Decreased Histamine Levels Research Articles

ELEVATED HISTAMINE LEVELS WITH NORMAL TRYPTASE IN ANAPHYLAXIS

<h3>Introduction</h3> The most commonly described pathway of anaphylaxis involves IgE mediated mast cell activation. Here we present three patients with elevated histamine, normal tryptase, and normal IgE. These findings suggest a non-mast-cell mediated pathway of anaphylaxis. All patients were placed on a low-histamine diet (LHD) following their anaphylaxis episodes with subsequent decrease in histamine and resolution of anaphylactic episodes. <h3>Cases Description</h3> The first patient was a 25-year-old male who presented to the emergency department with a histamine level of 6.0 (ng/mL). The patient experienced a second anaphylaxis episode a week later. Repeat histamine was 6.5. The patient was placed on a LHD, and follow-up testing demonstrated histamine of 1.6. The second patient was a 51-year-old male who presented to the emergency department for anaphylaxis. Laboratory studies after the event found histamine of 13.2, and the patient was subsequently placed on a LHD. Follow-up testing demonstrated histamine of 5.8. The third patient was a 33-year-old female that developed anaphylaxis after a patch test. Laboratory studies revealed histamine of >28.6. The patient was instructed to start a LHD. Subsequent testing demonstrated histamine of 10.8. <h3>Discussion</h3> Persistent elevation of histamine levels in the absence of elevated tryptase or IgE suggests a non-mast-cell mediated pathway of histamine release. Further studies should be performed in similar cases examining the potential of LHD as a treatment for anaphylaxis with elevated histamine and normal tryptase as LHD resulted in a decrease in histamine level and resolution of anaphylactic episodes.

Betahistine Attenuates Seizures, Neurodegeneration, Apoptosis, and Gliosis in the Cerebral Cortex and Hippocampus in a Mouse Model of Epilepsy: A Histological, Immunohistochemical, and Biochemical Study.

Epilepsy is a prevalent and chronic neurological disorder marked by recurring, uncontrollable seizures of the brain. Chronic or repeated seizures produce memory problems and induce damage to different brain regions. Histamine has been reported to have neuroprotective effects. Betahistine is a histamine analogue. The current research investigated the effects of convulsions on the cerebral cortex and hippocampus of adult male albino mice and assessed the possible protective effect of betahistine. Four groups of 40 adult male mice were organized: control, betahistine (10 mg/kg/day), pentylenetetrazole (PTZ) (40 mg/kg/ on alternate days), and Betahistine-PTZ group received betahistine 1 h before PTZ. PTZ induced a substantial rise in glutamate level and a considerable decrease in histamine level. Structural changes in the cerebral cortex and cornu ammonis (CA1) of the hippocampus were detected in the pattern of neuron degeneration. Some neurons were shrunken with dark nuclei, and others had faintly stained ones. Focal accumulation of neuroglial cells and ballooned nerve cells of the cerebral cortex were also detected. Cleaved caspase-3, glial fibrillary acidic protein, and ionized calcium-binding adaptor molecule 1 showed substantial increases, while synaptophysin expression was significantly reduced. Interestingly, these changes were less prominent in mice pretreated with betahistine. In conclusion, betahistine had shown neuroprotective properties against brain damage induced by convulsions.

Occurrence of Histamine in Commercial Cat Foods under Different Storage Conditions.

In fish-based foods, one of the effects of inappropriate storage can be the formation of biogenic amines. Among these, histamine is considered one of the most toxic. The purpose of the present study is to assess the occurrence of histamine in fish-based pet foods, and to evaluate the changes in histamine content during storage at different temperatures. For the analysis, an LC-MS/MS method was used. Fifty-eight pet foods were purchased, and an aliquot of them was analyzed just after opening the packages. Histamine was detected in 12 samples and concentrations ranged from 1.5 to 30.1 mg/kg. The remaining of each positive sample was divided into seven subsamples. One of them was used as a control sample and kept at −20 °C, while the other six were exposed to different environmental conditions. Samples exposed to room temperature showed no significant changes in histamine levels, while samples exposed to high temperatures showed significant increases in histamine content. Finally, samples exposed to refrigerator temperature showed a slight decrease in histamine levels. Under the experimental conditions, the EU limit of 100 mg/kg established for fishery products was never exceeded. These results seem to indicate a low risk of histamine intoxication in cats fed fish-based pet food.

Brassica oleracea Prevents HCl/Ethanol-Induced Gastric Damages in Mice

Brassica oleracea var. capitata L. (cabbage) is a popular vegetable with a wide range of pharmacological activities that help to promote human health. The present study investigated the beneficial effects of B. oleracea var. capitata L. extract (BOE) on HCl/ethanol (H/E)-induced gastric damages in mice. Pre-administration of BOE (25–100 mg/kg) for 7 consecutive days significantly decreased macroscopically visible lesion on the gastric mucosa induced by H/E. In addition, results from hematoxylin and eosin-stained gastric tissue showed that BOE inhibited invaded percentage of lesion and prevented the reduction in mucosal thickness in peri-ulcerative region. BOE significantly alleviated the H/E-mediated decreases in Alcian blue binding, total hexose, sialic acid, and collagen in the gastric tissue, suggesting BOE attenuates the gastric damage via preserving the integrity of gastric mucus. Moreover, BOE significantly decreased histamine level in the plasma and reduced mRNA levels associated with secreting gastric acid. Furthermore, BOE inhibited myeloperoxidase activity and suppressed nuclear factor-κB mRNA and its dependent inflammatory genes expression induced by H/E. BOE also strengthened antioxidant enzyme activity, with a mitigating H/E-mediated increase in malondialdehyde level of the gastric tissue. Thus, these results suggest that BOE has the potential to protect the gastric tissue via inhibiting gastric acid secretion, inflammation, and oxidative stress.

Chronic brain histamine depletion in adult mice induced depression-like behaviours and impaired sleep-wake cycle

Histamine acts as a neurotransmitter to regulate various physiological processes. Brain histamine is synthesized from an essential amino acid histidine in a reaction catalysed by histidine decarboxylase (Hdc). Hdc-positive neurons exist mainly in the tuberomammillary nucleus (TMN) of the posterior hypothalamus and project their axons to the entire brain. Recent studies have reported that a chronic decrease in histamine levels in the adult human brain was observed in several neurological disorders. However, it is poorly understood whether lower histamine levels play a causative role in those disorders. In the present study, we induced chronic histamine deficiency in the brains of adult mice to allow direct interpretation of the relationship between an impaired histaminergic nervous system and the resultant phenotype. To induce chronic brain histamine deficiency starting in adulthood, adeno-associated virus expressing Cre recombinase was microinjected into the TMN of Hdc flox mice (cKO mice) at the age of 8 weeks. Immunohistochemical analysis showed expression of Cre recombinase in the TMN of cKO mice. The reduction of histamine contents with the decreased Hdc expression in cKO brain was also confirmed. Behavioural studies revealed that chronic histamine depletion in cKO mice induced depression-like behaviour, decreased locomotor activity in the home cage, and impaired aversive memory. Sleep analysis showed that cKO mice exhibited a decrease in wakefulness and increase in non-rapid eye movement sleep throughout the day. Taken together, this study clearly demonstrates that chronic histamine depletion in the adult mouse brain plays a causative role in brain dysfunction.

Cellular Composition of Rat Thymus with Combined Effects of Carcinogen and Stress

The aim of the research was study the effects of experimental breast cancer and stress on the thymus of laboratory animals Material and methods . Thymus 40 white nonlinear female rats of the same age were investigated using luminescent-histochemical, general histological and immunohistochemical methods . The animals were divided into 3 groups. In the 1st group were intact animals. Rats of the 2nd group were injected with N-methyl-N-nitrosourea, causing breast cancer. Animals of the 3rd group experienced a combined effect of carcinogen and water-immobilization stress. Results. It was established that the administration of N-methyl-N-nitrosourea to female rats causes an increase in the size of the medullar and cortex of the thymus lobes. In cells of the premedullary and subcapsular zones, an increase in the level of serotonin and catecholamines is observed, and in cells of the premedullary zone, in the thymocytes of the cortex and medulla - a decrease in the level of histamine. The ratio (serotonin + histamine) / catecholamines decreases and the percentage of degranulated mast cells increases. Also, the number of mature T-lymphocytes and macrophages is increasing against the background of a decrease in the number of S-100+ cells. Combined effect of factors revealed a decrease in the size of the lobes of the organ, the replacement of the parenchyma with adipose and connective tissue, an increase in the content of serotonin and catecholamines, a significant decrease in histamine levels, with a decrease in the ratio (serotonin + histamine) / catecholamines in the same cells, an increase in mature forms of T-lymphocytes and macrophages, as well as a decrease in the percentage of dendritic cells. Conclusion. The combined effect causes a more pronounced disorganization of the morphofunctional state of the thymus and leads to the 4th phase of the accidental involution of the thymus with the development of atrophy and sclerosis of the organ.

Serum histamine and acetylcholine variations as new noninvasive biochemical markers in staging of experimental hepatocellular carcinoma.

Angiogenesis is a major prerequisite for hepatocellular carcinoma (HCC) development and progression. The present study aims to assess the potential role of two endogenous regulators of angiogenesis histamine (His) and acetylcholine (Ach), as possible biochemical markers for staging of HCC. Five groups of rats were used in this study: a control healthy group (I), another 4 intoxicated groups used for the induction of HCC with a high dose of diethyl nitrosamine (DENA, 200mg/kg, single I.P. dose), (II, III, IV, and V). Groups II, III, IV, and V were killed following 8, 16, 24, and 32weeks after DENA injection, respectively. Serum level of His and Ach was estimated using high-performance liquid chromatography technique coupled with diode array detector (HPLC-DAD), and alpha-fetoprotein (AFP) was measured using ELISA technique along with liver histological examination for all groups. Progression of HCC was estimated by histopathological examination. The results exhibited prominent increase in serum His and Ach levels during the early stages of HCC in group II, III in comparison with the control, and then His serum level declined to the normal level during the last stage of HCC development (group V).However, Ach elevation continued. AFP serum level showed marked increase, till 32 weeks after hepatocarcinogenesis. The decreased histamine level, combined to elevated AFP, indicates an early stage, while continued elevation of Ach with decreased His levels indicates a later stage of HCC. The combination of these two neurotransmitters to AFP may contribute to a noninvasive biochemical staging for HCC.

Control of Histamine Level in Oreochromis Niloticus Fillets Using Essential Oils

It was studied that effect of different essential oils on the histamine level in examined Oreochromis niloticus fillet samples. Accordingly, the addition of essentials oils (cinnamon and Oregano) was applied by (1%) against control group. The obtained results revealed that histamine levels in control samples increased by 24.8%; 70.1% and 94.5% with mean values of 18.84; 25.67, and 29.35 after chilling for 3; 6 and 9 days, respectively; meanwhile, the histamine mean concentration at zero time was 15.09 mg/kg. Concerning addition of cinnamon oil 1%, levels of histamine decreased to 18.7%; 46.6% and 77.0 % with mean values of 17.92; 22.13, and 26.71 after 3; 6 and 9 days, respectively. In contrast the addition of oregano oil 1%, to the examined O. niloticus fillet samples lead to significant decrease in histamine levels by 8.2%, 23.9% and 32.3% with mean values 16.33, 18.7 and 19.96 after 3, 6 and 9 days in 4C storage temperature, respectively. Finally, it can have concluded that the addition of oregano oil was superior for control of undesirable histamine in Oreochromis niloticus fillets.

Polydatin attenuated food allergyviastore-operated calcium channels in mast cell

To investigate the effect of polydatin (PD), a resveratrol glucoside, on mast cell degranulation and anti-allergic activity. After the rats were orally sensitized with ovalbumin (OVA) for 48 d and underwent PD treatment for 4 d, all the rats were stimulated by 100 mg/mL OVA for 24 h and then sacrificed for the following experiments. The small intestines from all the groups were prepared for morphology examination by hematoxylin and eosin staining. We also used a smooth muscle organ bath to evaluate the motility of the small intestines. The OVA-specific immunoglobulin E (IgE) production and interleukin-4 (IL-4) levels in serum or supernatant of intestinal mucosa homogenates were analyzed by enzyme-linked immunosorbent assay (ELISA). Using toluidine blue stain, the activation and degranulation of isolated rat peritoneal mast cells (RPMCs) were analyzed. Release of histamine from RPMCs was measured by ELISA, and regulation of PD on intracellular Ca(2+) mobilization was investigated by probing intracellular Ca(2+) with fluo-4 fluorescent dye, with the signal recorded and analyzed. We found that intragastric treatment with PD significantly reduced loss of mucosal barrier integrity in the small intestine. However, OVA-sensitization caused significant hyperactivity in the small intestine of allergic rats, which was attenuated by PD administration by 42% (1.26 ± 0.13 g vs OVA 2.18 ± 0.21 g, P < 0.01). PD therapy also inhibited IgE production (3.95 ± 0.53 ng/mL vs OVA 4.53 ± 0.52 ng/mL, P < 0.05) by suppressing the secretion of Th2-type cytokine, IL-4, by 34% (38.58 ± 4.41 pg/mL vs OVA 58.15 ± 6.24 pg/mL, P < 0.01). The ratio of degranulated mast cells, as indicated by vehicles (at least five) around the cells, dramatically increased in the OVA group by 5.5 fold (63.50% ± 15.51% vs phosphate-buffered saline 11.15% ± 8.26%, P < 0.001) and fell by 65% after PD treatment (21.95% ± 4.37% vs OVA 63.50% ± 15.51%, P < 0.001). PD mediated attenuation of mast cell degranulation was further confirmed by decreased histamine levels in both serum (5.98 ± 0.17 vs OVA 6.67 ± 0.12, P < 0.05) and intestinal mucosa homogenates (5.83 ± 0.91 vs OVA 7.35 ± 0.97, P < 0.05). Furthermore, we demonstrated that administration with PD significantly decreased mast cell degranulation due to reduced Ca(2+) influx through store-operated calcium channels (SOCs) (2.35 ± 0.39 vs OVA 3.51 ± 0.38, P < 0.01). Taken together, our data indicate that PD stabilizes mast cells by suppressing intracellular Ca(2+) mobilization, mainly through inhibiting Ca(2+) entry via SOCs, thus exerting a protective role against OVA-sensitized food allergy.

Role of Mast Cells and Basophils in IgE Responses and in Allergic Airway Hyperresponsiveness

We established a diphtheria toxin (DT)-based conditional deletion system using Il4 enhancer elements previously shown to be specific for IL-4 production in mast cells (MCs) or basophils (Mas-TRECK and Bas-TRECK mice). DT treatment of Bas-TRECK mice resulted in specific deletion of basophils, whereas both MCs and basophils were deleted in Mas-TRECK mice. DT-treated Mas-TRECK mice had impaired passive cutaneous anaphylaxis, IgE-mediated passive systemic anaphylaxis, and IgE-mediated chronic allergic inflammation, whereas DT-treated Bas-TRECK mice had impaired IgE-mediated chronic allergic inflammation. Using these mice, we also sought to tease out the role of MCs and basophils in airway hyperresponsiveness (AHR). Although MC deletion resulted in a slight increase in basal Ag-specific IgE levels and significant increases in basal IgE levels, we found that this deletion markedly impaired the AHR effector phase and was accompanied by decreased histamine levels. By contrast, basophil deletion had no effect on the AHR effector phase or on IgE production induced by systemic OVA immunization. Our results, using these newly established Mas-TRECK and Bas-TRECK models, demonstrated an indispensable role for MCs as effector cells in AHR.

Effect of Quercetin, Caffeic Acid and Caffeic Acid Phenylethyl Ester, Solubilized in Non-ionic Surfactants, on Histamine Release in vivo and in vitro

A practical hindrance in using many therapeutic agents is their limited solubility in aqueous matrixes. This is usually overcome by incorporating the active compounds in a matrix, with the aid of a non-ionic surfactant. Three water-insoluble natural polyphenols with inherent biological activity, quercetin (CAS 117-39-5), caffeic acid and caffeic acid phenylethyl ester, were solubilized in water, with the aid of Tween 80 (an esterified and polyethoxylated derivative of sorbitan), Solutol HS15 (a polyethoxylated derivative of 12-hydroxy-stearic acid), Cremophor RH40 (a ricinoleic acid derivative) or Cremophor EL and the effect of the solubilized polyphenols on histamine release was studied in vitro (mast cells) and in vivo in the rat. In vivo Cremophor EL alone increased, and Tween 80 decreased histamine plasma levels. All four groups injected with solubilized quercetin exhibited a decrease in their plasma histamine levels. Caffeic acid solubilized in Cremophor RH40 decreased histamine levels, too. In vitro Tween 80 increased histamine release in a dose-dependent mode. Quercetin in vitro inhibited histamine release in all solubilizers used. It is concluded that the ability of the studied polyphenols to release histamine is not only depending on the condition of the storage vesicles in the mast cells, but also on the surfactant used to solubilize them.

Reduced histamine levels and H3 receptor antagonist‐induced histamine release in the amygdala of Apoe−/− mice

The histamine H(3) receptor is a constitutively active G protein-coupled receptor for the neurotransmitter histamine that serves a negative feedback function. A role for the histamine H(3) receptor has been suggested in neurodegenerative diseases, such as Parkinsons disease and Alzheimer's disease. Mice deficient in apolipoprotein E (apoE), a protein involved in development, regeneration, neurite outgrowth, and neuroprotection, show increased measures of anxiety and reduced sensitivity to effects of histamine H(3) receptor antagonists on measures of anxiety. In this study, we tested whether in mice lacking apoE (Apoe-/-) histamine levels and histamine release in brain areas involved in the regulation of anxiety are altered. H(3) receptor antagonist-induced histamine release was lower in the amygdala of Apoe-/- than wild-type mice. In contrast, there were no genotype differences in histamine release in the hypothalamus. Consistent with these data, histamine immunohistochemistry revealed lower total and synaptic histamine levels in the central nucleus of the amygdala of Apoe-/- than wild-type mice. Such changes were not seen in the hypothalamus, hippocampus, or cortex. In Apoe-/- mice, chronically decreased histamine levels and reduced histamine release in the amygdala might contribute to increased measures of anxiety.

Effects of acute maximal electroshock and chronic transauricular kindled seizures on learning abilities in Sprague-Dawley rats

To investigate effects of acute maximal electroshock (MES) and chronic transauricular kindled seizures on learning abilities in Sprague-Dawley rats. An acute MES was induced by giving an alternating current (150 mA, 0.2 s) through ear-clip electrodes. Chronic transauricular kindled seizure was induced by repeated application of initially subconvulsive electrical stimulation (40 mA, 0.2 s) through ear-clip electrodes once every 24 h. An 8-arm radial maze (4 arms baited) was used to measure learning abilities. Histamine, glutamate and gamma-aminobutyric acid (GABA) were measured by high-performance liquid chromatography (HPLC). In the acquisition learning process, an acute MES increased reference memory errors but not working memory errors. In addition, it increased GABA levels in the hippocampus. On the other hand, chronic transauricular kindled seizures increased both working and reference memory errors in retrieval memory process, and this lasted for at least 3 weeks. Chronic transauricular kindled seizures induced CA1 neuron damage and a decrease in histamine levels in the hippocampus. Different types of kindling seizure produce different effects on cognitive behavior: (1) an acute MES impairs learning ability, which may be associated with an abnormal plasticity and an increase of GABA in the hippocampus; (2) the chronic transauricular kindled seizure impairs retrieval memory mainly, which may be related to CA1 neuron damage and a decrease in histaminergic activity in the hippocampus.

The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells

AbstractBasophil numbers are typically elevated in chronic myeloid leukemia (CML) and increase during disease progression. Histamine is an essential mediator and marker of basophils and is highly up-regulated in CML. We examined the biochemical basis of histamine synthesis in CML cells. The CML-specific oncoprotein BCR/ABL was found to promote expression of histidine decarboxylase (HDC) and synthesis of histamine in Ba/F3 cells. Moreover, the BCR/ABL tyrosine kinase inhibitors imatinib (STI571) and nilotinib (AMN107) decreased histamine levels and HDC mRNA expression in BCR/ABL-transformed Ba/F3 cells, in the CML-derived basophil cell line KU812, and in primary CML cells. Synthesis of histamine was found to be restricted to the basophil compartment of the CML clone and to depend on signaling through the PI3-kinase pathway. CML cells also expressed histamine receptors (HRs), including HR-1, HR-2, HR-4, and histamine-binding CYP450 isoenzymes which also serve as targets of HR antagonists. The HR-1 antagonists loratadine and terfenadine, which bind to CYP450, were found to counteract proliferation of CML cells, whereas no growth inhibition was observed with the HR-1 antagonist fexofenadine which is not targeted or metabolized by CYP450. Moreover, DPPE, an inhibitor of histamine-binding CYP450 isoenzymes, produced growth inhibition in CML cells. Together, these data show that BCR/ABL promotes histamine production in CML cells and that certain HR-targeting drugs exert antileukemic effects on CML cells.

Carnosine, a precursor of histidine, ameliorates pentylenetetrazole-induced kindled seizures in rat

Carnosine (β-alanyl- l-histidine) has been characterized as a putative neurotransmitter. However, so far, understanding of the role of carnosine in the brain is very limited. The objective of this study was to examine the effects of carnosine on the development of pentylenetetrazol (PTZ) kindling seizures and protection against the PTZ kindled seizures in rats. Chemical kindling was elicited by repeated intraperitoneal injection of PTZ (35 mg/kg) once every 48 h until the occurrence of Stage 4–5 seizures, and the seizure activity of kindling was recorded for 30 min. In an acute PTZ challenge study, 60 mg/kg PTZ was used to induce kindled seizure. Injection of carnosine (200, 500 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latencies for myoclonic jerks, in a dose- and time-dependent manner. In the seizure development process, 500 mg/kg carnosine also significantly delayed the onset of PTZ kindled seizures. In addition, carnosine significantly reversed decreased histamine levels induced by PTZ kindled seizure in the hippocampus. These results indicate that carnosine can protect against PTZ-induced seizures in both the development of kindling and the challenge process in rats. The results suggest that carnosine might be an endogenous anticonvulsant factor in the brain and can be used as a new antiepileptic drug in future.

Pharmacological effects of carcinine on histaminergic neurons in the brain.

1 Carcinine (beta-alanyl histamine) is an imidazole dipeptide. The present study was designed to characterize the pharmacological effects of carcinine on histaminergic activity in the brain and on certain neurobehavior. 2 Carcinine was highly selective for the histamine H3 receptor over H1 or H2 receptor (Ki (microM)=0.2939+/-0.2188 vs 3621.2+/-583.9 or 365.3+/-232.8 microM, respectively). 3 Carcinine at a dose of 20 mg kg(-1) slightly increased histidine decarboxylase (HDC) activity in the cortex (from 0.186+/-0.069 to 0.227+/-0.009 pmol mg protein(-1) min(-1)). In addition, carcinine (10, 20, and 50 mg kg(-1)) significantly decreased histamine levels in mice brain. 4 Like thioperamide, a histamine H3 receptor antagonist, carcinine (20, 50 microM) significantly increased 5-HT release from mice cortex slices, but had no apparent effect on dopamine release. 5 Carcinine (20 mg kg(-1)) significantly inhibited pentylenetetrazole-induced kindling. This inhibition was completely reversed by (R)-alpha-methylhistamine, a representative H3 receptor agonist, and alpha-fluromethylhistidine, a selective HDC inhibitor. 6 Carcinine (20 mg kg(-1)) ameliorated the learning deficit induced by scopolamine. This amelioration was reversed by (R)-alpha-methylhistamine as evaluated by the passive avoidance test in mice. 7 Like thioperamide, carcinine dose-dependently increased mice locomotor activity in the open-field test. 8 The results of this study provide first and direct evidence that carcinine, as a novel histamine H3 receptor antagonist, plays an important role in histaminergic neurons activation and might be useful in the treatment of certain diseases, such as epilepsy, and locomotor or cognitive deficit.

Estrogen receptors and metabolic activity in the human tuberomamillary nucleus: changes in relation to sex, aging and Alzheimer’s disease

The human tuberomamillary nucleus (TMN), that is the sole source of histamine in the brain, is involved in arousal, learning and memory and is impaired in Alzheimer’s disease (AD) as shown by the presence of cytoskeletal alterations, a reduction in the number of large neurons, a diminished neuronal metabolic activity and decreased histamine levels in the hypothalamus and cortex. Experimental data and the presence of sex hormone receptors suggest an important role of sex steroids in the regulation of the function of TMN neurons. Therefore, we investigated sex-, age- and Alzheimer-related changes in estrogen receptor α and β (ERα and ERβ) in the TMN. In addition, metabolic activity changes of TMN neurons were determined by measuring Golgi apparatus (GA) and cell size. In the present study, ERα immunocytochemical expression in AD patients did not differ from that in elderly controls. However, a larger amount of cytoplasmic ERβ was found in the TMN cells of AD patients. Earlier studies, using the GA size as a parameter, have shown a clearly decreased metabolic activity in the TMN neurons in AD. In the present study, the size of the GA did not change during aging, indicating the absence of strong metabolic changes. Cell size of the TMN neurons appeared to increase during normal aging in men but not in women. Concluding, the enhanced cytoplasmic expression of ERβ in the TMN may be involved in the diminished neuronal metabolism of these neurons in AD patients.

Tributyrin and lactitol synergistically enhanced the trophic status of the intestinal mucosa and reduced histamine levels in the gut of nursery pigs.

This study determined whether tributyrin and lactitol could synergistically facilitate the transition from milk to solid feed in nursery pigs. At 21 d after birth, 64 piglets were moved from the piggery to a production barn and fed a medicated diet. At 28 d after birth, the piglets were weighed and allotted into four groups and fed a standard nonmedicated diet (control) or the control diet with tributyrin (butanoic acid 1,2,3-propanetriyl ester; 10 g/kg), or with lactitol (beta-D-galactopyranosyl-(1-->4)-D-sorbitol; 3 g/kg), or with tributyrin (10 g/kg) plus lactitol (3 g/kg). On d 0, 14, and 42 after being fed the control or experimental diets, the animals were weighed, and animal health, feed intake, and feed conversion ratio were determined. On d 42, four piglets from each treatment were killed to measure the empty and full weight of the gut, as well as the weights of the liver and kidneys. The jejunum and cecum were sampled to analyze the luminal concentrations of lactic acid; short-chain fatty acids; and mono-, di-, and polyamines and to assess the mucosal status. Mortality after 42 d ranged from 19% for animals fed the control diet, to 6% for animals fed the tributyrin or lactitol diets, and to 0% for animals fed the tributyrin+lactitol diet. After 14 d, the ADG was 127% greater (P < 0.05) in animals fed the tributyrin+lactitol diet than in animals fed the control or tributyrin diets. After 42 d, animals fed the tributyrin+lactitol diet were heavier (P < 0.05) than animals fed the tributyrin diet. At slaughter, no differences (P > 0.05) in organ weights were observed. With the exception of animals fed the lactitol diet, wherein cecal lactic acid levels increased threefold (P < 0.01), the luminal concentrations of lactic acid and short-chain fatty acids were not different (P > 0.05). Among the various amines analyzed, the only response (P < 0.05) was a 66 and 49% decrease in histamine levels in the jejunum and cecum, respectively, in animals fed the tributyrin+lactitol diet compared to the control diet. In the jejunum of animals fed the lactitol or tributyrin+lactitol diets, the length of the villi was increased by 12% (P < 0.05) compared to animals fed the control diet, whereas the tributyrin diet did not have any effect on the villi (P > 0.05). In the cecum, the depths of the crypts were reduced (P < 0.001) by 18% in animals fed the lactitol diet and 45% in animals fed the tributyrin or tributyrin+lactitol diets compared to animals fed the control diet. In conclusion, a diet containing tributyrin and lactitol as nutribiotics resulted in lower histamine levels in the jejunum and cecum, as well as longer jejunal villi and shallower cecal crypts.

IgE and mast cell responses on intestinal allergen exposure: A murine model to study the onset of food allergy

Objective: Allergic reactions to food are characterized by enhanced allergen-specific IgE serum levels and the activation of intestinal mast cells. Here we describe a murine model for the onset of food allergy and the role of cytokines in the regulation of food-induced IgE responses. Methods: Mice were primed systemically with low doses of alum-precipitated ovalbumin. Subsequent intragastric challenge led to enhanced sensitization. Results: Compared with baseline ovalbumin-specific IgE levels before challenge (0.23 ± 0.06 optical density [OD] units), ovalbumin-challenged mice showed significantly elevated IgE levels (0.86 ± 0.23 OD units) after intragastric challenge, which were not observed in control animals (0.29 ± 0.06 OD units). IgE levels mirrored intestinal mast cell activation, measured by decreased histamine levels in duodenal specimens, in ovalbumin-challenged mice (92.6 ± 7.9 ng/0.1 gm tissue weight) but not in saline-challenged mice (135.4 ± 18.3 ng/0.1 gm tissue weight), compared with baseline levels (141.1 ± 4.1 ng/0.1 gm tissue weight). Changes in IgE and histamine levels after intragastric challenge could be blocked by treating the animals with neutralizing antibodies against IL-4 or IL-10. Although it is generally accepted that ingestion of food allergens leads to a state of immunologic unresponsiveness (i.e., oral tolerance), it is shown here that low-dose systemic priming followed by intragastric challenge leads to sensitization instead of unresponsiveness. Conclusions: Our murine model shows an important correlation between T h2 cytokines, IgE production, and histamine release. Hence, this in vivo model provides a useful tool with which the complex mechanism underlying sensitization to food allergens can be studied. (J Allergy Clin Immunol 1997;99:94-9.)

The effect of haloperidol on the histaminergic neuron system in the rat brain.

In this study, the effect of haloperidol on histamine (HA) levels, histidine decarboxylase (HDC) activities and the bindings of [3H]-(R)-alpha-methylhistamine ([3H]-(R)-alpha-MeHA) to histamine H3 receptors were investigated in the rat brain. Administration of 10 mg/kg of haloperidol decreased HA levels in the rat striatum and diencephalon, but increased HDC activities in rat striatum and diencephalon, although that of 5 mg/kg did not change them. Meanwhile, haloperidol inhibited the bindings of [3H]-(R)-alpha-MeHA to H3 receptor sites in the rat striatal membrane with a Ki value of 10.5 +/- 0.45 microM. These findings suggest that only a high dose of haloperidol increases HA synthesis and release as a histamine H3 receptor antagonist in the rat brain.