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PubMed2001

Auditory detection and discrimination in deaf cats: psychophysical and neural thresholds for intracochlear electrical signals.

More than 30,000 hearing-impaired human subjects have learned to use cochlear implants for speech perception and speech discrimination. To understand the basic mechanisms underlying the successful application of contemporary speech processing strategies, it is important to investigate how complex electrical stimuli delivered to the cochlea are processed and represented in the central auditory system. A deaf animal model has been developed that allows direct comparison of psychophysical thresholds with central auditory neuronal thresholds to temporally modulated intracochlear electrical signals in the same animals. Behavioral detection thresholds were estimated in neonatally deafened cats for unmodulated pulse trains (e.g., 30 pulses/s or pps) and sinusoidal amplitude-modulated (SAM) pulse trains (e.g., 300 pps, SAM at 30 Hz; 300/30 AM). Animals were trained subsequently in a discrimination task to respond to changes in the modulation frequency of successive SAM signals (e.g., 300/8 AM vs. 300/30 AM). During acute physiological experiments, neural thresholds to pulse trains were estimated in the inferior colliculus (IC) and the primary auditory cortex (A1) of the anesthetized animals. Psychophysical detection thresholds for unmodulated and SAM pulse trains were virtually identical. Single IC neuron thresholds for SAM pulse trains showed a small but significant increase in threshold (0.4 dB or 15.5 microA) when compared with thresholds for unmodulated pulse trains. The mean difference between psychophysical and minimum neural thresholds within animals was not significant (mean = 0.3 dB). Importantly, cats also successfully discriminated changes in the modulation frequencies of the SAM signals. Performance on the discrimination task was not affected by carrier rate (100, 300, 500, 1,000, or 1,500 pps). These findings indicate that 1) behavioral and neural response thresholds are based on detection of the peak pulse amplitudes of the modulated and unmodulated signals, and 2) discrimination of successive SAM pulse trains is based on temporal resolution of the envelope frequencies. Overall, our animal model provides a robust framework for future studies of behavioral discrimination and central neural temporal processing of electrical signals applied to the deaf cochlea by a cochlear implant.

Animals↗
PubMed2002

Neural representations of sinusoidal amplitude and frequency modulations in the primary auditory cortex of awake primates.

We investigated neural coding of sinusoidally modulated tones (sAM and sFM) in the primary auditory cortex (A1) of awake marmoset monkeys, demonstrating that there are systematic cortical representations of embedded temporal features that are based on both average discharge rate and stimulus-synchronized discharge patterns. The rate-representation appears to be coded alongside the stimulus-synchronized discharges, such that the auditory cortex has access to both rate and temporal representations of the stimulus at high and low frequencies, respectively. Furthermore, we showed that individual auditory cortical neurons, as well as populations of neurons, have common features in their responses to both sAM and sFM stimuli. These results may explain the similarities in the perception of sAM and sFM stimuli as well as the different perceptual qualities effected by different modulation frequencies. The main findings include the following. 1) Responses of cortical neurons to sAM and sFM stimuli in awake marmosets were generally much stronger than responses to unmodulated tones. Some neurons responded to sAM or sFM stimuli but not to pure tones. 2) The discharge rate-based modulation transfer function typically had a band-pass shape and was centered at a preferred modulation frequency (rBMF). Population-averaged mean firing rate peaked at 16- to 32-Hz modulation frequency, indicating that the A1 was maximally excited by this frequency range of temporal modulations. 3) Only approximately 60% of recorded units showed statistically significant discharge synchrony to the modulation waveform of sAM or sFM stimuli. The discharge synchrony-based best modulation frequency (tBMF) was typically lower than the rBMF measured from the same neuron. The distribution of rBMF over the population of neurons was approximately one octave higher than the distribution of tBMF. 4) There was a high degree of similarity between cortical responses to sAM and sFM stimuli that was reflected in both discharge rate- or synchrony-based response measures. 5) Inhibition appeared to be a contributing factor in limiting responses at modulation frequencies above the rBMF of a neuron. And 6) neurons with shorter response latencies tended to have higher tBMF and maximum discharge synchrony frequency than those with longer response latencies. rBMF was not significantly correlated with the minimum response latency.

Acoustic Stimulation↗
PubMed2005

S-adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn Study.

OBJECTIVE: To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors. METHODS AND RESULTS: In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [mum]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 microm (21.16; 75.98) and -32.15 microm (-59.09; -5.20), but high homocysteine was not (-15.11 microm (-42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors. CONCLUSIONS: In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

Aged↗
PubMed1993

Morphological determinants of echocardiographic patterns of mitral valve systolic anterior motion in obstructive hypertrophic cardiomyopathy.

BACKGROUND: The morphological determinants of mitral valve systolic anterior motion (SAM) and obstruction to left ventricular outflow in patients within the broad clinical spectrum of hypertrophic cardiomyopathy (HCM) are not completely understood, particularly the contribution of mitral leaflet length and size. METHODS AND RESULTS: To clarify this issue, mitral valve specimens from 43 patients with HCM and basal outflow obstruction were used to relate morphometric measurements of leaflet area to certain morphological and functional assessments of left ventricular outflow tract geometry and valvular motion obtained from echocardiograms in the same patients. Twenty-four patients (56%) had mitral valves of normal size (leaflet area < 12.0 cm2) and 19 patients (44%) had enlarged and elongated valves (area > or = 12.0 cm2). Compared with normal-sized mitral valves, the enlarged valves were situated more posteriorly in a larger left ventricular outflow tract (cross-sectional area, 3.3 +/- 1.0 versus 1.9 +/- 0.7 cm2 for normal-sized valves; p < 0.001) and also had greater systolic excursion of the anterior leaflet (16.2 +/- 4.5 versus 13.3 +/- 3.3 mm, p < 0.02), usually with a distinctive sharp-angled bend and localized contact of the leaflet tip with ventricular septum ("typical" SAM); this pattern of SAM was possible because the central and distal portions of the leaflet were relatively free of fibrous thickening. In contrast, normal-sized mitral valves were situated more anteriorally in a smaller left ventricular outflow tract and frequently showed a different mechanism of SAM and subaortic obstruction with relatively limited leaflet motion, absence of a sharp bend, and septal contact involving more substantial portions of the anterior leaflet and contiguous chordae ("atypical" SAM); mitral-septal apposition was effected in large measure by posterior ventricular septal motion. This pattern of SAM was invariably associated with a more diffuse pattern of fibrous thickening. CONCLUSIONS: Patients with obstructive HCM show patterns of mitral valve SAM that are diverse and determined largely by the interrelation of left ventricular outflow tract geometry, the size and mobility of the mitral leaflets, and the presence and distribution of fibrous thickening.

Adolescent↗
PubMed1984

Rat lung lavage surfactant enhances bacterial phagocytosis and intracellular killing by alveolar macrophages.

We have tested the effect of a preparation of rat lung lavage surfactant (SAM) on phagocytosis and intracellular killing of Staphylococcus aureus by rat alveolar macrophages (AMs). The SAM was isolated and purified by density gradient centrifugation. It was highly enriched in disaturated phosphatidylcholine, and invariably lowered the surface tension of a clean saline solution to less than 10 dynes/cm at 37 degrees C. We used a radiometric assay to measure phagocytosis as uptake by AMs of 14C phenylalanine labelled staphylococci, and intracellular killing as incorporation of 3H thymidine by viable staphylococci from the lysed AMs. When staphylococci were incubated with 100 to 300 micrograms of SAM, both phagocytosis and intracellular killing efficiency were enhanced. The mean numbers of intracellular staphylococci/AM were 24.3 +/- 3.8 and 18.3 +/- 3.0 in the SAM and control groups, respectively (p less than 0.001). The mean intracellular killing efficiency was 59.6 +/- 6.76% and 39.7 +/- 7.17% in the SAM and control groups, respectively (p less than 0.001). Previous studies have shown that unpurified rat lung lavage fluid enhances intracellular killing of staphylococci by AMs. Our results suggest that SAM may be the active principle in lung lavage fluid that enhances intracellular killing. In addition, in our test system, SAM enhanced staphylococcal phagocytosis by AMs.

Animals↗
PubMed1983

Chronic hyperglycemia reduces surface active material flux in tracheal fluid of fetal lambs.

I tested the hypothesis that chronic hyperglycemia alters fetal lung maturation by continuous infusion of glucose (14+/-2 mg/kg per min, mean+/-SE) from 112 up to 145 d gestation into six chronically catheterized fetal lambs from which tracheal fluid could be collected. Serum glucose levels (32+/-2 mg/dl) and serum insulin levels (38+/-4 muU/ml) in these glucose-treated fetuses were significantly higher than serum glucose levels (18+/-2 mg/dl, P < 0.001) and serum insulin levels (12+/-3 muU/ml, P < 0.001) in six chronically catheterized control fetuses of the same gestational ages. Glucose infusion to the fetuses did not alter maternal serum glucose (60+/-3 mg/dl) or serum insulin levels (35+/-5 muU/ml). Arterial blood gases (pH 7.34+/-0.01, Po(2) 24.3+/-0.5 mmHg, Pco(2) 41.5+/-0.9 mmHg), oxygen saturation (73+/-2%), hematocrit (31+/-1%), and tracheal fluid flow (2.4+/-0.1 ml/g per h) in the glucose-treated fetuses were not significantly different from controls. Among the control fetuses, surface active material (SAM) began to appear in tracheal fluid at 123 d gestation and was present in all six fetuses by 129 d gestation, whereas SAM did not appear at all in tracheal fluid of four of the glucose-treated fetuses, and appeared in two at low levels after 142 d gestation. SAM flux in the glucose-treated fetuses (<1 mug/g per h) was statistically lower than SAM flux in the control fetuses (60+/-9 mug/kg per h, P < 0.001). Between 130 and 140 d gestation, tracheal fluid phospholipid content rose fourfold, mixed lecithin content rose ninefold, disaturated phosphatidylcholine content rose fourfold in the control fetuses, whereas little or no increase in these measurements occurred in the glucose-treated fetuses (all differences significant). I conclude that chronic hyperglycemia with secondary hyperinsulinemia reduces SAM flux in tracheal fluid of fetal lambs. The reduction in SAM flux is attributed to low surface active phospholipid content of the SAM. A similar mechanism may operate in utero to cause respiratory distress in infants of diabetic mothers whose maternal glucose homeostasis is poorly controlled.

Animals↗
PubMed2004

Gene switching in Amoeba proteus caused by endosymbiotic bacteria.

The expression of genes for S-adenosylmethionine synthetase (SAMS), which catalyzes the synthesis of S-adenosylmethionine (AdoMet), a major methyl donor in cells, was studied in symbiont-free (D) and symbiont-bearing (xD) amoeba strains to determine the effect of bacterial endosymbionts. The symbionts suppressed the expression of the gene in host xD amoebae, but amoebae still exhibited about half the enzyme activity found in symbiont-free D amoebae. The study was aimed at elucidating mechanisms of the suppression of the amoeba's gene and determining the alternative source for the gene product. Unexpectedly, we found a second sams (sams2) gene in amoebae, which encoded 390 amino acids. Results of experiments measuring SAMS activities and amounts of AdoMet in D and xD amoebae showed that the half SAMS activity found in xD amoebae came from the amoeba's SAMS2 and not from their endosymbionts. The expression of amoeba sams genes was switched from sams1 to sams2 as a result of infection with X-bacteria, raising the possibility that the switch in the expression of sams genes by bacteria plays a role in the development of symbiosis and the host-pathogen interactions. This is the first report showing such a switch in the expression of host sams genes by infecting bacteria.

Amino Acid Sequence↗
PubMed1988

Comparison of salicylamide and acetaminophen and their prodrug disposition in dogs.

Comparative studies on the disposition of two pairs of drugs and their prodrugs, i.e., (1) salicylamide (SAM) and ethenzamide (ETB), (2) acetaminophen (NAPA) and phenacetin (PHT), were performed in dogs following intravenous and oral administration of the drugs. ETB and PHT were largely metabolized to SAM and NAPA, respectively, and SAM and NAPA thus formed or those directly administered were conjugated with sulfuric acid and glucuronic acid. It was found that the prodrugs, ETB and PHT, were more susceptible to first-pass metabolism than the corresponding parent drugs, SAM and NAPA, respectively at 30 mg/kg dose of each drug. Free NAPA levels in the blood of dogs receiving PHT were found to be considerably high, whereas free SAM levels in the blood of dogs receiving ETB were very low. These are consistent with results in humans which have been reported earlier, suggesting the similarity between dogs and humans. The ratio of sulfate to the sum of sulfate and glucuronide (S-ratio) as the area under blood concentration-time curve and urine were examined. The prodrugs (ETB and PHT) showed higher S-ratios than the corresponding parent drugs (SAM and NAPA). The S-ratios were greater than 0.6 in ETB and SAM and less than 0.5 in PHT and NAPA, indicating that sulfate formation was predominant in the former pair while glucuronide formation was predominant in the latter pair. No intestinal metabolism was found in the prodrugs. In the parent drugs, however, conjugation with sulfuric acid and glucuronic acid was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1991

Interaction of pentoxifylline with human erythrocytes. III. Comparison of fluidity change of erythrocyte membrane caused by S-adenosyl-L-methionine with that by pentoxifylline.

The change in fluidity by adding pentoxifylline to erythrocyte membranes was compared with that caused by S-adenosyl-L-methionine (SAM) by the method of electron spin resonance (ESR) spectroscopy. When SAM or pentoxifylline was added externally to the erythrocyte suspension (outside), the fluidity of the membrane bilayer was increased after incubation at 37 degrees C. However, the fluidity change in the inner part of the bilayer was relatively small compared to that in its outer part. These fluidity changes were dependent on the incubation time and the temperature. When the erythrocyte suspension was preincubated overnight at 4 degrees C in the presence of drugs (inside), the fluidity of the inner part of the membrane changed significantly. Nevertheless, that of the outer part of the lipid bilayer was not affected. Such an asymmetric fluidity change in the lipid bilayer was not observed by the addition of other xanthine derivatives such as caffeine, theophylline and theobromine. S-Adenosyl-L-homocysteine suppressed and MgCl2 enhanced the increase of the membrane fluidity by SAM or pentoxifylline. Furthermore, the effects of SAM and pentoxifylline on erythrocyte deformability were determined by a filtering technique method. In increasing order the additive effects of SAM and pentoxifylline on the erythrocyte filterability were SAM (outside) less than pentoxifylline (inside) less than pentoxifylline (outside) less than SAM (inside). These results suggest that pentoxifylline also affects the membrane fluidity through the enzymatic methylation of phospholipids.

Erythrocyte Membrane↗
PubMed1992

An assessment of mucosal damage in vivo: effect of oral pretreatment with 5-fluorouracil on the intestinal first-pass metabolism of salicylamide in rabbits.

An assessment of 5-fluorouracil (5-FU)-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The mucosal damage in the intestine 48 h after oral administration of 5-FU (30 mg/kg) was examined using a scanning electron microscope. By the oral pretreatment with 5-FU, the morphological changes of jejunal and ileal mucosa were recognized compared with the control. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with 5-FU, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with 5-FU orally. However, the blood concentration of SAMG after intravenous administration of SAM was not increased compared with the control. These findings suggest that the change in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage by oral pretreatment with 5-FU. The alteration of intestinal first-pass metabolism of a marker compound may be utilized for the assessment of intestinal mucosal damage in vivo.

Administration, Oral↗
PubMed2003

Translational to vibrational energy conversion during surface-induced dissociation of n-butylbenzene molecular ions colliding at self-assembled monolayer surfaces.

Translational to vibrational (T-->V) energy conversion in the course of inelastic collisions of n-butylbenzene molecular ions with thiolate self-assembled monolayer (SAM) gold surfaces is studied to better understand internal energy uptake by the hyperthermal projectile ions. The projectile ion is selected by a mass spectrometer of BE configuration and product ions are analyzed using a quadrupole mass analyzer after kinetic energy selection with an electric sector. The branching ratio for formation of the fragment ions m/z 91 and m/z 92, measured over a range of collision energies, is used to estimate the average internal energy with the aid of calculations based on unimolecular dissociation kinetics [Rice-Ramsperger-Kassel-Marcus (RRKM) theory]. The measured T-->V conversion efficiencies (the fraction of the laboratory kinetic energy converted into internal energy) are 11 approximately 12% for dodecanethiolate SAM (H-SAM) and 19 approximately 20% for 2-perfluorooctylethanethiolate SAM (F-SAM), respectively, over ranges of a few 10s of eV. The values are similar to those reported earlier for other thermometer molecules undergoing surface collisions. Chemical sputtering leading to ionization of the surface is a prominent feature of the surface-induced dissociation (SID) spectra of n-butylbenzene acquired using the H-SAM surface but not the F-SAM surface because of the lower ionization energy of the former.

Journal Article↗
PubMed1993

Spontaneous development of anti-collagen type II antibodies with NTA, and anti-DNA antibodies in senescence-accelerated mice.

We previously reported that circulating natural thymocytotoxic autoantibody (NTA) and IgG-anti-DNA antibodies were the major serological characteristics of a substrain of SAM, SAM-P/1. We present here a study of ageing in which we further measured and compared various kinds of circulating IgG antibodies including anti-collagen type II, rheumatoid factor (RF), and anti-2,4,-dinitrophenol (DNP), between SAM-P/1 and control SAM-R/1 mice. The results showed that age-associated increases in anti-collagen type II antibodies in SAM-P/1 were distinctively higher than those in SAM-R/1 when the mice were over 4 months of age, and the increases were significantly correlated with increases in NTA, anti-DNA antibodies, RF activities and anti-DNP antibodies. Anti-collagen type II antibody activity was not significantly inhibited by preincubating the antibodies with DNA, IgG-Fc and DNP-BSA samples. These findings suggest that antibodies specifically directed against collagen type II can be produced in a background of polyclonal B cell activation, and that these antibodies in association with NTA and anti-DNA antibodies may play a pathogenic role in the development of accelerated senescence in SAM-P/1 mice.

Aging↗
PubMed2004

Smoking-attributable mortality among British Columbia's first nations populations.

OBJECTIVES: First Nations (FN) people have high smoking rates and there is a need to examine their mortality related to smoking. METHODS: Smoking-attributable fractions and smoking-attributable mortality (SAM) rates were calculated for the FN and British Columbia (BC) populations during 1997 and 2001. RESULTS: Among FN adults, total age- and gender-adjusted SAM rates were 39.9 and 28.6 per 10,000 during 1997 and 2001, with potentially 19.0% and 17.3% of all deaths being preventable if smoking were eliminated. Among the BC adult population, total SAM age- and gender-adjusted rates were 27.8 and 25.3 per 10,000 during 1997 and 2001, and up to 21.8% and 20.8% of deaths were potentially preventable if smoking were eliminated. Among FN infants, SAM crude rates were 6.8 and 3.6 per 10,000 during 1997 and 2001, with 8.0% and 8.3% of infant deaths being potentially preventable if smoking were eliminated. Infant SAM crude rates among the general population were 1.4 per and 1.0 per 10,000 during 1997 and 2001 and 2.8% and 2.3% of deaths were potentially preventable if smoking were eliminated. CONCLUSIONS: Total adult age- and gender-adjusted SAM rates for both populations were substantive. Additional interventions that prevent and reduce tobacco use by FN people are indicated, particularly given their high rates of smoking. The high total SAM rates for FN infants also suggest the need for interventions.

Adult↗
PubMed2001

Measurement of activity in older adults: reliability and validity of the Step Activity Monitor.

The purpose of this study was to test the reliability and validity of the Step Activity Monitor (SAM) when used with older adults. A total of 30 subjects with a mean age of 86 +/- 6.1 participated in the study. Sixty one-minute walks were measured with the SAM, and two observers visually counted steps. Four participants wore the SAM for 6 to 48 hours and maintained activity diaries. The intraclass correlation for the SAM recordings was R = .84. There was an overall step counting accuracy of 96%. The diaries supported the SAM data for those who wore the SAM for extended periods. The SAM is an easy to use, comfortable, valid, and reliable measure of activity in older adults and particularly may be useful to triangulate measurement of activity in these individuals.

Aged↗
PubMed2002

[Effect of tiaoxin recipe on learning and memory related gene expression in hippocampus of senescence accelerated mice].

OBJECTIVE: To study the effect of Tiaoxin Recipe (TXR) on learning and memory related gene expression in hippocampus of senescence accelerated mice (SAM). METHODS: Changes of learning and memory related gene expression, including mineralocorticoid receptor (MR), presenile protein 1 and 2 (PS-1, PS-2), tau, APP, apoE and bcl-2 in hippocampus of SAM were determined by reverse transcription polymerase chain reaction (RT-PCR). The effect of TXR were tested. E2020 was used as the drug for control. RESULTS: Compared with those in the same aged mice, in the 5-month old SAM, levels of gene expression of MR, tau, PS-2 and APP were significantly higher, that of apo-E lower, levels of gene expression PS-1 and bcl-2 were unobviously changed; while in the 12-month old SAM, gene expression of MR and tau were higher, bcl-2 was lower and PS-1, PS-2, apoE and APP were also unobviously changed. Continuously orally taken TXR could correct the abnormality of MR, tau and apoE gene expression in hippocampus of 5-month SAM and that of MR and bcl-2 in 12-month SAM. CONCLUSION: Continuously orally taken of TXR has the effect of regulating and correcting learning and memory related gene expression in hippocampus of 5-month and 12-month SAM.

Aging↗
PubMed2005

Sound speed scanning acoustic microscopy for biomedical applications.

Since 1985, we have been developing a scanning acoustic microscope (SAM) system for biomedical use and have been investigating the acoustic properties of various organs and disease states by using this SAM system. In biomedicine, SAM is useful for intraoperative pathological examination, study of low-frequency ultrasonic images, and assessment of biomechanics at a microscopic level. Recently, we have proposed a new concept -- acoustic microscopy -- using a single pulsed wave instead of continuous waves used in conventional SAM systems. In the present study, we compared two systems by measuring the same biological material. The sound speed image obtained by sound speed microscopy corresponded well to that obtained using a conventional SAM system. Lesions with hyaline degeneration showed a lower sound speed when compared with that of normal myocardium. Frequency domain analysis of amplitude and phase by both methods also showed similar characteristics. Although the data acquisition time of one frame was greater than that in conventional SAM, the total time required for calculation was significantly shorter. The SAM system can be applied to intraoperative pathological examination.

Animals↗
PubMed1985

[Mechanism of systolic anterior motion of the mitral valve in dogs].

The mechanism of systolic anterior motion (SAM) of the mitral valve remains somewhat controversial. We previously reported that SAM can be produced in dogs using dobutamine infusion. In the present study, dobutamine infusion, dextran infusion and venesection were performed in 13 anesthetized closed-chest dogs to study the mechanism of SAM. The degree of SAM was determined by M-mode echocardiography. End-systolic and end-diastolic short-axis areas of the left ventricle at the level of the chordae tendineae and the fractional area changes were measured by two-dimensional echocardiography. SAM was produced in six of the 13 dogs during dobutamine infusions (Group 1), but not in the other seven dogs (Group 2). During dobutamine infusions, % fractional area changes were greater in Group 1 (85 +/- 5; mean +/- standard deviation) than in Group 2 (65 +/- 15) (p less than 0.01), and the end-systolic short-axis area of the left ventricle was smaller in Group 1 (0.7 +/- 0.4 cm2) than in Group 2 (1.9 +/- 0.3 cm2) (p less than 0.01), although no significant change was observed between Groups 1 and 2 in the end-diastolic short-axis area of the left ventricle. Subsequent injections of dextran (mean 340 ml) in Group 1, decreased the degree of SAM and increased the end-diastolic and end-systolic short-axis areas of the left ventricle. Subsequently, venesections (mean 400 ml) in Group 1 resulted in increases in the degrees of SAM and decreases in the end-diastolic and end-systolic short-axis areas of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Effects of S-adenosyl-L-methionine on the cerebral energy metabolism and microcirculation in the rats subjected to transient forebrain ischemia].

Effects of S-adenosyl-L-methionine (SAM) on the improvement of cerebral energy metabolism and microcirculation were examined in postischemic rat brain. Male Wistar rats, whose vertebral arteries were electrically cauterized last day, were subjected to forebrain ischemia by temporary clipping of both common carotid arteries. After 60 min of ischemic insult, they were intravenously administered with SAM at doses of 30 or 100 mg/kg; this was followed by recirculation for 60 min. To determine cerebral concentrations of energy metabolites, the brain was frozen in situ. Adenine nucleotides (ATP, ADP, AMP) were assayed by anion-exchange HPLC system, and other metabolites (PCr, glucose, lactate, pyruvate) were analyzed by enzymatic fluorometry. In order to estimate regional cerebral blood flow (rCBF) and glucose utilization, double-tracer autoradiography was undertaken using 14C-iodoantipyrine (14C-IAP) and 18F-fluorodeoxyglucose (18F-FDG). In animals without SAM treatment (60-60 group), energy metabolites did not recover and neither CBF nor glucose uptake restored during 60 min of recirculation. In contrast, in SAM-treated animals (60-60 SAM group), values of the energy metabolites improved significantly and both CBF and glucose uptake recovered, though incompletely. These results indicate that SAM is able to improve postischemic cerebral microcirculation and energy metabolism. For mechanisms of the effects, it is suggested to the enhancement of erythrocyte deformability by phospholipid methylation, the stabilization of mitochondria, and the normalization of injured metabolic reactions. Therefore, we conclude that SAM is able to be effective clinically as a drug treated for the acute phase of cerebrovascular diseases.

Animals↗