Risk of HCC decreases in HBV-related patients with cirrhosis acquired recompensation: A retrospective study based on Baveno VII criteria.

BACKGROUND: Antiviral therapy improves the clinical outcomes of patients with HBV-related cirrhosis. In this study, we aimed to evaluate the incidence rate of HCC in patients with HBV-related recompensated, compensated, or decompensated cirrhosis based on the latest Baveno VII criteria. METHODS: In this two-center retrospective study, HBV-related patients with cirrhosis were enrolled and treated with first-line nucleos(t)ide analogues therapy for at least 12 months. Participants were classified into 3 groups: (1) compensated group, (2) decompensated group, or (3) recompensated group according to Baveno VII criteria. Multivariate regression models and propensity score matching were used to identify the predictors of HCC. RESULTS: Of the 404 patients recruited, during a median follow-up of 44.5 months (interquartile range 26.8, 57.0 months), 233 (57.7%), 100 (24.8%), and 71(17.6%) patients had compensated, recompensated, and decompensated cirrhosis. In total, 38 developed HCC. The cumulative incidence of HCC development at 2, 4, and 6 years was 1.3%, 5.4%, and 20.0% in the compensated group, 1.2%, 5.2%, and 24.5% in the recompensated group, and 2.1%, 23.6%, and 41.8% in the decompensated group, respectively. In the multivariate Cox regression model, compared with the recompensated group, the decompensated group had a significant increased risk for the development of HCC (aHR 2.55; 95% CI: 1.240-5.240; p = 0.027), while the compensated group had similar HCC risk for the development of HCC (aHR 1.41; 95% CI: 0.540-3.730; p = 0.835). Propensity score-matching analysis between the recompensated and compensated groups (84 pairs) and propensity score-matching analysis between the recompensated and decompensated groups (62 pairs) showed similar results. CONCLUSIONS: Achieving recompensation reduced the risk of HCC in patients with HBV-related decompensated cirrhosis, while the risk remained comparable to that of compensated cirrhosis.

Gut-derived ß-amyloid: Likely a centerpiece of the gut-brain axis contributing to Alzheimer's pathogenesis.

Peripheral ß-amyloid (Aß), including those contained in the gut, may contribute to the formation of Aß plaques in the brain, and gut microbiota appears to exert an impact on Alzheimer's disease (AD) via the gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused on uncovering the potential interactions among gut-derived Aß in aging, gut microbiota, and AD pathogenesis. To achieve this goal, the expression levels of Aß and several key proteins involved in Aß metabolism were initially assessed in mouse gut, with key results confirmed in human tissue. The results demonstrated that a high level of Aß was detected throughout the gut in both mice and human, and gut Aß42 increased with age in wild type and mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, the gut microbiome of mice was characterized by 16S rRNA sequencing, and we found the gut microbiome altered significantly in aged APP/PS1 mice and fecal microbiota transplantation (FMT) of aged APP/PS1 mice increased gut BACE1 and Aß42 levels. Intra-intestinal injection of isotope or fluorescence labeled Aß combined with vagotomy was also performed to investigate the transmission of Aß from gut to brain. The data showed that, in aged mice, the gut Aß42 was transported to the brain mainly via blood rather than the vagal nerve. Furthermore, FMT of APP/PS1 mice induced neuroinflammation, a phenotype that mimics early AD pathology. Taken together, this study suggests that the gut is likely a critical source of Aß in the brain, and gut microbiota can further upregulate gut Aß production, thereby potentially contributing to AD pathogenesis.

Expression Pattern of p62 in Primary Age-Related Tauopathy: Staging of p62 in PART.

The present study analyzed the distribution pattern of p62 immunoreactivity in brains of primary age-related tauopathy (PART) and Braak NFT matched pre-AD and Alzheimer's disease (AD) patients using immunohistochemistry in combination with semi-quantitative evaluation. In PART and AD brains, p62 was found positive in seven regions, including the neocortex, thalamus, basal ganglia, hippocampus, brainstem, cerebellar dentate nucleus, and the cervical spinal cord. There was a positive correlation between the Braak NFT stage and the distribution of p62 expression. Six stages of expression of p62 were proposed from the present study. Expression of p62 in the hippocampus of PART and AD was classified stage I, the brainstem stage II, the thalamus stage I _I _I, the basal ganglia stage IV, the neocortex stage V, the cerebellum and the cervical spinal cord stage VI. The hippocampus was the site initially affected by p62, especially the CA1 and the subiculum. They might be the earliest accumulation site of p62.

Screening of Siderophore-Producing Bacteria and Their Effects on Promoting the Growth of Plants.

Iron deficiency is a major global agricultural problem. Siderophores can help organisms to uptake iron in form of siderophore-Fe3+ complexes and then in the cell cytosol, iron is reducted and released in ferrous form. This research aimed to obtain some efficient siderophore-producing bacterial strains and evaluate their plant growth-promoting effects in the iron-deficit environment. Two strains, Brucella sp. E7 and Pseudomonas brassicae W7, were isolated from rhizosphere soil. Both strains could produce maximum siderophores under the optimal conditions. Plant promoting experiment showed that many indicators of Vigna radiata seedling were all increased significantly by strain E7/W7 or the consortium of E7 + W7. Under no-iron and high iron stress, the inoculation treatment also showed growth promotion effects on both Vigna radiata and Lolium multiflorum. These results indicated that the potential ability of strain E7 and W7 in increasing agricultural production as a growth-promoting agent in iron-deficit soil.

Profiling multiple heavy metal contamination and bacterial communities surrounding an iron tailing pond in Northwest China.

Northwest China is abundant in iron ore reserves and has become one of the important iron ore mining bases in China. However, the contamination and microbial community structure of iron tailing ponds in Northwest China have not been extensively investigated. In the present study, we characterized the main physicochemical properties, the multiple heavy metal contamination, and the bacterial community structure of the soils surrounding an iron tailing pond in Linze County, Zhangye city, Gansu Province. The tailing-associated soils were barren, exhibiting alkaline pH and low organic matter (OM), total nitrogen (TN) and total potassium (TK) compared with the control areas. There was considerable multiple heavy metal pollution in the iron tailing pond, mainly including lead (Pb), manganese (Mn), arsenic (As), cadmium (Cd), zinc (Zn), iron (Fe) and copper (Cu). Among the 303 identified core operational taxonomic units (OTUs), Actinobacteria, Proteobacteria and Deinococcus-Thermus were predominant at the phylum level, and Blastococcus, Arthrobacter, Marmoricola, Kocuria, Truepera, and Sphingomonadaceae were prevalent at a finer taxonomic level. The bacterial richness and diversity of the tailing samples were significantly lower than those of the reference samples. RDA, VPA and Spearman correlation analyses showed that the soil pH, CEC, OM, TP, TK, Cd, Pb, Ni, Zn, As and Mn had significant effects on the bacterial community composition and distribution. This work profiles the basic features of the soil physicochemical properties, the multiple heavy metal contamination and the bacterial community structure in an iron tailing pond in Northwest China, thereby providing a foundation for the future ecological remediation of the iron tailing environment in the area.

Rapid membrane effect of estrogens on stimulation of corticotropin-releasing hormone.

BACKGROUND: Classic nuclear-initiated estrogen signaling stimulates corticotropin-releasing hormone (CRH) gene expression as a transcription factor. However, the possible mechanism by which membrane-initiated estrogen signaling (MIES) influences CRH expression remains unclear. There are indications that MIES may upregulate nitric oxide (NO) production through the phosphatidylinositol 3-hydroxy kinase (PI3K) and potentially through the mitogen-activated protein kinase (MAPK) pathway. OBJECTIVES: We investigated the effect of MIES-mediated kinase pathways on CRH expression with or without NO synthesis. METHOD: In SK-N-SH cell culture, estradiol-bovine serum albumin (E2-BSA) was used as the specific membrane estrogen receptor activator, with a specific NO donor, and/or inhibitors for NO synthase (NOS), PI3K, MAPK, protein kinase A (PKA), and protein kinase C (PKC). RESULTS: E2-BSA significantly increased NO and CRH levels in the medium and NOS1-mRNA levels in the cells. In addition, NO donor up-regulated CRH expression, while NOS-inhibitor down-regulated it. When the inhibitor of MAPK and/or the inhibitor of PI3K was added to the medium, only the latter appeared to significantly block the stimulating effect of E2-BSA on NO synthesis, and this was accompanied by an increased CRH expression in the medium. We further studied the effect of the MIES-PKC-mediated pathway on CRH expression, with or without NOS-inhibitor, while the MIES-PKA(-PI3K) pathway served as a control. We found that MIES-PKC upregulated CRH expression independent of NO synthesis. CONCLUSION: MIES can efficiently upregulate CRH expression via various intracellular kinase pathways and may thus be a crucial component in the stress response.

Primary age-related tauopathy in a Chinese cohort.

Primary age-related tauopathy (PART) is characterized by the presence of tau neurofibrillary tangles (NFTs) which are typically observed in Alzheimer's disease (AD) brains, with few or without ß-amyloid (Aß) plaques. The diagnosis of PART can be categorized into "definite" or "possible" depending on the amount of Aß plaques. Definite PART is diagnosed when NFTs are observed and the Braak stage is ≤IV, with Thal Aß Phase 0 (Crary et al., 2014). According to the neuropathological diagnostic criteria, we reported that PART was frequently observed in the Chinese population according to our findings from specimens in our brain bank, with 47% of brain bank subjects meeting the criteria for PART. There is no consensus on the nature of PART. It remains to be elucidated whether PART is an early form of AD or a novel tauopathy (Duyckaerts et al., 2015; Jellinger et al., 2015).

Primary Age-Related Tauopathy in Human Subcortical Nuclei.

The present study aimed to determine the spatial distribution patterns of hyperphosphorylated tau-immunoreactive cells in subcortical nuclei of post-mortem human brain with primary age-related tauopathy (PART). Subcortical tauopathy has important pathological and clinical implications. Expression of tau was examined in different subcortical regions of definite PART cases with a Braak neurofibrillary tangle stage >0 and ≤IV, and with a Thal phase 0 (no beta-amyloid present). Post-mortem brain tissue of PART was studied using immunohistochemistry and subsequent semi-quantitative assessment with Braak NFT stage -matched pre-Alzheimer's disease (AD) and AD cases as a control. Expression of tau was frequently found in subcortical nuclei including the substantia nigra, inferior colliculus, locus coeruleus, medulla oblongata in the brainstem, the caudate, putamen, nucleus globus pallidus in the striatum, the hypothalamus, thalamus, subthalamus in the diencephalon, and the cervical spinal cord in both PART and AD, but not in the dentate nucleus of the cerebellum. A positive correlation was found between the Braak NFT stage and the tau distribution (qualitative)/tau density (quantitative) in PART and AD. Brainstem nuclei were commonly involved in early PART with NFT Braak stage I/II, there was no preference among the substantia nigra, inferior colliculus, locus caeruleus and medulla oblongata. The prevalence and severity of tau pathology in subcortical nuclei of PART and AD were positively correlated with NFT Braak stage, suggesting that these nuclei were increasingly involved as PART and AD progressed. Subcortical nuclei were likely the sites initially affected by aging associated tau pathology, especially the brainstem nuclei including the substantia nigra, inferior colliculus, locus caeruleus and medulla oblongata.

Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models.

BACKGROUND: Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. METHOD: Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. RESULTS: Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. CONCLUSION: Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences.

Analysis of growth and lipid production characteristics of Chlorella vulgaris in artificially constructed consortia with symbiotic bacteria.

The aim was to study the effect of artificially constructed consortia of microalgae-bacterial symbionts on growth and lipid production by Chlorella vulgaris (C. vulgaris), as well as the inter-relationship between microalgae and bacterial in a photoautotrophic system. The results showed that compared to an axenic culture of C. vulgaris, H1 co-culture system (axenic C. vulgaris-Stenotrophomona smaltophilia) had the strongest effect on the C. vulgaris growth. The biomass, specific growth rate and maximum productivity of C. vulgaris were increased by 21.9, 20.4, and 18%, respectively. The bacteria in co-culture system had a significant effect on the accumulation of lipid and fatty acid components of C. vulgaris: the content of lipid was increased by 8.2-33.83%, and the components of the saturated fatty acids and oleic acids also had an obvious improvement. The results indicate that the microalgae-bacterial co-culture system can improve microalgal biomass and the quality of biodiesel.

Aromatase changes in depression: A postmortem and animal experimental study.

A hyperactive hypothalamo-pituitary-adrenal (HPA) axis is a prominent feature in depression. It has been shown that androgens inhibit HPA activity and that estrogens stimulate it. We have therefore investigated, in human postmortem hypothalamus, whether depression features an increase in aromatase, which is the rate-limiting enzyme for the conversion of androgens to estrogens. In addition, we have tested the effect of an aromatase inhibitor on depression-like symptoms in a frequently used animal model for depression. At first, aromatase immunoreactivity (ir) was quantified in the central part of the hypothalamic paraventricular nucleus (PVN) of 10 major depressive disorder (MDD) patients and 10 well-matched control subjects. Subsequently an animal experimental study was performed using the chronic unpredictable mild stress (CUMS) rats as depression model. The effect of administration of 1,4,6-androstatriene-3,17-dione (ATD), an aromatase inhibitor, was investigated by silastic capsule implantation. In the postmortem study, the amount of PVN aromatase-ir decreased significantly in the MDD group compared to the controls (P=0.029). In the animal study, ATD was found to cause significantly increased testosterone (T) levels, both in plasma and in the hypothalamus. However, ATD administration did not show significant effects on the depression-like behaviors or plasma corticosterone levels in CUMS rats. Based on our observations in human postmortem material and the animal experiment, we have to conclude that alterations in aromatase in adulthood do not seem to play a major role in the pathogenesis of the symptoms of depression.

A sensitive and practical RP-HPLC-FLD for determination of the low neuroactive amino acid levels in body fluids and its application in depression.

Ion-exchange high performance liquid chromatography (HPLC) generally fails as a method to determine low levels of free amino acids (AAs) in body fluids. Here we present a modified reversed-phase HPLC (RP-HPLC) protocol for the determination of AAs in body fluids and its application in mood disorder patients. We improved a previous research protocol by modifying i) sample preparation, including deproteination, ii) derivitization, including derivating agent and condition, and iii) sample separation, which is mainly determined by the pH value, the components and the additives of the mobile phases. The combination of these modifications, together with fluorescence detection (FLD), allows sensitive and practical determination of free AA levels in body fluids of depressive patients. This protocol was validated by determining the postmortem cerebrospinal fluid (CSF) glutamic acid (Glu) and γ-aminobutyric acid (GABA) levels of 8 major depressive disorder (MDD) patients, 9 bipolar disorder (BD) patients, and 19 well-matched controls, while also testing the plasma and CSF AA levels of living MDD patients. CSF Glu and GABA levels were both significantly decreased in MDD but not in BD patients. The data indicate that this RP-HPLC-FLD protocol is applicable for detection of low levels of neuroactive AAs in body fluids, as well as for routine clinical applications.

[Comparative Study of Benzotriazole Electrochemical Oxidation at Boron-doped Diamond and PbO2 Anodes].

Electrochemical systems were built to investigate the degradation of benzotriazole (BTA) on boron-doped diamond (BUU) and PbO2 anodes and give an insight into the mineralization ability of two electrodes in terms of the amount and activity of hydroxyl radicals. Results of bulk electrolysis showed that both BDD and PbO2 displayed perfect BTA degradation performance after 12 hours' electrolysis, with the removal percentages of 99. 48% and 98. 36%, respectively, while the mineralization ability of BDD was much stronger than that of PbO2, with the efficiency of 87. 69% for BDD and 35. 96% for PbO2. Less hydroxyl radical and hydrogen production in BDD system suggested the less amount of active sites on BDD surface, thus further verified that the generated hydroxyl radical amount was not the primary factor determining the mineralization ability of anodes. However, BDD displayed larger binding energy of adsorbed oxygen and thinner adsorption layer than those of PbO2, indicating that the BDD electrode surface was of greater catalytic activity, thus the generated hydroxyl radicals were more free, which was the key to its better mineralization ability.

Effect of pentobarbital and isoflurane on acute stress response in rat.

BACKGROUND: Anesthesia administration before sacrificing animals is a common practice in stress-related studies, but the effect of anesthesia on the results remains understudied. We aimed to reveal the interference of different anesthetics, i.e. intraperitoneal (i.p.) sodium-pentobarbital injection or isoflurane inhalation, with the acute stress responses in rats. METHODS: Rats were randomly divided into foot shock (FS) and non-stressed control groups, and further grouped according to the sacrificing procedure: direct decapitation, decapitation after i.p. sodium-pentobarbital injection, or isoflurane inhalation. There was also a non-stressed group sacrificed by decapitation following i.p. saline injection. Plasma levels of corticosterone (CORT), testosterone and estradiol, hypothalamic stress-related molecule mRNA expression of corticotropin-releasing hormone, arginine vasopressin and oxytocin, and frontal lobe stress-related molecule mRNA expression of NMDA receptor subunit NR2B, GABAA receptor and the neuronal-type nicotinic acetylcholine receptor were measured. RESULTS: FS significantly increased plasma CORT levels in direct decapitation and isoflurane groups, while this stress response 'disappeared' following i.p. sodium-pentobarbital injection. In control animals, both the injection of saline and pentobarbital caused a significant increase of plasma CORT. Neither the sex hormone levels nor the mRNA expression of stress-related molecules in the brain showed significant differences among the groups. CONCLUSION: The injection of the anesthetic compound rather than the compound itself may cause extra stress which interferes with the plasma CORT levels, but not with plasma sex hormone levels nor with the brain mRNA expression. Isoflurane inhalation leaves the stress response intact and is also optimal from an ethical point of view.

Using brachial-ankle pulse wave velocity to screen for metabolic syndrome in community populations.

The aim of this study is to investigate the viability of using brachial-ankle pulse wave velocity (baPWV) as a primary tool to screen metabolic syndrome (MetS), and to explore the risk factors of MetS in community populations. A total of 1914 subjects completed medical examination in Shanghai. BaPWV was significantly associated with the components of MetS. The area under curve (AUC) and its 95% confidence interval (CI) in total group were 62.50% and 60.00%-65.30% with the appropriate cut-off point being 1435 cm/sec. The AUC (95%CI) of three subgroups (40-50 yrs, 50-60 yrs and over 60 yrs group) were 75.30% (67.48%-83.35%), 63.35% (58.96%-67.60%), 55.37% (51.19%-60.01%), respectively. A clear pattern surfaced in the process of investigation: the younger were the subjects group, the better receiver operating characteristic (ROC) efficacy would emerge; and the higher sensitivity was, the better negative predictive value (NPV) would be. Male gender, high baPWV values, elevated uric acid (UA) and excess hypersensitive C reaction protein (hs-CRP) levels were stayed in the two regression models as the independent risk factors for MetS. We conclude that baPWV may serve as a potential screening tool for MetS at the cut-off point of 1435 cm/sec.

Sex differences in the stress response in SD rats.

Sex differences play an important role in depression, the basis of which is an excessive stress response. We aimed at revealing the neurobiological sex differences in the same study in acute- and chronically-stressed rats. Female Sprague-Dawley (SD) rats were randomly divided into 6 groups: chronic unpredictable mild stress (CUMS), acute foot shock (FS) and controls, animals in all 3 groups were sacrificed in proestrus or diestrus. Male SD rats were randomly divided into 3 groups: CUMS, FS and controls. Comparisons were made of behavioral changes in CUMS and control rats, plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), and of the hypothalamic mRNA-expression of stress-related molecules, i.e. estrogen receptor α and ß, androgen receptor, aromatase, mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone, arginine vasopressin and oxytocin. CUMS resulted in disordered estrus cycles, more behavioral and hypothalamic stress-related molecules changes and a stronger CORT response in female rats compared with male rats. Female rats also showed decreased E2 and T levels after FS and CUMS, while male FS rats showed increased E2 and male CUMS rats showed decreased T levels. Stress affects the behavioral, endocrine and the molecular response of the stress systems in the hypothalamus of SD rats in a clear sexual dimorphic way, which has parallels in human data on stress and depression.

Can we early diagnose metabolic syndrome using brachial-ankle pulse wave velocity in community population?

BACKGROUND: The prevalence of metabolic syndrome (MetS) increased recently and there was still not a screening index to predict MetS. The aim of this study was to estimate whether brachial-ankle pulse wave velocity (baPWV), a novel marker for systemic arterial stiffness, could predict MetS in Chinese community population. METHODS: A total of 2 191 participants were recruited and underwent medical examination including 1 455 men and 756 women from June 2011 to January 2012. MetS was diagnosed according to the criteria of the International Diabetes Federation (IDF). Multiple Logistic regressions were conducted to explore the risk factors of MetS. Receiver operating characteristic (ROC) curve was performed to estimate the ideal diagnostic cutoff point of baPWV to predict MetS. RESULTS: The mean age was (45.35±8.27) years old. In multiple Logistic regression analysis, the gender, baPWV and smoking status were risk factors to MetS after adjusting age, gender, baPWV, walk time and sleeping time. The prevalence of MetS was 17.48% in 30-year age population in Shanghai. There were significant differences (χ(2) = 96.46, P < 0.05) between male and female participants on MetS prevalence. According to the ROC analyses, the ideal cutoff point of baPWV was 1 358.50 cm/s (AUC = 60.20%) to predict MetS among male group and 1 350.00 cm/s (AUC = 70.90%) among female group. CONCLUSION: BaPWV may be considered as a screening marker to predict MetS in community Chinese population and the diagnostic value of 1 350.00 cm/s was more significant for the female group.

Decreased plasma neuroactive amino acids and increased nitric oxide levels in melancholic major depressive disorder.

BACKGROUND: Amino acid neurotransmitters and nitric oxide (NO) are involved in the pathogenesis of major depressive disorder (MDD). Here we want to establish whether changes in their plasma levels may serve as biomarker for the melancholic subtype of this disorder. METHODS: Plasma levels of glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), and NO were determined in 27 medicine-naïve melancholic MDD patients and 30 matched controls. Seven of the MDD patients participated also in a follow-up study after 2 months' antidepressant treatment. The relationship between plasma and cerebral-spinal fluid (CSF) levels of these compounds was analyzed in an additional group of 10 non-depressed subjects. RESULTS: The plasma levels of Asp, Gly and GABA were significantly lower whereas the NO levels were significantly higher in melancholic MDD patients, also after 2 months of fluoxetine treatment. In the additional 10 non-depressed subjects, no significant correlation was observed between plasma and CSF levels of these compounds. CONCLUSION: These data give the first indication that decreased plasma levels of Asp, Gly and GABA and increased NO levels may serve as a clinical trait-marker for melancholic MDD. The specificity and selectivity of this putative trait-marker has to be investigated in follow-up studies.

High-performance liquid chromatographic determination of histamine in biological samples: the cerebrospinal fluid challenge--a review.

Histamine, a neurotransmitter crucially involved in a number of basic physiological functions, undergoes changes in neuropsychiatric disorders. Detection of histamine in biological samples such as cerebrospinal fluid (CSF) is thus of clinical importance. The most commonly used method for measuring histamine levels is high performance liquid chromatography (HPLC). However, factors such as very low levels of histamine, the even lower CSF-histamine and CSF-histamine metabolite levels, especially in certain neuropsychiatric diseases, rapid formation of histamine metabolites, and other confounding elements during sample collection, make analysis of CSF-histamine and CSF-histamine metabolites a challenging task. Nonetheless, this challenge can be met, not only with respect to HPLC separation column, derivative reagent, and detector, but also in terms of optimizing the CSF sample collection. This review aims to provide a general insight into the quantitative analyses of histamine in biological samples, with an emphasis on HPLC instruments, methods, and hyphenated techniques, with the aim of promoting the development of an optimal and practical protocol for the determination of CSF-histamine and/or CSF-histamine metabolites.

Reduced GAD(65/67) immunoreactivity in the hypothalamic paraventricular nucleus in depression: a postmortem study.

BACKGROUND: Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter. It diminishes the activity of the hypothalamo-pituitary-adrenal (HPA) axis, which plays an important role in the pathogenesis of depression. The present study aimed at determining GABAergic input in the hypothalamic paraventricular nucleus (PVN) in depression and its correlation with the activity of corticotropin-releasing hormone (CRH) neurons. METHODS: The density of glutamic acid decarboxylase (GAD)(65/67)-immunoreactivity (ir) was quantified in the postmortem hypothalamic PVN of 9 major depressive (MDD) and 5 bipolar depressive (BD) patients, together with 12 matched controls, whose CRH-expressing neuron numbers had been determined in a previous study. RESULTS: There was a 43% significant reduction of the density of GAD(65/67)-ir in the PVN in MDD (P=0.028) and a 20% non-significant decrease in BD patients. In addition, there was a significant negative correlation between the density of GAD(65/67)-ir and the number of CRH-ir neurons in the PVN in the depression group (Rho=-0.527, P=0.032), but not in the control group. LIMITATIONS: The samples were relatively small and the depression group had used antidepressants. CONCLUSION: A diminished GABAergic input to the PVN may contribute to the activation of CRH-ir neurons in depression, most prominently in MDD, which provides a rationale for prescribing GABAergic agonists for these patients.