Efficacy of Oral Administration of a Heat-Killed Lactobacillus gasseri OLL2809 on Patients of Japanese Cedar Pollinosis with High Japanese-Cedar Pollen-Specific IgE

A randomized, double-blind, placebo-controlled clinical trial was conducted to determine whether oral administration of heat-killed Lactobacillus gasseri OLL2809 would affect the immune response and reduce the symptoms of Japanese cedar pollinosis (JCP) in subjects with JCP. Following a 1-week pre-observation period, the subjects were randomly divided into two groups and were orally administered a placebo or tablets containing 100 mg of L. gasseri OLL2809 per d for 8 weeks during the pollen season in 2007. The results showed no obvious differences between the groups. Supplementary subgroup analysis revealed that the OLL2809 subgroups with CAP-RAST scores of 4 or 5 exhibited improvement in nasal symptoms scores and serum allergy-related items, including Japanese cedar pollen-specific IgE levels. L. gasseri OLL2809 was found to be effective in reducing symptoms in subjects with a high predisposition to allergies by modulating systemic immune systems.     

Monomolar Etherification of Methyl 4, 6-O-Benzylidene-α- and β-d-Glucopyranosides

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.     

Valsartan Orodispersible Tablets: Formulation, <Emphasis Type="Italic">In vitro</Emphasis>/<Emphasis Type="Italic">In vivo</Emphasis> Characterization

Valsartan orodispersible tablets have been developed at 40-mg dose, with the intention of facilitating administration to patients experiencing problems with swallowing and hopefully, improving its poor oral bioavailability. Work started with selecting drug compatible excipients depending on differential scanning calorimetric analysis. A 3³ full factorial design was adopted for the optimization of the tablets prepared by freeze-drying technique. The effects of the filler type, the binder type, and the binder concentration were studied. The different tablet formulas were characterized for their physical properties, weight variation, disintegration time, surface properties, wetting properties, and in vitro dissolution. Amongst the prepared 27 tablet formulas, formula number 6 (consisting of 4:6 valsartan:mannitol and 2% pectin) was selected to be tested in vivo. Oral bioavailability of two 40 mg valsartan orodispersible tablets was compared to the conventional commercial tablets after administration of a single dose to four healthy volunteers. Valsartan was monitored in plasma by high-performance liquid chromatography. The apparent rate of absorption of valsartan from the prepared tablets (C _max = 2.879 μg/ml, t _max = 1.08 h) was significantly higher than that of the conventional tablets (C _max = 1.471 μg/ml, t _max = 2.17 h), P ≤ 0.05. The relative bioavailability calculated as the ratio of mean total area under the plasma concentration–time curve for the orodispersible tablets relative to the conventional ones was 135%. The results of the in vivo study revealed that valsartan orodispersible tablets would be advantageous with regards to improved patient compliance, rapid onset of action, and increase in bioavailability.     

Lactobacillus gasseri PA-3, but not L. gasseri OLL2996, reduces the absorption of purine nucleosides in rats

Lactobacillus gasseri PA-3 (PA-3) is a bacterial strain with a strong ability to degrade purine nucleosides. We previously showed that PA-3 incorporates purines in vitro and that oral administration of PA-3 and purines to rats attenuated their absorption of purines. It remains unclear whether these effects of PA-3 depend on bacterial strains. This study therefore compared the abilities of PA-3 and another bacterial strain of L. gasseri, OLL2996, which has shown decreased ability to degrade purine nucleosides in vitro, to incorporate purine nucleosides and to inhibit the absorption of purines fed to rats. Each bacterial strain was incubated in the presence of ¹⁴C-adenosine or ¹⁴C-inosine and the incorporation of each purine was evaluated by measuring their radioactivity. In vivo, rats were fed ¹⁴C-labeled purines along with PA-3 or OLL2996 and the absorption of these ¹⁴C-labeled purines was evaluated by analyzing radioactivity of blood samples. PA-3 incorporated about twice as much ¹⁴C-adenosine and ¹⁴C-inosine as OLL2996. The elevation of radioactivity levels in blood was 10–20% lower in rats treated with PA-3 than in control rats, after feeding with both ¹⁴C-adenosine and ¹⁴C-inosine as purines. In contrast, treatment with OLL2996 did not have statistically significant effects on radioactivity compared with the control group. These results indicate that the magnitude of bacterial inhibition of purine absorption is dependent on bacterial strain, correlating at least partly with the ability to incorporate and degrade purines.     

Characterization of Temperate <Emphasis Type="Italic">Lactobacillus gasseri</Emphasis> Phage LgaI and Its Impact as Prophage on Autolysis of Its Lysogenic Host Strains

We show by electron microscopy that Lactobacillus gasseri phage LgaI, a temperate phage residing in the chromosome of Lactobacillus gasseri ATCC33323, belongs to the family of Myoviridae phages. The LgaI DNA is packed by the “head-full” mechanism, as demonstrated by analysis of restriction patterns of heated (74°C) or non-heated DNA. By isolating prophage-cured cells, we were able to demonstrate phage LgaI to be responsible for the strong autolytic phenotype observed for Lactobacillus gasseri ATCC33323. In addition, we show that a copy of the LgaI prophage resides in the chromosome of Lactobacillus gasseri NCK102. The LgaI prophage was not inducible in L. gasseri NCK102-adh by mitomycin C, however, it apparently contributed to the autolytic phenotype of this strain.     

The PTS transporters of <Emphasis Type="Italic">Lactobacillus gasseri</Emphasis> ATCC 33323

Background  

Lactobacilli can utilize a variety of carbohydrates which reflects the nutrient availability in their respective environments. A common lactobacilli in the human gastrointestinal tract, Lactobacillus gasseri, was selected for further study. The currently available annotation of the L. gasseri ATCC 33323 genome describes numerous putative genes involved in carbohydrate utilization, yet the specific functions of many of these genes remain unknown.     

Chitosan and Enteric Polymer Based Once Daily Sustained Release Tablets of Aceclofenac: <Emphasis Type="BoldItalic">In Vitro</Emphasis> and <Emphasis Type="BoldItalic">In Vivo</Emphasis> Studies

The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like IR spectroscopic and differential scanning calorimetry showed the absence of drug–excipient interactions. The tablets were found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7) was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters of M-7 and marketed tablets was observed (p > 0.05; 95% confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies at different conditions are required to confirm these results.     

地屈孕酮联合醋酸曲普瑞林用于子宫内膜异位症术后的临床效果

目的:研究地屈孕酮联合醋酸曲普瑞林用于子宫内膜异位症术后的临床效果。方法:选择2015年1月～2017年12月在我院接受腹腔镜手术治疗的398例子宫内膜异位症患者,根据患者入院的顺序编号,采用奇偶数法将其分为两组,每组各199例。对照组术后单纯口服地屈孕酮治疗,每次月经后的第2 d服用,1片/次,2次/d,共服用药6个月。观察组术后采用地屈孕酮联合醋酸曲普瑞林治疗,即肌肉注射醋酸曲普瑞林,3.75 mg/次,1次/月,共连续给药6次。比较两组的疗效、治疗前后血清学指标、痛经、盆腔痛及性交痛程度的变化。结果:治疗后,观察组的总有效率明显高于对照组(P0.05);两组的血清黄体生成激素(Luteinizing hormone,LH)和促卵泡生成素(Follicle-stimulating hormone,FSH)水平均未明显改变(P0.05),而血清雌二醇(Estradiol,E_2)、糖类抗原125(Carbohydrate antigen,CA125)和血管内皮生长因子(Vascular endothelial growth factor,VEGF)水平均较治疗前明显降低(P0.05),且观察组以上指标均明显低于对照组(P0.05)。两组治疗后痛经、盆腔痛及性交痛积分均较治疗前明显降低(P0.05),且观察组明显低于对照组(P0.05)。结论:子宫内膜异位症术后采取地屈孕酮联合醋酸曲普瑞林具有显著的治疗效果,能有效缓解患者的疼痛症状,并改善血清学相关指标,从而有效改善子宫内膜异位症术后的临床效果。     

Widespread Emergence of Multidrug Resistant <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> Isolated from CSF Samples

Bacterial infections of the central nervous system, especially acute infections such as bacterial meningitis require immediate, invariably empiric antibiotic therapy due to the widespread emergence of resistance among bacterial species. Nosocomial infections by Pseudomonas aeruginosa have been described with an increasing trend towards multidrug resistance. P. aeruginosa isolates n = 53 (66%) isolated from the cerebrospinal fluid (CSF) were used for this study. Antibiotic resistance in 53 P. aeruginosa clinical isolates from 80 CSF samples were evaluated. Of these, n = 42 (80%) of the isolates showed multidrug resistance to more than eight antibiotics and n = 17 (32%) isolates were found to be imipenem resistant P. aeruginosa (IMPR-Pa). Genotypical examination by ERIC based PCR revealed minor genetic variations. Polymicrobial infections are common in the CSF samples. However, high prevalence of P. aeruginosa as an opportunistic pathogen has been developing with increased resistance to antimicrobial agents and thus becoming a significant threat.     

An 8-week randomized,double-blind,placebo-controlled study to evaluate the efficacy and safety of red Platycodon grandiflorus root extract on enhancement of immune function

BackgroundThe immune-enhancing effects of red Platycodon grandiflorus root extract (RPGE) has been reported in vitro and in vivo, but there are few studies on humans. Therefore, this study aimed to investigate the efficacy and safety of RPGE in enhancing immune function in healthy subjects.Subjects and methodsAn 8-week randomized, double-blind, parallel, placebo-controlled clinical trial was conducted at the Gachon University Gil Medical Center, Incheon, South Korea. A total of 100 adults aged 20–75 years with white blood cell counts of 3000–10,000 cell/µL were randomly divided into two groups (RPGE group, 50 and placebo group, 50) using a computer-generated random list with a 1:1 allocation ratio. The subjects consumed RPGE (2 times/day, 2 tablets/time, 375 mg RPGE powder/tablet) or placebo for 8 weeks. All test foods for the human study were coded and administered under double-blind conditions. The primary outcome was a change in the NK cell activity after 8 weeks of treatment compared to the baseline.ResultsAmong 100 subjects enrolled for the study, 87 completed the study. NK cell activity (p = 0.005) and IFN-γ level (p = 0.003) of the RPGE group (n = 41) were higher than those of the placebo group (n = 46). The findings of the safety assessment revealed absence of clinically significant changes in any test and serious adverse events throughout the study.ConclusionIn conclusion, these results demonstrate the efficacy and safety of RPGE, suggesting it to be a beneficial agent for enhancing immune function in humans.Trial registrationCRIS Registration Number KCT0005945, https://cris.nih.go.kr.     

The Effects of Synbiotic Supplementation on Carotid Intima-Media Thickness,Biomarkers of Inflammation,and Oxidative Stress in People with Overweight,Diabetes, and Coronary Heart Disease: a Randomized,Double-Blind,Placebo-Controlled Trial

Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidant actions. The aim of this study was to evaluate the effects of synbiotic supplementation on carotid intima-media thickness (CIMT), biomarkers of inflammation, and oxidative stress in people with overweight, diabetes, and coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was conducted and involved 60 people with overweight, diabetes, and CHD, aged 50–85 years old. Participants were randomly allocated into two groups to take either synbiotic supplements containing three probiotic bacteria spices Lactobacillus acidophilus strain T16 (IBRC-M10785), Lactobacillus casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 × 10⁹ CFU/g each) plus 800 mg inulin or placebo (n = 30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention period to determine metabolic variables. After the 12-week intervention, compared with the placebo, synbiotic supplementation significantly reduced serum high-sensitivity C-reactive protein (hs-CRP) (− 3101.7 ± 5109.1 vs. − 6.2 ± 3163.6 ng/mL, P = 0.02), plasma malondialdehyde (MDA) (− 0.6 ± 1.0 vs. − 0.1 ± 0.3 μmol/L, P = 0.01), and significantly increased nitric oxide (NO) levels (+ 7.8 ± 10.3 vs. − 3.6 ± 6.9 μmol/L, P < 0.001). We did not observe any significant changes of synbiotic supplementation on other biomarkers of oxidative stress and CIMT levels. Overall, synbiotic supplementation for 12 weeks among people with overweight, diabetes, and CHD had beneficial effects on serum hs-CRP, plasma NO, and MDA levels; however, it did not have any effect on other biomarkers of oxidative stress and CIMT levels.

     

Circulating miR-3613-5p but not miR-125b-5p,miR-199a-3p,and miR-451a are biomarkers of endometriosis

ObjectiveThis study aimed to assess the utility of circulating miR-125b-5p, miR-199a-3p, miR-451a, and miR-3613-5p as biomarkers of endometriosis.Study designPatients with stage III or IV of endometriosis according to the revised American Society of Reproductive Medicine (rASRM) staging classification, as well as control women, were recruited. We created a prospective study conducted on a group of 48 patients (n = 25 controls, n = 24 endometriosis) who had laparoscopic surgery. Blood samples were taken and plasma miRNA levels were measured by quantitative real-time polymerase chain reaction (RT-qPCR) and assessed with AUC and ROC curves.ResultsMiR-451a and miR-3613-5p were significantly decreased in the plasma of endometriosis patients. miR-451a had a receiver-operating characteristic (ROC) area under the curve 0.8283 and miR-3613-5p had a ROC area under the curve 0.7617. The concentration of circulating miR-125b-5p and miR-199-3p did not differ between endometriosis patients and controls. Plasma miRNA levels did not change with BMI, smoking status, fertility problems, or menstrual pain according to the VAS scale (p > 0.05).ConclusionCirculating miR-451a and miR-3613-5p levels significantly differed between endometriosis and controls. However, the levels of miR-451a were discordant with previous studies. Therefore, miR-3613-5p may have better potential as the endometriosis biomarker. Circulating miR-125b-5p and miR-199a-3p cannot be used as reliable markers of endometriosis.     

Length‐weight relationships for five freshwater fish species from the Utinga State Park,Northeast Amazon,Brazil

Length–weight relationships (LWR) were estimated for five most abundant fish species occurring in the Utinga State Park within the metropolitan area of Belém, State of Pará, Northern Brazil. Data were obtained from specimens of Curimata knerii (n = 75), Gasteropelecus levis (n = 54), Hemigrammus rodwayi (n = 82), Hyphessobrycon bentosi (n = 69), and Pristobrycon calmoni (n = 76) collected in July 2013 with seines (1.5 mm mesh), sieves (1 mm mesh), and gill nets (40–120 mm mesh) in the main waterbodies. All LWRs are novel for science, increasing knowledge on biological information of the Neotropical freshwater fish.     

Relationship between prevalence of trematode parasite <Emphasis Type="Italic">Diplostomum</Emphasis> sp. and population density of its snail host <Emphasis Type="Italic">Lymnaea stagnalis</Emphasis> in lakes and ponds in Finland

Diplostomum sp. is a trematode parasite that infects aquatic snails, e.g. Lymnaea stagnalis (Gastropoda: Lymnaeidae), fish, and fish-eating birds. Ponds and lakes (n = 28) located in Finland between latitudes 61°45′N and 65°30′N were sampled for L. stagnalis, the first intermediate host for Diplostomum sp. L. stagnalis were found in 22 sites out of 28, and Diplostomum sp. in 10 of the 22 snail populations. Among the L. stagnalis populations that were infected by Diplostomum sp., the mean prevalence was 12.8%. Diplostomum sp. occurred in only one out of the seven L. stagnalis populations in four large lakes, but in 9 out of the 16 L. stagnalis populations in small lakes. In the pooled data, a positive correlation (r _s = 0.427; P = 0.047; n = 22) between L. stagnalis density and Diplostomum sp. prevalence was found. The results suggest that Diplostomum sp. is fairly common in L. stagnalis populations in small lakes but rare in large lakes. Furthermore, although trematode parasites, in general, should have a negative effect on snail population density, the study indicates that the relationship between host density and parasite prevalence may greatly differ for individual trematode species, such as Diplostomum sp.     

Isolation and Confirmation of <Emphasis Type="Italic">Listeria</Emphasis> Species from Seafood off Goa Region by Polymerase Chain Reaction

Several food borne outbreaks have highlighted the importance of Listeria monocytogenes to the public health and have been recognized as an emerging, important food borne pathogen, and a causative agent of listerioses. A number of genes are involved in the manifestation of Listeria virulence, hlyA is one among them. In the present study, 111 marine fish samples including prawns, finfishes and bivalves were screened for the presence of Listeria species. The isolates were characterized biochemically and further L. monocytogenes were confirmed by polymerase chain reaction (PCR) technique using the hlyA gene as a tool to differentiate between L. monocytogenes and other non-pathogenic Listeria species. Out of 111 samples 5 (4.5%) samples were positive for L. monocytogenes. Among the three different types of samples bivalves were found to have maximum percent (12.5) of L. monocytogenes followed by prawns (3.84) and finfishes (2.9). Among all the 111 samples, 15 (13.51%) samples were positive for other Listeria species. It was observed that Listeria occurrence is more in shellfishes than in fin fishes. All the isolates were sensitive towards five different antibiotics in sequence ciprofloxacin > sulphafurazole > norfloxacin > ampicillin and gentamicin.     

Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized,double‐blind,placebo‐controlled,multicenter trial: The MASTERS trial

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double‐blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p < .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p = .007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228.     

Genetic diversity of Listeria monocytogenes serotype 1/2a strains collected in Brazil by Multi-Virulence-Locus Sequence Typing

Listeria monocytogenes is an opportunistic pathogen with the ability to adapt to different environmental conditions, resulting in safety issues for food producers. Foods contaminated by L. monocytogenes can represent a risk if consumed by susceptible individuals such as elderly, pregnant women and the immunocompromised. The aim of this study was to evaluate the genetic diversity of a collection of L. monocytogenes isolated from different matrices in Brazil during the period of 1979–2015. A total of 51 L. monocytogenes serotype 1/2a strains isolated from clinical samples (n = 3) and food samples (n = 48) were characterized by Multi-Virulence-Locus Sequence Typing (MVLST). The strains were assigned to nine virulence types (VT): VT-11 (n = 3, 5·9%), VT-45 (n = 27, 52·9%), VT-59 (n = 11, 21·6%), VT-68 (n = 3, 5·9%), VT-94 (n = 2, 3·9%), VT-107 (n = 2, 3·9%), VT-184 (n = 1, 1·9%), VT-185 (n = 1, 1·9%) and VT-186 (n = 1, 1·9%); and four of them (VT-11, VT-45, VT-59 and VT-68) have already been associated with cases of listeriosis worldwide. The VT-11, VT-59 (Epidemic Clone V) and VT-186 were identified in blood culture samples, as well as in different classes of foods. It is recommended that the epidemiological surveillance agencies evaluate the risk that foods contaminated with L. monocytogenes VTs pose to susceptible populations.     

Severe, primary dysmenorrhea treated with naproxen. A prospective, double-blind, crossover investigation

26 women aged 15–45 with severe, primary dysmenorrhea were treated with naproxen (NAPROSYN^R, SYNTEX) and placebo during 2 × 2 consecutive menstrual cycles in a randomized, double-blind crossover study.The dosage of naproxen was 500 mg (2 tablets) initially, followed by 250 mg as needed, with a maximum of 1250 mg daily. In most cases medication started at the first sign of menstrual distress.80 per cent of the women preferred naproxen to placebo. The number of tablets taken during each menstruation fell from a mean of 17.8 in the placebo period to 5.1 in the naproxen period. Likewise, additional analgesics fell from 7.1 to 1.6 and hours of bed rest from 16.4 to 1.2. Total number of days of sick leave per two men-struations decreased from 40 to 7. These differences are statistically significant (P < 0.001).The side effects were mild. CNS or gastrointestinal side effects were not seen. Naproxen changed the amount of bleeding in 12 and delayed bleeding in three. Two dev loped acne, which however gradually diminished during the next five bleeding periods treated with naproxen.The influence of prostaglandin synthetase inhibitors on the ovarian production of steroids is discussed.     

Flow‐injection determination of cysteine in pharmaceuticals based on luminol–persulphate chemiluminescence detection

A flow injection (FI) method is reported for the determination of l‐ cysteine, based on its enhancement on chemiluminescence (CL) emission of luminol oxidized by sodium persulphate in alkaline solution. The calibration graph was linear over the range 1.0 × 10^–9–5.0 × 10^–7 mol/L (r² = 0.9992), with relative standard deviations (RSDs) in the range 1.1–2.3% (n = 4). The limit of detection (3σ blank) was 5.0 × 10^–10 mol/L with a sample throughput of 120/h. The method was applied to pharmaceuticals and the results obtained were in reasonable agreement with the amount labelled. The proposed method was also applied to cysteine in synthetic amino acid mixtures. Calibration graphs of N‐acetylcysteine and glutathione over the range 1.0–50 × 10^–8 and 0.5–7.5 × 10^–7 mol/L were also established (r² = 0.998 and 0.9986) with RSDs in the range 1.0–2.0% (n = 4), and the limits of detection (3σ blank) were 5.0 × 10^–9 and 1.0 × 10^–8 mol/L, respectively. Copyright © 2008 John Wiley & Sons, Ltd.