Coexistence of Alterations of Gastrointestinal Function and Mechanical Allodynia in the Reserpine-Induced Animal Model of Fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a disorder characterized by widespread chronic pain as core symptom and a broad range of comorbidities. Despite the prevalence of gastrointestinal (GI) comorbidities in patients with FM, GI functions have rarely been investigated in animal models of FM. AIMS: The purpose of the present study is to investigate the coexistence of alterations of GI function in the reserpine-induced myalgia (RIM) rat, a validated FM model associated with disruption of monoamine system. METHODS: Paw withdrawal threshold (von Frey hair test) was assessed as pain-associated indicator. Gastric emptying (13C breath test), small intestinal transit (charcoal meal test), and fecal water content were investigated as GI functions. RESULTS: The specific regimen of reserpine for the RIM rat, i.e., 1 mg/kg s.c., once daily for three consecutive days, caused a reduction of paw withdrawal threshold (i.e., mechanical allodynia) on days 3, 5, and 7 after the first injection. The 13CO2 excreted from the RIM rat was significantly increased on day 7. The RIM rat exhibited an acceleration of small intestinal transit on day 5. Fecal water content collected from the RIM rat was significantly increased on days 3 and 5. The amount of noradrenaline was significantly decreased in GI tissues on days 3, 5, and 7 in the RIM rat. Conclusions This study revealed that accelerated gastric emptying, accelerated small intestinal transit, and increase in fecal water content coexist with mechanical allodynia in the RIM rat, simulating the coexistence of chronic pain and alterations of GI function in patients with FM.

Novel effect of α-lactalbumin on the yohimbine-induced hot flush increase of the tail skin temperature in ovariectomized rats.

5-Hydroxytryptamine (5-HT) and noradrenaline have been thought to play important roles in the mechanism of hot flush. Then, to clarify the relation between serotonergic and adrenergic nervous systems on the mechanism of hot flush, the effect of paroxetine, 5-HT reuptake inhibitor (SSRI) was evaluated on the yohimbine-induced hot flush increase of tail skin temperature in ovariectomized female rats. Yohimbine (adrenaline α2 antagonist) significantly increased the tail skin temperature in course of time. Clonidine (adrenaline α2 agonist) significantly attenuated this effect. Paroxetine also significantly inhibited the increase of tail skin temperature by yohimbine. α-Lactalbumin having SSRI activity in vitro study also significantly inhibited the increase of tail skin temperature, but not significantly decreased the initial temperature. This difference may explain the different mechanism between paroxetine (SSRI) and α-lactalbumin, suggesting new mechanism of hot flush.

Bovine milk-derived α-lactalbumin prevents hepatic fibrosis induced by dimethylnitrosamine via nitric oxide pathway in rats.

The present study was designed to evaluate the hepatoprotective potential of α-lactalbumin (αLA) against dimethylnitrosamine (DMN)-induced toxic insults in the rat liver. The liver damage was induced in rats by the repeated administration of DMN (10 mg/kg, i.p.) on three consecutive days per week for three weeks. The rats were maintained on either a standard AIN-93 M or αLA-enriched diet starting one week before the DMN injection until the termination of the experiment. The DMN treatment produced a progressive increase in the plasma markers (aspartate aminotransferase, alanine aminotransferase, total bililbin, hyarulonic acid, and matrix metalloproteinase-2) in 28 days after the first DMN injection. Dietary treatment with αLA significantly reduced the DMN-induced damage toward normalcy. NＧ-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, significantly attenuated the hepatoprotective effect of αLA. These findings show that αLA has a marked suppressive effect on hepetic fibrosis through a nitric oxide-mediated mechanism.

Effects of L-tryptophan on gastric emptying evaluated by breath test in relation to gastric accommodation evaluated by Barostat in rats.

Gastric emptying has been known to correlate the pyloric sphincter contractile function and distention-induced gastric relaxation (gastric accommodation). In the present study, the effects of L-tryptophan on the gastric emptying and accommodation were evaluated by breath test using [1-(13)C]acetic acid and Barostat study, respectively, in rats. L-Tryptophan significantly decreased Cmax and AUC120min and delayed Tmax, indicating the inhibition of gastric emptying. L-Tryptophan significantly enhanced the gastric accommodation. These findings show that L-tryptophan may inhibit the gastric emptying through the enhanced gastric accommodation. Therefore, L-tryptophan may be useful for the therapy of postprandial dyspepsia, especially for early satiety.

Sequential observation of implanted endometriosis by laparoscopy in rats: correlation between the prevalence rate and the estrous cycle.

This study aimed to clarify the correlation between the estrous cycle and prevalence rate of endometriosis by sequential laparoscopy in Wistar-Imamichi female rats. The peritoneal implantation of endometrial tissue was performed in four estrous cycle rats (proestrus, estrus, metestrus, and diestrus). One week after implantation, the volume of the ectopic endometriosis was measured, and sequential laparoscopy was performed for 4 weeks to observe the prevalence rate. Five weeks after implantation, the volume of the ectopic endometriosis was measured again after laparoscopy. One week after implantation, the volume of endometriosis was significantly larger in proestrus and estrus rats than metestrus and diestrus rats. Prevalence rate was decreased with time. Five weeks after implantation, the prevalence rate and volume were higher and larger in the metestrus, diestrus, and estrus rats than in the proestrus rats. These results show that the estrous cycle affects the change of ectopic endometriosis. The decrease of prevalence rate was slow in metestrus, diestrus, and estrus rats as compared to that in proestrus rats. The volume of ectopic endometriosis showed little decrease with time when the endometrial tissue was implanted during the metestrus and diestrus portion of the cycle. Moreover, sequential laparoscopy made it possible to observe the prevalence rate of endometriosis.

Effects of Lactobacillus gasseri OLL2809 on the induced endometriosis in rats.

We have reported an inhibitory effect of Lactobacillus gasseri OLL2809 (OLL2809) on the growth of mouse endometrial tissue in the abdominal cavity. The present study aimed to investigate the efficacy of Lactobacillus gasseri OLL2809 (OLL2809) on pre-existing endometriosis implanted on the abdominal wall in diestrus Wistar-Imamichi female rats. One week after implantation, the volume of the endometrial tissue was measured after laparotomy. OLL2809 and dienogest were administered for 4 weeks. OLL2809 significantly enhanced the decrease in the volume (p<0.01) as compared with control. Complete healing was observed in two of nine rats, but in none of the control group. Dienogest did not show significant efficacy. These findings suggest that OLL2809 is useful not only in therapy of pre-existing endometriosis but also in the prevention of the growth of endometrial tissue.

Treatment Outcomes of Anticoagulant Therapy and Temporary Inferior Vena Cava Filter Implantation for Pregnancy Complicated by Venous Thrombosis.

Objective: Although deep vein thrombosis (DVT) followed by pulmonary thromboembolism (PE) is a critical complication during pregnancy, there have been few reports about its intrapartum management. We evaluated intrapartum management by using a temporary inferior vena cava filter (IVCF) in pregnant women with PE/DVT. Materials and Methods: Eleven women with PE/DVT during pregnancy between January 2004 and December 2016 were included. The patients were hospitalized for intravenous unfractionated heparin infusion after acute PE/DVT onset. Seven patients were discharged and continued treatment with subcutaneous injection of heparin at the outpatient unit. IVCF was implanted 1-3 days before delivery in 10 patients. Anticoagulant therapy was discontinued 6-12 h before delivery. We retrospectively analyzed rates of maternal or perinatal death, and recurrence of symptomatic PE/DVT. Results: One patient was diagnosed as having PE/DVT and 10 had DVT alone. One patient suffered hemorrhagic shock during delivery; however, maternal or perinatal death and recurrence of symptomatic PE/DVT did not occur in any patient. Conclusion: Maternal or perinatal death and recurrence of symptomatic PE/DVT was not seen in women diagnosed as having PE/DVT during pregnancy and treated with anticoagulant therapy and IVCF.

Gastric emptying after artificial ulceration in rats: differences due to the site of the ulcer and the effects of prokinetic drugs.

Background This study aimed to evaluate the effects of the position of an acetic acid-induced gastric ulcer and the effects of prokinetic drugs on gastric emptying. Materials and Methods Male Sprague-Dawley rats were used in this study. Acetic acid ulcers were induced either in the region between the fundus and pylorus on the anterior wall of the stomach or in the glandular region on the greater curvature of the stomach to determine whether there were regional differences in the effect of the ulcers. Gastric emptying was evaluated with a breath test using [1-13C] acetic acid. In addition, the effects of the prokinetic drugs, metoclopramide and mosapride, on gastric emptying were also evaluated. Results Acetic acid induced ulcers in the region between the fundus and pylorus on the anterior wall of the stomach significantly delayed gastric emptying as compared with control rats, but not the acetic acid induced ulcers in the glandular region on the greater curvature of the stomach. Metoclopramide and mosapride did not improve the delayed gastric emptying even at doses that enhanced gastric emptying in normal rats. Conclusion These findings show that gastric emptying is influenced by the position of the ulcer and the region between the fundus and pylorus on the anterior wall plays an important role in gastric emptying. Moreover, it was found that metoclopramide and mosapride do not improve the delayed gastric emptying caused by acetic acid ulcers induced on the anterior wall in the region between the fundus and pylorus.

Correlation Between Gastric Emptying and Gastric Adaptive Relaxation Influenced by Amino Acids.

BACKGROUND/AIMS: Amino acids have many physiological activities. We report the correlation between gastric emptying and gastric adaptive relaxation using tryptophan and amino acids with a straight alkyl chain, hydroxylated chain, and branched chain. Here we sought to further clarify the correlation between gastric emptying and gastric adaptive relaxation by using other amino acids. METHODS: In Sprague-Dawley rats, gastric emptying was evaluated by a breath test using [1-13C] acetic acid. The expired 13CO2 pattern, Tmax, Cmax, and AUC120min values were used as evaluation items. Gastric adaptive relaxation was evaluated in a barostat experiment. Individual amino acids (1 g/kg) were administered orally 30 minutes before each breath test or barostat test. RESULTS: L-phenylalanine and L-tyrosine did not influence gastric emptying. All other amino acids, ie, L-proline, L-histidine, L-cysteine, L-methionine, L-aspartic acid, L-glutamic acid, L-asparagine, L-arginine, L-glutamine, and L-lysine significantly delayed and inhibited gastric emptying. L-Cysteine and L-aspartic acid significantly enhanced and L-methionine and L-glutamine significantly inhibited gastric adaptive relaxation. L-Phenylalanine moved the balloon toward the antrum, suggesting strong contraction of the fundus. Tmax showed a significant positive correlation (r = 0.709), and Cmax and AUC120min each showed negative correlations (r = 0.613 and 0.667, respectively) with gastric adaptive relaxation. CONCLUSION: From the above findings, it was found that a close correlation exists between gastric emptying and adaptive relaxation, suggesting that enhanced gastric adaptive relaxation inhibits gastric emptying.

Effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying evaluated using a non-invasive breath test in conscious rats.

AIM: Some amino acids been known to influence gastric emptying. Thus we have evaluated the effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying. MATERIALS AND METHODS: Gastric emptying was evaluated in rats after feeding with Racol (nutrient formulae) containing [1-(13)C] acetic acid. Using a breath test, the content of (13)CO2 in their expired air was measured by infrared analyzers. Rats were orally administered with test amino acids, while control rats were administered orally with distilled water. RESULTS: The expired (13)CO2 content in the expired air increased with time, peaked after about 30 min and decreased thereafter. Among the amino acids having an alkyl chain, L-serine, L-alanine and L-glycine, significantly decreased the (13)CO2 content and Cmax, and delayed Tmax, suggesting inhibition and delay of gastric emptying. AUC(120min) values of L-alanine and L-glycine also decreased significantly. L-Threonine significantly decreased (13)CO2 content and delayed Tmax, but had no influence on Cmax and AUC(120min) values, suggesting a delay of gastric emptying. L-Isoleucine and L-leucine and L-valine significantly decreased (13)CO2 content, suggesting inhibition of the gastric emptying, but Cmax, Tmax and AUC(120min) values were not significantly affected. CONCLUSION: The results show that the amino acids used in the present study had different effects on gastric emptying. Moreover, it was found that inhibition and delay of gastric emptying were clearly classifiable by analyzing the change in (13)CO2 content of the expired air and the Cmax, Tmax and AUC(120min) values.

IgG4-related pleural disease diagnosed by a re-evaluation of chronic bilateral pleuritis in a patient who experienced occasional acute left bacterial pleuritis.

A 78-year-old man with cryptogenic chronic bilateral lymphoplasmacytic pleuritis, diagnosed based on left parietal pleural biopsy specimens obtained by pleuroscopy, developed acute left bacterial pleuritis. The left pleural effusion was neutrophil dominant, however, the right pleural effusion showed lymphoplasmacytic infiltration. Laboratory examinations revealed that his serum IgG4 concentration was increased, with a higher level of IgG4 in the right pleural effusion. Re-evaluation of the previous biopsy specimens using an immunostaining method revealed numerous IgG4-positive plasma cell infiltrations with IgG4-positive/IgG-positive plasma cells at 85.4%. Accordingly, the new diagnosis of this patient was considered to be chronic bilateral IgG4-related pleuritis.