Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy.

IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.

Prevention of recurrent benign paroxysmal positional vertigo with vitamin D supplementation: a meta-analysis.

RESEARCH BACKGROUND: Vitamin D insufficiency/deficiency is known to be related to occurrences and recurrences of benign paroxysmal positional vertigo (BPPV). However, the efficacy of vitamin D supplementation in reducing recurrences of BPPV remains to be established. We performed a meta-analysis to determine the therapeutic effects of vitamin D supplementation, with or without calcium, for preventing recurrences of BPPV. METHODS: We searched the PubMed, the Embase, the Web of Science and the reference lists of the articles. We included randomized or non-randomized trials that determined the efficacy of supplementing vitamin D or related compounds, alone or with calcium, in comparison to placebo or no intervention in preventing recurrences of BPPV. The primary outcome was the number of patients with BPPV recurrences. Data were collected and pooled using a weighted relative risk (RR) with corresponding 95% CIs, where possible, by adopting the fixed-effect or random-effect model according to the heterogeneity among the studies. The between-study heterogeneity was tested using the χ2 test and the I2 statistic, and funnel plots were used to evaluate any publication bias. RESULTS: We included five trials (four non-randomized trials and one randomized controlled trial) with a total of 1250 participants. The analyses showed a significant preventive effect on the recurrences of BPPV (RR = 0.37; 95% CI = 0.18-0.76; p = 0.007 with the random-effects model) with supplementation of vitamin D. Although a considerable heterogeneity was detected among the studies, the sensitivity analyses showed the reliability and stability of our results. CONCLUSIONS: Vitamin D supplementation provides a benefit for secondary prevention of BPPV. Supplementation of vitamin D should be considered in patients with frequent attacks of BPPV, especially when serum vitamin D is subnormal.

Lactobacillus paracasei HY7015 Promotes Hair Growth in a Telogenic Mouse Model.

In this study, we describe the effects of Lactobacillus paracasei HY7015 (HY7015) on promoting mouse hair growth. Since our purpose was to increase hair growth through oral administration, medicinal yeast, at a suitable concentration for application in mice, was used as a positive control. First, experiments were conducted to determine the effect of HY7015 on proliferation of hair follicle dermal papilla cells (HFDPC), which are important contributors to hair growth. HY7015 stimulated HFDPC proliferation in vitro and increased their secretion of vascular endothelial growth factor and insulin-like growth factor-1. In mouse experiments, oral administration of HY7015 promoted hair growth and hair follicle maturation in the dorsal skin, as well as increasing growth factor levels in mouse serum. In summary, we demonstrate that L. paracasei HY7015 consumption can promote hair growth by stimulating HFDPC proliferation and growth factor secretion. Follow-up studies are warranted to determine the underlying mechanism, using various approaches, including investigation of changes in intestinal microbiota and alteration of gene and protein expression.

Fermented Red Ginseng Alleviates Ovalbumin-Induced Inflammation in Mice by Suppressing Interleukin-4 and Immunoglobulin E Expression.

Ginseng (the root of Panax ginseng Meyer) has been reported to have many biologic therapeutic effects, including anti-inflammatory properties, and ginsenosides are considered as one of the factors responsible for these therapeutic effects. To improve their therapeutic action, probiotic bacteria are used to ferment and chemically transform ginsenosides in red ginseng (RG). In this study, we aimed to investigate the beneficial effects of RG fermented by probiotic bacteria (FRG) against ovalbumin (OVA)-induced allergic rhinitis in a mouse model. We induced the mouse model via OVA inhalation; experimental results revealed increased immunoglobulin E (IgE) and interleukin (IL)-4 levels, leading to Th2-type cytokine response. The mice with induced allergy were then orally administered RG and FRG over 2 weeks, as a result of which, IL-4 and IgE levels in bronchoalveolar lavage fluid, nasal fluid, and serum were found to be ameliorated more effectively by FRG than by RG, suggesting that FRG has better immune regulatory effects than RG. FRG also downregulated immune cell levels, such as those of eosinophils and basophils, and significantly decreased the thickness of OVA-induced respiratory epithelium compared to RG. Collectively, the results showed that FRG treatment alleviates inflammation, thereby extending a protective effect to mice with OVA-induced inflammatory allergic rhinitis.

Lactic Acid Bacteria and Natural Product Complex Ameliorates Ovalbumin-Induced Airway Hyperresponsiveness in Mice.

The incidence of respiratory diseases, such as asthma, has substantially increased in recent times owing to environmental changes, such as air pollution. Induction of a chronic inflammatory response begins with production of biologically active mediators from the airway epithelium, which attracts and recruits inflammatory cells into the lung airway. In our previous study, we confirmed that Lactobacillus casei HY2782 and Bifidobacterium animalis spp. lactis HY8002 could improve lung inflammation in the COPD animal model. In this study, we investigated the effect of the HY2782 complex against airway hyperresponsiveness by using an ovalbumin (OVA)-induced animal model. An orally administered HY2782 complex on OVA-induced allergic asthma in a BALB/c mouse model was used. The present results showed that the HY2782 complex suppressed total immunoglobulin E in serum and bronchoalveolar lavage fluid (BALF). The cytokine production profile in BALF and serum revealed that the HY2782 complex showed reduced levels of Th2 cytokines among immune factors released due to the elevated allergic response. Levels of inflammatory mediators in BALF, MCP-1, MIP-2, and CXCL-9 were decreased by oral administration of the HY2782 complex. Lower numbers of eosinophils and neutrophils in BALF suggested that inflammation was ameliorated by the HY2782 complex. Histological observation of lung sections also showed infiltration of fewer cells. From results, we suggested that the HY2782 complex effectively responds to improvement of the immune response and airway hypersensitivity reaction because of the anti-inflammatory effect of the Pueraria lobata root extract and antioxidant effect of HY2782.

Omega-7 oil increases telomerase activity and accelerates healing of grafted burn and donor site wounds.

This study investigated the efficacy of Omega-7 isolated from the sea buckthorn oil (Polyvit Co., Ltd, Gangar Holding, Ulaanbaatar, Mongolia) in ovine burn wound healing models. In vitro, proliferation (colony-forming rate) and migration (scratch) assays using cultured primary ovine keratinocytes were performed with or without 0.025% and 0.08% Omega-7, respectively. The colony-forming rate of keratinocytes in the Omega-7 group at 72 and 96 h were significantly higher than in the control (P < 0.05). The percentage of closure in scratch assay in the Omega-7 group was significantly higher than in the control at 17 h (P < 0.05). In vivo, efficacy of 4% Omega-7 isolated from buckthorn oil was assessed at 7 and 14 days in grafted ovine burn and donor site wounds. Telomerase activity, keratinocyte growth factor, and wound nitrotyrosine levels were measured at day 14. Grafted sites: Un-epithelialized raw surface area was significantly lower and blood flow was significantly higher in the Omega-7-treated sites than in control sites at 7 and 14 days (P < 0.05). Telomerase activity and levels of keratinocyte growth factors were significantly higher in the Omega-7-treated sites after 14 days compared to those of control (P < 0.05). The wound 3-nitrotyrosine levels were significantly reduced by Omega-7. Donor sites: the complete epithelialization time was significantly shorter and blood flow at day 7 was significantly higher in the Omega-7-treated sites compared to control sites (P < 0.05). In summary, topical application of Omega-7 accelerates healing of both grafted burn and donor site wounds. Omega-7 should be considered as a cost-efficient and effective supplement therapy for burn wound healing.

Update on benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo worldwide. This review considers recent advances in the diagnosis and management of BPPV including the use of web-based technology and artificial intelligence as well as the evidence supporting the use of vitamin D supplements for patients with BPPV and subnormal serum vitamin D.

Prevention of benign paroxysmal positional vertigo with vitamin D supplementation: A randomized trial.

OBJECTIVE: To assess the effect of vitamin D and calcium supplementation in preventing recurrences of benign paroxysmal positional vertigo (BPPV). METHODS: We performed an investigator-initiated, blinded-outcome assessor, parallel, multicenter, randomized controlled trial in 8 hospitals between December 2013 and May 2017. Patients with confirmed BPPV were randomly assigned to the intervention (n = 518) or the observation (n = 532) group after successful treatment with canalith repositioning maneuvers. The primary outcome was the annual recurrence rate (ARR). Patients in the intervention group had taken vitamin D 400 IU and 500 mg of calcium carbonate twice a day for 1 year when serum vitamin D level was lower than 20 ng/mL. Patients in the observation group were assigned to follow-ups without further vitamin D evaluation or supplementation. RESULTS: The intervention group showed a reduction in the ARR (0.83 [95% confidence interval (CI), 0.74-0.92] vs 1.10 [95% CI, 1.00-1.19] recurrences per 1 person-year) with an incidence rate ratio of 0.76 (95% CI, 0.66-0.87, p < 0.001) and an absolute rate ratio of -0.27 (-0.40 to -0.14) from intention-to-treat analysis. The number needed to treat was 3.70 (95% CI, 2.50-7.14). The proportion of patients with recurrence was also lower in the intervention than in the observation group (37.8 vs 46.7%, p = 0.005). CONCLUSIONS: Supplementation of vitamin D and calcium may be considered in patients with frequent attacks of BPPV, especially when serum vitamin D is subnormal. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with BPPV, vitamin D and calcium supplementation reduces recurrences of BPPV.

Gastroprotective Effects of Cudrania tricuspidata Leaf Extracts by Suppressing Gastric cAMP and Increasing Gastric Mucins.

Cudrania tricuspidata has been used as an East Asian folk remedy to treat various symptoms. Recently, scientific evidence of the efficacy of C. tricuspidata has emerged. The objective of this study was to elucidate protective role of C. tricuspidata in the gastric mucosa using pylorus-ligated Sprague-Dawley rats and primary parietal cells. C. tricuspidata ethanol extracts attenuated gastric mucosal damage, secretion, and juice acidity in pylorus-ligated rats; however, it did not affect expression of gastric acid-related genes [muscarinic acetylcholine receptor M3 receptor (M3R), histamine H2-receptors (H2R), and cholecystokinin-2/gastrin receptors (CCK2R)] or serum gastrin concentrations. Furthermore, extracts greatly reduced levels of gastric cyclic adenosine monophosphate (cAMP) and significantly increased mRNA levels of gastric-type mucins (MUC5AC and MUC6). To identify the mode of action of C. tricuspidata extract in regulating gastric acid secretion, intracellular cAMP and mRNA for H2R, M3R, and CCK2R were measured in primary parietal cells. mRNA levels of H2R, M3R, and CCK2R did not significantly differ following treatment with C. tricuspidata extract, whereas cAMP induced by the H2R-specific agonist was significantly decreased. C. tricuspidata may therefore reduce gastric acid secretion by inhibiting H2R activity rather than regulating mRNA expression. These finding suggest that ethanol extracts of C. tricuspidata inhibit H2R-related gastric acid secretion and increase gastric mucus to help prevent gastric mucosal damage. Therefore, C. tricuspidata extract has potential to be used in foods and medicines to prevent diseases related to gastric mucosal damage, such as gastritis and functional dyspepsia.

Lactobacillus HY2782 and Bifidobacterium HY8002 Decrease Airway Hyperresponsiveness Induced by Chronic PM2.5 Inhalation in Mice.

Epidemiological studies have shown that exposure to particulate matter (PM) is associated with adverse health effects. Inhalation of fine particulate matter (PM2.5) is associated with elevated pulmonary diseases. However, the molecular mechanism underlying the initiation of lung inflammation following inhalation is unclear. In this study, we investigated the beneficial effects of two probiotics, Lactobacillus casei HY2782 and Bifidobacterium lactis HY8002, against PM-induced pulmonary inflammation. Model mice were subjected to chronic exposure of PM2.5. The results showed that PM2.5 enhanced oxidative stress and led to Th2 cytokine responses in the mice. PM2.5-exposed mice were orally administered with HY2782 and HY8002 from the day of first exposure to the end point of the study. The results showed that HY2782 ameliorated PM 2.5 exposure-enhanced leukocyte migration and activation of proinflammatory cytokines. HY2782 and HY8002 also prevented exacerbation of eosinophil and neutrophil infiltration in the bronchoalveolar lavage fluid. HY2782 and HY8002 significantly increased scavenging of PM2.5-induced reactive oxygen species and activated superoxide dismutase and catalase activity in the blood. These results indicate that the probiotics HY2782 and HY8002 protect against PM-induced pulmonary inflammation.

Impaired Calcium Metabolism in Benign Paroxysmal Positional Vertigo: A Topical Review.

BACKGROUND AND PURPOSE: Although acute attacks of benign paroxysmal positional vertigo (BPPV) may be treated with canalith repositioning maneuvers, there have been no well-designed prospective trials to prevent this highly prevalent and recurrent disorder. This topical review explores the evidence related to the association between deficient calcium metabolism and BPPV. We also describe the development of therapeutic options to prevent recurrences of BPPV and introduce results from a recent randomized controlled trial on the effect of vitamin D and calcium supplementation in preventing BPPV recurrences. SUMMARY OF KEY POINTS: The literature describes 3 lines of evidence on association of impaired calcium metabolism and development of BPPV: (1) decreased bone mineral density was more frequently observed in persons with BPPV than in healthy controls; (2) estrogen plays a vital role in maintenance of otoconia, and estrogen deficiency appears to precipitate degeneration of otoconia and development of BPPV; and (3) lower serum vitamin D level is associated with development of BPPV, and supplementation of vitamin D and calcium carbonate may reduce further attacks of BPPV in persons with BPPV and subnormal serum vitamin D level. RECOMMENDATIONS FOR CLINICAL PRACTICE: Restoration of impaired calcium metabolism with supplementation of vitamin D or estrogen should be considered in the treatment of individuals with frequent recurrences of BPPV. Future randomized controlled trials are mandatory to validate these supplementation therapies in individuals with recurrent BPPV.

Factors Associated with Vitamin D Status Among Korean Female Adolescents.

PURPOSE: The prevalence of vitamin D deficiency among female adolescents in South Korea is the highest in East Asia. Therefore, this study aims to identify factors associated with vitamin D status among female adolescents in South Korea. DESIGN AND METHODS: This cross-sectional descriptive study was conducted using a data set from the fifth Korean National Health and Nutrition Examination Survey (2010-2012). Participants comprised 734 female adolescents aged 12-18 years. A general linear model using a complex samples design was employed. RESULTS: The mean vitamin D level of the participants was 14.90 ng/mL. Among these participants, 87.6% had a vitamin D deficiency. As their age increased by one year, their vitamin D level decreased by 0.47 ng/mL. Female adolescents with a low household income had vitamin D levels lower by 1.88 ng/mL than those with a high household income. Vitamin D levels in female adolescents who skipped lunch was lower by 3.41 ng/mL than those who had lunch. CONCLUSION: The prevalence of vitamin D deficiency among female adolescents in South Korea is considerable. The findings suggest that age, socioeconomic status, and skipping a meal were associated with vitamin D status in female adolescents, but physical activity was not. PRACTICE IMPLICATIONS: As the findings of this study indicate, older female adolescents and those from lower household incomes may be at higher risk for lower levels of Vitamin D. Counseling female adolescents as to dietary measures to avoid vitamin D deficiency is advised. Preventive health for at risk female adolescents includes provision of health education and counseling.

Simultaneous recording of cervical and ocular vestibular-evoked myogenic potentials.

OBJECTIVE: To increase clinical application of vestibular-evoked myogenic potentials (VEMPs) by reducing the testing time by evaluating whether a simultaneous recording of ocular and cervical VEMPs can be achieved without a loss in diagnostic sensitivity and specificity. METHODS: Simultaneous recording of ocular and cervical VEMPs on each side during monaural stimulation, bilateral simultaneous recording of ocular VEMPs and cervical VEMPs during binaural stimulation, and conventional sequential recording of ocular and cervical VEMPs on each side using air-conducted sound (500 Hz, 5-millisecond tone burst) were compared in 40 healthy participants (HPs) and 20 patients with acute vestibular neuritis. RESULTS: Either simultaneous recording during monaural and binaural stimulation effectively reduced the recording time by ≈55% of that for conventional sequential recordings in both the HP and patient groups. The simultaneous recording with monaural stimulation resulted in latencies and thresholds of both VEMPs and the amplitude of cervical VEMPs similar to those found during the conventional recordings but larger ocular VEMP amplitudes (156%) in both groups. In contrast, compared to the conventional recording, simultaneous recording of each VEMP during binaural stimulation showed reduced amplitudes (31%) and increased thresholds for cervical VEMPs in both groups. CONCLUSIONS: The results of simultaneous recording of cervical and ocular VEMPs during monaural stimulation were comparable to those obtained from the conventional recording while reducing the time to record both VEMPs on each side. CLINICALTRIALSGOV IDENTIFIER: NCT03049683.

Altered processing of otolithic information in isolated lateral medullary infarction.

Ocular and cervical vestibular-evoked myogenic potentials (VEMPs) evaluate the function of otolithic pathways in central as well as peripheral vestibular disorders. This study aimed to determine the associations and dissociations of otolithic dysfunction in lateral medullary infarction (LMI), the most well-known disorder of central vestibulopathy. At the Dizziness Clinic of a referral-based University Hospital, 45 patients with isolated LMI (28 men, mean age = 55.6 ± 12.5) had evaluation of the ocular tilt reaction (OTR), tilt of the subjective visual vertical (SVV), and ocular and cervical VEMPs from Janurary 2011 to August 2015 during the acute phase, 1-11 days from the symptom onset (median = 2 days). Almost all (42/45, 93 %) patients showed at least one component of the OTR or SVV tilt that was invariably ipsiversive. In contrast, oVEMPs were abnormal only in 12 (27 %) and cVEMPs in 13 (29 %) patients. Only three patients showed abnormal results in all the tests of the OTR, SVV tilt, and ocular and cervical VEMPs. Abnormal oVEMPs were more common in patients with the OTR than those without (38 vs 6 %, Pearson X 2 test, p = 0.021). In contrast, abnormality of cVEMPs showed no correlation with the presence of OTR (28 vs 31 %, Pearson X 2 test, p = 0.795). In patients with LMI, ipsiversive OTR is invariable, but abnormalities of oVEMPs and cVEMPs were much less common and mostly dissociated even in the patients with abnormal results. This discrepancy in otolithic dysfunction suggests different anatomical substrates and/or dissimilar reciprocal modulation for processing of each otolithic signal in central vestibular structures located in the dorsolateral medulla.

Cervical and ocular vestibular-evoked myogenic potentials in vestibular neuritis: comparison between air- and bone-conducted stimulation.

To clarify the changes of cervical (cVEMP) and ocular (oVEMP) vestibular evoked myogenic potentials induced by air-conducted sound (ACS) and bone-conducted vibration (BCV) in patients with vestibular neuritis (VN), patients with VN (n = 30) and normal controls (n = 45) underwent recording of cVEMP and oVEMP in response to ACS (1,000 Hz, 5 ms, tone bursts) and BCV (500 Hz, short tone burst). Patients with VN showed a high proportion of oVEMP abnormalities in response to both ACS (80.0 %) and BCV at the forehead (Fz, 73.3 %) or the mastoid (76.7 %). In contrast, cVEMPs were mostly normal with both ACS and BCV in the patients. The dissociations in the abnormalities of cVEMP and oVEMP induced by ACS and BCV at the mastoids and at the forehead in patients with VN suggest that oVEMP reflects functions of the superior vestibular nerve and most likely the utricular function. The results of our study suggest that oVEMP induced by either ACS or BCV appears to depend on integrity of the superior vestibular nerve, possibly due to the utricular afferents travelling in it. In contrast, cVEMP elicited by either ACS or BCV may reflect function of the saccular afferents running in the inferior vestibular nerve.

Evolution of abnormal eye movements in Wernicke's encephalopathy: correlation with serial MRI findings.

A 33-year-old woman with Wernicke's encephalopathy (WE) due to poor oral intake after allogeneic stem cell transplantation for acute myeloid leukemia showed a sequential development of bilateral gaze-evoked nystagmus (GEN), rightward gaze palsy, and upbeat nystagmus. Initial MRIs obtained when she had GEN only showed a lesion involving the medullary tegmentum, and follow-up MRIs revealed additional lesions in the pontine and midbrain tegmentum along with development of rightward gaze palsy, and finally bilateral medial thalamus lesions in association with upbeat nystagmus. The evolution of abnormal ocular motor findings and serial MRI changes in our patient with WE provide imaging evidence on relative vulnerability of the neural structures, and on the progression of lesions and ocular motor findings in thiamine deficiency.