Effects of Melatonin,Progestagens, and the Ram on Out-of-Season Reproduction in Swedish Landrace Finewool Sheep

One hundred twenty-one Swedish Landrace Finewool ewes were treated with progestagen sponges (P), teaser ram stimulation (R), or melatonin implants plus teaser ram stimulation (M) in preparation for breeding with whole rams in August. Blood progesterone analyses from ewes in the R and M groups gave no evidence of luteal activity before the introduction of teaser rams. There were no significant differences between treatments for pregnancy rate (~90%). The P group had the most compact lambing season, while median breeding dates for M and R groups were delayed by one cycle. In those groups, the introduction of breeding rams was later found to have been too late. M and R differed significantly for probable conception date but not for lambing dates. Circa 30% of M ewes did not have a short 6 day ovulation cycle after the first ovulation, which resulted in a less concentrated lambing season than the other methods. Although no significant differences in litter size were seen among the 3 treatments, M had the highest group average, 2.25. The ewes in this study were not in very deep anestrous in the middle of August. This supports the conclusion that treatment with exogenous hormones is not necessary to breed Swedish Landrace Finewool ewes successfully in late August/early September.     

Innate Immune Receptors in Human Airway Smooth Muscle Cells: Activation by TLR1/2, TLR3, TLR4, TLR7 and NOD1 Agonists

Background

Pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs), recognize microbial components and trigger a host defense response. Respiratory tract infections are common causes of asthma exacerbations, suggesting a role for PRRs in this process. The present study aimed to examine the expression and function of PRRs on human airway smooth muscle cells (HASMCs).

Methods

Expression of TLR, NLR and RLR mRNA and proteins was determined using real-time RT-PCR, flow cytometry and immunocytochemistry. The functional responses to ligand stimulation were investigated in terms of cytokine and chemokine release, cell surface marker expression, proliferation and proteins regulating the contractile state.

Results

HASMCs expressed functional TLR2, TLR3, TLR4, TLR7 and NOD1. Stimulation with the corresponding agonists Pam₃CSK₄, poly(I:C), LPS, R-837 and iE-DAP, respectively, induced IL-6, IL-8 and GM-CSF release and up-regulation of ICAM-1 and HLA-DR, while poly(I:C) also affected the release of eotaxin and RANTES. The proliferative response was slightly increased by LPS. Stimulation, most prominently with poly(I:C), down-regulated myosin light chain kinase and cysteinyl leukotriene 1 receptor expression and up-regulated β₂-adrenoceptor expression. No effects were seen for agonist to TLR2/6, TLR5, TLR8, TLR9, NOD2 or RIG-I/MDA-5.

Conclusion

Activation of TLR2, TLR3, TLR4, TLR7 and NOD1 favors a synthetic phenotype, characterized by an increased ability to release inflammatory mediators, acquire immunomodulatory properties by recruiting and interacting with other cells, and reduce the contractile state. The PRRs might therefore be of therapeutic use in the management of asthma and infection-induced disease exacerbations.     

Deprived TLR9 Expression in Apparently Healthy Nasal Mucosa Might Trigger Polyp-Growth in Chronic Rhinosinusitis Patients

Background

The origin of nasal polyps in chronic rhinosinusitis is unknown, but the role of viral infections in polyp growth is clinically well established. Toll-like receptors (TLRs) have recently emerged as key players in our local airway defense against microbes. Among these, TLR9 has gained special interest in viral diseases. Many studies on chronic rhinosinusitis with nasal polyps (CRSwNP) compare polyp tissue with nasal mucosa from polyp-free individuals. Knowledge about changes in the turbinate tissue bordering the polyp tissue is limited.

Objectives

To analyse the role of TLR9 mediated microbial defense in tissue bordering the polyp.

Methods

Nasal polyps and turbinate tissue from 11 patients with CRSwNP and turbinate tissue from 11 healthy controls in total were used. Five biopsies from either group were analysed immediately with flow cytometry regarding receptor expression and 6 biopsies were used for in vitro stimulation with a TLR9 agonist, CpG. Cytokine release was analysed using Luminex. Eight patients with CRSwNP in total were intranasally challenged with CpG/placebo 24 hours before surgery and the biopsies were collected and analysed as above.

Results

TLR9 expression was detected on turbinate epithelial cells from healthy controls and polyp epithelial cells from patients, whereas TLR9 was absent in turbinate epithelial cells from patients. CpG stimulation increased the percentage cells expressing TLR9 and decreased percentage cells expressing VEGFR2 in turbinate tissue from patients. After CpG stimulation the elevated levels of IL-6, G-CSF and MIP-1β in the turbinate tissue from patients were reduced towards the levels demonstrated in healthy controls.

Conclusion

Defects in the TLR9 mediated microbial defense in the mucosa adjacent to the anatomic origin of the polyp might explain virus induced polyp growth. CpG stimulation decreased VEGFR2, suggesting a role for CpG in polyp formation. The focus on turbinate tissue in patients with CRSwNP opens new perspectives in CRSwNP-research.     

Inactivation of lactate dehydrogenase by UV radiation in the 300 nm wavelength region

Summary The effect of UV radiation on lactate dehydrogenase (LDH) was investigated. LDH from bovine heart was exposed to 3.6–18 kJ/m² of ultraviolet (UV) radiation in the 300 nm wavelength region. The activity of LDH was observed to decrease as a function of the dosage of UV radiation. The inactivation of LDH was independent of exposure rate at constant dosage of UV radiation. The decrease of LDH activity caused by UV 300 nm radiation was coupled to a decrease of the maximal velocity (V _max) while the Michaelis constant (K _m ) remained unchanged. The absorption spectrum of the LDH changed during exposure to UV radiation suggesting an alteration of tryptophan in the LDH molecule.On leave from Department of Ophthalmology, Ren-Ji Hospital affiliated to Shanghai No. 2 Medical University, Shanghai, People's Republic of China