Levels Of NAA Research Articles

1H magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in bipolar disorder patients

Background Magnetic resonance spectroscopy studies (MRS) reported abnormally low levels of N-acetylaspartate (NAA, a marker of neuronal integrity) in dorsolateral prefrontal cortex (DLPFC) of adult bipolar patients, suggesting possible neuronal dysfunction. Furthermore, recent MRS reports suggested possible lithium-induced increase in NAA levels in bipolar patients. We examined with in vivo 1H MRS NAA levels in the DLPFC of adult bipolar patients. Methods Ten DSM-IV bipolar disorder patients (6 lithium-treated, 4 drug-free) and 32 healthy controls underwent a short echo-time 1H MRS session, which localized an 8 cm 3 single-voxel in the left DLPFC using a STEAM sequence. Results No significant differences between the two groups were found for NAA, choline-containing molecules (GPC+PC), or phosphocreatine plus creatine (PCr+Cr) (Student t-test, p>0.05). Nonetheless, NAA/PCr+Cr ratios were significantly increased in lithium-treated bipolar subjects compared to unmedicated patients and healthy controls (Mann–Whitney U-test, p<0.05). Limitations Relatively small sample size may have reduced the statistical power of our analyses and the utilization of a single-voxel approach did not allow for the examination of other cortical brain areas. Conclusions This study did not find abnormally reduced levels of NAA in left DLPFC of adult bipolar patients, in a sample of patients who were mostly on medications. However, elevated NAA/PCr+Cr ratios were shown in lithium-treated bipolar patients. Longitudinal 1H MRS studies should further examine NAA levels in prefrontal cortex regions in untreated bipolar patients before and after mood stabilizing treatment.

Brain mitochondrial injury in human immunodeficiency virus–seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors

Nucleoside reverse transcriptase inhibitors (NRTIs) suppress human immunodeficiency virus (HIV) replication, but are often associated with mitochondrial toxicity. Although well studied outside of the central nervous system, no investigation has examined the effects of these drugs on brain mitochondria of individuals living with HIV. The authors used proton magnetic resonance spectroscopy to evaluate NRTI-related changes in brain mitochondria. N-acetylaspartate (NAA; sensitive to alterations in mitochondrial integrity) was measured in frontal lobe white and gray matter of 18 HIV+ individuals taking didanosine and/or stavudine (two NRTIs likely to cause mitochondrial toxicity), 14 HIV+ individuals taking zidovudine and lamivudine, 16 HIV+ individuals not currently taking antiretrovirals, and 17 HIV- controls. The HIV+ groups were comparable on demographic measures, estimates of illness severity, and estimated length of HIV infection. Those taking didanosine and/or stavudine had a significant 11.4% decrease in concentrations of frontal white matter NAA compared to HIV- controls, whereas NAA levels of the other HIV+ groups were intermediate. Group differences in metabolites were not found in frontal gray matter. Lower levels of frontal white matter NAA were associated with longer periods of didanosine and/or stavudine treatment (r = -.41, P = .06). Levels of NAA were not related to length of zidovudine/lamivudine treatment (r = -.04, P = .44). Furthermore, taking more than one of stavudine, didanosine, and abacavir increased the likelihood of having reduced NAA. The results are consistent with previous studies finding HIV-related changes in neuronal integrity. However, because NRTIs can injure mitochondria, we propose that the observed reductions in NAA in individuals taking didanosine and/or stavudine may be the result of depleted brain mitochondria and/or alterations in cellular respiration. Measurement of brain metabolites sensitive to impairments in energy metabolism, including NAA, may aid in early detection of subclinical NRTI-mediated mitochondrial toxicity.

Thinning York Imperial Apple with Chemical Combinations

Six-year-old York/M.9 trees were used to evaluate combinations of chemicals for fruit thinning. In one experiment a factorial combination of 2 levels of carbaryl (0 or 600 mg·L-1) and 5 levels of 6-BA (0, 40, 80, 120, and 160 mg·L-1) were sprayed when fruit diam. averaged 10.5 mm. Carbaryl significantly reduced fruit set, number of fruit/tree, yield efficiency, and crop density, and increased fruit weight. The main effect of 6-BA did not significantly influence any response variable. Two variables were significantly influenced by the carbaryl × 6-BA interaction. In the absence of carbaryl, fruit set was reduced and fruit weight was increased by 6-BA at concentrations less than 160 mg·L-1, but the addition of 6-BA to carbaryl was no more effective than carbaryl alone. In a second experiment, a factorial combination of 2 levels of carbaryl (0 vs. 600 mg·L-1), 2 levels of NAA (0 vs. 5 mg·L-1), and 2 levels of ethephon (0 vs. 450 mg·L-1) were sprayed when fruit when fruit diam. averaged 10.5 mm. Carbaryl and NAA reduced fruit set by about 30%, but ethephon overthinned and reduced set by 65%. When the other materials were combined with ethephon, thinning was similar to ethephon alone. The combination of carbaryl and NAA was no more effective than either material alone. The lowest values for yield, yield efficiency, and numbers of fruit per tree were associated with the combination of ethephon plus NAA. Ethephon was the only material that increased fruit weight.

Effect of angiotensin-receptor blockade on reduced cerebrovascular reserve and neuronal mass in diabetic hypertensives

P-332 Key Words: Diabetic Hypertension, Cerebral Circulation, Angiotensin Receptor Blocker

Therapeutic Options in Prevention and Treatment of Aspartoacylase Gene Mutation Resulting Abnormalities in Canavan Disease

Canavan disease (CD) is an autosomal recessive disorder, caused by mutations in the aspartoacylase gene resulting enzyme deficiency. Patients with CD have accumulation of NAAG and NAA in the brain resulting elevated urinary NAAG and NAA. Aspartoacylase gene mutation in the mouse led to multiple genomic abnormalities. Pathophysiological processes implicated in CD include spongy degeneration of the brain possibly by the abnormal genes expression / metabolic levels of NAAG, NAA, aspartate, glutamate, glutamate transporter-EAAT4, GABA receptor-GABRA6 and GABA. In addition, high expression of cell death inducing agents includes serine proteinase inhibitor 2, caspase 11 and interleukin 1- beta. Osteoporosis is also an important consequence in the CD mouse. Each of these pathways offers potential therapeutic targets and pharmacological manipulation.

Regeneration of a Tetraploid Clone from Callus Culture of Asparagus officinalis L. through Somatic Embryogenesis

A tetraploid callus line of Asparagus officinalis L. was identified from 4 regenerated callus lines. Plants were regenerated from these callus lines following somatic embryogenesis and the tetraploid clone of this species was established in the field with 80% survival rate. The embryogenic callus was induced in Murashige and Skoog's (MS) medium in presence of α-naphthaleneacetic acid (NAA) (0.2 mg/l) and kinetin (0.02 mg/l) and proliferated as well as maintained in 2,4-dichlorophenoxyacetic acid (2,4-D) (1.0 mg/l) containing MS medium. Somatic embryos were initiated in Gelrite-solidified MS medium with variable levels of NAA and 6-(γ-γ-dimethylallylamino) purine (2ip). A higher level of carbohydrate enhanced embryo conversion efficiency. The embryos induced in presence of 10% glucose for 2 weeks and subsequently transferred to 2% sucrose level showed higher conversion rate than those maintained in 3% sucrose concentration. Karyotype analysis of diploid and tetraploid clones revealed exact duplication of the diploid set in tetraploid plants.

Favorable effect on neuronal viability in the anterior cingulate gyrus due to long-term treatment with atypical antipsychotics: an MRSI study.

In the present study, we evaluated 23 chronic schizophrenic patients under stable clinical conditions to determine the association between neuronal viability, as measured by in vivo(1)H magnetic resonance spectroscopic imaging (MRSI), and antipsychotic drug effects in the anterior cingulate cortex. Careful screening of the medication history showed that 11 of these patients had been treated with traditional neuroleptics only, while the others had switched to atypical antipsychotics due to non-response to traditional drugs. The group of patients receiving typical neuroleptic medication showed a mean NAA that was lower than in the group of patients receiving atypical antipsychotic drugs. Removing the duration of illness effect indicated a significant correlation between the NAA signal in the anterior cingulate gyrus and time on atypical drugs in patients under long-term atypical antipsychotic treatment. In contrast, patients with traditional medication revealed progressive decrease in the NAA level. These results suggest a favorable effect on neuronal viability in the anterior cingulate gyrus due to long-term treatment with atypical antipsychotics.

Analysis of volume MRI and MR spectroscopic imaging data for the evaluation of patients with brain tumors.

The combination of volumetric MRI and multivoxel localized MR spectroscopic imaging (MRSI) data provides the potential for quantifying variations in tissue morphology and function. These techniques have numerous applications for the evaluation of neurological diseases. While state-of-the-art whole-body MR scanners are able to acquire both types of data, there have been relatively few reports which have presented clinical applications of the technology. One of the reasons for this has been the need to develop software for reconstruction and reliable interpretation of 3D imaging and spectral data. In this article, we describe the strategy developed for quantitative analysis of combined MRI and MRSI examinations from patients with brain tumors and evaluate the key components of this procedure using both simulations and empirical data from phantoms, normal volunteers, and patients. Important factors are the use of volume or interleaved multislice anatomic images as a reference, the reconstruction and correction of the spectral data for frequency, phase, and baseline distortions and consideration of the characteristics of the coil, RF pulses used for spatial selection, and phase encoding procedures. These studies show that the metabolic parameters most critical for distinguishing tumor from normal and necrotic tissue were relative levels of choline and NAA. Levels of creatine and lactate were found to be variable, both in terms of their spatial distribution within individual lesions and between different patients.

Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors

The goal of this study was to determine whether presurgical metabolite levels measured by 3D MR Spectroscopic Imaging (MRSI) can accurately detect viable cancer within human brain tumor masses. A total of 31 patients (33 exams, 39 pathology correlations) with brain tumors were studied prior to surgical biopsy and/or resection. The 3D MRSI was obtained with a spatial resolution of 0.2 to 1 cc throughout the majority of the mass and adjacent brain tissue using PRESS-CSI localization. Levels of choline, creatine and NAA were estimated from the locations of the resected tissue and normalized to normal appearing brain tissue. The data were correlated with subsequent histologic analysis of the biopsy tissue samples. Although there were large variations in the metabolite ratios, all regions of confirmed cancer demonstrated significant choline levels and a mean choline/NAA ratio of 5.84 + 2.58 with the lowest value being 1.3. This lowest value is greater than 4 standard deviations above the mean (0.52 ± 0.13) found in 8 normal volunteers. The choline signal intensities in confirmed cancers were significantly elevated compared to normal appearing brain tissue with a mean ratio of 1.71 ± 0.69. Spectra with no significant metabolite levels were observed in the non-enhancing necrotic core of the tumor masses. The results of this study indicate that 3D MRSI of brain tumors can detect abnormal metabolite levels in regions of viable cancer and grades and can differentiate cancer from necrosis and/or normal brain tissue.

260. A 1H-MRSI hippocampal study in bipolar patients with a history of alcohol abuse

Bipolar illness has the highest lifetime prevalence rate for co-morbid substance abuse, specifically alcohol, than other Axis I diagnoses. MRI studies have shown the hippocampus to be susceptible to the neurotoxicity of alcohol. The purpose of this study was to evaluate the aggregate neuropathology of this co-morbidity by proton magnetic resonance spectroscopic imaging (1H-MRSI). This study is a post-hoc analysis of our previous 1H-MRSI study which found decreased NAA in bilateral hippocampi in bipolar patients compared to controls (Bertolino et al., 1999). 17 patients with bipolar I disorder were scanned on a 1.5T GE magnet (pulse sequence; TR 2200 msec, TE 272 msec, voxel resolution 1.4 ml). Metabolite levels of NAA, creatine + phosphocreatine (CRE), and choline compounds (CHO) were measured as ratios of the areas under each peak. Blind to the 1H-MRSI data, the medical record and SKID were reviewed to identify a history of alcohol abuse (x sobriety: 55 months). All patients were symptomatic only of their mood disorder and were not currently abusing alcohol. Unpaired t-tests were utilized to evaluate diagnostic group differences. The mean NAA/CHO ratio in 1 & r hippocampus was higher in patients with a history of alcohol abuse in comparison to patients without such history (1: 1.28 ± 0.21 vs. 1.04 ± 0.27; n = 17, t = 1.84, p = 0.08; r: 1.26 ± 0.15 vs. 1.07 ± 0.18; t = 2.35, p = 0.03). Similar findings were noted for NAA/CRE ratio in 1 hippocampus (1: 1.64 ± 0.24 vs. 1.34 ± 0.27; t = 2.29, p = 0.036 r: 1.63 ± .17 vs. 1.35 ± 0.3, t = 2.09, p = 0.053). These data were particularly striking when analyzed by gender for men. (NAA/CHO: 1; 1.29 ± 0.24 vs. 0.93 ± 0.05, n = 10, t = 3.46, p = 0.009, r; 1.29 ± 0.15 vs. 1.02 ± 0.13, t = 2.98, p = 0.018) (NAA/CRE: 1; 1.66 ± 0.27 vs. 1.21 ± 0.09, t = 3.49, p = 0.008, r; 1.67 ± 0.14 vs. 1.31 ± 0.30, t = 2.43, p = 0.04). These data suggest differential 1H-MRS pathology in bipolar patients with and without a history of alcohol abuse. As previous studies have reported a decrease in NAA in bipolar patients, these ratios, in patients with a history of alcohol abuse may suggest a greater decrease in CHO and CRE signals or a reactive increase in NAA. To what extent these abnormalities suggest differential degrees of neuronal loss (NAA) and/or subsequent glial hyperplasia (CHO) and the persistence of these abnormalities despite abstinence require further controlled investigation.

EFFECTS OF DIFFERENT PHYSIOCHEMICAL FACTORS ON REGENERATION OF CYMBOPOGON POLYNEUROS STAPF VIA CALLUS CULTURE AND SUBSEQUENT CHROMOSOMAL STABILITY

In vitro regeneration of Cymbopogon polyneuros Stapf was obtained through callus culture using leaf base, node, and root as explants. Callus was induced from different explants with 2–5 mg/1 α-naphthalene acetic acid (NAA) and 1–2 mg/1 kinetin in Murashige and Skoog's (MS) basal medium. High frequency shoots were noticed from leaf-base callus supplemented with 3.5 mg/1 6-benzylaminopurine (BA), L-arginine, adenine, and a low level of NAA (0.2 mg/1). About 80–85 shoot buds were obtained from ca. 200 mg of callus per culture. The individual shoots produced root in the presence of 0.5–3 mg/1 indole 3-butyric acid or its potassium salt. Regenerated plants were cytologically and phenotypically stable. Regenerants were transplanted into soil and subsequently transferred to the field.

Mast cells contain large quantities of secretagogue-sensitive N-acetylaspartate.

Mast cells play a central role in both immediate allergic reactions and inflammation. A functional nerve-mast cell interaction has been proposed, given the morphological association between mast cells and neuropeptide-containing peripheral nerves. We now show that purified rat peritoneal mast cells contain large quantities of N-acetylaspartate (NAA; 747.50 nmol/mg of protein). Mast cell levels of NAA were rapidly reduced, by 64.0 and 86.4%, following treatment with compound 48/80 and mastoparan, respectively. These secretagogues strongly decreased mast cell histamine content over the same time period, suggesting also that NAA is stored in secretory granules. The data are the first to show that NAA is present in an immune effector cell type. Because NAA may be involved in myelin synthesis and glutamyl peptide metabolism, NAA released from mast cells following nervous or other stimuli could participate in neuroimmune interactions. Mast cells in multiple sclerosis plaques may contribute to the reported elevations in brain NAA in this disease.

Plant Regeneration inAsparagus verticillatusL.

ABSTRACT Conditions that would promote in vitro organogenesis from explants of Asparagus verticillatus were investigated. Induction of callus was affected by light intensity and combinations of 2,4-dichlorophenoxyacetic acid (2,4-D) and kinetin (Rn), 2,4-D and 6-benzylaminopurine (BAP), and d-napthalene acetic acid (NAA) and Kn. The induction of shoots from callus required 6-benzylaminopurine (BAP) or 6-benzylamino-9(2-tetrahydropyranyl) adenine (BPA), L-arginine, a low level of NAA, and the source of calli. Roots were produced from individual shoots in presence of indole-3-acetyl-L-alanine (IAA-L-alanine).

The Effect of Slow-release Polymeric Derivatives of Auxins (NAA and 2,4-D) on Regeneration of Achimenes in Vitro

Polymeric formulations of plant growth regulators (PGR) are high-molecular weight systems in which the PGR unit can be slowly released providing prolonged action and effectiveness in a wide range of concentrations. In this study, Achimene explants were used for testing the biological activity of polymeric derivatives of NAA and 2,4-D. Shoots of Achimenes `Bella', obtained from leaf segments cultured in vitro, were transferred for 8 weeks on Murashige and Skoog (MS) medium supplemented with different levels of conventional or polymeric NAA (0, 0.01, 0.05, 0.1, 0.5, 1.0, 1.5, 2.0, 2.5 mg·liter–1) and 2.4-D (0, 0.01, 0.05, 0.1, 0.5, 1.0, 1.5 mg·liter–1), each combined with three levels of BAP (0, 0.1, 0.5 mg·liter–1). Compared to conventional NAA, twice as many shoots proliferated with higher dry weight, at 0.5 0.1, 1.0, or 1.5 mg·liter–1 polymeric NAA with 0.5 mg·liter–1 BAP. In another trial, the combination of 0.05 or 0.1 mg·liter–1 polymeric 2,4-D with 0.1 BAP gave more shoot and vigorous growth without callus formation, compared to conventional 2.4-D These results suggest that the polymeric derivatives of auxins used in this study enhance regeneration and growth of Achimenes in vitro more effectively than conventional formulations, at greater concentrations, without causing toxic or inhibitory effects.

Influence of photoperiod and medium formulation on peanut somatic embryogenesis

Somatic embryos were produced from peanut (Arachis hypogaea L.) immature zygotic cotyledons. Comparisons were made of the level of α-naphthaleneacetic acid during induction, nitrogen formulation of the medium, and photoperiod. Over 70% embryogenesis was obtained regardless of NAA level used. Percent embryogenesis and number of embryos were markedly lower in explants induced on NAA compared to 2,4-D. Embryo production was not greatly affected by either the use of Murashige & Skoog versus Finer & Nagasawa salts or light versus dark culture conditions. However, embryo morphology was noticeably affected by photoperiod. Embryos produced under a 16 h photoperiod were tough, woody and difficult to separate for subsequent germination and conversion. Those produced under a 0-h photoperiod were succulent and pliable.

EVALUATION OF SOMACLONES REGENERATED FROM LEAVES OF `THORNLESS EVERGREEN' BLACKBERRY

Plants were regenerated in vitro from intact lamina of Rubus laciniatus Willd. `Thornless Evergreen' (TE), a chimeral thornless form of `Evergreen' blackberry, which carries a thornless gene only in its epidermal tissue. Leaves without petioles or axillary buds were harvested from proliferating cultures and explanted onto modified Murashige and Skoog (MS) medium with various levels of BA, NAA and thidiazuron (TDZ). TDZ gave more consistent regeneration than BA. Up to 100% regeneration was observed with 0.2 μM TDZ plus NAA (0.25 or 1.0 μM) or 0.1 μM TDZ plus 1.0 μM NAA.Regenerants from chimeral TE and a pure thornless somaclone (IL 6-6), were classified according to stem and petiole morphology and presence or absence of prickles. Most (74%) of the regenerants from chimeral TE showed marked stem and petiole twisting compared to 4% of the regenerants from IL 6-6. The plants with straightest petioles tended to have the most prickles. These regenerants have been field planted. Additional observations of these regenerants will be discussed.

1H magnetic resonance spectroscopy of extracts of human epileptic neocortex and hippocampus.

We used high-resolution 1H magnetic resonance spectroscopy to determine the concentrations of several metabolites (lactate, alanine, N-acetylaspartate [NAA], gamma-aminobutyrate, glutamate, aspartate, creatine, cholines, taurine, inositol, and succinate) in tissue from patients undergoing surgical treatment of intractable epilepsy, and correlated the metabolite profiles with the results of histopathologic analysis of the excised tissue. We found no differences in metabolite levels for tissue from actively spiking or nonspiking neocortical sites in temporal lobe epilepsy patients. In neocortical tissue from patients with chronic localized encephalitis (Rasmussen's encephalitis), the metabolite concentrations varied with the severity and extent of the encephalitis. In tissue showing mild encephalitis and mild histologic abnormalities, the metabolite levels differed little from those found for nonencephalitic neocortical tissue. Tissue showing marked abnormalities and extensive encephalitis had decreased NAA, glutamate, cholines, and inositol. In hippocampal tissue from temporal lobe epilepsy patients, the levels of NAA, glutamate, and aspartate were lower and the levels of alanine, taurine, and inositol were higher than in neocortical tissue from the same patients. The decrease in the levels of NAA and glutamate was greater in gliotic hippocampal tissue. The results suggest that in vivo 1H magnetic resonance spectroscopy may aid in diagnosing the extent of chronic localized encephalitis and the severity of hippocampal gliosis.

Stable regeneration in Asparagus cooperi Baker as controlled by different factors

For in vitro regeneration spear, shoot tip, internode, node and root of mature plants of Asparagus cooperi were used as explants. Induction of callus from different explants depended on the photoperiod in addition to a specific combination of α-napthalene acetic acid (NAA) and kinetin (Kn) in the basal medium. The development of shoots from callus required 6-benzylaminopurine (BA), l-arginine, adenine and a low level of NAA. The individual shoots produced roots in the presence of indole-3-butyric acid (IBA) or indole-3-butyric acid containing potassium salt (KIBA). Regenerated plants were cytologically and phenotypically stable.

In Vitro Shoot Formation and Elongation of Dwarf Pomegranate

Fig. 1. Effect of BA (A) and NAA (B) concentration on in vitro shoot formation and elongation of Punica granatum ‘Nana’ on MS medium supplemented with either 2.0 μM NAA (A) or 2.0 μM BA (B). Each data point represents the mean ± 1 SE of 20 cultures. Dwarf pomegranate (Punica granatum L. ‘Nana’) is used for landscape, indoor culture, and bonsai. Adventitious shoot formation has been reported in anther and leaf callus cultures of tree pomegranate (Moriguchi et al., 1987; Omura et al., 1987). In vitro propagation has also been reported for tree pomegranate (Mascarenhas et al., 1981). However, we found no information on in vitro propagation of dwarf pomegranate. In this paper, we report in vitro shoot formation from nodal sections of dwarf pomegranate. Terminal shoots with seven to 10 nodes were excised from actively growing plants of dwarf pomegranate maintained in a greenhouse. Shoots were surface-disinfected as described previously (Zhang et al., 1987) and then cut to provide nodal sections (≈ 5 mm long). The explants were placed vertically in 25 × 100 mm culture tubes each containing 10 ml modified MS medium (Murashige and Skoog, 1962; Zhang et al., 1987). For shoot formation and elongation, the medium was supplemented with the following combinations of plant growth regulators: 1) with the NAA (1-naphthaleneacetic acid) level fixed at 2.0 μM, BA [ N -(phenylmethyl)-l H purin6-amine] levels were 0, 0.5, 1.0, 2.0, 4.0, 8.0, or 16.0 μM; and 2) with the BA level fixed at 2 μM, NAA levels were 0, 0.5, 1.0,

Adventitious shoot regeneration from in vitro leaves of several pear cultivars (Pyrus communis L.)

An efficient adventitious shoot regeneration system was developed for pear (Pyrus communis L.), using leaves from in vitro proliferating shoots. Under optimal conditions, bud regeneration frequencies of ‘Comice’, ‘Passe-Crassane’, ‘Williams’ and ‘Conference’ ranged from 60% to 97%, with the mean number of shoots per regenerating leaf ranging from 3.2 to 6.6. Despite the great variability in responses of the different cultivars, in general an initial dark exposure of at least 20 days was required. Ammonium and total nitrogen proved to play an essential role: intermediate NH4 + concentrations were suitable for regeneration. The balance between NH4 + and NO3 - also influenced regeneration; optimal regeneration occured on media with a 1:3 NH4 +/NO3 - ratio. TDZ at 1 μM was less efficient than higher concentrations, whatever the NAA level. Finally, length and growth regulator composition of the two phases (induction and expression) influenced the regeneration rate of ‘Conference’.