Innate Immunity to Aspergillus Species

Summary: All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused by Aspergillus species, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses to Aspergillus species is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses against Aspergillus species that dictate the outcome of this host-microbe interaction.     

Serological Evidence of Canine Herpesvirus‐1 in Dogs of Kerman City,South‐east of Iran

Canine herpes virus‐1 (CHV‐1) is an alphaherpesvirus, which causes foetal and neonatal death as well as fertility problems in dogs. The virus is presumed to be enzootic in dogs all over the world, but no information was found about the seroprevalence of CHV‐1 from middle‐east countries. Therefore, this study was aimed to determine the seroprevalence of CHV‐1 among dogs in Kerman (south‐east of Iran). Blood samples were taken from 47 privately owned and 35 kennelled dogs, respectively. The entire sampled dogs were apparently healthy. Indirect immunofluorescence antibody (IFA) assay was used to detect antibodies against CHV‐1 in all sera. The overall CHV‐1 seroprevalence was estimated 20.7%, which was 22.9% and 19.1% for kennelled and owned dogs, respectively. Sex, parity and raising status (owned or kennels) did not differ significantly between seropositive and seronegative dogs. However, the infection rate was significantly higher in dogs older than 3 in comparison with younger groups (15.9% vs. 4.8%, P ≤ 0.05). In conclusion, this study revealed that CHV‐1 could be considered endemic in Iran, and more epidemiological researches are needed to identify the geographical distribution of diseases in Iran.     

Cardiovascular compression of the esophagus and spread of gastro‐esophageal reflux

Background Factors that determine the spread of gastro‐esophageal reflux (GER) along the length of the esophagus are not known. We investigated if cardiovascular (CV) compressions on the esophagus may determine the spread of refluxate into the proximal esophagus. Methods High‐resolution manometry (HRM) and multi‐channel intra‐luminal impedance recording (MIIR) were performed simultaneously in 10 normal subjects in the recumbent and upright positions. Pulsatile pressure increases on the esophagus (marker of CV compression) were identified on the HRM. Spread of refluxate into the esophagus was determined by the MIIR. Key Results Cardiovascular compression zones were observed in the esophagus in 9 out of 10 subjects in recumbent position. Forty percent of GER episodes were limited to the distal esophagus in the recumbent position and CV compression pressure was greater than distal esophageal pressure at the time of GER in all such cases. On the other hand, distal esophageal pressure was greater than CV compression pressure when the refluxate extended into the proximal esophagus. In the upright position, CV compression was less frequent than recumbent position and only 12% of GER episodes were limited to the distal esophagus. Conclusions & Inferences Cardiovascular compression of the esophagus is frequently observed in normal healthy subject and restricts the spread of refluxate into the proximal esophagus.     

Low Helicobacter pylori eradication rates with 4- and 7-day regimens in an Iranian population

BACKGROUND: In Iran, there is insufficient information on the efficacy of Helicobacter pylori eradication regimens shorter than 10 days. This study aims at assessing the efficacy of 4- and 7-day H. pylori eradication regimens in a high-incidence area of gastric cancer in Iran. METHODS: Subjects with an endoscopic diagnosis of gastritis, positive urease test, and a histological diagnosis of chronic gastritis were enrolled. Patients were randomly assigned to one of three groups: AOC7 (1000 mg amoxicillin, 20 mg omeprazole, and 500 mg clarithromycin twice daily for 7 days), FOT4 (200 mg furazolidone, 20 mg omeprazole, and 500 mg tetracycline twice daily for 4 days) and FOT7 (the same treatment as the FOT4 group but for 7 days). Sensitivity to these antibiotics was determined in all isolates recovered from culture. The efficacy of eradication was assessed 8 weeks after the end-of-treatment by the 14C-urea breath test. RESULTS: One hundred and twenty-eight patients were enrolled in the study. Culture was positive for 84 patients and none of these were resistant to amoxicillin, tetracycline or furazolidone, 1.2% were resistant to clarithromycin and 32.1% to metronidazole. Forty-five, 41 and 42 patients were randomly allocated to the AOC7, FOT4, and FOT7 groups, respectively. The intention-to-treat eradication rates were 35.5, 17.1, and 23.8% for the AOC7, FOT4, and FOT7 groups, respectively. CONCLUSION: Treatment regimens of 4 or 7 days are unacceptable for H. pylori infection in Iran, even in the presence of a favorable sensitivity profile.     

Overexpression of endothelial NO synthase induces angiogenesis in a co-culture model

OBJECTIVE: Angiogenesis is a complex multistep process that involves endothelial cell (EC) migration, proliferation and differentiation into vascular tubes. NO has been reported to be a downstream mediator in the angiogenic response to a variety of growth factors, but the mechanisms by which NO promotes neovessel formation is not clear. We hypothesized that NO directly contributes to EC migration and capillary tube formation. METHODS: Since previous studies have noted important biological differences between NO produced pharmacologically by NO-donor compounds compared to that from NO synthase (NOS), we used a cell-based gene transfer approach to increase NO production in a co-culture model of in vitro angiogenesis. Rat smooth muscle cells (SMCs) were transfected with plasmids containing VEGF(121), VEGF(165) (SMC(VEGF)), endothelial NOS (SMC(eNOS)) or the empty vector (SMC(Cont)). Expression of the eNOS in SMC(eNOS) was confirmed by Northern analysis, NADPH-diaphorase activity, and nitrite/nitrate levels, whereas VEGF production was confirmed using ELISA. Calf pulmonary artery ECs (CPAECs) were cultured on the fibrin matrix with (co-culture) or without underlying SMCs (monoculture). RESULTS: Co-culture of ECs with SMC(Cont) had no effect on EC differentiation compared with EC in monoculture (differentiation index, DI=2.8+/-3.4 vs. 2.1+/-2.8, respectively, NS). In contrast, co-culture with SMC(eNOS) resulted in the formation of extensive capillary-like structures within 48 h (DI=17.2+/-5.9, P<0.001 versus SMC(Cont)), which was significantly inhibited using a NOS inhibitor, L-NAME (3 mM) (DI=4.5+/-3.04, P<0.001 versus SMC(eNOS)). Similarly, SMC(VEGF121) induced an angiogenic response (DI=14.2+/-3.8), which was also significantly inhibited by L-NAME (DI=5.9+/-1.8, P<0.05). In using the Boyden chamber model, SMC(eNOS), but not SMC(Cont) increased EC migration to a similar extent as SMC(VEGF121), and both were significantly inhibited with L-NAME. CONCLUSIONS: These data support an important paracrine role for endogenously produced NO in EC migration and differentiation in vitro, and suggest that the cell-based eNOS gene transfer may be a useful approach to increase new blood vessel formation in vivo.     

Caprine cauda epididymal sperm motility pattern in the capacitation medium supplemented with leptin

Leptin is an adipocyte-derived hormone with a role in the reproductive system through metabolic signals. Studies have suggested that binding of leptin to its receptors which have been found in human and boar sperm activates biochemical pathways leading to sperm capacitation. The present study was designed to explore the effects of leptin on sperm kinetic pattern during capacitation in vitro. Epididymal spermatozoa were obtained from 30 adult goat testes in six replicates and incubated in capacitation medium (Ca²⁺-free Tyrode’s medium, Sperm-TALP) supplemented with 0 (Con, control group), 10 and 100 ng/mL (L10 and L100 groups, respectively). Motion parameters were assessed using computer-assisted sperm analysis system at 10, 30, 60, 120 and 240 min after sperm incubation at 37°C and 6 % CO₂. Exposure of spermatozoa to two different doses of leptin caused a significant increase (p?<?0.05) in total and progressive sperm motility, curvilinear and straight line velocity, linearity (Lin), mean angular displacement, amplitude of lateral head displacement (ALH) and beat cross-frequency (BCF) compared to the control group specially up to 60 min. There was not any significant difference between L10 and L100 groups in the evaluated parameters except for the first 10 min that L100 had better result in increasing Lin, ALH and BCF (p?<?0.05) and at the time of 240 min in which L10 showed a significant increase in all motion parameters. In conclusion, this study showed that leptin supplementation had significant effects on sperm motility patterns and so could enhance the sperm capacitation process.     

Fatal Case of Plasmodium vivax Malaria in a Splenectomized Patient

Malaria is a major problem in tropical and sub-tropical countries, with high morbidity and mortality. Splenectomy makes patients more susceptible to serious bacterial and parasitic infections. We report for the first time in Iran a fatal case of Plasmodium vivax malaria, confirmed by microscopic and molecular (Semi-nested multiplex PCR) tests in a patient who had undergone splenectomy due to hemolytic anemia.     

Role of CXCR2/CXCR2 ligands in vascular remodeling during bronchiolitis obliterans syndrome

Angiogenesis and vascular remodeling support fibroproliferative processes; however, no study has addressed the importance of angiogenesis during fibro-obliteration of the allograft airway during bronchiolitis obliterans syndrome (BOS) that occurs after lung transplantation. The ELR(+) CXC chemokines both mediate neutrophil recruitment and promote angiogenesis. Their shared endothelial cell receptor is the G-coupled protein receptor CXC chemokine receptor 2 (CXCR2). We found that elevated levels of multiple ELR(+) CXC chemokines correlated with the presence of BOS. Proof-of-concept studies using a murine model of BOS not only demonstrated an early neutrophil infiltration but also marked vascular remodeling in the tracheal allografts. In addition, tracheal allograft ELR(+) CXC chemokines were persistently expressed even in the absence of significant neutrophil infiltration and were temporally associated with vascular remodeling during fibro-obliteration of the tracheal allograft. Furthermore, in neutralizing studies, treatment with anti-CXCR2 Abs inhibited early neutrophil infiltration and later vascular remodeling, which resulted in the attenuation of murine BOS. A more profound attenuation of fibro-obliteration was seen when CXCR2(-/-) mice received cyclosporin A. This supports the notion that the CXCR2/CXCR2 ligand biological axis has a bimodal function during the course of BOS: early, it is important for neutrophil recruitment and later, during fibro-obliteration, it is important for vascular remodeling independent of neutrophil recruitment.