Dietary Supplementation of Vitamin B12 to Rats Fed High-Amylose Cornstarch Normalizes Propionate Fermentation in the Colon.

Since propionate exerts several physiological effects, maintenance of its normal colonic fermentation is essential. To investigate whether vitamin B12 (VB12) is essential for normal propionate fermentation by colonic bacteria, via the succinate pathway, we examined if high-amylose cornstarch (HACS) feeding activated such a pathway, if high HACS feeding impaired propionate fermentation, and if oral VB12 supplementation normalized propionate fermentation. Male rats were given control, 20% HACS or 3% fucose diets (Expt. 1); a VB12-free control diet or one supplemented with 5-30% HACS (Expt. 2); and the 20% HACS diet supplemented with 0.025-25 mg/kg of VB12 (Expt. 3), for 14 d. HACS feeding significantly increased cecal succinate concentration, activating the succinate pathway (Expt. 1). Cecal cobalamin concentration in 20% and 30% HACS groups was about 75% of that in the control group (Expt. 2). Cecal succinate and propionate concentrations significantly increased and decreased in 30% HACS groups, respectively, compared with the control group. Although HACS group supplemented with 0.025 mg/kg of VB12 had a low concentration of cecal propionate, adding high amounts of VB12 to HACS diets provided sufficient amounts of VB12 to rat ceca and increased cecal propionate concentration (Expt. 3). Compared with the non-HACS group, the relative abundance of Akkermansia muciniphila, but not Bacteroides/Phocaeicola, was lower in the HACS counterpart and showed improvement with increased VB12 doses. To summarize, feeding high HACS decreased and increased cecal VB12 and succinate concentrations, respectively. Furthermore, colonic delivery of sufficient amounts of VB12 to rats likely reduced accumulation of succinate and normalized propionate fermentation.

Photocatalytic CO2 Reduction Using an Osmium Complex as a Panchromatic Self-Photosensitized Catalyst: Utilization of Blue, Green, and Red Light.

The photocatalytic reduction of carbon dioxide (CO2) represents an attractive approach for solar-energy storage and leads to the production of renewable fuels and valuable chemicals. Although some osmium (Os) photosensitizers absorb long wavelengths in the visible-light region, a self-photosensitized, mononuclear Os catalyst for red-light-driven CO2 reduction has not yet been exploited. Here, we discovered that the introduction of an Os metal to a PNNP-type tetradentate ligand resulted in the absorption of light with longer-wavelength (350-700 nm) and that can be applied to a panchromatic self-photosensitized catalyst for CO2 reduction to give mainly carbon monoxide (CO) with a total turnover number (TON) of 625 under photoirradiation (λ≥400 nm). CO2 photoreduction also proceeded under irradiation with blue (λ0=405 nm), green (λ0=525 nm), or red (λ0=630 nm) light to give CO with >90 % selectivity. The quantum efficiency using red light was determined to be 12 % for the generation of CO. A catalytic mechanism is proposed based on the detection of intermediates using various spectroscopic techniques, including transient absorption, electron paramagnetic resonance, and UV/Vis spectroscopy.

Successful excision of an inflammatory endobronchial polyp using biopsy forceps with improvement in FEV1 in a patient with allergic bronchopulmonary aspergillosis: A case report.

Inflammatory endobronchial polyps (IEPs) are rare, benign bronchial tumors posing diagnostic and therapeutic challenges owing to limited data. A 55-year-old man, receiving treatment for allergic bronchopulmonary aspergillosis, presented with a one-week history of fever and purulent sputum. Diagnosed with pneumonia, he received antimicrobial treatment. However, because of persistent symptoms, an endobronchial tumor was suspected on computed tomography. IEP was confirmed through flexible bronchoscopy with forceps biopsy, and polyp removal improved symptoms, lung function, and imaging.

Pretreatment asthma control test score as a predictive score for clinical remission after bronchial thermoplasty in younger patients with severe asthma and preserved lung function.

OBJECTIVE: Bronchial thermoplasty (BT) decreases the incidence of asthma exacerbations, emergency room visits, and hospitalizations among patients with severe asthma. Predictors of BT effectiveness remain unclear as its mechanism of action and invasiveness remain obscure. This study aimed to identify factors that could predict BT outcomes. METHODS: Two respiratory physicians treated 20 consecutive patients with severe asthma using BT. The patients were assigned to groups based on clinical remission following an expert consensus proposed in 2020. Predictors of clinical remission were analyzed using asthma control test (ACT) score, pulmonary function and blood tests, and fractional exhaled nitric oxide. RESULTS: At baseline, the median age was 44 years (interquartile range [IQR], 31.0-52.8), and pre-bronchodilator (pre-BD) percent predicted forced expiratory volume in one second (%FEV1) was 85.9% (IQR, 74.8-100.5). Six (30%) patients achieved clinical remission. Among the patients treated with biologics, 20% had clinical remission, and 20% discontinued biologic therapy. The pre-BT ACT score was significantly lower in the group with than without remission (11.0 [IQR, 8.0-14.5] vs. 15.0 [IQR, 11.0-17.3], p = .016). Adverse events did not significantly differ between the groups. CONCLUSIONS: To the best of our knowledge, this is the first study to use clinical remission as a criterion for evaluating BT efficacy. The pre-BT ACT score might a the predict response to BT in younger adult patients with severe asthma and pre-BD %FEV1 ≥ 70%.

Hemodialysis requirement after the first dose of durvalumab following chemoradiation therapy: a case report.

Durvalumab is the first immune check point inhibitor that was approved for use following concurrent platinum-based chemoradiation, in patients with unresectable stage III non-small cell lung cancer. The new treatment regimen of durvalumab administered after chemoradiation resulted in higher response rates and required careful immune-related adverse effects management. We experienced a rare case of severe acute kidney injury (AKI) requiring hemodialysis after only the first dose of durvalumab, in a patient who was diagnosed with immune-related AKI by renal biopsy. Although severe (Grade 3 or more) immune-related AKI occurred in 0.9% of patients treated with durvalumab, some drugs and radiation may increase immune-related AKI. Further research is needed to identify the clinical characteristics of patients who tend to develop severe AKI so as to prevent it, by reviewing such rare cases as ours.

Safety of Readministration of EGFR-TKI After Onset of Interstitial Lung Disease in Advanced EGFR-Mutated NSCLC: A Systematic Review and Meta-Analysis.

BACKGROUND: In patients with epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitor (TKI) interruption due to EGFR-TKI-induced interstitial lung disease (ILD) is a factor for shorter overall survival (OS). Several retrospective cohort studies have reported an OS-prolonging effect of the readministration of EGFR-TKIs. This study aimed to determine the safety of readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. METHODS: The PubMed, CINAHL, and Web of Science databases were systematically searched until May 30, 2023. The primary outcome was successful readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. RESULTS: A total of 690 patients were included in this meta-analysis. The initial EGFR-TKI-induced ILD rate was 13.6% (95% confidence interval [CI]:6.4-20.9). Readministration rate of EGFR-TKI after onset of EGFR-TKI-induced ILD was 40.2% (95% CI: 26.7-53.7). The successful readministration rate of EGFR-TKIs after onset of EGFR-TKI-induced ILD was 81.9% (95% CI: 73.8-90.0). Successful rate of EGFR-TKI readministration in patients with Grade 2 or higher adverse events post initial EGFR-TKI therapy was 76.1% (95% CI: 55.6-96.6). CONCLUSIONS: Although initial EGFR-TKI-induced ILD has a relatively high incidence, EGFR-TKI readministration after the onset of EGFR-TKI-induced ILD may be a viable treatment option.

Differentiating primary central nervous system lymphoma from glioblastoma by time-dependent diffusion using oscillating gradient.

BACKGROUND: This study aimed to elucidate the impact of effective diffusion time setting on apparent diffusion coefficient (ADC)-based differentiation between primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBMs) and to investigate the usage of time-dependent diffusion magnetic resonance imaging (MRI) parameters. METHODS: A retrospective study was conducted involving 21 patients with PCNSLs and 66 patients with GBMs using diffusion weighted imaging (DWI) sequences with oscillating gradient spin-echo (Δeff = 7.1 ms) and conventional pulsed gradient (Δeff = 44.5 ms). In addition to ADC maps at the two diffusion times (ADC7.1 ms and ADC44.5 ms), we generated maps of the ADC changes (cADC) and the relative ADC changes (rcADC) between the two diffusion times. Regions of interest were placed on enhancing regions and non-enhancing peritumoral regions. The mean and the fifth and 95th percentile values of each parameter were compared between PCNSLs and GBMs. The area under the receiver operating characteristic curve (AUC) values were used to compare the discriminating performances among the indices. RESULTS: In enhancing regions, the mean and fifth and 95th percentile values of ADC44.5 ms and ADC7.1 ms in PCNSLs were significantly lower than those in GBMs (p = 0.02 for 95th percentile of ADC44.5 ms, p = 0.04 for ADC7.1 ms, and p < 0.01 for others). Furthermore, the mean and fifth and 95th percentile values of cADC and rcADC were significantly higher in PCNSLs than in GBMs (each p < 0.01). The AUC of the best-performing index for ADC7.1 ms was significantly lower than that for ADC44.5 ms (p < 0.001). The mean rcADC showed the highest discriminating performance (AUC = 0.920) among all indices. In peritumoral regions, no significant difference in any of the three indices of ADC44.5 ms, ADC7.1 ms, cADC, and rcADC was observed between PCNSLs and GBMs. CONCLUSIONS: Effective diffusion time setting can have a crucial impact on the performance of ADC in differentiating between PCNSLs and GBMs. The time-dependent diffusion MRI parameters may be useful in the differentiation of these lesions.

Differentiating brain metastasis from glioblastoma by time-dependent diffusion MRI.

BACKGROUND: This study was designed to investigate the use of time-dependent diffusion magnetic resonance imaging (MRI) parameters in distinguishing between glioblastomas and brain metastases. METHODS: A retrospective study was conducted involving 65 patients with glioblastomas and 27 patients with metastases using a diffusion-weighted imaging sequence with oscillating gradient spin-echo (OGSE, 50 Hz) and a conventional pulsed gradient spin-echo (PGSE, 0 Hz) sequence. In addition to apparent diffusion coefficient (ADC) maps from two sequences (ADC50Hz and ADC0Hz), we generated maps of the ADC change (cADC): ADC50Hz - ADC0Hz and the relative ADC change (rcADC): (ADC50Hz - ADC0Hz)/ ADC0Hz × 100 (%). RESULTS: The mean and the fifth and 95th percentile values of each parameter in enhancing and peritumoral regions were compared between glioblastomas and metastases. The area under the receiver operating characteristic curve (AUC) values of the best discriminating indices were compared. In enhancing regions, none of the indices of ADC0Hz and ADC50Hz showed significant differences between metastases and glioblastomas. The mean cADC and rcADC values of metastases were significantly higher than those of glioblastomas (0.24 ± 0.12 × 10-3mm2/s vs. 0.14 ± 0.03 × 10-3mm2/s and 23.3 ± 9.4% vs. 14.0 ± 4.7%; all p < 0.01). In peritumoral regions, no significant difference in all ADC indices was observed between metastases and glioblastomas. The AUC values for the mean cADC (0.877) and rcADC (0.819) values in enhancing regions were significantly higher than those for ADC0Hz5th (0.595; all p < 0.001). CONCLUSIONS: The time-dependent diffusion MRI parameters may be useful for differentiating brain metastases from glioblastomas.

Development and validation of the Japanese version of EPDS-P for indirect screening of paternal perinatal depression based on maternal reporting: Protocol for a prospective longitudinal observational study.

AIMS: The main purpose of this study is to develop an indirect screening system for paternal perinatal depression based on the female partner's assessment in the Japanese population. The Japanese version of the Edinburgh Postnatal Depression Scale-Partner (EPDS-P) will be used as the indirect screening tool, and its accuracy will be studied in this longitudinal prospective observational study. METHODS: Public health nurses and midwives at the participating community health center are currently inviting couples to participate, and are distributing self-rating scales to the participants. The primary evaluation scales being used in this study are the Japanese versions of the Center for Epidemiologic Studies Depression Scale (CES-D) and the Japanese version of the EPDS-P which evaluates paternal perinatal depression by women. We will evaluate EPDS-P performance against CES-D, including accuracy, sensitivity, specificity, and correlations. RESULTS AND CONCLUSIONS: Perinatal depression is a mental illness that occurs between pregnancy and postpartum within the 12 months, and it is known to increase the risk of adversely impacting on child development. Men may also experience a psychosocial crisis during their partners' perinatal period. Although it was recently reported that the EPDS-P can indirectly detect paternal perinatal depression, there is, as yet, insufficient evidence of this because the previous studies had relatively small sample sizes and were limited to cross-sectional studies in the postpartum period. The development of a screening system for paternal perinatal depression using the EPDS-P will lead to increased awareness of the disease and provide an opportunity to establish a family-based support system in Japan.

Integrated analysis of effect of daisaikoto, a traditional Japanese medicine, on the metabolome and gut microbiome in a mouse model of nonalcoholic fatty liver disease.

Dysregulation of lipid metabolism and diabetes are risk factors for nonalcoholic fatty liver disease (NAFLD), and the gut-liver axis and intestinal microbiome are known to be highly associated with the pathogenesis of this disease. In Japan, the traditional medicine daisaikoto (DST) is prescribed for individuals affected by hepatic dysfunction. Herein, we evaluated the therapeutic potential of DST for treating NAFLD through modification of the liver and stool metabolome and microbiome by using STAM mice as a model of NAFLD. STAM mice were fed a high-fat diet with or without 3 % DST for 3 weeks. Plasma and liver of STAM, STAM with DST, and C57BL/6J ("Normal") mice were collected at 9 weeks, and stools at 4, 6, and 9 weeks of age. The liver pathology, metabolome and stool microbiome were analyzed. DST ameliorated the NAFLD activity score of STAM mice and decreased the levels of several liver lipid mediators such as arachidonic acid and its derivatives. In normal mice, nine kinds of family accounted for 94.1 % of microbiome composition; the total percentage of these family was significantly decreased in STAM mice (45.6 %), and DST administration improved this imbalance in microbiome composition (65.2 %). In stool samples, DST increased ursodeoxycholic acid content and altered several amino acids, which were correlated with changes in the gut microbiome and liver metabolites. In summary, DST ameliorates NAFLD by decreasing arachidonic acid metabolism in the liver; this amelioration seems to be associated with crosstalk among components of the liver, intestinal environment, and microbiome.

Dietary Supplementation with Sodium Butyrate Reduces High-sucrose Diet-induced Hepatic Accumulation of Triacylglycerols and Expression of Fatty Acid Synthesis Enzymes in Rats.

We investigated the effects of dietary supplementation with sodium butyrate (NaB) on the lipid levels, gene expression, and proteins related to lipid metabolism in nonalcoholic fatty liver disease (NAFLD) rat models fed a high-sucrose diet for 3 weeks. Supplementation with 1% and 3% NaB reduced high-sucrose-induced hepatic triacylglycerol levels and expression of genes and proteins related to fatty acid synthesis, such as fatty acid synthase and malic enzyme, in a dose-dependent manner. NaB supplementation did not affect hepatic cholesterol levels or expression of genes related to ß-oxidation. NaB may prevent high-sucrose-induced NAFLD by repressing the fatty acid synthesis pathway.

Characteristics of risk factors for acute kidney injury among inpatients administered sulfamethoxazole/trimethoprim: a retrospective observational study.

BACKGROUND: Sulfamethoxazole/trimethoprim (SMX/TMP) potentially increases the serum creatinine levels, resulting in acute kidney injury (AKI). However, the clinical characteristics of the AKI associated with SMX/TMP and the risk factors for its development have not been fully characterized. METHODS: A retrospective cohort observational analysis was conducted on adult inpatients who started SMX/TMP treatment at the Tokyo Women's Medical University, Yachiyo Medical Center, from April 2018 to March 2020. The primary outcome was AKI, defined as an increase in serum creatinine level of ≥ 50% from baseline. Multivariate logistic regression analysis was used to determine the risk factors for the AKI associated with SMX/TMP. RESULTS: Of the 281 patients, 32 (11.4%) developed AKI. The multivariate logistic regression analysis identified that body mass index (BMI) (odds ratio [OR] = 0.86, 95% confidence interval [95% CI] 0.76-0.97, p < 0.01), presence of hypertension (OR = 2.69, 95% CI 1.11-6.49, p = 0.02), SMX/TMP daily dose (OR = 1.16, 95% CI 1.03-1.30, p = 0.02), and concomitant loop diuretic use (OR = 2.91, 95% CI 1.08-7.78, p = 0.04) were the associated risk factors for AKI in patients who were administered SMX/TMP. CONCLUSIONS: This study showed that low BMI, hypertension, high-dose SMX/TMP, and concomitant loop diuretic use increased the risk of AKI in patients administered SMX/TMP. Clinicians should consider monitoring the renal function in patients at a high risk of AKI.

MTCL2 promotes asymmetric microtubule organization by crosslinking microtubules on the Golgi membrane.

The Golgi complex plays an active role in organizing asymmetric microtubule arrays, which are essential for polarized vesicle transport. The coiled-coil protein MTCL1 stabilizes microtubules nucleated from the Golgi membrane. Here, we report an MTCL1 paralog, MTCL2, which preferentially acts on the perinuclear microtubules accumulated around the Golgi. MTCL2 associates with the Golgi membrane through the N-terminal coiled-coil region and directly binds microtubules through the conserved C-terminal domain without promoting microtubule stabilization. Knockdown of MTCL2 significantly impaired microtubule accumulation around the Golgi, as well as the compactness of the Golgi ribbon assembly structure. Given that MTCL2 forms parallel oligomers through homo-interaction of the central coiled-coil motifs, our results indicate that MTCL2 promotes asymmetric microtubule organization by crosslinking microtubules on the Golgi membrane. Results of in vitro wound healing assays further suggest that this function of MTCL2 enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration. Additionally, the results demonstrated the involvement of CLASPs and giantin in mediating the Golgi association of MTCL2.

TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells.

Unsatisfied kinetochore-microtubule attachment activates the spindle assembly checkpoint to inhibit the metaphase-anaphase transition. However, some cells eventually override mitotic arrest by mitotic slippage. Here, we show that inactivation of TORC1 kinase elicits mitotic slippage in budding yeast and human cells. Yeast mitotic slippage was accompanied with aberrant aspects, such as degradation of the nucleolar protein Net1, release of phosphatase Cdc14, and anaphase-promoting complex/cyclosome (APC/C)-Cdh1-dependent degradation of securin and cyclin B in metaphase. This mitotic slippage caused chromosome instability. In human cells, mammalian TORC1 (mTORC1) inactivation also invoked mitotic slippage, indicating that TORC1 inactivation-induced mitotic slippage is conserved from yeast to mammalian cells. However, the invoked mitotic slippage in human cells was not dependent on APC/C-Cdh1. This study revealed an unexpected involvement of TORC1 in mitosis and provides information on undesirable side effects of the use of TORC1 inhibitors as immunosuppressants and anti-tumor drugs.

Ghrelin Enhancer, the Latest Evidence of Rikkunshito.

Rikkunshito is a Japanese herbal medicine (Kampo) that has been attracting attention and researched by many researchers not only in Japan but also worldwide. There are 214 rikkunshito articles that can be searched on PubMed by August 2021. The reason why rikkunshito has attracted so much attention is due to an epoch-making report (Gastroenterology, 2008) discovered that rikkunshito promotes the secretion of the orexigenic peptide ghrelin. Since then, many researchers have discovered that rikkunshito has a direct effect on the ghrelin receptor, GHS-R1a, and an effect of enhancing the ghrelin signal to the brain. Additionally, a lot of evidence that rikkunshito is expected to be effective for various gastrointestinal diseases have also been demonstrated. Numerous basic and clinical studies have suggested that rikkunshito affects (i) various discomforts caused by anticancer drugs, gastroesophageal reflux disease, functional dyspepsia, (ii) various stress-induced anorexia, (iii) hypophagia in the elderly, and (iv) healthy lifespan. In this review, as one who discovered the ghrelin enhancer effect of rikkunshito, we will review the research of rikkunshito so far and report on the latest research results.

Evaluation of the efficacy of LAMP-based SARS-CoV-2 detection with simple RNA extraction from nasopharyngeal swabs: A prospective observational study.

The Loopamp SARS-CoV-2 Detection Kit is used for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Loop-mediated isothermal amplification (LAMP) is based on a measurement principle that can be used with a relatively simple device. Detection using this kit requires viral RNA extraction from samples with the QIAGEN QIAamp Viral Mini Kit (QIAGEN extraction) or the Loopamp Viral RNA Extraction Kit (Eiken extraction), which are recommended by the manufacturer. However, the efficacy of LAMP-based SARS-CoV-2 detection using these extraction methods has not been compared. In this study, we aimed to compare the results of genome extraction and detection from nasopharyngeal swab samples using the QIAGEN and Eiken extraction kits. The present study involved patients who presented to the Rinku General Medical Center with suspected COVID-19 (25 positive and 26 negative cases). A comparison of the results obtained using each extraction method with those obtained via PCR showed that the positive, negative, and overall concordance rates between QIAGEN extraction and PCR were 96.0% (24/25 samples), 100% (26/26), and 98.0% (50/51; κ = 0.96, 95% CI = 0.69-1.00), respectively. Results with Eiken extraction were also favorable, with positive, negative, and overall concordance rates of 88.0% (22/25), 100% (26/26), and 94.1% (48/51; κ = 0.88, 95% CI = 0.61-1.00), respectively. Favorable results were obtained using both QIAGEN and Eiken extraction kits. Since Eiken extraction can be completed in a few minutes, it enables prompt and reliable testing for SARS-CoV-2 detection.

Involvement of Ghrelin Dynamics in Stress-Induced Eating Disorder: Effects of Sex and Aging.

Stress, a factor that affects appetite in our daily lives, enhances or suppresses appetite and changes palatability. However, so far, the mechanisms underlying the link between stress and eating have not been fully elucidated. Among the peripherally produced appetite-related peptides, ghrelin is the only orexigenic peptide, and abnormalities in the dynamics and reactivity of this peptide are involved in appetite abnormalities in various diseases and psychological states. This review presents an overview of the research results of studies evaluating the effects of various stresses on appetite. The first half of this review describes the relationship between appetite and stress, and the second half describes the relationship between the appetite-promoting peptide ghrelin and stress. The effects of sex differences and aging under stress on appetite are also described.

Dark Rearing Promotes the Recovery of Visual Cortical Responses but Not the Morphology of Geniculocortical Axons in Amblyopic Cat.

Monocular deprivation (MD) of vision during early postnatal life induces amblyopia, and most neurons in the primary visual cortex lose their responses to the closed eye. Anatomically, the somata of neurons in the closed-eye recipient layer of the lateral geniculate nucleus (LGN) shrink and their axons projecting to the visual cortex retract. Although it has been difficult to restore visual acuity after maturation, recent studies in rodents and cats showed that a period of exposure to complete darkness could promote recovery from amblyopia induced by prior MD. However, in cats, which have an organization of central visual pathways similar to humans, the effect of dark rearing only improves monocular vision and does not restore binocular depth perception. To determine whether dark rearing can completely restore the visual pathway, we examined its effect on the three major concomitants of MD in individual visual neurons, eye preference of visual cortical neurons and soma size and axon morphology of LGN neurons. Dark rearing improved the recovery of visual cortical responses to the closed eye compared with the recovery under binocular conditions. However, geniculocortical axons serving the closed eye remained retracted after dark rearing, whereas reopening the closed eye restored the soma size of LGN neurons. These results indicate that dark rearing incompletely restores the visual pathway, and thus exerts a limited restorative effect on visual function.

Relationship between Orexigenic Peptide Ghrelin Signal, Gender Difference and Disease.

Growth hormone secretagogue receptor 1a (GHS-R1a), which is one of the G protein-coupled receptors (GPCRs), is involved in various physiological actions such as energy consumption, growth hormone secretion promoting action, and cardiovascular protective action. The ligand was searched for as an orphan receptor for a while, but the ligand was found to be acylated ghrelin (ghrelin) discovered by Kangawa and Kojima et al. in 1999. Recently, it has also been reported that dysregulation of GHS-R1a mediates reduced feeding in various diseases. On the other hand, since the physiological effects of ghrelin have been studied exclusively in male mice, few studies have been conducted on gender differences in ghrelin reactivity. In this review, we describe (1) the characteristics of GHS-R1a, (2) the role of ghrelin in hypophagia due to stress or anticancer drugs, and (3) the gender differences in the physiological effects of GHS-R1a and the influence of stress on it.

Vulnerability to psychological stress-induced anorexia in female mice depends on blockade of ghrelin signal in nucleus tractus solitarius.

BACKGROUND AND PURPOSE: Women have a higher incidence of eating disorders than men. We investigated whether the effects of ghrelin on feeding are affected by sex and stress, and to elucidate the mechanisms that may cause sex differences in stress-mediated anorexia, focusing on ghrelin. EXPERIMENTAL APPROACH: Acylated ghrelin was administered to naïve and psychologically stressed male and female C57BL/6J mice, followed by measurements of food intake and plasma hormone levels. Ovariectomy was performed to determine the effects of ovary-derived oestrogen on stress-induced eating disorders in female mice. The numbers of Agrp or c-Fos mRNA-positive cells and estrogen receptor α/c-Fos protein-double-positive cells were assessed. KEY RESULTS: Ghrelin administration to naïve female mice caused a higher increase in food intake, growth hormone secretion, Agrp mRNA expression in the arcuate nucleus and c-Fos expression in the nucleus tractus solitarius (NTS) than in male mice. In contrast, psychological stress caused a more sustained reduction in food intake in females than males. The high sensitivity of naïve females to exogenous ghrelin was attenuated by stress exposure. The stress-induced decline in food intake was not abolished by ovariectomy. Estrogen receptor-α but not -ß antagonism prevented the decrease in food intake under stress. Estrogen receptor-α/c-Fos-double-positive cells in the NTS were significantly increased by stress only in females. CONCLUSION AND IMPLICATIONS: Stress-mediated eating disorders in females may be due to blockade of ghrelin signalling via estrogen receptor-α activation in the NTS. Targeting the ghrelin signal in the brain could be a new treatment strategy to prevent these disorders.