MnSOD also protected the morphology of diabetic hearts and completely normalized contractility in diabetic cardiomyocytes. These results showed that elevating MnSOD provided extensive protection to diabetic mitochondria and provided overall protection to the diabetic heart.

Animals↗

Cross-contamination control in prosthodontic practice.

Prosthodontic patients are generally a high-risk group relative to their potential to transmit infectious diseases as well as acquire them. There has been a recent increase in awareness of the need for cross-infection control measures to protect against possible routes of transmission frequently ignored in the past. This article is essentially a literature review of cross-infection control measures especially relevant to removable prosthodontic practice. Cross-contamination control measures are considered within the following categories: patient evaluation, personal protection, instrument and equipment contamination, clinical technique, impression handling, and laboratory asepsis.

Cross Infection↗

A correlation between the relative predisposition of MHC class II alleles to type 1 diabetes and the structure of their proteins.

In human type 1 diabetes (T1D) and in its murine model, the major histocompatibility complex (MHC) class II molecules, human leukocyte antigens (HLA)-DQ and -DR and their murine orthologues, IA and IE, are the major genetic determinants. In this report, we have ranked HLA class II molecule-associated T1D risk in a two-sided gradient from very high to very low. Very low risk corresponded to dominant protection from T1D. We predicted the protein structure of DQ by using the published crystal structures of different allotypes of the murine orthologue of DQ, IA. We discovered marked similarities both within, and cross species between T1D protective class II molecules. Likewise, the T1D predisposing molecules showed conserved similarities that contrasted with the shared patterns observed between the protective molecules. We also found striking inter-isotypic conservation between protective DQ, IA allotypes and protective DR4 subtypes. The data provide evidence for a joint action of the class II peptide-binding pockets P1, P4 and P9 in disease susceptibility and resistance with a main role for P9 in DQ/IA and for P1 and P4 in DR/IE. Overall, these results suggest shared epitope(s) in the target autoantigen(s), and common pathways in human and murine T1D.

Adolescent↗

The olive oil antioxidant hydroxytyrosol efficiently protects against the oxidative stress-induced impairment of the NObullet response of isolated rat aorta.

The Mediterranean diet, which is abundant in antioxidants, is associated with a relatively low incidence of coronary heart disease. Olive oil and olives, which contain the antioxidants hydroxytyrosol, oleuropein, and tyrosol, are important components of this diet. In this study, the effects of oxidative stress on the nitric oxide radical (NO(*))-mediated relaxation of rat aorta and the protection by these antioxidants were determined. Cumene hydroperoxide (CHP) was used to mimic oxidative stress induced by lipid hydroperoxides, which is mediated by the formation of hydroxyl radicals (OH(*)). CHP (300 microM) impaired the NO(*)-mediated relaxation of rat aorta by the acetylcholine receptor agonist carbachol (P < 0.05). This was due to a reduction in NO(*) production. A diminished NO(*)-mediated relaxation disturbs the vascular tone and leads to a rise in blood pressure, which is a well-established risk factor for coronary heart disease. Hydroxytyrosol (10 microM) efficiently protected the aorta against the CHP-induced impairment of the NO(*)-mediated relaxation (P < 0.05). Oleuropein, tyrosol, and homovanillic alcohol, a major metabolite of hydroxytyrosol, did not show protection. Moreover, hydroxytyrosol was found to be a potent OH(*) scavenger, which can be attributed to its catechol moiety. Because of its amphiphilic characteristics (octanol-water partitioning coefficient = 1.1), hydroxytyrosol will readily cross membranes and provide protection in the cytosol and membranes, including the water-lipid interface. The present study provides a molecular basis for the contribution of hydroxytyrosol to the benefits of the Mediterranean diet.

Animals↗