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Inhibition of mouse-killing behavior by S-adenosyl-L-methionine in midbrain raphe-lesioned and olfactory-bulbectomized rats.

The effect of S-adenosyl-L-methionine (SAM), a methyl donor, on mouse-killing behavior in rats with lesions of the midbrain raphe nuclei and in olfactory-bulbectomized rats was investigated. Systemic administration of SAM at doses of 180 and 320 mg/kg IP caused a significant inhibition of both kinds of mouse-killing behavior. The inhibitory effects of SAM on both types of mouse-killing behavior were almost equipotent. Microinjection of SAM at 10-100 micrograms/rat into the lateral ventricle also inhibited mouse-killing behavior induced by raphe lesions in a dose-dependent manner. The ED50 value of SAM for this effect was 38.6 (18.4-81.4) micrograms/rat. It is concluded that SAM has inhibitory effects on mouse-killing behavior in both raphe-lesioned and olfactory-bulbectomized rats through a site of action in the central nervous system.

Animals↗

Characterization of a nucleolar 2'-O-methyltransferase and its involvement in the methylation of mouse precursor ribosomal RNA.

A nucleolar 2'-O-methyltransferase, partially purified from isolated mouse nucleoli, catalyzes the methylation of each of the four nucleosides, although to different levels depending on the RNA substrate. Similar to most methyltransferases which use S-adenosyl-L-methionine (SAM) as the methyl donor, the nucleolar 2'-O-methyltransferase was shown to bind S-adenosyl-L-homocysteine (SAH) (Kd = 0.17 microM), a product of the transfer reaction, as tightly as SAM (Kd = 0.24 microM). Binding assays also demonstrated stereospecificity about the sulfonium center of SAM. The naturally occurring S-chiral form of SAM had a 10-fold higher binding affinity than the R-chiral form. In addition, the alpha-amino group of the methionine moiety and the 6-amino group of the adenine moiety were shown to be required for maximal binding. The relative high affinity for both SAM and SAH may reflect a mechanism by which ribosome biogenesis is, in part, coordinated with cell growth, since a decrease in SAM:SAH ratio correlates with decreasing levels of 2'-O-methylation. The availability of unmethylated, in vitro-derived rRNA transcripts has made it possible to explore questions relating to the specificity for the RNA substrate. Using an in vitro-derived 28S rRNA transcript, the enzyme selectively methylated the sequence AmGmCm that occurs in a single-stranded bridge spanning two highly conserved structural domains of 28S rRNA. These results demonstrated that the purified nucleolar 2'-O-methyltransferase was sufficient to accurately methylate this region of 28S rRNA, and were taken to support the involvement of this nucleolar enzyme in the posttranscriptional methylation of the 47S precursor ribosomal RNA transcript.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗

Similarities in the age-related hippocampal deposition of periodic acid-schiff-positive granules in the senescence-accelerated mouse P8 and C57BL/6 mouse strains.

With advancing age clusters of abnormal granules positive for periodic acid-Schiff appear in the hippocampus of C57BL/6 (B6) mice and the senescence-accelerated mouse (SAM) P8. The granules can also be visualized with a polyclonal antibody to a 110,000 mol. wt laminin-binding protein and stain specifically with a monoclonal antibody to heparan sulfate proteoglycan. The present study used light and electron-microscopic analysis to compare the staining and morphological properties of these granules in SAM P8 hippocampus with those in B6 hippocampus at different ages. The results of the light-microscopic analysis revealed that granules in SAM P8 and B6 had similar morphology, staining characteristics and distribution patterns, and appeared to have a close association with astrocytic process. The onset of granules in SAM P8 mice (at two to three months of age) was earlier than that observed in B6 mice (at four to six months of age), but the maximum incidence was similar in both strains. Electron-microscopic analysis revealed that the granules in SAM P8 and B6 mice also had a very similar ultrastructure. Granules in both strains were surrounded by a discontinuous membrane and contained mostly crystalline-like, degenerated material. The successive ultrastructural changes from the exterior to interior of the granules suggest that the degenerative process was initiated outside the granules and that degenerative structures migrate inward. Astrocytes and heparan sulfate proteoglycan are closely associated with beta-amyloid deposits in Alzheimer's disease. The presence of astrocyte-associated heparan sulfate proteoglycan-positive material in aged SAM P8 and B6 mice might model age-related alterations in glia function possibly involved in human cerebral amyloidogenesis.

Aging↗

The burden of smoking-attributable mortality among African Americans--Indiana, 1990.

Recent trends in smoking prevalence in Indiana indicate a slow decline in smoking prevalence among adults aged 18 years of age and under. Despite this decline, the smoking prevalence has remained consistently higher among Blacks compared to Whites. The purpose of this investigation was to evaluate the extent of mortality due to cigarette smoking in 1990 among Blacks and Whites in the state of Indiana. Estimates of smoking-attributable mortality (i.e., smoking-attributable mortality [SAM] and years of potential life lost [YPLL] associated with smoking in 1990 were calculated using SAMMEC, a software program developed by the Centers for Disease Control and Prevention and designed to measure the disease impact associated with cigarette smoking. Although the SAM and YPLL for Whites accounted for the greatest percentage of total SAM and total YPLL, SAM rates and YPLL rates were higher among Blacks compared to Whites, for both men and women. The SAM rate for Black men was 4% higher than that of White men and 9% higher for Black women compared to White women. Similarly, the YPLL to life expectancy rate for Black men was 7% higher than the YPLL rate for White men and 29% higher for Black women compared to White women. The greater burden of tobacco-related mortality among Blacks is evidenced through higher SAM and YPLL rates compared to Whites. It is imperative that high-risk populations be targeted at national, state, and local levels through anti-tobacco campaigns.

Adult↗

Interindividual variability in the urinary excretion of inorganic arsenic metabolites by C57 BL/6J mice: possible involvement of a thiol/disulfide exchange mechanism.

The 24-h urine of 75 C57 BL/6J mice injected s.c. with 0.5 mg/kg arsenic as sodium arsenite were examined for creatinine, S-adenosylmethionine (SAM), urea and inorganic arsenic metabolites including inorganic arsenic (ASi), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). There was interindividual variability of about a 10-fold range in the 24-h urinary excretion of creatinine (80-642 micrograms/24 h, variability (cv) of 33%), SAM (7.5-67.2 micrograms/24 h, cv of 38%), urea (9.5-89.7 mg/24 h, cv of 36%), ASi (0.1-1.6 microgram/24 h, cv of 48%), MMA (0.17-2.1 micrograms/24 h, cv of 50%), DMA (0.73-8.13 micrograms/24 h, cv of 32%) and total arsenic metabolites (1.0-10.4 micrograms/24 h, cv of 31%). Interindividual differences, varying by as much as 5-7-fold, were also found in the urinary proportion of ASi (3-23%, cv of 41%) and MMA (5-22%, cv of 37%), but not in the urinary proportion of DMA (64-90%, cv of 7%). The 24-h urinary excretion of all arsenic metabolites correlated with the 24-h urinary excretion of urea (r = 0.81), creatinine (r = 0.88) and SAM (r = 0.83) as did the 24-h urinary excretion of urea with creatinine (r = 0.94) and SAM (r = 0.86), and the 24-h urinary excretion of creatinine with SAM (r = 0.94). Taken together, these results suggest that the overall intracellular glutathione (GSH)-dependent redox state, as reflected by the 24-h urinary excretion of SAM and creatinine, is involved in the interindividual variability in total arsenic metabolite excretion by C57 BL/6J mice. These preliminary results were also discussed with regard to the involvement of intracellular GSH-dependent redox state in the regulation of the reduction and of the methylation steps of arsenic, and to interindividual variability in the urinary excretion of total arsenic metabolites as a possible complicating factor in the biological monitoring of occupational exposure to arsenic.

Animals↗

Self-administration of medication by patients and family members during hospitalization.

The current trend of shorter hospital stays has heightened concern about the adequacy of preparation of patients and their families to understand and follow prescribed medication regimens properly following discharge. Cooperative Care, an education-intensive unit incorporating a living-in family member or friend acting as a 'care partner,' has had a self-administration of medication program (SAM) for the past 16 years. This paper describes SAM and reports on two studies of its effectiveness. The first was a 1-week survey of all patients (151) admitted to the unit. 126 (83.4%) were taking a mean of five medications, with a range of one to 17. Of those, 102 (80.9%) were able to participate in SAM independently, and 11 (8.7%) were on SAM with supervision by their care partners. The second study reviewed medication administration errors within Cooperative Care and the traditional nursing units of Tisch Hospital over a 4-year period (1991-1994). Cooperative Care accounted for 19.4% of discharges (22,164/114,206) and 10.3% of patient days (97,037/944,230), but only 4.6% of medication errors (80/1723). The medication error rate per 1000 discharges was 3.6 for Cooperative Care, and 17.8 for the traditional units. Comparative error rates per 10,000 medication orders were 3.06 at Cooperative Care and 4.01 on the traditional units. 74.8% of Cooperative Care patients were on SAM, but only 30% of the errors were attributed to patients or care partners. The other errors were attributed to nursing staff (50%), equipment defects (12.5%) or pharmacists (5%). Our data indicate that SAM during hospitalization is a safe and effective modality of care.

Adult↗

Delphinidin 3-sambubioside, a Hibiscus anthocyanin, induces apoptosis in human leukemia cells through reactive oxygen species-mediated mitochondrial pathway.

Delphinidin 3-sambubioside (Dp3-Sam), a Hibiscus anthocyanin, was isolated from the dried calices of Hibiscus sabdariffa L. Dp3-Sam could induce a dose-dependent apoptosis in human leukemia cells (HL-60) as characterized by cell morphology, DNA fragmentation, activation of caspase-3, -8, and -9, and inactivation of poly(ADP)ribose polymerase (PARP). Molecular data showed that Dp3-Sam induced Bid truncation, mitochondrial membrane potential (DeltaPsi(m)) loss, and cytochrome c release from mitochondria to cytosol. Moreover, Dp3-Sam caused a time- and dose-dependent elevation of intracellular reactive oxygen species (ROS) level in HL-60 cells, and antioxidants such as N-acetyl-L-cysteine (NAC) and catalase could effectively block Dp3-Sam-induced ROS generation, caspase-3 activity, and DNA fragmentation. These data indicate that Dp3-Sam might induce apoptosis in HL-60 cells through a ROS-mediated mitochondrial dysfunction pathway. These findings enhance our understanding for anticancer function of Hibiscus anthocyanins in herbal medicine.

Anthocyanins↗

Accelerometer monitoring of home- and community-based ambulatory activity after stroke.

OBJECTIVES: To investigate the utility of a novel microprocessor-linked Step Watch Activity Monitor (SAM) to quantify ambulatory activity after stroke and to evaluate the validity and reliability of conventional accelerometers to measure free-living physical activity in this population. DESIGN: Cross-sectional with repeated measures of 2 separate 48-hour recordings in 17 persons wearing an ankle-mounted SAM and Caltrac, a hip-mounted mechanical accelerometer. SETTING: Home and community. PARTICIPANTS: Seventeen subjects with chronic hemiparetic gait after stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The SAM derived stride counts per day and Caltrac estimated the daily caloric expenditure of physical activity. RESULTS: SAM data revealed that stroke patients had a mean strides per day +/- standard deviation of 3035+/-1944 and demonstrated a broad range of daily activity profiles (400-6472 strides). SAM test-retest reliability was high across separate monitoring periods (r=.96, P<.001). Although Caltrac also revealed a broad range of daily activity calories (346+/-217 kcal/d; range, 83-1222 kcal/d), reliability was poor (r=.044, P=not significant) and Caltrac accounted for only 64% of the ambulatory activity quantified by the SAM. CONCLUSIONS: Microprocessor-linked accelerometer monitoring, but not conventional accelerometers, are accurate and highly reliable for quantifying ambulatory activity levels in stroke patients. These findings support the utility of personal status monitoring of ambulatory activity as an outcomes instrument and metric in programs to increase physical activity and cardiovascular health after stroke.

Activities of Daily Living↗

Midterm results of the edge-to-edge technique for complex mitral valve repair.

BACKGROUND: The edge-to-edge technique (E2E) has been advocated for the complex repair of myxomatous mitral valves. We compared outcomes of E2E performed in patients at risk for systolic anterior motion (SAM) versus outcomes in patients with residual mitral regurgitation (MR) after repair completion. METHODS: A total of 1,612 patients had repair of myxomatous mitral valves between June 1997 and December 2003 at Brigham and Women's Hospital. The E2E was used in 72 (4.5%) patients. Fifty-two patients (52/72; group I) had E2E for persistent MR after complex repair. Twenty patients (20/72; group II) had E2E for high risk of post-repair SAM and left ventricular outflow tract obstruction. Mean age of the patients was 61 +/- 14 years; 47 were male, average New York Heart Association class at admission was 2.4 +/- 0.6, and mean left ventricular ejection fraction was 56 +/- 12%. RESULTS: The operative mortality was zero. Immediate postoperative MR was significantly improved in all patients compared with the preoperative grade (p value < 0.0005). Mean follow-up was 388 days. In those in whom E2E was used for residual MR without SAM risk (group I), postoperative MR (> or = 2+) was detected in 15 of 52 patients at 6 months. In group II, SAM was completely eliminated and the mean MR grade in the immediate postoperative period was 0.5 +/- 0.7. There was no long-term recurrence of MR in group II. CONCLUSIONS: This study suggests that E2E eliminates SAM and long-term MR in patients with pre-repair echocardiographic predictors of SAM. The E2E is not efficacious in preventing long-term recurrent MR if performed for residual MR after complex mitral repair.

Aged↗

The effect of surface charge on hydroxyapatite nucleation.

Both the charged surfaces and condition of supersaturated solutions are thought to be the important factors that greatly affect the nucleation of hydroxyapatite (HAp) onto the substrates. In the present study self-assembled monolayers (SAM) terminated with amino (NH2-SAM) and hydroxyl (OH-SAM) headgroups were employed to generate the positively and negatively charged surfaces, respectively. The soaking experiments for HAp nucleation were carried out in the supersaturated solutions (1.5 SBF) with Ca2+ and PO4(3-) ions concentrations 1.5 times higher than in simulated body fluid (SBF). The stability of solutions deeply depends on pH values if other factors (temperature, ionic series and their concentration, etc.) are fixed. Consequently, the opposite micropatterns of HAp films were observed on the UV-patterned SAM with NH2 and OH terminals in a stable solution (1.5 SBF, pH=7.2) where no particles formed and in an unstable solution (1.5 SBF, pH=7.6) where homogeneous nucleation occurred. The preferential nucleation of HAp was found on negative surface (OH-SAM) in a stable supersaturated solution, while selective deposition of HAp was formed on positive surface (NH2-SAM) in the unstable solution. Considering the latter results, it is conceivable that the electrostatic adhesion of microparticles formed in the solution dominated the formation of HAp in the unstable solution.

Adsorption↗

Fibrinogen adsorption, platelet adhesion and activation on mixed hydroxyl-/methyl-terminated self-assembled monolayers.

The effect of surface wettability on fibrinogen adsorption, platelet adhesion and platelet activation was investigated using self-assembled monolayers (SAMs) containing different ratios of longer chain methyl- and shorter chain hydroxyl-terminated alkanethiols (C15CH3 vs. C11OH) on gold. Protein adsorption studies were performed using radiolabeled human fibrinogen (HFG). Platelet adhesion and activation studies with and without pre-adsorbed fibrinogen, albumin and plasma were assessed using scanning electron microscopy (SEM) and a glutaraldehyde-induced fluorescence technique (GIFT). Results demonstrated a linear decrease of HFG adsorption with the increase of OH groups on the monolayer (increase of the hydrophilicity). Platelet adhesion and activation also decrease with increase of hydrophilicity of surface. Concerning SAMs pre-immersed in proteins, fibrinogen adsorption was related with high platelet adhesion and activation. The passivant effect of albumin on platelet adhesion and activation was only demonstrated on SAMs contained C11OH. When all the blood proteins are present (plasma) platelet adhesion was almost absent on SAMs with 65% and 100% C11OH. This could be explained by the higher albumin affinity of the SAMs with 65% C11OH and the lower total protein adsorption associated with SAMs with 100% C11OH.

Adsorption↗

Cerebral plasmalogens and aldehydes in senescence-accelerated mice P8 and R1: a comparison between weaned, adult and aged mice.

In contrast with senescence-accelerated mice R1, SAM P8 show abnormal aging characteristics. Changes occurring during aging could be mainly caused by free radical reactions. The brain is a plasmalogen-rich tissue. These particular phospholipids may act as endogenous antioxidants, be oxidized and release long chain aldehydes and alpha-hydroxyaldehydes during oxidative stress. The aim of this study was to examine by GC/MS the age- and strain-related levels of plasmalogens, aldehydes and alpha-hydroxyaldehydes in brain homogenates of SAM P8 and R1 at weaning, 5 months and 9 months of age in order to better understand the differences between both strains. In SAM R1, the evolution of brain plasmalogen levels corresponded to characteristics of normal aging: an increase from weaned to adult mice followed by a decrease characterizing the normal loss of myelin. By contrast to SAM R1, there was no change in the plasmalogen content in SAM P8 brain. The levels of aldehydes and alpha-hydroxyaldehydes were similar for both strains, they remained constant between adult and aged mice. Specific changes in the aging of SAM P8 were not explained by cerebral levels of these oxidative products. Other mechanisms related to the toxicity of aldehydes and alpha-hydroxyaldehydes could be considered.

Age Factors↗

Masking release for consonant features in temporally fluctuating background noise.

Consonant identification was measured for normal-hearing listeners using Vowel-Consonant-Vowel stimuli that were either unprocessed or spectrally degraded to force listeners to use temporal-envelope cues. Stimuli were embedded in a steady state or fluctuating noise masker and presented at a fixed signal-to-noise ratio. Fluctuations in the maskers were obtained by applying sinusoidal modulation to: (i) the amplitude of the noise (1st-order SAM masker) or (ii) the modulation depth of a 1st-order SAM noise (2nd-order SAM masker). The frequencies of the amplitude variation fm and the depth variation f'm were systematically varied. Consistent with previous studies, identification scores obtained with unprocessed speech were highest in an 8-Hz, 1st-order SAM masker. Reception of voicing and manner also peaked around fm=8 Hz, while the reception of place of articulation was maximal at a higher frequency (fm=32 Hz). When 2nd-order SAM maskers were used, identification scores and received information for each consonant feature were found to be independent of f'm. They decreased progressively with increasing carrier modulation frequency fm, and ranged between those obtained with the steady state and the 1st-order SAM maskers. Finally, the results obtained with spectrally degraded speech were similar across all types of maskers, although an 8% improvement in the reception of voicing was observed for modulated maskers with fm < 64 Hz compared to the steady-state masker. These data provide additional evidence that listeners take advantage of temporal minima in fluctuating background noises, and suggest that: (i) minima of different durations are required for an optimal reception of the three consonant features and (ii) complex (i.e., 2nd-order) envelope fluctuations in background noise do not degrade speech identification by interfering with speech-envelope processing.

Adult↗

Adsorption behaviors of poly(amido amine) dendrimers with an azacrown core and long alkyl chain spacers on solid substrates.

Adsorption behaviors of functional poly(amido amine) dendrimers with an azacrown core and long alkyl chain spacers were investigated on gold and self-assembled monolayer (SAM) by means of time course attenuated total reflection-surface enhanced infrared absorption and surface plasmon resonance spectroscopies. While 1.5th and 2.5th generation (G1.5 and G2.5) ester-terminated dendrimers were slightly adsorbed on all substrates examined, the adsorption of G2 amine-terminated dendrimer increased in the order dodecanethiol SAM<bare gold<3-mercaptopropionic acid (MPA) SAM. The time course results also revealed that the G2 dendrimer displayed the steep increase of adsorption on the bare gold, followed by the slight progress of adsorption. G2 dendrimers adsorbed on MPA SAM involved their subsequent conformational rearrangement, while the adsorption equilibrium was quickly attained for G3 dendrimer on the MPA SAM. It was supported that G3 dendrimer was adsorbed with the perpendicularly extended structure on the MPA SAM substrate, and G2 dendrimer varied its conformation from the globular structure to the extended one perpendicular to the substrate.

Journal Article↗

Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis.

Homocysteine (Hcy), an intermediate in methionine metabolism, has been proposed to be involved in hepatic fibrogenesis. Impaired liver function can alter Hcy metabolism. The aim of the present study was to determine plasma Hcy alterations in acute obstructive cholestasis and the subsequent biliary cirrhosis. Cholestasis was induced by bile duct ligation and sham-operated and unoperated rats were used as controls. The animals were studied on the days 7th, 14th, 21st and 28th after the operation. Plasma Hcy, cysteine, methionine, nitric oxide (NO) and liver S-adenosyl-methionine (SAM), S-adenosyl-homocysteine (SAH), SAM to SAH ratio and glutathione were measured. Chronic L-NAME treatment was also included in the study. Plasma Hcy concentrations were transiently elevated by the day 14th after bile duct ligation (P < 0.01) and subsequently returned to control levels. Similar relative fluctuations in plasma Hcy were observed in BDL rats after intraperitoneal methionine overload. Plasma methionine, cysteine and nitrite and nitrate were significantly increased after bile duct ligation. SAM to SAH ratio was diminished by the 1st week of cholestasis and remained significantly decreased throughout the study. These events were accompanied by a decrease in GSH to GSSG ratio in the liver. Chronic L-NAME treatment improved SAM to SAH ratio and prevented the elevation of plasma Hcy and methionine (P < 0.05) while couldn't influence the other parameters. In conclusion, this study demonstrates alterations in plasma Hcy and liver SAM and SAH contents in precirrhotic stages and in secondary biliary cirrhosis, for the first time. In addition, we observed that plasma Hcy concentrations in BDL rats follow a distinct pattern of alteration from what has been previously reported in other models of cirrhosis. NO overproduction may contribute to plasma Hcy elevation and liver SAM depletion after cholestasis.

Analysis of Variance↗

The methyl folate trap. A physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid induced exacerbation of subacute combined degeneration in pernicious anaemia.

It is suggested that in man the methyl folate trap is a normal physiological response to impending methyl group deficiency resulting from a very low supply of methionine. This decreases cellular S-adenosyl-methionine (SAM), which puts at risk important methylation reactions, including those required to maintain myelin. In order to protect these methylation reactions, the cell has evolved two mechanisms to maintain supplies of methionine and SAM as a first priority. (a) Decreased SAM causes the folate co-factors to be directed through the cycle involving 5-methyl-tetrahydrofolate (5-methyl-THF) and methionine synthetase and away from the cycles that produce purines and pyrimidines for DNA synthesis. This enhances the remethylation of homocysteine to methionine and SAM. In addition, by restricting DNA biosynthesis and with it cell, division, competition for methionine for protein synthesis is reduced. Thus, whatever methionine is available is conserved for the vital methylation reactions in the nerves, brain, and elsewhere. (b) 5-methyl-THF, the form in which almost all folate is transported in human plasma, must react with intracellular homocysteine before it can be retained by the cell as a polyglutamate. Since homocysteine is derived entirely from methionine, methionine deficiency will cause intracellular folate deficiency, and the rate of mitosis of rapidly dividing cells will be reduced. although these two processes have evolved as a response to methionine deficiency, they also occur in B12 deficiency, which the cell mistakenly interprets as lack of methionine. the resulting response is inappropriate and gives rise to a potentially lethal anaemia. In these circumstances the methylation reactions are also partly protected by the reduced rate of cell division. This explains why administration of folic acid, which induces cell division and use of methionine in protein synthesis, impairs methylation of myelin and precipitates or exacerbates subacute combined degeneration (SCD). During folate deficiency methionine biosynthesis is also diminished. As in methionine deficiency, the body responds to decreasing availability of SAM by diverting folate away from DNA biosynthesis towards the remethylation of homocysteine to methionine and SAM. The selective use pf available folate to conserve methionine, together with the ability of nerve tissue to concentrate folate form the plasma, explains the absence of SCD in folate deficiency.

Acute Disease↗

The role of surface functional groups in calcium phosphate nucleation on titanium foil: a self-assembled monolayer technique.

Surface functional groups play important roles in nucleating calcium phosphate deposition on surgical titanium implants. In this study, various functional groups were introduced onto the surface of commercially pure titanium foils using a self-assembled monolayer (SAM) technique. An organic silane, 7-oct-1-enyltrichlorosilane (OETS) was used and -OH, -PO4H2, -COOH groups were derived from its unsaturated double bond. Ti foils were first oxidized in concentrated H2SO4/H2O2. ESCA and contact angle measurements were used to characterize the SAM surfaces and confirm the presence of various functional groups. A fast calcium phosphate deposition experiment was carried out by mixing Ca2+- and (PO4)(3-)-containing solutions in the presence of the surface-modified Ti samples at pH 7.4 at room temperature in order to verify the nucleating abilities of these functional groups. SEM, Raman spectroscopy, XRD and ATR-FTIR results showed that poorly crystallized hydroxyapatite (HA) can be deposited on the SAM surfaces with -PO4H2 and -COOH functional groups, but not onto the SAM with -CH=CH2 and -OH. -PO4H2 exhibited a stronger nucleating ability than that of -COOH. The oxidized Ti sample also showed some calcium phosphate deposition but to a lesser extent as compared to SAM surfaces with -PO4H2 and -COOH. The pre-deposited HA can rapidly induce biomimetic apatite layer formation after immersion in 1.5 SBF for 18 h regardless of the amount of pre-deposited HA. The results suggested that the pre-deposition of HA onto these functionalized SAM surfaces might be an effective and fast way to prepare biomimetic apatite coatings on surgical implants.

Biocompatible Materials↗

Beneficial effects of S-adenosyl-L-methionine on blood-brain barrier breakdown and neuronal survival after transient cerebral ischemia in gerbils.

We have studied the beneficial effects of S-adenosyl-L-methionine (SAM) tosylate on blood-brain barrier (BBB) breakdown and neuronal survival after transient cerebral ischemia in gerbils. BBB breakdown experiments were performed in pentobarbital anesthetized gerbils subjected to 10 min of bilateral carotid artery occlusion and 6 h of reperfusion. For BBB breakdown measurements, SAM (120 mg/kg, i.p.) was administered to gerbils just after occlusion and thereafter every hour up to 5 h. Fluorometric measurements quantified the blood-brain permeability tracer, Evans blue (EB). SAM treatment significantly reduced the BBB breakdown as indicated by reduced levels of EB fluorescence. Neuronal count experiments were conducted in gerbils subjected to transient ischemia and 7 days of reperfusion. For neuronal count experiments SAM (15-120 mg/kg) was administered at 6 and 12 h after reperfusion, and twice each day thereafter for 7 days. SAM dose dependently protected the hippocampal CA1 neurons assessed by histopathological methods. SAM has a beneficial effect on the outcome of ischemic injury by reducing the BBB breakdown and neuronal death.

Animals↗