EPs® 7630 Stimulates Tissue Repair Mechanisms and Modifies Tight Junction Protein Expression in Human Airway Epithelial Cells.

Airway epithelium repair after infection consists of wound repair, re-synthesis of the extracellular matrix (ECM), and tight junction proteins. In humans, EPs® 7630 obtained from Pelargonium sidoides roots reduces the severity and duration of acute respiratory tract infections. The effect of EPs® 7630 on tissue repair of rhinovirus-16 (RV-16) infected and control human airway epithelial cells was assessed for: (i) epithelial cell proliferation by manual cell counts, (ii) epithelial wound repair by "scratch assay", (iii) ECM composition by Western-blotting and cell-based ELISA, and (iv) epithelial tight junction proteins by Western-blotting. EPs® 7630 stimulated cell proliferation through cAMP, CREB, and p38 MAPK. EPs® 7630 significantly improved wound repair. Pro-inflammatory collagen type-I expression was reduced by EPs® 7630, while fibronectin was increased. Virus-binding tight junction proteins desmoglein2, desmocollin2, ZO-1, claudin1, and claudin4 were downregulated by EPs® 7630. The RV16-induced shift of the ECM towards the pro-inflammatory type was prevented by EPs® 7630. Most of the effects of EPs® 7630 on tissue repair and regeneration were sensitive to inhibition of cAMP-induced signaling. The data suggest that EPs® 7630-dependent modification of epithelial cell metabolism and function might underlie the faster recovery time from viral infections, as reported by others in clinical studies.

Infections and diabetes: Risks and mitigation with reference to India.

BACKGROUND AND AIMS: The link between diabetes and increased risk of infectious disease has long been recognized, but has re-entered sharp focus following the COVID-19 pandemic. METHODS: A literature search was conducted in PubMed for articles in English on diabetes and infection. RESULTS: Diabetes predisposes to infections through alterations in innate and acquired immune defenses. Outcomes of infection are worse in people with uncontrolled diabetes, and infection can worsen hyperglycemia in hitherto well controlled diabetes (bidirectional relationship). Diabetes does not increase the risk of infection with COVID-19 per se, but predisposes to severe disease and poor outcomes. COVID-19 has also been linked to deterioration of glycemic control as well as new-onset diabetes. CONCLUSIONS: Clinicians caring for people with diabetes should be aware of the increased risk of infections in this population, as well as the possibility of worsening hyperglycemia. A holistic approach with frequent monitoring of blood glucose levels and appropriate titration of medications, along with close attention to nutritional status, is essential to ensure the best possible outcomes.

Zinc and respiratory tract infections: Perspectives for COVID­19 (Review).

In view of the emerging COVID­19 pandemic caused by SARS­CoV­2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID­19. In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS­CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin­converting enzyme 2 (ACE2), known to be the receptor for SARS­CoV­2. Improved antiviral immunity by zinc may also occur through up­regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti­inflammatory activity by inhibiting NF­κB signaling and modulation of regulatory T­cell functions that may limit the cytokine storm in COVID­19. Improved Zn status may also reduce the risk of bacterial co­infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID­19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID­19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator­induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required.

Vitamin D in pediatric health and disease.

Several scientific societies established that vitamin D (VD), in its metabolized form 25(OH)D, levels higher than 20 ng/mL are sufficient to ensure optimal bone health, while 25(OH)D levels higher than 30 ng/mL are needed to favor VD extraskeletal actions. However, it has been estimated that approximately 30% of children and 60% of adults worldwide are VD deficient and insufficient, respectively. This is the reason why it is important to provide a practical approach to VD supplementation for infants, children, and adolescents. It is the pediatrician's role to evaluate the modifiable lifestyle risk factors for deficiency, particularly a reduced sun exposure, following an evidence-based approach, and to suggest VD supplementation only when there is a rational reason to support its use.

Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples.

Herbal medicine, including traditional Chinese medicine (TCM), is widely used worldwide. Herbs and TCM formulas contain numerous active molecules. Basically, they are a kind of cocktail therapy. Herb-drug, herb-food, herb-herb, herb-microbiome, and herb-disease interactions are complex. There is potential for both benefit and harm, so only after understanding more of their mechanisms and clinical effects can herbal medicine and TCM be helpful to users. Many pharmacologic studies have been performed to unravel the molecular mechanisms; however, basic and clinical studies of good validity are still not enough to translate experimental results into clinical understanding and to provide tough evidence for better use of herbal medicines. There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Understanding study validation, pharmacologic effects, drug interactions, indications and clinical effects, adverse effects and limitations, can all help clinicians in providing adequate suggestions to patients. At present, it would be better to use herbs and TCM formulas according to their traditional indications matching the disease pathophysiology and their molecular mechanisms. To unravel the molecular mechanisms and understand the benefits and harms of herbal medicine and TCM, there is still much work to be done.

Greater Efficacy of Black Ginseng (CJ EnerG) over Red Ginseng against Lethal Influenza A Virus Infection.

Black ginseng (BG, CJ EnerG), prepared via nine repeated cycles of steaming and drying of fresh ginseng, contains more accessible acid polysaccharides and smaller and less polar ginsenosides than red ginseng (RG) processed only once. Because RG exhibits the ability to increase host protection against viral respiratory infections, we investigated the antiviral effects of BG. Mice were orally administered either BG or RG extract at 10 mg/kg bw daily for two weeks. Mice were then infected with a A(H1N1) pdm09 (A/California/04/2009) virus and fed extracts for an additional week. Untreated, infected mice were assigned to either the negative control, without treatments, or the positive control, treated with Tamiflu. Infected mice were monitored for 14 days to determine the survival rate. Lung tissues were evaluated for virus titer and by histological analyses. Cytokine levels were measured in bronchoalveolar lavage fluid. Mice treated with BG displayed a 100% survival rate against infection, while mice treated with RG had a 50% survival rate. Further, mice treated with BG had fewer accumulated inflammatory cells in bronchioles following viral infection than did mice treated with RG. BG also enhanced the levels of GM-CSF and IL-10 during the early and late stages of infection, respectively, compared to RG. Thus, BG may be useful as an alternative antiviral adjuvant to modulate immune responses to influenza A virus.

Increased risk of refeeding syndrome-like hypophosphatemia with high initial amino acid intake in small-for-gestational-age, extremely-low-birthweight infants.

BACKGROUND: Recent nutrition guidelines for extremely-low-birth-weight infants (ELBWIs) recommend implementation of high initial amino acid (AA) supplementation in parenteral nutrition. OBJECTIVE: We sought to evaluate the influence of AA intake on refeeding syndrome-like electrolyte disturbances including hypophosphatemia in ELBWIs. STUDY DESIGN: Medical records of 142 ELBWIs were reviewed. Demographic, nutritional, outcome, and electrolyte data were compared between ELBWIs with initial low (1.5 g/kg/day) and high (3 g/kg/day) AA intake. Multivariate analysis was conducted to determine the odds ratio of hypophosphatemia with high AA intake and small-for-gestational-age (SGA) ELBWIs. RESULTS: The incidence of hypophosphatemia and severe hypophosphatemia increased from 51% and 8% in period I to 59% and 20% in period II, respectively (p = 0.36 and < 0.01). Specifically, SGA ELBWIs showed higher incidence of hypophosphatemia than appropriate-for-gestational age (AGA) ELBWIs in period II, whereas there was no difference in period I. For severe hypophosphatemia, SGA ELBWIs presented a 27% incidence versus a 2% incidence in AGA ELBWIs, even with low initial AA intake. Despite no difference in phosphate intake between infants with and without hypophosphatemia, serum phosphate level reached a nadir at the sixth postnatal day and gradually recovered over the second week in infants with hypophosphatemia. In multivariate analyses, the odds ratios for severe hypophosphatemia were 3.6 and 6.6 with high AA intake and SGA status, respectively, with the highest being 18.0 with combined high AA intake and SGA status. CONCLUSIONS: In summary, high initial AA intake significantly increased the risk of refeeding syndrome-like electrolyte dysregulations including severe hypophosphatemia in ELBWIs. In SGA ELBWIs, the risk of electrolyte disturbance was significantly higher, even with low initial AA intake. Therefore, new tailored parenteral nutrition protocols starting with lower energy intake and a gradual increase over the first week may be warranted for application in high-risk SGA ELBWIs.

Host-Based Diagnostics for Acute Respiratory Infections.

PURPOSE: The inappropriate use of antimicrobials, especially in acute respiratory infections (ARIs), is largely driven by difficulty distinguishing bacterial, viral, and noninfectious etiologies of illness. A new frontier in infectious disease diagnostics looks to the host response for disease classification. This article examines how host response-based diagnostics for ARIs are being used in clinical practice, as well as new developments in the research pipeline. METHODS: A limited search was conducted of the relevant literature, with emphasis placed on literature published in the last 5 years (2014-2019). FINDINGS: Advances are being made in all areas of host response-based diagnostics for ARIs. Specifically, there has been significant progress made in single protein biomarkers, as well as in various "omics" fields (including proteomics, metabolomics, and transcriptomics) and wearable technologies. There are many potential applications of a host response-based approach; a few key examples include the ability to discriminate bacterial and viral disease, presymptomatic diagnosis of infection, and pathogen-specific host response diagnostics, including modeling disease progression. IMPLICATIONS: As biomarker measurement technologies continue to improve, host response-based diagnostics will increasingly be translated to clinically available platforms that can generate a holistic characterization of an individual's health. This knowledge, in the hands of both patient and provider, can improve care for the individual patient and help fight rising rates of antibiotic resistance.

Effect of Flavonoids on Upper Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis.

Previous research on animals indicates flavonoid compounds have immunomodulatory properties; however, human research remains inconclusive. The aim of this systematic review was to assess the efficacy of dietary flavonoids on upper respiratory tract infections (URTIs) and immune function in healthy adults. A created search strategy was run against Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and EMBASE classic, CINAHL, and AMED. The returned studies were initially screened, and 2 reviewers independently assessed the remaining studies for eligibility against prespecified criteria. Fourteen studies, of 387 initially identified, were included in this review, and the primary outcome measure was the effect of flavonoids on URTI incidence, duration, and severity. Of the included studies, flavonoid supplementation ranged from 0.2 to 1.2 g/d. Overall, flavonoid supplementation decreased URTI incidence by 33% (95% CI: 31%, 36%) compared with control, with no apparent adverse effects. Sick-day count was decreased by 40% with flavonoid supplementation, although unclear. Differences in bio-immune markers (e.g., interleukin-6, tumor necrosis factor-α, interferon-γ, neutrophils) were trivial between the intervention and control groups during the intervention and after exercise when a postintervention exercise bout was included. These findings suggest that flavonoids are a viable supplement to decrease URTI incidence in an otherwise healthy population.

The Vitamin D Assessment (ViDA) Study: design of a randomized controlled trial of vitamin D supplementation for the prevention of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures.

Observational studies have shown that low vitamin D status is associated with an increased risk of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. We recruited 5110 Auckland adults, aged 50-84 years, into a randomized, double-blind, placebo-controlled trial to test whether vitamin D supplementation protects against these four major outcomes. The intervention is a monthly cholecalciferol dose of 100,000IU (2.5mg) for an estimated median 3.3 years (range 2.5-4.2) during 2011-2015. Participants were recruited primarily from family practices, plus community groups with a high proportion of Maori, Pacific, or South Asian individuals. The baseline evaluation included medical history, lifestyle, physical measurements (e.g. blood pressure, arterial waveform, lung function, muscle function), and a blood sample (stored at -80°C for later testing). Capsules are being mailed to home addresses with a questionnaire to collect data on non-hospitalized outcomes and to monitor adherence and potential adverse effects. Other data sources include New Zealand Ministry of Health data on mortality, hospitalization, cancer registrations and dispensed pharmaceuticals. A random sample of 438 participants returned for annual collection of blood samples to monitor adherence and safety (hypercalcemia), including repeat physical measurements at 12 months follow-up. The trial will allow testing of a priori hypotheses on several other endpoints including: weight, blood pressure, arterial waveform parameters, heart rate variability, lung function, muscle strength, gait and balance, mood, psoriasis, bone density, and chronic pain.

Network pharmacology study on the mechanism of traditional Chinese medicine for upper respiratory tract infection.

Traditional Chinese medicine (TCM) is a multi-component and multi-target agent and could treat complex diseases in a holistic way, especially infection diseases. However, the underlying pharmacology remains unclear. Fortunately, network pharmacology by integrating system biology and polypharmacology provides a strategy to address this issue. In this work, Reduning Injection (RDN), a well-used TCM treatment in the clinic for upper respiratory tract infections (URTIs), was investigated to interpret the molecular mechanism and predict new clinical directions by integrating molecular docking, network analysis and cell-based assays. 32 active ingredients and 38 potential targets were identified. In vitro experiments confirmed the bioactivities of the compounds against lipopolysaccharide (LPS)-stimulated PGE2 and NO production in RAW264.7 cells. Moreover, network analysis showed that RDN could not only inhibit viral replication but also alleviate the sickness symptoms of URTIs through directly targeting the key proteins in the respiratory viral life cycle and indirectly regulating host immune systems. In addition, other clinical applications of RDN such as neoplasms, cardiovascular diseases and immune system diseases were predicted on the basis of the relationships between targets and diseases.

Role of the zinc uptake ABC transporter of Moraxella catarrhalis in persistence in the respiratory tract.

Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains of M. catarrhalis tested. A mutant in which the znu gene cluster is knocked out shows markedly impaired growth compared to the wild type in medium that contains trace zinc; growth is restored to wild-type levels by supplementing medium with zinc but not with other divalent cations. Thermal-shift assays showed that the purified recombinant substrate binding protein ZnuA binds zinc but does not bind other divalent cations. Invasion assays with human respiratory epithelial cells demonstrated that the zinc ABC transporter of M. catarrhalis is critical for invasion of respiratory epithelial cells, an observation that is especially relevant because an intracellular reservoir of M. catarrhalis is present in the human respiratory tract and this reservoir is important for persistence. The znu knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the zinc uptake ABC transporter mediates uptake of zinc in environments with very low zinc concentrations and is critical for full virulence of M. catarrhalis in the respiratory tract in facilitating intracellular invasion of epithelial cells and persistence in the respiratory tract.

Clinical dose findings of sitafloxacin treatment: pharmacokinetic-pharmacodynamic analysis of two clinical trial results for community-acquired respiratory tract infections.

The adequacy of sitafloxacin clinical dose regimens was assessed by comparing the efficacy of the administration of 100 mg sitafloxacin once daily (100 mg qd group) and 50 mg sitafloxacin twice daily (50 mg bid group). Patients with respiratory tract infections caused by pneumococci were orally treated with sitafloxacin (100 mg qd or 50 mg bid) for 7 days. The clinical efficacy, pneumococci eradication rate, safety, and pharmacokinetic and pharmacodynamic indices of the two groups were then assessed. The clinical efficacy was 93.5 % in both groups. The pneumococci eradication rate was 98.2 % in the 100 mg qd group and 92.7 % in the 50 mg bid group. The mean of the free AUC0-24h divided by the minimum inhibitory concentration (MIC) (fAUC0-24h/MIC) did not differ significantly between the 100 mg qd (103.24) and the 50 mg bid groups (105.25). The mean of the free C peak divided by the MIC (fC peak/MIC) was higher in the 100 mg qd group (10.19) than in the 50 mg bid group (6.53). The pathogen eradication rate was 98.9 % (89/90) when the fAUC0-24h/MIC was greater than 30, and the eradication rate was 98.9 % (89/90) when the fC peak/MIC was greater than 2. The incidences of adverse drug reactions were 33.7 % in the 100 mg qd group and 40.4 % in the 50 mg bid group. No obvious differences in the efficacy and safety were observed between the dosage groups. For cases in which a sufficiently high C peak is necessary to ensure the susceptibility of the pathogens to the drug, 100 mg sitafloxacin once daily should be administered.

The novel Sinupret® dry extract exhibits anti-inflammatory effectiveness in vivo.

Sinupret® is frequently used as a herbal medicinal product to treat sinusitis, and it was assumed that anti-inflammatory effects might contribute to its overall beneficial properties. Here, we investigated the effects of a Sinupret® drug mixture (SIN) as well as of the novel Sinupret® dry extract (SIN DE) with the latter containing higher concentrations of active ingredients, in an in vivo model of acute inflammation, the carrageenan-induced pleurisy in rats. Both SIN and SIN DE were administered to rats orally at doses of 100mg/kg (low dose) and 500mg/kg (high dose) 1h prior to intrapleural injection of carrageenan. Although both SIN and SIN DE significantly reduced the exudate volume and leukocyte numbers in the pleural exudate at the high and the low dose 4h after carrageenan injection, the novel SIN DE was more efficient than SIN at the low dose, implying higher efficiency. In parallel, the novel dry extract SIN DE, but not SIN, at 500mg/kg significantly lowered the levels of prostaglandin (PG)E(2) in the exudates and reduced the amounts of cyclooxygenase (COX)-2 protein in the lungs. Together, SIN and SIN DE exert significant oral anti-inflammatory effects, which rationalize their therapeutic use in the management of sinusitis and other viral/microbial nasal infections that are associated with inflammation. Moreover, our results suggest that based on the higher efficiency and the accompanied reduction of COX-2 expression and PGE(2) formation, the novel dry extract SIN DE might be superior over the former SIN drug mixture.

[Polarized light as an epigenetic factor in inhibition of inflammation; a genome-wide expression analysis in recurrent respiratory diseases of children]. / A polarizált fény epigenetikai tényezo a gyulladásgátlásban; teljesgenom-szintu expressziós analízis gyermekkori visszatéro légúti megbetegedésekben.

UNLABELLED: Whole-body polarized light therapy has been primarily investigated in various clinical observations and in a few in vitro model systems. AIMS: In the present study, clinical and molecular effects of whole-body polarized light treatment on children suffering from recurrent respiratory infection were studied. METHODS: Incidence and duration of respiratory symptoms as well as the length of appropriate antibiotic therapy have been measured. Simultaneously, genome-wide gene expression pattern was examined by whole genome cDNA microarray in peripheral lymphocytes of children. RESULTS: Twenty of twenty five children showed a marked clinical improvement, while in five of twenty five had poor or no changes. Gene expression pattern of the peripheral lymphocytes of the patients was compared in favorable and poor responders. Lymphocytes of the children with a documented improved clinical response to polarized light therapy showed a decrease in the expression of chemokine genes, such as CXCL1, CXCL2, IL-8 and in that of the tumor necrosis alpha (TNFα) gene. On the contrary, a rapid elevation was found in the expression of gene encoding for CYP4F2, a leukotriene-B(4)-metabolizing enzyme. In children with poor clinical response to polarized light therapy, no similar changes were detected in the gene expression pattern of the lymphocytes. CONCLUSIONS: Improved clinical symptoms and modified gene expression profile of lymphocytes reveals anti-inflammatory effect upon whole body polarized light irradiation.

The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer.

The role of vitamin D (VitD) in calcium and bone homeostasis is well described. In the last years, it has been recognized that in addition to this classical function, VitD modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. VitD deficiency appears to be frequent in industrialized countries. Especially patients with lung diseases have often low VitD serum levels. Epidemiological data indicate that low levels of serum VitD is associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases. Several lung diseases, all inflammatory in nature, may be related to activities of VitD including asthma, COPD and cancer. The exact mechanisms underlying these data are unknown, however, VitD appears to impact on the function of inflammatory and structural cells, including dendritic cells, lymphocytes, monocytes, and epithelial cells. This review summarizes the knowledge on the classical and newly discovered functions of VitD, the molecular and cellular mechanism of action and the available data on the relationship between lung disease and VitD status.

Suppression of interleukin (IL)-8 and human beta defensin-2 secretion in LPS-and/or IL-1ß-stimulated airway epithelial A549 cells by a herbal formulation against respiratory infections (BNO 1030).

AIM OF THE STUDY: A special ethanolic-aqueous extract from seven traditional medicinal plants (BNO 1030) has been used for several decades to treat recurrent infections of the respiratory tract. Considering the potential role of interleukin-8 (IL-8) and human beta defensin-2 (hBD-2) in inflammation, we investigated the effect of BNO 1030 on lipopolysaccharide (LPS) from Pseudomonas aeruginosa or IL-1ß-induced inflammatory mediators in A549 human type II alveolar epithelial cells. MATERIALS AND METHODS: A549 cells were stimulated with LPS (100 µg/ml) or IL-1ß (50 ng/ml) in the presence of the preparation and the secretion of IL-8 and hBD-2 were measured after 18 h and 24h in cell free supernatants using enzyme-linked immunosorbent assays (ELISA). Cell viability and cell growth was investigated by propidium iodide uptake and WST-1 assay, respectively. RESULTS: BNO 1030 inhibited the secretion of IL-8 and hBD-2 at non-cytotoxic concentrations (0.1-100 µg/ml; cell growth inhibitory concentration, 50% (IC(50))=678 ± 87.6 µg/ml). Stimulation by IL-1ß led to a 7-fold activation of IL-8 secretion, which was reduced by 37.7 ± 4.1% (p<0.05) after incubation with 100 µg/ml BNO 1030. Inducible hBD-2 was suppressed by 91.8 ± 15.6% (p<0.01) at the same concentration of BNO 1030 (IC(50)=0.7 ± 0.1 µg/ml). The 2-fold increase of IL-8 secretion by LPS-stimulated cells was completely abolished at concentration of 50 µg/ml BNO 1030 (IC(50)=5.7±3.6 µg/ml). CONCLUSION: BNO 1030 suppressed the secretion of IL-8 and hBD-2 in cultured epithelial A549 cells. These results support its use as a phytotherapeutic product prepared from traditional remedies in inflammatory diseases, especially those affecting the respiratory tract.

[Effects of Chinese herbal medicine Bushen Gubiao Recipe on toll-like receptor 4 and CD4(+)CD25(+)foxp3(+) regulatory T cells in mice with recurrent respiratory tract infections].

OBJECTIVE: To evaluate the effects of Bushen Gubiao Recipe (BGR), a compound traditional Chinese herbal medicine, on toll-like receptor 4 (TLR4) signaling pathway and CD4(+)CD25(+)foxp3(+)regulatory T cells (CD4(+)CD25(+)foxp3(+)Tregs) in mice with recurrent respiratory tract infections (RRTIs). METHODS: A mouse model of kidney-yang deficiency which simulated physical characteristics of RRTIs was established by intraperitoneal injection of hydrocortisone for 14 d. The model mice were divided into 4 groups, model group, high-dose BGR group, low-dose BGR group, and nucleic acid and casein oral solution group. They were administered respectively with distilled water, high-dose BGR (50 g/kg body weight), low-dose BGR (25 g/kg body weight) and nucleic acid and casein oral solution. Besides, a normal control group was set up and gastrogavage with distilled water. The effect of intervention was evaluated 4 weeks later by estimating the changes in behaviors of mice. Expressions of TLR4 and nuclear factor-kappa B (NF-κB) p65 in lung tissue were detected by immunohistochemical SABC method, the expression of TLR4 mRNA in lung tissue was detected by fluorescence quantitative-polymerase chain reaction (FQ-PCR), and the level of blood CD4(+)CD25(+)foxp3(+) Tregs was determined by flow cytometry. RESULTS: A kidney-yang deficiency mouse model with RRTIs was successfully established by intraperitoneal injection of hydrocortisone. BGR could improve the abnormal behavioral condition of the mice and enhance the expressions of TLR4 and NF-κB p65 in the lung tissue. Expression of TLR4 mRNA in high-dose BGR group was higher than that in model group (P<0.05), while the difference was not statistically significant between high-dose BGR group and low-dose BGR group (P>0.05). Levels of CD4(+)CD25(+)foxp3(+)Tregs in high-dose BGR group and nucleic acid and casein oral solution group were lower than that in model group (P<0.05), while the difference was not statistically significant between high-dose BGR group and low-dose BGR group (P>0.05). CONCLUSION: BGR can improve the behavior of the kidney-yang deficiency mice, and improve the innate immune function by up-regulating TLR/NF-κB signaling pathway. BGR can adjust the immune imbalance of T-helper cell (Th) 1/Th2 through reducing the activity of CD4(+)CD25(+)foxp3(+)Tregs and enhancing the immune response of Th1 type.

Effect of a probiotics supplementation on respiratory infections and immune and hormonal parameters during intense military training.

This study examined the effect of a probiotics supplementation on respiratory tract infection (RTI) and immune and hormonal changes during the French Commando training (3-week training followed by a 5-day combat course). Cadets (21 +/- 0.4 years) received either a probiotics (n = 24) or a placebo (n = 23) supplementation over the training period. We found no difference in the RTI incidence between groups but a significantly greater proportion of rhinopharyngitis in the probiotic group (p < 0.05). Among immune parameters, the major finding was an immunoglobulin A decrease after the combat course only in the placebo group (p < 0.01), but the difference between the two groups was not significant. A greater increase in dehydroepiandrostane sulfate was observed in the probiotics group after the combat course (p < 0.05). This study suggested that the benefits of a probiotics supplementation in a multistressor environment relied mainly on its capacity to prevent the infection to spread throughout the respiratory tract.

Moxifloxacin in respiratory tract infections.

Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including Gram-positive (Streptococcus pneumoniae), Gram-negative (Haemophilus influenzae, Moraxella catarrhalis), and atypical strains (Chlamydia pneumoniae, Mycoplasma pneumoniae), as well as multi-drug resistant S. pneumoniae, including strains resistant to penicillin, macrolides, tetracyclines, trimethoprim/sulfamethoxazole and some fluoroquinolones. Moxifloxacin is highly concentrated in lung tissue, and has demonstrated rapid eradication rates. The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400mg/day. The ratio of the area under the concentration-time curve to MIC of moxifloxacin is the highest among the fluoroquinolones against S. pneumoniae. The clinical efficacy of moxifloxacin has been shown in controlled studies of community-acquired pneumonia (CAP), exacerbations of chronic bronchitis (CB) and acute bacterial rhinosinusitis. Moxifloxacin has demonstrated a faster resolution of symptoms in CAP and exacerbations of CB patients compared with first-line therapy. It has also demonstrated better eradication in exacerbations of CB compared with standard therapy, in particular the macrolides. Treatment guidelines should take into account the results of clinical trials with moxifloxacin in order to establish the role of this antimicrobial in the therapeutic arsenal against respiratory tract infections.