ß_lactam antibiotics against drug addiction: A novel therapeutic option.

Drug addiction as a problem for the health of the individual and the society is the result of a complex process in which there is an interaction between brain nuclei and neurotransmitters (such as glutamate). ß-lactam antibiotics, due to their enhancing properties on the glutamate transporter glutamate transporter-1, can affect and counteract the addictive mechanisms of drugs through the regulation of extracellular glutamate. Since glutamate is a key neurotransmitter in the development of drug addiction, it seems that ß-lactams can be considered as a promising treatment for addiction. However, more research in this field is necessary to identify other mechanisms involved in their effectiveness. This article is a review of the studies conducted on the effect of ß-lactam administration in preventing the development of drug addiction, as well as their possible cellular and molecular mechanisms. This review suggests the clinical use of ß-lactam antibiotics that have weak antimicrobial properties (such as clavulanic acid) in the treatment of drug dependence.

Combined adjuvant effects of ambient vapor-phase organic components and particulate matter potently promote allergic sensitization and Th2-skewing cytokine and chemokine milieux in mice: The importance of mechanistic multi-pollutant research.

Although exposure to ambient particulate matter (PM) is linked to asthma, the health effects of co-existing vapor-phase organic pollutants (vapor) and their combined effects with PM on this disease are poorly understood. We used a murine asthma model to test the hypothesis that exposure to vapor would enhance allergic sensitization and this effect would be further strengthened by co-existing PM. We found that vapor and PM each individually exerted adjuvant effects on OVA sensitization. Co-exposure to vapor and PM during sensitization further enhanced allergic lung inflammation and OVA-specific antibody production which was accompanied by pulmonary cytokine/chemokine milieu that favored T-helper 2 immunity (i.e. increased IL-4, downregulation of Il12a and Ifng, and upregulation of Ccl11 and Ccl8). TNFα, IL-6, Ccl12, Cxcl1 and detoxification/antioxidant enzyme responses in the lung were pollutant-dependent. Inhibition of lipopolysaccharide-induced IL-12 secretion from primary antigen-presenting dendritic cells correlated positively with vapor's oxidant potential. In conclusion, concurrent exposure to vapor and PM led to significantly exaggerated adjuvant effects on allergic lung inflammation which were more potent than that of each pollutant type alone. These findings suggest that the effects of multi-component air pollution on asthma may be significantly underestimated if research only focuses on a single air pollutant (e.g., PM).

Epithelial integrity, junctional complexes, and biomarkers associated with intestinal functions.

An intact intestinal barrier is crucial for immune homeostasis and its impairment activates the immune system and may result in chronic inflammation. The epithelial cells of the intestinal barrier are connected by tight junctions, which form an anastomosing network sealing adjacent epithelial cells. Tight junctions are composed of transmembrane and cytoplasmic scaffolding proteins. Transmembrane tight junction proteins at the apical-lateral membrane of the cell consist of occludin, claudins, junctional adhesion molecules, and tricellulin. Cytoplasmic scaffolding proteins, including zonula occludens, cingulin and afadin, provide a direct link between transmembrane tight junction proteins and the intracellular cytoskeleton. Each individual component of the tight junction network closely interacts with each other to form an efficient intestinal barrier. This review aims to describe the molecular structure of intestinal epithelial tight junction proteins and to characterize their organization and interaction. Moreover, clinically important biomarkers associated with impairment of gastrointestinal integrity are discussed.

The Role of Recombinant Fibroblast Growth Factor 1 in Enhancing the Angiogenesis in Random Cutaneous Flaps in Animal Model of Rat.

BACKGROUND: Randomized skin flaps have been used as a basic treatment modality for covering skin defects for a long time but they have always been in the risk of an inherent ischemia. Fibroblast growth factor 1 is a known angiogenic factor in in vitro studies which has shown conflicting results in in vivo investigation. We aimed to determine the effect of recombinant fibroblast growth factor on the angiogenesis rate of random cutaneous flap in animal model of rats. METHODS: This experimental study was conducted on 24 adult male rats randomized to 2 groups. In the first group FGF1 was injected subdermally in equally divided doses and distances of random flap surface in days 1, 3 and 5. In second group, normal saline was injected as control. Flap surgery was done on day 21 after first injection. The extent of necrosis and angiogenesis (mean vessel density) were assessed in day 14 after surgery. RESULTS: The mean percentage of clinically apparent necrosis was 35.2% (±10.5) in intervention (FGF1) group and 38.1% (±8.7) in control (normal saline), respectively. Mean vessel density was 86.20±5.6/mm2 in control group and 90.17±5.5/mm2 in intervention group, which showed no statistically significant difference. CONCLUSION: Mean vessel density and mean percentage of clinically apparent necrosis area were similar in 2 groups of rats with random cutaneous flaps receiving FGF1 or normal saline.

Trigger Thumb in Twins: Case Report.

Although trigger finger is common, pediatric trigger thumb is uncommon. In trigger thumb the finger is held in flexed position. The etiology of trigger finger is unknown and can occur isolated without any relation to other syndromes, however there are some evidences that suggest genetic etiology. We reported 2.5 year old twins both having bilateral trigger thumb. Grandfather of the twins had the disease. Although trigger thumb and finger have the same presentation, they can involve different anatomical structures. Bent or straightening of thumb or finger would produce painful popping and clicking and the affected finger or thumb can get stuck in bent and extended position. Based on physical examination and symptoms trigger finger are classified into four stages and each has its own treatment. There are evidences that support congenital hypothesis in pediatric trigger thumb such as bilateral presentation in identical twins, first degree familiar association and etc. Before the 1st year of life, 30% of trigger thumb will get resolved and it is better to postpone the surgery until 2 year of age. A1 pulley release has a good result in pediatric trigger thumb treatment.

Omega-3 Polyunsaturated Fatty Acid Intervention Against Established Autoimmunity in a Murine Model of Toxicant-Triggered Lupus.

Workplace exposure to respirable crystalline silica dust (cSiO2) has been etiologically linked to the development of lupus and other human autoimmune diseases. Lupus triggering can be recapitulated in female NZBWF1 mice by four weekly intranasal instillations with 1 mg cSiO2. This elicits inflammatory/autoimmune gene expression and ectopic lymphoid structure (ELS) development in the lung within 1 week, ultimately driving early onset of systemic autoimmunity and glomerulonephritis. Intriguingly, dietary supplementation with docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid (PUFA) found in fish oil, beginning 2 week prior to cSiO2 challenge, prevented inflammation and autoimmune flaring in this novel model. However, it is not yet known how ω-3 PUFA intervention influences established autoimmunity in this murine model of toxicant-triggered lupus. Here we tested the hypothesis that DHA intervention after cSiO2-initiated intrapulmonary autoimmunity will suppress lupus progression in the NZBWF1 mouse. Six-week old NZWBF1 female mice were fed purified isocaloric diet for 2 weeks and then intranasally instilled with 1 mg cSiO2 or saline vehicle weekly for 4 consecutive weeks. One week after the final instillation, which marks onset of ELS formation, mice were fed diets supplemented with 0, 4, or 10 g/kg DHA. One cohort of mice (n = 8/group) was terminated 13 weeks after the last cSiO2 instillation and assessed for autoimmune hallmarks. A second cohort of mice (n = 8/group) remained on experimental diets and was monitored for proteinuria and moribund criteria to ascertain progression of glomerulonephritis and survival, respectively. DHA consumption dose-dependently increased ω-3 PUFA content in the plasma, lung, and kidney at the expense of the ω-6 PUFA arachidonic acid. Dietary intervention with high but not low DHA after cSiO2 treatment suppressed or delayed: (i) recruitment of T cells and B cells to the lung, (ii) development of pulmonary ELS, (iii) elevation of a wide spectrum of plasma autoantibodies associated with lupus and other autoimmune diseases, (iv) initiation and progression of glomerulonephritis, and (v) onset of the moribund state. Taken together, these preclinical findings suggest that DHA supplementation at a human caloric equivalent of 5 g/d was an effective therapeutic regimen for slowing progression of established autoimmunity triggered by the environmental toxicant cSiO2.

Effect of suvorexant on morphine tolerance and dependence in mice: Role of NMDA, AMPA, ERK and CREB proteins.

The major problems of morphine use in the clinic are its tolerance and dependence. This study aimed to investigate the effect of suvorexant, a dual orexin receptor antagonist, on morphine-induced dependence and tolerance in mice and evaluate the level of NMDA, AMPA, ERK, p-ERK, CREB and p-CREB proteins in the brain. Tolerance and dependence were induced by repeated injection of morphine in mice (three times a day for 3 days, 50, 50, and 75 mg/kg /day). To evaluate the effects of the drugs on morphine-induced tolerance and dependence, suvorexant (30, 60 and 90 mg/kg), clonidine (positive control, 0.1 mg/kg) and saline were injected intraperitoneally 30 min before each injection of morphine. Tolerance and locomotor activity were assessed by tail-flick and open-field tests, respectively. The effect of suvorexant on the naloxone (5 mg/kg, ip)-induced morphine withdrawal, was also evaluated. Finally, the expression of proteins in the brain of mice was measured by western blot. Administration of suvorexant with morphine significantly reduced morphine-induced tolerance. Also, suvorexant attenuated the naloxone-precipitated opioid withdrawal. Suvorexant decreased morphine-enhanced levels of CREB and p-ERK proteins but did not affect the expression of NMDA and AMPA proteins compared to the morphine group. Suvorexant reduced morphine-induced tolerance and dependence through the inhibition of orexin receptors as well as changes in CREB and p-ERK protein levels in the brain.

Comparative Analgesic Effects of Intradermal and Subdermal Injection of Sterile Water on Active Labor Pain.

BACKGROUND: The labor pain is one of the factors encouraging pregnant women for cesarean section delivery. Recently, intradermal and subdermal injection of distilled water has shown to be effective in improving this pain. OBJECTIVES: The present study aimed to determine which method has a greater impact on labor pain reduction. METHODS: In this double-blind, randomized clinical trial, 121 nulliparous women with a gestational age of ≥ 37 weeks were randomly divided into three groups: (1) 0.5 cc sterile water injection subdermally at four sacral points with insulin needles (n = 40); (2) 0.5 cc sterile water injection intradermally (n = 39); and (3) needle contact with the mentioned points as the placebo (n = 42). Before the intervention, the VAS score was measured for labor pain, and it was repeated 10, 30, 60, and 90 min after the intervention. The results were compared between the three groups. RESULTS: Before the intervention, the mean VAS pain score had no significant difference between the three groups. However, 30, 60, and 90 min after the intervention, the mean pain score was significantly lower in the intradermal and subdermal injection groups than in the control group (P = 0.001); however, the difference between the intradermal and subdermal injection groups was not significant. CONCLUSIONS: The injection of distilled water by either intradermal or subdermal method was associated with a significant reduction in the pain score during labor, but there was no difference between these two methods in terms of decreasing labor pain. As sterile water injection is a safe, effective, and low-cost method, it is proposed to increase the knowledge of midwives and obstetricians about this method.

Comparison of the Never Repair with Fibrin Glue and Perineural Micro-Suture in Rat Model.

BACKGROUND: Many different methods for nerve repair have been introduced. Nerve repair with micro-suture is the gold standard one; however, the use of fibrin glue is a promising method. This study compared the never repair with fibrin glue and perineural micro-suture in rat model. METHODS: Ten 3-4 month old male rats, weighting between 250-300 grams were divided into two groups. Left sciatic nerves of the rats were transected and repaired with fibrin glue (TissucolR) in one group (A) and direct peri-neural micro-suture in another group (B). The time of nerve repair was compared between the two groups after 8 weeks. A biopsy from was taken from anastomosis site and the histopathological assessment was undertaken for axonal growth rate after anastomosis and compared between the two groups. RESULTS: The time of repair in group A was significantly lower than group B. Axonal growth rate was pretty similar between the two groups, and the difference was not significant. The mean (SD) time for repair of nerves with micro-sutures was 7.1 (1.5) minutes and the mean (SD) for repair of nerves with fibrin glue was 2.5 (0.5) minutes and the difference was significant. The number of calcification such as psammoma bodies was significantly higher in fibrin glue group. CONCLUSION: Nerve repair with fibrin glue was shown to be simpler and more time saving. The number of axons after the repair was not different in the two groups. We showed that fibrin glue may have more tissue reactions compared with micro-sutures.

Dietary Docosahexaenoic Acid Prevents Silica-Induced Development of Pulmonary Ectopic Germinal Centers and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse.

Ectopic lymphoid structures (ELS) consist of B-cell and T-cell aggregates that are initiated de novo in inflamed tissues outside of secondary lymphoid organs. When organized within follicular dendritic cell (FDC) networks, ELS contain functional germinal centers that can yield autoantibody-secreting plasma cells and promote autoimmune disease. Intranasal instillation of lupus-prone mice with crystalline silica (cSiO2), a respirable particle linked to human lupus, triggers ELS formation in the lung, systemic autoantibodies, and early onset of glomerulonephritis. Here we tested the hypothesis that consumption of docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid with anti-inflammatory properties, influences the temporal profile of cSiO2-induced pulmonary ectopic germinal center formation and development of glomerulonephritis. Female NZBWF1 mice (6-wk old) were fed purified isocaloric diets supplemented with 0, 4, or 10 g/kg DHA - calorically equivalent to 0, 2, or 5 g DHA per day consumption by humans, respectively. Beginning at age 8 wk, mice were intranasally instilled with 1 mg cSiO2, or saline vehicle alone, once per wk, for 4 wk. Cohorts were sacrificed 1, 5, 9, or 13 wk post-instillation (PI) of the last cSiO2 dose, and lung and kidney lesions were investigated by histopathology. Tissue fatty acid analyses confirmed uniform dose-dependent DHA incorporation across all cohorts. As early as 1 wk PI, inflammation comprising of B (CD45R+) and T (CD3+) cell accumulation was observed in lungs of cSiO2-treated mice compared to vehicle controls; these responses intensified over time. Marked follicular dendritic cell (FDC; CD21+/CD35+) networking appeared at 9 and 13 wk PI. IgG+ plasma cells suggestive of mature germinal centers were evident at 13 wk. DHA supplementation dramatically suppressed cSiO2-triggered B-cell, T-cell, FDC, and IgG+ plasma cell appearance in the lungs as well as anti-dsDNA IgG in bronchial lavage fluid and plasma over the course of the experiment. cSiO2 induced glomerulonephritis with concomitant B-cell accumulation in the renal cortex at 13 wk PI but this response was abrogated by DHA feeding. Taken together, realistic dietary DHA supplementation prevented initiation and/or progression of ectopic lymphoid neogenesis, germinal center development, systemic autoantibody elevation, and resultant glomerulonephritis in this unique preclinical model of environment-triggered lupus.

Association between +4259 T>G and -574 G>T Polymorphisms of TIM-3 with Asthma in an Iranian Population.

T-cell immunoglobulin and mucin domain (TIM)-3 have been shown to negatively regulate Th1 cell-mediated immunity. Activation of TIM-3 by galectin-9 induces Th1 cell apoptosis, which may contribute to skewing of immune response towards Th2-dominant immunity. The aim of this study was to determine whether certain genetic variations of TIM-3 influence predisposition to asthma in a sample of Iranian population. This case-control study was conducted on 209 patients with asthma and 200 healthy controls. The +4259 T>G and -574 G>T polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and amplification refractory mutation system-PCR(ARMS-PCR). Total serum IgE was further measured with ELISA. Notably, +4259T > G and-574G>T polymorphisms of TIM-3 were significantly associated with the susceptibility to asthma. In addition, the present study showed a significant difference between the distribution frequency of the GT + TT genotype and T allele on the +4259 T>G and -574 G>T locus between the groups.However, no correlation between the +4259 T > G and -574G > T polymorphisms and total serum IgE levels were observed. Together these results suggest that the TIM-3 +4259 T>G and -574 G>T polymorphisms are greatly associated with the susceptibility of Iranian population to asthma, which could open up new horizons for  better understanding of the pathophysiology, diagnostic, prognostic and therapeutic approaches of asthma.

Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: insight into the role of structure and size : Structure-activity relationships of non-digestible oligosaccharides.

PURPOSE: The direct effects of galacto-oligosaccharides (GOS), including Vivinal® GOS syrup (VGOS) and purified Vivinal® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To investigate structure-activity relationships, the effects of individual DP fractions of VGOS were evaluated. Moreover, the obtained results with GOS were compared with Caco-2 monolayers incubated with fructo-oligosaccharides (FOS) and inulin. METHODS: Caco-2 monolayers were pretreated (24 h) with or without specific oligosaccharides or DP fractions of VGOS (DP2 to DP6) before being exposed for 12 or 24 h to the fungal toxin deoxynivalenol (DON). Transepithelial electrical resistance and lucifer yellow permeability were measured to investigate barrier integrity. A calcium switch assay was used to study the reassembly of tight junction proteins. Release of CXCL8, a typical marker for inflammation, was quantified by ELISA. RESULTS: In comparison with PGOS, FOS and inulin, VGOS showed the most pronounced protective effect on the DON-induced impairment of the monolayer integrity, acceleration of the tight junction reassembly and the subsequent CXCL8 release. DP2 and DP3 in concentrations occurring in VGOS prevented the DON-induced epithelial barrier disruption, which could be related to their high prevalence in VGOS. However, no effects of the separate DP GOS fractions were observed on CXCL8 release. CONCLUSIONS: This comparative study demonstrates the direct, microbiota-independent effects of oligosaccharides on the intestinal barrier function and shows the differences between individual galacto- and fructo-oligosaccharides. This microbiota-independent effect of oligosaccharides depends on the oligosaccharide structure, DP length and concentration.

The intestinal barrier as an emerging target in the toxicological assessment of mycotoxins.

Mycotoxins, the secondary metabolites of fungal species, are the most frequently occurring natural food contaminants in human and animal diets. Risk assessment of mycotoxins focused as yet on their mutagenic, genotoxic and potential carcinogenic effects. Recently, there is an increasing awareness of the adverse effects of various mycotoxins on vulnerable structures in the intestines. In particular, an impairment of the barrier function of the epithelial lining cells and the sealing tight junction proteins has been noted, as this could result in an increased translocation of luminal antigens and pathogens and an excessive activation of the immune system. The current review aims to provide a summary of the available evidence regarding direct effects of various mycotoxins on the intestinal epithelial barrier. Available data, based on different cellular and animal studies, show that food-associated exposure to certain mycotoxins, especially trichothecenes and patulin, affects the intestinal barrier integrity and can result in an increased translocation of harmful stressors. It is therefore hypothesized that human exposure to certain mycotoxins, particularly deoxynivalenol, as the major trichothecene, may play an important role in etiology of various chronic intestinal inflammatory diseases, such as inflammatory bowel disease, and in the prevalence of food allergies, particularly in children.

Effects of Vitamin D on Endometriosis-Related Pain: A Double-Blind Clinical Trial.

BACKGROUND Endometriosis is a disabling disease of reproductive-age women. Dysmenorrhea, dyspareunia, and pelvic pain are the main symptoms of endometriosis. Its etiology is not clear. Endometriosis may have various causes, including vitamin D deficiency, but its effect is controversial. MATERIAL AND METHODS In this double-blind clinical trial, we enrolled patients with endometriosis diagnosed and treated by laparoscopy, with scores of at least 3 for of dysmenorrhea and/or pelvic pain at 8 weeks after surgical treatment. They were randomly prescribed vitamin D (50 000 IU weekly for 12 weeks) or placebo. Severity of pain in the 2 groups (placebo and treatment) was compared by VAS test at 24 weeks after surgical treatment. RESULTS There were 19 patients in the vitamin D group and 20 in the placebo group. Baseline characteristics in the 2 groups were similar. Following the treatment with vitamin D or placebo, we did not find significant differences in severity of pelvic pain (p=0.24) and dysmenorrhea (p=0.45) between the 2 groups. Mean pelvic pain at 24 weeks after laparoscopy in the vitamin D group was 0.84±1.74 and in placebo group it was 0.68±1.70 (p=0.513). Mean dysmenorrhea was 2.10±2.33 in the vitamin D group and 2.73±2.84 in the placebo group (p=0.45). CONCLUSIONS After ablative surgery for endometriosis, vitamin D treatment did not have a significant effect in reducing dysmenorrhea and/or pelvic pain.

Deoxynivalenol and Its Modified Forms: Are There Major Differences?

Considering the diverse toxic effects of the Fusarium toxin deoxynivalenol (DON), its common occurrence in wheat-based products, and its stability during processing, DON constitutes an increasing health concern for humans and animals. In addition to the parent compound DON, human and animal exposure encompasses the acetylated fungal metabolites 3-acetyl-deoxynivalenol (3ADON) and 15-acetyl-deoxynivalenol (15ADON) as well as the plant-derived DON-glucoside (DON3G) and the bacterial product de-epoxy-DON (DOM-1). In the current study we used the well-established Caco-2 cell model to compare the effects of these naturally occurring forms of DON on cell viability and markers of barrier integrity, as well as on the release of the pro-inflammatory chemokine chemokine CXC motif ligand (CXCL8). Results show that 3ADON is less potent in inducing adverse effects on barrier integrity when compared to DON, whereas 15ADON appears to be slightly more potent than DON. In contrast, DON3G and DOM-1 exerted no measurable adverse effects on the intestinal barrier. It was also demonstrated that galacto-oligosaccharides (GOS) are able to protect epithelial cells against DON and its acetylated forms, which suggests that GOS are beneficial food additives in the protection of vulnerable segments of the human population against adverse effects of DON and its derivatives.

Folic acid supplementation reduces plasma homocysteine in postmenopausal women.

Plasma homocysteine, which is increased after menopause, can be a risk factor for cardiovascular disease and osteoporosis. The purpose of the present study was to determine the effect of folic acid supplementation on plasma homocysteine in postmenopausal women. The study was performed as a randomized placebo controlled trial on 48 healthy postmenopausal women (aged 50-70 years) and plasma homocysteine of all women was measured. In the case group, folic acid, and in the control group, placebo was prescribed. The second plasma homocysteine was measured 16-17 weeks later and was compared in the two groups. There was no significant difference between the two groups according to age, BMI, parity, duration of menopause and the first plasma homocysteine level. Plasma homocysteine level was significantly lower in the case group than control group 16 weeks after folic acid administration (10.33 ± 3.51 µmol/l vs 13.21 ± 3.11 µmol/l, p=0.004). There was no significant correlation between plasma homocysteine level and BMI and parity. However, there was a weak-moderate positive correlation between plasma homocysteine and age (p<0.05, r=0.33), and there was a significant but weak correlation between plasma homocysteine and duration of menopause (p=0.05, r=0.28).

Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions.

BACKGROUND: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease--actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). METHODS: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. RESULTS: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (2.33 µg/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 µg/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. CONCLUSION: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. GENERAL SIGNIFICANCE: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy.

Dendritic cells inversely regulate airway inflammation in cigarette smoke-exposed mice.

The recruitment and activation of inflammatory cells into the respiratory system is considered a crucial feature in the pathophysiology of chronic obstructive pulmonary disease (COPD). Because dendritic cells (DCs) have a pivotal role in the onset and regulation of immune responses, we investigated the effect of modulating DC subsets on airway inflammation by acute cigarette smoke (CS) exposure. CS-exposed mice (5 days) were treated with fms-like tyrosine kinase 3 ligand (Flt3L) and 120g8 antibody to increase total DC numbers and deplete plasmacytoid DCs (pDCs), respectively. Flt3L treatment decreased the number of inflammatory cells in the bronchoalveolar lavage (BALF) of the smoke-exposed mice and increased these in lung tissue. DC modulation reduced IL-17 and increased IL-10 levels, which may be responsible for the suppression of the BALF cells. Furthermore, depletion of pDCs led to increased infiltration of alveolar macrophages while restricting the presence of CD103(+) DCs. This study suggests that DC subsets may differentially and compartment-dependent influence the inflammation induced by CS. pDC may play a role in preventing the pathogenesis of CS by inhibiting the alveolar macrophage migration to lung and increasing CD103(+) DCs at inflammatory sites to avoid extensive lung tissue damage.

Hawthorn ethanolic extracts with triterpenoids and flavonoids exert hepatoprotective effects and suppress the hypercholesterolemia-induced oxidative stress in rats.

OBJECTIVES: The current study was aimed to determine the bioactive constituents and biological effects of the Crataegus monogyna ethanolic extracts from bark, leaves and berries on hypercholesterolemia. MATERIALS AND METHODS: Oleanolic acid, ursolic acid, quercetin and lupeol concentrations were quantified by HPLC. Total phenol content and radical scavenging activity of extracts were also measured. The hypocholesterolemic, antioxidant, and hepatoprotective effects of the extracts were examined in hypercholesterolemic rats and compared with orlistat. RESULTS: The highest phenol content, oleanolic acid, quercetin and lupeol levels and free radical scavenging potency were found in the bark extract, and the highest ursolic acid level was found in the berries extract. Orlistat and extracts significantly (P<0.05) lowered the hypercholesterolemia-increased serum level of hepatic enzymes and lipid peroxidation level. Hawthorn's extracts protected from hepatic thiol depletion and improved the lipid profile and hepatic damages. CONCLUSION: Data suggested that hawthorn's extracts are able to protect from hypercholesterolemia-induced oxidative stress and hepatic injuries. Moreover, the hypocholesterolemic effect of extracts was found comparable to orlistat.