CC and CXC chemokines induce airway smooth muscle proliferation and survival

The increase in airway smooth muscle (ASM) mass is a major structural change in asthma. This increase has been attributed to ASM cell (ASMC) hyperplasia and hypertrophy. The distance between ASMC and the epithelium is reduced, suggesting migration of smooth muscle cells toward the epithelium. Recent studies have suggested a role of chemokines in ASMC migration toward the epithelium; however, chemokines have other biological effects. The objective of the current study is to test the hypothesis that chemokines (eotaxin, RANTES, IL-8, and MIP-1α) can directly influence ASMC mass by increasing the rate of proliferation or enhancing the survival of these cells. Human ASMCs were exposed to different concentrations of eotaxin, RANTES, IL-8, or MIP-1α. To test for proliferation, matched control and stimulated ASMC were pulsed with [(3)H]thymidine, or ASMCs were stained with BrdU and then analyzed with flow cytometry. Apoptosis was measured using Annexin V staining and flow cytometry. Expression of phosphorylated p42/p44 and MAPKs was assessed by Western blot. In a concentration-dependent manner, chemokines including eotaxin, RANTES, IL-8, and MIP-1α increased ASMC's [(3)H]thymidine incorporation and DNA synthesis. IL-8, eotaxin, and MIP-1α decreased the rate of apoptosis of ASMCs compared with the matched controls. A significant increase in phosphorylated p42/p44 MAPKs was seen after treating ASMCs with RANTES and eotaxin. Moreover, inhibition of p42/p44 MAPK phosphorylation reduced the level of chemokine-induced ASM proliferation. We conclude that chemokines might contribute to airway remodeling seen in asthma by enhancing the number and survival of ASMCs.     

Human Health Risk from Metals in Fish from Saudi Arabia: Consumption Patterns for Some Species Exceed Allowable Limits

Fish are a healthful source of protein, but contaminants in some fish pose a risk. While there are multiple risk assessments from Europe and North America, there are far fewer for other parts of the world. We examined the risks from mercury, arsenic, lead, and other metals in fish consumed by people in Jeddah area, Saudi Arabia, using site-specific data on consumption patterns and metal levels in fish. The U.S. Environmental Protection Agency's Hazard Quotient (HQ) and cumulative Hazard Index (HI) for non-cancer endpoints and Carcinogenic Index for cancer were used to determine the health risk based on fish consumption rates. Of the 13 fish species examined, HQ was greater than 1 (indicating elevated risk) in two species for arsenic, and seven species for methylmercury. The cumulative HI for all metals was above 1 for all but three species of fish at the mean consumption rates. Generally, fish species with HI above 1 for one sampling location, had HI above 1 for all sampling locations. The implications of these findings are discussed in the light of strategies for reducing risk from fish consumption while encouraging dietary intakes of fish with low mercury and arsenic levels.     

Infrapopulations of Procamallanus elatensis Fusco & Overstreet, 1979 (Nematoda: Camallanidae) in the rabbitfish Siganus rivulatus (Teleostei, Siganidae) from the Saudi coast of the Red Sea

Factors regulating gastrointestinal nematode infrapopulations are to a great extent density-dependent. Here, 23 natural infrapopulations (41-281 individuals) of the viviparous nematode Procamallanus elatensis (Camallanidae) from the fish Siganus rivulatus were found distributed in a well-defined fundamental niche (posterior 55% of the intestine). Immature worms were mostly found in the anterior third of this niche, while mature worms were found in aggregations posterior to them and followed by gravid females in the posterior 20% of the intestine. This distribution strongly suggests that worms migrate towards the posterior intestine while they mature, copulate and reproduce. In small infrapopulations, the sex ratios were distinctly female-biased and the number of gravid females was low. In large infrapopulations, the sex ratios were distinctly male-biased and the number of gravid females was high. However, the mean lengths of both immature males and females and mature females decreased dramatically as the infrapopulation size increased, while those of mature males increased significantly. These results strongly suggest intraspecific competition and density-dependent regulation of mean worm length, and the increase in the mean length of mature males strongly suggests intense sexual selection and competition between mature males. Production of larvae by female worms decreased significantly as the infrapopulation size increased, suggesting a density-dependent reduction in female worm fertility. The results are statistically significant and strongly suggest that infrapopulation self-regulation is through density-dependent mechanisms, in which development of immature worms, infrapopulation size, sex ratio, sexual selection and carrying capacity of the fundamental niche play essential roles in shaping and regulating the infrapopulations.     

The prevalence and associated risk factors of restless legs syndrome among Saudi adults

Sleep and Biological Rhythms - The aim of this cross-sectional study was to determine the prevalence, risk factors, other associated sleep disorders and commodities of Restless Legs Syndrome (RLS)...     

IL-17 Enhances Chemotaxis of Primary Human B Cells during Asthma

IL-17 is a pro-inflammatory mediator that is believed to play a critical role in regulating tissue inflammation during asthma, COPD, as well as other inflammatory disorders. The level of expression of IL-17 has been shown to be upregulated in lung bronchial tissue of asthmatic patients. Several reports have provided further evidence that this cytokine could play a key role in enhancing the migration of inflammatory as well as structural cells of the bronchial lung tissue during asthma and COPD. B cell infiltration to sites of inflammation during inflammatory disorders such as bowel disease, asthma and COPD has been reported. Accordingly, in this study we hypothesized that IL-17 may exert a chemotactic effect on primary B cells during asthma. We observed that B cells from asthmatic patients expressed significantly higher levels of IL-17RA and IL-17RC, compared to those of healthy subjects. Using an in-vitro migration assay, B cells were shown to migrate towards both IL-17A and IL-17F. Interestingly, blocking IL-17A and IL-17F signaling using either anti-IL-17R antibodies or MAP kinase inhibitors prevented in vitro migration of B cell towards IL-17. These observations indicate a direct chemotactic effect of IL-17 cytokines on primary peripheral blood B cells with higher effect being on asthmatic B cells. These findings revealed a key role for IL-17 in enhancing the migration of B cells to the lung tissue during asthma or COPD.     

The life cycle of Gyliauchen volubilis Nagaty, 1956 (Digenea: Gyliauchenidae) from the Red Sea

Although nothing is known about gyliauchenid life cycles, molecular phylogenetic studies have placed the Gyliauchenidae Fukui, 1929 close to the Lepocreadiidae Odhner, 1905. The gyliauchenid Gyliauchen volubilis Nagaty, 1956 was found in the intestine of its type-host, Siganus rivulatus, a siganid fish permanently resident in a lagoon within the mangrove swamps on the Egyptian coast of the Gulf of Aqaba. Larval forms of this trematode (mother sporocysts, rediae and cercariae) were found in the gonads and digestive gland of Clypeomorus clypeomorus (Gastropoda: Cerithiidae), a common snail in the same lagoon. So, this life cycle of G. volubilis was elucidated under natural conditions: eggs are directly ingested by the snail; mother sporocysts and rediae reach their maturity 3-6 and 11-13 weeks post-infection; rediae contain 23-29 developing cercariae; fully developed cercariae are gymnocephalus, without penetration glands, emerge from the snail during the night 16-18 weeks post-infection and rapidly encyst on aquatic vegetation (no second intermediate host); encysted metacercariae are not progenetic; 4-day-old metacercariae encysted on filamentous algae fed to S. rivulatus developed into fully mature worms 6-8 weeks post-infection. The cycle was completed in about 26 weeks and followed one of the three known patterns of lepocreadiid life cycles, and except for the gymnocephalus cercariae, the other larval stages are very similar to those of lepocreadiids. Generally, the life cycle of G. volubilis implicitly supports the phylogenetic relationship of Gyliauchenidae and Lepocreadiidae inferred from molecular phylogenetic studies.     

Infrapopulations of Gyliauchen volubilis Nagaty, 1956 (Trematoda: Gyliauchenidae) in the rabbitfish Siganus rivulatus (Teleostei: Siganidae) from the Saudi coast of the Red Sea

In hermaphroditic helminth parasites, infrapopulation size or mating group size mostly affects some processes acting within the infrapopulation. Here, 30 natural infrapopulations (12-154 individuals) of the intestinal trematode Gyliauchen volubilis Nagaty, 1956 from the fish Siganus rivulatus consisting of newly excysted juveniles, immature and mature worms were found distributed in a well-defined fundamental niche (anterior 40% of the intestine). In small infrapopulations, all stages of the parasite were alive. In larger infrapopulations, differential mortality was only and consistently observed among newly excysted juveniles, and gradually increased to include most or all juveniles in the largest infrapopulations. Among mature worms, the mean worm length seemed unaffected by the infrapopulation size. However, the ratio mean testis size-mean ovary size, a reliable indicator of resource allocation to the male function and of opportunities for cross fertilization, significantly increased with mating group size. In small infrapopulations, all stages of the parasite were scattered along the niche, and never seen in mating pairs (possibly reproduced by self-fertilization). In larger infrapopulations, newly excysted juveniles and immature worms were scattered along the anterior two thirds of the niche, while mature worms were constantly found aggregated in its posterior third (narrow microhabitat), where some were arranged in mating pairs. The probability of mating reciprocally or unilaterally was dependent on body size. The mean number of uterine eggs per worm significantly decreased and their mean sizes significantly increased with mating group size. The results are statistically significant and suggest that infrapopulation self-regulation is greatly associated with its size.     

Symptoms and risk for obstructive sleep apnea among sample of Saudi Arabian adults

The aim of this study was to determine the risk and symptoms for obstructive sleep apnea (OSA) among Saudi Arabian adults. This cross-sectional survey among healthy participants was conducted at King Abdulaziz Medical City-Riyadh (KAMC-R). The Berlin Questionnaire (BQ) was used to assess the risk of OSA, and Epworth Sleepiness Scale (ESS) was used to measure excessive daytime sleepiness (EDS) as a manifestation of OSA in participants. The total number of participants was 2095, mean age of the sample was 42.3 (±15.5) years and 848 (40.7%) were females. Using BQ, 31.9% of the participants were classified as high risk for OSA (33.4% among females and 31.1% among males). The risk for OSA increased with age: 19.4% among the young group (≤29 years), 35.2% among the middle-aged (30–59 years), and 41% among the elderly (≥60 years). The risk of symptomatic OSA by combining both BQ and ESS was 7.8% and increased with age (5.5% among the young group, 8.5% among the middle-aged, and 9.7% among the elderly), but there was no difference between gender (8% among females vs. 7.7% among males). This study showed that the risk for OSA is very high, is equal in both genders and it increases with age and obesity.

     

Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils

Background

Subepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-β and IL-11, however, the mechanism regulating this process is not fully understood.

Objective

In this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines.

Methods

Eosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-β and IL-11 was determined using real time PCR and ELISA assays.

Results

The basal expression levels of eosinophil derived TGF-β and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-β and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release.

Conclusions

Th17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases.     

Infrapopulations of Sclerocollum saudii Al-Jahdali, 2010 (Acanthocephala: Cavisomidae) in the rabbitfish Siganus rivulatus (Teleostei, Siganidae) from the Saudi coast of the Red Sea

In infrapopulations of helminth parasites, density-dependent effects, through some form of intra- and interspecific competition, play an important role in shaping and regulating the infrapopulations. The mechanisms responsible for these processes have often been observed in laboratory studies and rarely studied under natural conditions. Here, 24 natural infrapopulations (77-447 individuals) of the acanthocephalan Sclerocollum saudii Al-Jahdali, 2010 from the fish Siganus rivulatus consisted of cystacanths, newly excysted juveniles, immature and mature worms, distributed in a well-defined fundamental niche (anterior 60% of the intestine). Each of these stages exhibited a significantly different longitudinal distribution within this niche. In small infrapopulations, cystacanths and newly excysted juveniles were found in the sixth 10% of the intestine, immature worms in the fifth 10% and mature worms in the anterior 40% of the intestine. However, their proportions followed a clear ascending order in each infrapopulation, and the female-male ratios of both immature and mature worms were distinctly female-biased. In large infrapopulations, mature worms existed partially in the site of immature ones, where a differential mortality among immature females was constantly observed. However, the proportions of immature worms increased significantly and those of mature worms decreased significantly, the mean lengths of immature and mature females decreased dramatically and the female-male ratios were distinctly male-biased. The mean sizes of immature and mature males seemed stable through all infrapopulations. The distribution of mature males and females suggests intense male-male competition for access to females, and reveals that larger females are copulated prior to the smaller ones. The results are statistically significant and suggest that infrapopulation self-regulation is through density-dependent mechanisms, in which immature females may play a key role.