Decrease In Histamine Content Research Articles

Effect of Propolis on Experimental Allergic Conjunctivitis in Rats

Background and Aim: The purpose of the present study is to provide a basis for the use of propolis as a therapeutic agent for allergic conjunctivitis. Methods: The effect of propolis eye drops on experimental allergic conjunctivitis in rats was investigated. The allergic conjunctivitis in rats was occurred by sensitization and challenge of egg albumin and the number of eye scratching, hyperemia, chemosis, vascular permeability and histamine content in conjunctival tissue and tears were assayed. Results: Propolis significantly inhibited allergic symptoms including eye scratching, hyperemia and chemosis observed in conjunctivitis compared with the control group. Furthermore, this agent significantly inhibited increased vascular permeability induced by antigen and histamine release from the rat conjunctiva in correlation with a decrease in histamine content in tears. Conclusion: The efficacy of the propolis on allergic conjunctivitis in rats may be attributable to the antiallergic and anti-inflammatory action.

Combination treatment for allergic conjunctivitis – Plant derived histidine decarboxylase inhibitor and H1 antihistaminic drug

Aim of present investigation was to study the effect of catechin and the combination of catechin and cetirizine in ovalbumin induced animal model of allergic conjunctivitis. Guinea pigs were divided into 5 groups: normal control, disease control, disease treated with catechin 100 mg/kg, disease treated with cetirizine 10 mg/kg, disease treated with combination of catechin and cetirizine, 50 mg/kg & 5 mg/kg respectively. Sensitization was carried out by intraperitoneal injection of ovalbumin for the period of 14 day. Simultaneously, catechin was administered orally for 14 days while, cetirizine was administered at the day of experiment. Determination of clinical scoring, mast cell and blood histamine content, histidine decarboxylase activity from stomach was carried out. Vascular permeability was measured by dye leakage after secondary challenge of allergen and conjunctival tissues were subjected for histopathological examinations. Treatment with catechin, cetirizine and combination showed significant (P < 0.05) decrease in clinical scoring and vascular permeability. While, catechin 100 mg/kg and catechin 50 mg/kg showed significant (P < 0.05) decrease in histamine content in mast and blood. The treatment also showed significant (P < 0.05) decrease in the histidine decarboxylase enzyme activity. However, cetirizine group did not show any difference in enzyme activity as well as histamine content. Histopathological examination also showed improvement in ulceration and decrease in edema and inflammation in all treatment groups. From the present study, we can conclude that catechin exhibits potent anti-allergic activity by histidine decarboxylase enzyme inhibition and combination shown significant anti-allergic activity at reduced dose by both enzyme inhibition as well as inhibition of histamine receptors.

ASSESSMENT OF WOUND HEALING ACTIVITY OF DAPHNE OLEOIDES SUBSP. KURDICA: IDENTIFICATION OF THE ACTIVE COMPONENTS USING BIOASSAY GUIDED ISOLATION METHOD

s. PHYTOPHARM 2012 M 76 Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy] ТОМ 10/2012/2 CRS) and aspirin (4h ASP) induced ulceration. The ulcer index and % protection was calculated. The gastric juice collected from 4h Pl rats was studied for the effects on gastric volume, ph, free acid, total acid-pepsin output, dNA gastric juice cell shedding and mucosal cell proliferation. biochemical estimation such as histamine content, mucus content and hkATPase inhibitory activity was also evaluated. The effect of APf on stomach histopathology was also studied. Statistical analysis was done by one way ANOVA followed by dunnett’s post hoc test for multiple comparisons against control group. The difference was considered to be significant when P < 0.05. Oral treatment of APf (200 and 400 mg/kg, p. o.) for 7 days showed significant protection against acute gastric ulcer induced by 4h Pl and 95 % EtOh, but was found to have no effect on CRS and ASP-induced gastric ulceration. The gastric studies showed that treatment with APf signiccantly increased the gastric juice ph, decrease the gastric volume and total acid-pepsin output and significantly reduced the gastric juice cell shedding. A significant decrease in histamine content and a reduction in free phosphate ions responsible for hkATPase inhibitory activity were also observed. in conclusion, the results of the present study indicate that the gastroprotective activity of APf contributes mainly to the peripheral effects on the gastric secretion and the probable mechanism underlying behind such activity might be both due to the possible inhibition on the histaminic (h 2 ) receptor and hkATPase pump. INVESTIGATION OF THREE TRITERPENE ACIDS AGAINST CANCER CELL PROLIFERATION ACTIVITY © Khoo Gaik Ming, Clausen Morten Rahr, Larsen Erik Department of Food Science, Aarhus University, Kirstinebjergvej 10, DK-5792 Aarslev, Denmark The object of this study was to investigate the inhibitory effect of betulinic acid, oleanolic acid and ursolic acid on human colon cancer cell proliferation activity. Triterpene acids are members of the terpene family and are widely distributed in food plants. A rosehip fraction containing a mixture of betulinic acid, oleanolic acid and ursolic acid displayed inhibitory effect against the release of pro-inflammatory cytokine interleukin-6 with the combination of oleanolic acid/betulinic acid and ursolic acid/betulinic acid displaying significant synergistic inhibitory effects (1). Our results showed that these three compounds also displayed good inhibitory effect against cancer cell proliferation activity at the concentration of 10μg/ml. both betulinic acid and ursolic acid displayed strong inhibition against hT-29 (88 % and 79 %, respectively) and SW-480 (76 % and 82 %, respectively), but a moderate to weak inhibition against Caco-2 (19 % and 22 %, respectively). Oleanolic acid displayed only moderate inhibition against Caco-2 (49 %), very weak inhibition against hT-29 (7 %) and no inhibition against SW-480. No synergistic effects were observed between combinations of the triterpene acids. We only found an additive effect in the combination of oleanolic acid/ursolic acid and only against proliferation of hT-29. Antagonistic effects between the pure compounds were observed when betulinic acid was one of the components in the combination. Although betulinic acid and ursolic acid showed good inhibitory effects against all three cancer cell lines, their combination displayed antagonistic effects and showed poor inhibition against cancer cell proliferations. however, these triterpenic acids and their combination effects should be further investigated in different in vitro or in vivo experiment to confirm their bioactivities and mechanism. Reference: (1) Saaby l., Moesby l., hansen E. W., Christensen S. b. (2011). isolation of immunomodulatory triterpene acids from a standardized rose hip powder (Rosa canina l.). Phytotherapy Research, 25, 195–201. DECURSIN AND RELATED COMPOUNDS INHIBIT VASCULAR ENDOTHELIAL MIGRATION BY SPHINGOSINE KINASE INHIBITION © Lee Yong-Moon, Shin Kyong-Oh, Seo Cho-Hee, Kim Tack-Joong College of Pharmacy, Chungbuk National University, Cheongju, South Korea Division of Biological Science and Technology, Yonsei University, Wonju, South Korea The pyranocoumarin compound decursin isolated from the herb, Angelica gigas, are known to possess potent anti-inflammatory activities. however, little is known about their anti-angiogenic activity. here, we investigated the anti-angiogenic effects of decursin by the changes of sphingolipid metabolites

INVESTIGATION OF THREE TRITERPENE ACIDS AGAINST CANCER CELL PROLIFERATION ACTIVITY

s. PHYTOPHARM 2012 M 76 Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy] ТОМ 10/2012/2 CRS) and aspirin (4h ASP) induced ulceration. The ulcer index and % protection was calculated. The gastric juice collected from 4h Pl rats was studied for the effects on gastric volume, ph, free acid, total acid-pepsin output, dNA gastric juice cell shedding and mucosal cell proliferation. biochemical estimation such as histamine content, mucus content and hkATPase inhibitory activity was also evaluated. The effect of APf on stomach histopathology was also studied. Statistical analysis was done by one way ANOVA followed by dunnett’s post hoc test for multiple comparisons against control group. The difference was considered to be significant when P < 0.05. Oral treatment of APf (200 and 400 mg/kg, p. o.) for 7 days showed significant protection against acute gastric ulcer induced by 4h Pl and 95 % EtOh, but was found to have no effect on CRS and ASP-induced gastric ulceration. The gastric studies showed that treatment with APf signiccantly increased the gastric juice ph, decrease the gastric volume and total acid-pepsin output and significantly reduced the gastric juice cell shedding. A significant decrease in histamine content and a reduction in free phosphate ions responsible for hkATPase inhibitory activity were also observed. in conclusion, the results of the present study indicate that the gastroprotective activity of APf contributes mainly to the peripheral effects on the gastric secretion and the probable mechanism underlying behind such activity might be both due to the possible inhibition on the histaminic (h 2 ) receptor and hkATPase pump. INVESTIGATION OF THREE TRITERPENE ACIDS AGAINST CANCER CELL PROLIFERATION ACTIVITY © Khoo Gaik Ming, Clausen Morten Rahr, Larsen Erik Department of Food Science, Aarhus University, Kirstinebjergvej 10, DK-5792 Aarslev, Denmark The object of this study was to investigate the inhibitory effect of betulinic acid, oleanolic acid and ursolic acid on human colon cancer cell proliferation activity. Triterpene acids are members of the terpene family and are widely distributed in food plants. A rosehip fraction containing a mixture of betulinic acid, oleanolic acid and ursolic acid displayed inhibitory effect against the release of pro-inflammatory cytokine interleukin-6 with the combination of oleanolic acid/betulinic acid and ursolic acid/betulinic acid displaying significant synergistic inhibitory effects (1). Our results showed that these three compounds also displayed good inhibitory effect against cancer cell proliferation activity at the concentration of 10μg/ml. both betulinic acid and ursolic acid displayed strong inhibition against hT-29 (88 % and 79 %, respectively) and SW-480 (76 % and 82 %, respectively), but a moderate to weak inhibition against Caco-2 (19 % and 22 %, respectively). Oleanolic acid displayed only moderate inhibition against Caco-2 (49 %), very weak inhibition against hT-29 (7 %) and no inhibition against SW-480. No synergistic effects were observed between combinations of the triterpene acids. We only found an additive effect in the combination of oleanolic acid/ursolic acid and only against proliferation of hT-29. Antagonistic effects between the pure compounds were observed when betulinic acid was one of the components in the combination. Although betulinic acid and ursolic acid showed good inhibitory effects against all three cancer cell lines, their combination displayed antagonistic effects and showed poor inhibition against cancer cell proliferations. however, these triterpenic acids and their combination effects should be further investigated in different in vitro or in vivo experiment to confirm their bioactivities and mechanism. Reference: (1) Saaby l., Moesby l., hansen E. W., Christensen S. b. (2011). isolation of immunomodulatory triterpene acids from a standardized rose hip powder (Rosa canina l.). Phytotherapy Research, 25, 195–201. DECURSIN AND RELATED COMPOUNDS INHIBIT VASCULAR ENDOTHELIAL MIGRATION BY SPHINGOSINE KINASE INHIBITION © Lee Yong-Moon, Shin Kyong-Oh, Seo Cho-Hee, Kim Tack-Joong College of Pharmacy, Chungbuk National University, Cheongju, South Korea Division of Biological Science and Technology, Yonsei University, Wonju, South Korea The pyranocoumarin compound decursin isolated from the herb, Angelica gigas, are known to possess potent anti-inflammatory activities. however, little is known about their anti-angiogenic activity. here, we investigated the anti-angiogenic effects of decursin by the changes of sphingolipid metabolites

Occurrence of Biogenic Amines and Polyamines in Spinach and Changes during Storage under Refrigeration

Biogenic amines and polyamines were studied in 18 market samples of spinach. Histamine and spermidine were detected in relatively high amounts in all samples within the ranges of 9.5-69.7 and 15.6-53.0 mg/kg, respectively. Other biologically active amines were either detected at low levels or not found at all. Changes in amine content during storage at 6 degrees C were studied. The content of most of the amines remained constant during storage, with the exception of spermidine and histamine. Spermidine showed a clear decreasing trend, whereas histamine significantly increased in all trials, but decreased at the end of the storage in two of the trials. Trials showing a decrease in histamine content also showed the highest spermidine decrease and recorded the highest pH values. Microbial loads throughout storage were also followed, with Pseudomonadaceae and Enterobacteriaceae being the predominant bacterial groups. Trials with higher microbial loads in initial samples also showed the highest histamine content in these samples. Potential explanations for both the formation and the degradation of histamine during storage are discussed.

Ephedrae herba (Mao) decreased histamine content in RBL-2H3 cells

The effect of Ephedrae herba (Mao) on histamine content was investigated. When rat basophilic leukemia (RBL-2H3) cells were incubated for 48h with Mao, Mao decreased histamine content in a concentration-dependent manner. However, the ratio of released histamine to total histamine was scarcely affected by Mao treatment when RBL-2H3 cells were stimulated by ionomycin. On the other hand, the content of β-hexosaminidase, another marker of degranulation, was only slightly decreased by Mao. The expression level of the active form (53kDa) of L-histidine decarboxylase, the enzyme which synthesizes histamine, was partially suppressed by Mao. Furthermore, Mao significantly suppressed proliferation of RBL-2H3 cells in a concentration-dependent manner. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine revealed an increasing effect of Mao on cAMP level in RBL-2H3 cells. Since this result suggested that Mao may stimulate adenylate cyclase, we evaluated the effect of adenylate cyclase inhibitor SQ 22536 on Mao-induced decrease in histamine content. As a result, we showed that SQ 22536 did not have a reducing effect of Mao. From these results it is understood that Mao decreased histamine content by inhibiting cell proliferation and expression of histidine decarboxylase. However, these effects are not related to the increase in cAMP.

Caffeic Acid Inhibits Compound 48/80-Induced Allergic Symptoms in Mice

The effect of caffeic acid on scratching behavior and vascular permeability changes induced by compound 48/80 in ICR mice were investigated. An oral dose of 500 mg/kg of caffeic acid significantly inhibited scratching behavior and vascular permeability induced by compound 48/80. The inhibitory effects of daily administration of lower doses of caffeic acid, 100 and 200 mg/kg, were also investigated; and it was found that 200 mg/kg significantly inhibited compound 48/80-induced scratching behavior after the second week of consecutive administration. The effect of 200 mg/kg of caffeic acid on scratching behavior was observed up to the third week of the treatment. The decrease in histamine content induced by compound 48/80 was significantly antagonized by 200 mg/kg. The findings suggest that caffeic acid may be effective for treating itch and edema in allergic dermatitis.

Histidine enhances carbamazepine action against seizures and improves spatial memory deficits induced by chronic transauricular kindling in rats1

To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats. Chronic transauricular kindling was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. An 8-arm radial maze (4 arms baited) was used to measure spatial memory, and histamine and gamma-amino-butyric acid levels were measured by high performance liquid chromatography (HPLC). Chronic transauricular kindling produced a significant impairment of spatial memory and a marked decrease in histamine content in the hypothalamus, the brainstem, and the hippocampus. Injection of histidine (1000 mg/kg or 1500 mg/kg, ip) significantly inhibited transauricular kindled seizures. Injection of histidine at lower doses (200 mg/kg or 500 mg/kg, ip) had no appreciable anticonvulsant effect when administered alone, whereas it significantly potentiated the protective effects of CBZ against kindled seizures. CBZ had no ameliorative effect on memory deficit, but, in contrast, histidine (200 mg/kg or 500 mg/kg, ip) alone or co-administered with CBZ significantly ameliorated the memory deficits induced by the seizures. Chronic transauricular kindling is a very useful animal model for evaluating memory deficits associated with epilepsy, and histidine has both a potentiate effect on the anticonvulsant efficacy of CBZ and an ameliorative effect on the spatial memory deficits induced in this model. Histidine at a specific dosage range might serve as a beneficial adjuvant for the clinical treatment of epilepsy, especially when accompanied by impaired spatial memory.

Increasing Effect by Simultaneous Use of Levocabastine and Pemirolast on Experimental Allergic Conjunctivitis in Rats

The effect of the simultaneous use of 0.025% levocabastine hydrochloride eye drops (levocabastine) and 0.1% pemirolast potassium ophthalmic solution (pemirolast) on experimental allergic conjunctivitis in rats was investigated. Levocabastine and pemirolast significantly inhibited allergic conjunctivitis compared with the control group when separately administered. In addition, the simultaneous use of both drugs inhibited allergic conjunctivitis more potently than the original activity of levocabastine or pemirolast. Furthermore, the simultaneous use of levocabastine and pemirolast also significantly inhibited increased vascular permeability induced by antigen compared with levocabastine or pemirolast alone, respectively. Levocabastine and pemirolast inhibited histamine release from the rat conjunctiva in correlation with a decrease in histamine content in tears. When levocabastine and pemirolast were simultaneously applied to the eyes, histamine release from the conjunctiva was greater than for the original activities of both drugs. Similar to histamine release from the conjunctiva, the histamine content in tears induced by the simultaneous use of both drugs was significantly decreased compared with levocabastine and pemirolast alone, respectively. A potentiating effect induced by the simultaneous use of levocabastine and pemirolast may be attributable to the antihistaminic activity of levocabastine and histamine release inhibition by levocabastine and pemirolast.

The biphasic effects of cyclopentenone prostaglandins, prostaglandin J 2 and 15-deoxy-Δ 12,14-prostaglandin J 2 on proliferation and apoptosis in rat basophilic leukemia (RBL-2H3) cells

Mast cells produce chemical mediators, including histamine and arachidonate metabolites such as prostaglandin D 2 (PGD 2) after antigen stimulation. Cyclopentenone prostaglandins of the J series, prostaglandin J 2 (PGJ 2) and 15-deoxy-Δ 12,14-prostaglandin J 2 (15d-PGJ 2), are thought to be derivatives of PGD 2. In this study, the biphasic effects of the PGJ 2 and 15d-PGJ 2 on proliferation and apoptosis in rat basophilic leukemia cells (RBL-2H3), a tumor analog of mast cells, were examined. At low concentrations, 1 or 3 μM PGJ 2 and 15d-PGJ 2 induced cell proliferation, respectively. At high concentrations (10–30 μM) both the inhibition of viability and decrease in histamine content in RBL-2H3 cells were dose dependent. These effects were independent of the nuclear hormone receptor, peroxisome proliferator-activated receptor γ (PPARγ), since troglitazone, an agonist of PPARγ did not cause any effects in RBL-2H3 cells. Cell death induced by PGJ 2 and 15d-PGJ 2 was the result of apoptotic processes, since RBL-2H3 cells treated with 30 μM of the prostaglandins had condensed nuclei, DNA fragmentation and increase in activities of caspase-3 and -9. Moreover, PGJ 2 or 15d-PGJ 2-induced apoptotic effects were prevented by the caspase inhibitor, z-VAD-fmk. In conclusion, the PGJ 2 or 15d-PGJ 2-induced apoptosis in RBL-2H3 cells occurs mainly via mitochondrial pathways instead of by PPARγ-dependent mechanisms.

Effects of the NMDA antagonist MK-801 on radial maze performance in histidine-deficient rats

We examined the effects of a histidine-deficient diet on brain histamine contents as well as on learning and memory using the eight-arm radial maze in rats. A significant decrease in histamine content in the hippocampus was observed after long-term feeding of rats with a histidine-deficient diet. At the same time, significant enhancement of the acquisition process in radial maze performance was also observed. Pyrilamine did not show a significant effect on radial maze performance in histidine-deficient rats. On the other hand, pyrilamine caused a significant spatial memory deficit in control rats. Scopolamine was effective in inhibiting spatial memory in both histidine-deficient and control rats. MK-801 caused spatial memory deficits more potently in histidine-deficient rats than in controls. Brain glycine contents showed a significant increase in the hippocampus in histidine-deficient rats. These results indicated that the spatial memory deficits induced by MK-801 in histidine-deficient rats are closely related to increased glycine levels and activation of NMDA receptors.

INHIBITORY EFFECT OF MURINE KIDNEY EXTRACTS ON MAST CELLS DERIVED FROM HUMAN UMBILICAL CORD BLOOD

We examined the effect of aqueous murine kidney extract (MKE) on the growth of mast cells prepared from the liquid culture of human umbilical cord blood CD34+ cells in the presence of a combination of recombinant human stem cell factor (SCF) and interleukin-6 (IL-6). Cultured cells were mature mast cells that expressed CD117 antigen on their surface, a specific marker for human mast cell, and they contained 6.53 pg histamine per cell. Adding MKE resulted in a 53% inhibition of mast cell growth and a 40% decrease in histamine content in mast cells in a serum-free liquid culture stimulated by SCF and IL-6. The inhibitory molecule for the growth of human mature mast cells was estimated at about 30 kDa of protein from gel-filtration HPLC. This fraction also inhibited the growth of murine peritoneal cells-derived mast cells. These results suggest that MKE contains regulator(s) that suppress the growth of mast cells and histamine synthesis, and that act beyond species specificity.

Decreased brain histamine content in hypocretin/orexin receptor-2 mutated narcoleptic dogs

A growing amount of evidence suggests that a deficiency in hypocretin/orexin neurotransmission is critically involved in animal and human forms of narcolepsy. Since hypocretin-containing neurons innervate and excite histaminergic tuberomammillary neurons, altered histaminergic neurotransmission may also be involved in narcolepsy. We found a significant decrease in histamine content in the cortex and thalamus, two structures important for histamine-mediated cortical arousal, in Hcrtr-2 mutated narcoleptic Dobermans. In contrast, dopamine and norepinephrine contents in these structures were elevated in narcoleptic animals, a finding consistent with our hypothesis of altered catecholaminergic transmission in these animals. Considering the fact that histamine promotes wakefulness, decreases in histaminergic neurotransmission may also account for the sleep abnormalities in hypocretin-deficient narcolepsy.

Distribution of histamine in laying hen ovary.

In a laying hen, histamine was found to be present in all compartments of the ovary, i.e. stroma with follicles < 1 mm, small white (1-4 mm), large white (4-8 mm), atretic white, yellow preovulatory (8-35 mm) and postovulatory follicles. Stroma containing non-yolky follicles exhibited the highest histamine concentration (6080 +/- 331 ng/g wet wt. tissue) which differed significantly (P < 0.01) from histamine levels observed in all examined classes of ovarian follicles. High histamine concentration was found in small, large and atretic white follicles as well as in older postovulatory follicles whereas low levels of histamine contained yellow preovulatory and younger postovulatory follicles. Population of yolky white follicles presented significant (P < 0.01) differences in histamine level among small (4280 +/- 333), atretic (2940 +/- 193) and large (2010 +/- 110 ng/g) follicles. Within hierarchy of yellow preovulatory (F7-F1) follicles initial decrease in histamine concentration, from 859.3 +/- 51.5 ng/g in F7 follicle to 363.9 +/- 28.3 ng/g in F4 follicle, was followed by the increase as follicle matured, reaching the highest level in F1 follicle (711.4 +/- 35.9 ng/g). In postovulatory (P1-P5) follicles histamine concentration gradually increased as they were getting older, from 604.3 +/- 49.3 ng/g in P1 follicle to 2253 +/- 197 ng/g in P5 follicle. Determination of histamine in relation to ovulation revealed significant (P < 0.01) difference both in histamine concentration and content between the largest preovulatory F1 follicle and the largest postovulatory P1 follicle, being 0.5 h before and 0.5 h after ovulation, respectively. It is suggested that in chicken, ovarian histamine may play a role in the follicular development and/or the ovulatory process.

Influence of histamine depletion on learning and memory recollection in rats.

To clarify the role of endogenous histamine in learning and memory, the effect of alpha-fluoromethylhistidine on active avoidance response in rats was studied. alpha-Fluoromethylhistidine (20-100 mg/kg or 10-50 micrograms) significantly (P < 0.05 or P < 0.01) prolonged the response latency in active avoidance response when administered by either intraperitoneal or intracerebroventricular injection. These effects were dose-related and long lasting. A prolongation of the response latency induced by an intraperitoneal injection of alpha-fluoromethylhistidine (100 mg/kg) was antagonized by intracerebroventricular injection of histamine (10 and 20 ng) in a dose-dependent manner. In addition, the acquisition of this response was retarded by a consecutive intracerebroventricular injection of alpha-fluoromethylhistidine (50 micrograms), whereas histamine (100 ng) facilitated the response acquisition when administered by the same route. Both intraperitoneal (100 mg/kg) and intracerebroventricular injection of alpha-fluoromethylhistidine (50 micrograms) significantly (P < 0.05 or P < 0.01) decreased the brain histamine content, especially in the hippocampus and hypothalamus. When alpha-fluoromethylhistidine (50 micrograms) was injected intracerebroventricularly, there is a high correlation between a prolongation of the response latency and a decrease in histamine content of these brain areas. Based on these findings, it was concluded that an intimate relation may exist between a prolongation of response latency in the active avoidance response and a decrease in the brain histamine content; endogenous histamine may play an important role in learning and memory recollection in rats.

Histamine release from nasal mucosal mast cells in patients with chronic hypertrophic non-allergic rhinitis, after parasympathetic nerve stimulation

The vidian nerve provides the main parasympathetic nerve supply to nasal respiratory and maxillary sinus mucosa, and its electrical stimulation causes apparent secretory and vasodilatatory effects in animals. The present investigation was carried out in 8 patients with chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.) undergoing therapeutic vidian nerve resection. The vidian nerve was electrically stimulated before the resection. Samples were taken from nasal sinus mucosa for histamine determination and microscopical observation before and after the stimulation period. Vidian nerve stimulation causes a significant decrease in histamine content and mast cell density in the mucosa sample, differentially influenced by eserine and atropine pretreatment.

Pathogenesis of Lupus Dermatoses in Autoimmune Mice

We measured histamine concentration and its metabolizing enzymes in the skin of MRL/Mp-lpr/lpr (MRL/l) and BXSB mice to clarify the contribution of histamine metabolism to the mechanisms of the development of lupus dermatoses. The concentration of histamine seemed to differ with the mouse strain. The activity of histamine-N-methyltransferase (HMT), one of two major metabolizing enzymes, was significantly lower in the tail and back skin of MRL/l mice at the age of 5 months than in the control MRL/Mp-+/+(MRL/n) mice, although there were no characteristic differences among several mouse strains of 1 mo of age. In the back skin of MRL/l mice, an age-dependent decrease of HMT activity was observed along with a corresponding decrease in histamine concentration, whereas an age-dependent increase of both HMT activity and histamine concentration was demonstrated in BXSB mice and other control mouse strains. Autoimmune-prone male BXSB mice and non-autoimmune female BXSB mice at 5 mo of age showed similar HMT activity. Corticosteroid treatment restored HMT activity in the skin of MRL/l mice but not in MRL/n mice. In addition, the change in HMT activity in MRL/l mice treated with corticosteroid appeared earlier than changes in clinicopathological examinations including skin eruptions, dermatopathology and proteinuria. Diamine oxidase (DAO) activity, another major metabolizing enzyme, was not detected in the skin of any autoimmune or control mouse strains. These findings suggest that the low activity of HMT in the skin of MRL/l mice plays a significant pathological role in the development of spontaneous lupus-like eruption. In other mouse strains, it is assumed that HMT activity is regulated by genetic factors.

受身皮膚アナフィラキシーモデルにおけるＫＰ‐１３６のアレルギー反応抑制作用

The pharmacological properties of KP-136 were studied using cutaneous reactions in rats and guinea pigs. KP-136 remarkably inhibited the passive cutaneous anaphylaxis (PCA) with intravenous and oral dosing. However, the inhibitory effect of KP-136 had an apparent species difference. Thus, KP-136 was more effective on rat PCA than that of guinea pig. In four rat cutaneous reactions produced by three allergic reactions and compound 48/80, KP-136 was remarkably effective on two homologous PCA induced by IgE and IgGa. The intravenous and oral doses for 50% inhibition on the PCA were 0.2 mg/kg to 0.4 mg/kg and 0.5 mg/kg to 0.9 mg/kg, respectively. KP-136 was scarcely effective on cutaneous reactions elicited by intradermal injection of histamine and serotonin which are main chemical mediators in rat homologous PCA. However, KP-136 blocked the degranulation of mast cells and decrease of histamine content in skin elicited by the PCA. In addition, KP-136 showed a potent inhibition on the immunological release of histamine from rat peritoneal exudate cells. The concentration for 50% inhibition on the histamine release was 5 ng/ml. These findings indicate that KP-136 is an oral potent inhibitor on PCA, and it acts by blocking the release of chemical mediator(s) from mast cells.

Histamine storage and formation in canine gastric mucosa ‐ effect of pentagastrin stimulation

Histamine storage and formation in the dog gastric mucosa were studied during basal conditions and after pentagastrin stimulation. Histamine formation (histidine decarboxylase activity), histamine content as well as the density of mast cells of the oxyntic gland mucosa were evenly distributed. Histamine content of the mucosa was significantly correlated to the density of mucosal mast cells. In the basal secretory state, histamine formation and histamine content of the oxyntic gland mucosa were of the same magnitude as in the antral mucosa. Pentagastrin stimulation induced a small but significant decrease in histamine content of the oxyntic gland mucosa and a subsequent acceleration in the rate of amine formation. Neither histamine content nor histidine decarboxylase activity of the antral mucosa was affected by pentagastrin infusion.

Stimulation and resection of Vidian nerve in patients with chronic hypertrophic non-allergic rhinitis: effect on histamine content in nasal mucosa.

Parasympathetic innervation of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.). The present study investigated the effect of Vidian nerve stimulation and resection on the histamine contents and on the morphological pattern in mucosal samples of patients with C.H.N.A.R. Vidian nerve stimulation determines a significant decrease in histamine content in the samples examined; microscopical observations showed significant variations in the glandular, stromal and vascular components. The changes indicate an enhanced secretory activity, intensive vasodilatation and active degranulation of mast cells, which were significantly decreased in number in the samples obtained after 90 sec of stimulation. The neurectomy of the Vidian nerve resolves quite completely the clinical symptomatology and in parallel decreases the mucosal histamine contents, which are increased in patients with C.H.N.A.R. before the operation in comparison with the normal controls.