Interictal alterations of thalamic metabolic concentration ratios in migraine without aura detected by proton magnetic resonance spectroscopy

Aim of the work

To detect interictal changes of the metabolic concentration ratios in the thalami of patients with migraine without aura by using 1H-MRS.

Materials and methods

Twenty-two patients of migraine without aura were enrolled in this study in addition to 10 healthy controls. Patients were further divided into 2 subgroups; 12 with left-sided migraine and 10 with right-sided migraine. Patients were imaged interictally with multivoxel 1H-MRS for measuring the NAA/Cho, NAA/Cr, Cho/Cr, MI/NAA and Lac/NAA ratios in both thalami.

Results

Each of the mean NAA/Cho and NAA/Cr ratios was significantly decreased in patients compared to controls, and also on the contralateral side compared to the side of migraine in each subgroup of patients. In contrary, no significant difference was found in Cho/Cr, MI/NAA and Lac/NAA ratios between patients and controls, as well as on comparing both sides in each subgroup of patients. Furthermore, increased duration of illness and frequency of attacks were significantly associated with decreased NAA/Cho and NAA/Cr ratios as well as increased MI/NAA and Lac/NAA ratios.

Conclusion

Migraine without aura is associated with thalamic interictal changes in the mean metabolite concentration ratios, detected with multivoxel 1H-MRS.     

旋覆代赭汤对反流性食管炎大鼠食管组织舒缩神经递质的影响

目的:观察旋覆代赭汤及原方倍用甘补组方对反流性食管炎(RE)模型大鼠食管舒缩神经递质活力的影响。方法:将110只雄性Wistar大鼠随机分成正常对照组、假手术组和造模组。将造模组大鼠制备成反流性食管炎动物模型后随机分为模型对照组、旋覆代赭汤原方组、原方倍用甘补方组、西药对照组。进而观察食管下段黏膜组织形态学变化及食管组织及血浆ChAT及NOS活力的表达情况。结果:原方组、甘补组及西药组大鼠食管组织ChAT活力较模型组明显提高,差异有统计学意义(P<0.05);原方组、甘补组及西药组大鼠食管组织NOS活力较模型组明显降低,差异有统计学意义(P<0.05)。结论:旋覆代赭汤能够通过影响食管组织及血浆舒缩神经递质合成酶活力,改善食管组织的舒缩功能。     

In vivo 1H MRS of WSU‐DLCL2 human non‐Hodgkin's lymphoma xenografts: response to rituximab and rituximab plus CHOP

In order to identify early ¹H MRS metabolic markers of response to rituximab immunotherapy and to rituximab plus CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, and prednisone) combination therapy, we performed an in vivo MRS investigation of a non‐Hodgkin's lymphoma (NHL) xenograft model. Human WSU‐DLCL2 NHL cells were subcutaneously implanted into flanks of female severe combined immunodeficient mice. When tumor volumes reached ～600 mm³, rituximab was administered for three weekly cycles at a dose of 25 mg/kg per cycle with or without CHOP. Before and after treatment, tumor lactate (Lac) and total choline (tCho) were detected using the selective multiple quantum coherence sequence and the stimulated echo acquisition mode sequence, respectively. Rituximab produced a small tumor growth delay (～5 days), whereas treatment with rituximab plus CHOP (RCHOP) led to ～20% tumor regression after three cycles of therapy. After one cycle of rituximab, the tCho/H₂O ratio had decreased significantly (5%, P = 0.003), whereas the Lac/H₂O ratio had not changed (P = 0.58). Both Lac/H₂O and tCho/H₂O had decreased after one cycle of RCHOP treatment (26%, P = 0.001; 10%, P = 0.016, respectively). After two cycles of RCHOP, Ki67 assay of histological tumor specimens indicated ～40% decrease in proliferation (P < 0.001) in the RCHOP‐treated tumors; no change was detected after treatment with rituximab alone. This study suggests that decreases in tCho/H₂O are more sensitive indices of response to rituximab, whereas decreases in Lac/H₂O are more sensitive to response to CHOP combination therapy. Copyright © 2008 John Wiley & Sons, Ltd.     

Cyto- and Chemoarchitecture of Basal Forebrain Cholinergic Neurons in the Common Marmoset (Callithrix Jacchus)

The cyto- and chemoarchitecture of basal forebrain cholinergic neurons (BFCN) was investigated in the lower primate, the common marmoset (Callithrix jacchus). A large population of magnocellular, hyperchromic, and choline acetyltransferase (ChAT)-positive neurons was detected in the marmoset basal forebrain. The distribution of these neurons was similar to those in higher primates. Thus, ChAT-positive neurons were observed in the medial septum (Ch2), the vertical (Ch2) and horizontal (Ch3) limbs of the diagonal band of Broca, and the nucleus basalis of Meynert (Ch4). The Ch4 complex was relatively well differentiated and displayed distinct sectors. We detected anterior (Ch4a, with a medial and a lateral subdivision), intermediate (Ch4i, with a dorsal and a ventral subdivision), and posterior (Ch4p) sectors in the marmoset Ch4. The Ch4i was relatively small while the Ch4p was large. Similar to the rodent, the marmoset Ch1 extended quite a distance posteriorly, and the Ch4p displayed a major interstitial component distributed within the globus pallidus, its medullary laminae, and the internal capsule. Virtually all of the marmoset BFCN displayed acetylcholinesterase activity, and low affinity (p75^NTR) and high affinity (Trk) neurotrophin receptor immunoreactivity. A majority contained immunoreactivity for calbindin-D_28K and calretinin. Many of the Ch4 neurons also displayed tyrosine hydroxylase immunoreactivity. The BFCN lacked galanin immunoreactivity, but were innervated by galanin-positive fibers. None of the marmoset BFCN were NADPH-d-positive. Thus, the BFCN display major anatomical and biochemical differences in the marmoset when compared with higher primates. The marmoset BFCN also display many characteristics common to other primates. This fact, combined with the relatively short life span of the marmoset, indicates that this species may be ideal for studies of age-related changes in the BFCN.     

Combined DCE‐MRI and single‐voxel 2D MRS for differentiation between benign and malignant breast lesions

Dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) and proton (1H) magnetic resonance spectroscopy (MRS) provide structural and biochemical information, including vascular volume, vascular permeability and tissue metabolism. In this study, we performed analysis of the enhancement characteristic from DCE‐MRI and the biochemical information provided by two‐dimensional (2D) Localized Correlated Spectroscopy (L‐COSY) MRS to determine the sensitivity and specificity of using DCE‐MRI alone compared to the combination with 2D MRS. The metabolite ratios from the 2D MRS spectra were analyzed using multivariate statistical analyses to determine a method capable of automatic separation of the patient cohort into malignant and benign lesions. A total of 24 lesions were studied with 21 diagnosed accurately using the enhancement characteristics alone resulting in sensitivity and specificity of 100% and 73%, respectively. Analysis of the 2D MRS data demonstrated a significant difference (p < 0.05) in 12 of 18 metabolite ratios analyzed for malignant compared to benign lesions. Previous research focused on utilizing the choline signal to noise ratio (SNR) as a marker for malignancy has been verified using 2D MRS in this study. Using Fisher's linear discriminant test using water (WAT)/olefinic fat diagonal (UFD), choline (CHO)/fat (FAT), CHO/UFD, and FAT/methyl fat (FMETD) as predictors the sensitivity and specificity increased to 92% and 100%, respectively. Using the Classification and Regression Tree (CART) statistical analysis the resulting sensitivity and specificity were 100% and 91%, respectively, with the most accurate predictor for differentiating malignant and benign determined to be FAT/FMETD. The cases within the study that presented a indeterminate diagnosis using DCE‐MRI alone were able to be accurately diagnosed when the metabolic information from 2D MRS was incorporated. The results suggest improved breast cancer detection through the combination of morphological and enhancement information from DCE‐MRI and metabolic information from 2D MRS. Copyright © 2010 John Wiley & Sons, Ltd.     

The cholinergic system of the human hindbrain studied by choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry

A map of cholinergic cells of the human brainstem identified by immunohistochemistry of choline acetyltransferase (ChAT) is presented, along with a map of acetylcholinesterase (AChE)-containing cells and fibers. ChAT-positive structures belong to 4 brainstem systems: the cranial motor nuclei; the parabrachial complex; the reticular system; and the vestibular system. All motor nuclei of the cranial nerves, as well as the nucleus supraspinalis, are ChAT-positive. The positively staining structures of the parabrachial system include the nucleus tegmentali pedunculopontinus, and the nuclei parabrachialis medialis and lateralis. Nuclei of the reticular system containing some ChAT-positive cells include the nucleus reticularis pontis oralis and caudalis, the nucleus reticularis tegmenti pontis, the nucleus reticularis gigantocellularis, the nucleus reticularis lateralis and the formatio reticularis centralis (medulla). Structures of the vestibular and auditory systems which contain some ChAT-positive cells include the nucleus vestibularis lateralis, and the nuclei olivaris superioris medialis and lateralis. All ChAT-positive structures stain strongly for AChE. AChE-positive, ChAT-negative structures were noted in several sensory systems. The substantia nigra, locus coeruleus and raphe nuclei, known to contain non-cholinergic cells, also stain positively. The significance of the AChE-positive, ChAT-negative staining in most structures remains to be determined. A knowledge of the cholinergic systems of human brain may be important to an understanding of the pathology of a number of diseases.     

Effect of combined or separate administration of piracetam and choline on learning and memory in the rat

Different groups of rats received combined or separate administration of different doses of piracetam (P1:100, P2:200, and P4:400 mg/kg) and choline (C1:100 and C2:200 mg/kg). Compared to control treatment, C1 significantly improved performance in a delayed alternation (DA) task, while P1, P2, P4 or P1C1 had no effect. Moreover, rats receiving P2C1 and P4C1 were significantly inferior in acquiring DA to rats receiving the vehicle or separate administration of P1, P2 or C1. The different treatments with combined or separate administration of P and C had no effect on spontaneous locomotor activity and two-way avoidance conditioning. In a recognition-task only groups C1 and P4 were able to discriminate between familiar and new objects. The combined or separate administration of P1 and C1 on NA, DA, DOPAC, 5-HT, 5-HIAA levels, CAT activity and choline uptake were measured in frontal cortex and hippocampus: the only significant effect was a 5-HT increase in the hippocampus of rats treated with C1.     

A correlated light and electron microscopic immunocytochemical study of cholinergic terminals and neurons in the rat amygdaloid body with special emphasis on the basolateral amygdaloid nucleus

The cholinergic innervation of the rat basolateral amygdaloid nucleus (BL) was determined by the immunocytochemical localization of the acetylcholine biosynthetic enzyme, choline acetyltransferase (ChAT). ChAT-immunoreactive (ChAT-IR) elements were observed throughout the BL in the form of fine puncta and varicose fibers. Electron microscopy revealed that the immunoreactive puncta represented small terminals (0.3-1.2 micron), most of which formed synaptic contacts with unlabeled dendritic shafts or spines. Less frequently, ChAT-IR terminals established synaptic contacts with large neuronal cell bodies, which had all the characteristics of projection neurons as defined on the basis of axonal projections to the ventral striatum. ChAT-IR terminals were sometimes seen to form synaptic contacts with small neuronal cell bodies, including those of ChAT-IR neurons. The ChAT-IR boutons contained pleomorphic clear vesicles of varying size, and the large majority of the synapses were of the symmetric type. Small ChAT-IR neurons were observed in all parts of the BL. Although the ChAT-IR cell bodies varied widely in shape from typical fusiform to round, most had a more or less oval shape with a major diameter of 10-14 micron. Most of the ChAT-IR neurons seemed to display a radial bipolar dendritic pattern, but multipolar cells were also observed. The ChAT-IR neurons contained an indented nucleus, which was often eccentrically located and surrounded by a thin or moderately thin rim of cytoplasm. The results obtained are discussed in relation to a quasi-cortical organization of the BL.     

Conjugated linoleic acid alters caveolae phospholipid fatty acid composition and decreases caveolin-1 expression in MCF-7 breast cancer cells

Conjugated linoleic acid (CLA) refers to a group of biologically active fatty acids that exhibit anticarcinogenic properties; however, the mechanism of action remains poorly understood. Caveolae are specialized plasma membrane structures that affect many facets of cancer cell function, including growth, cell signaling, and apoptosis. Therefore, one potential mechanism could be alteration of caveolae lipid composition and function. We hypothesized that CLA can alter the lipid microenvironment of caveolae and alter expression of the major caveolae-resident protein, caveolin-1. MCF-7 human breast cancer cells were treated with a vehicle control, linoleic acid (LA), or CLA for 3 days after which total cell lysate, plasma membrane, and caveolae membrane fractions were isolated. Our findings indicate that CLA readily incorporates into caveolae (Δ9cis,11trans-18:2 being the major isomer) and maybe preferentially enriched in specific phospholipid species. Furthermore, caveolin-1 localization to caveolae after treatment with CLA was decreased relative to either control- or LA-treated cells, without changes in total cellular levels of protein relative to vehicle-control treated cells. Taken together, our results suggest that further investigation of a potential therapeutic role for CLA in modulating caveolae function in breast cancer is merited.     

曲拉通X—100影响脑内递质及合成酶免疫组化定位

目的；研究曲拉通Ｘ－１００是否会改变脑内质及合成酶免疫组织化学定位特征，及是否与其浓度有关。材料与方法：观察了高，低浓度ＴＴＸ预处理脑切片，对胆碱乙酰化酶，Ｐ物质和γ－氨基丁酸样免疫反应神经元胞体及终末，在树Ｑｕ内侧隔核，斜带核及海马，免疫组化定位的影响。并在树Ｑｕ和猫脑探索了缓冲低浓度梯度酒精替代ＴＴＸ的可能性。结果：在树Ｑｕ脑，当ＴＴＸ为０．１％时，内侧隔核，斜带核三类神经元胞体染色变浅，数量