Lactobacillus rhamnosus GG and Streptococcus thermophilus induce suppressor of cytokine signalling 3 (SOCS3) gene expression directly and indirectly via interleukin-10 in human primary macrophages

In the present study we have characterized T helper type 2 (Th2) [interleukin (IL)-10]/Th1 (IL-12) cytokine expression balance in human primary macrophages stimulated with multiple non-pathogenic Gram-positive bacteria used in the food industry and as probiotic substances. Bacteria representing Lactobacillus, Bifidobacterium, Lactococcus, Leuconostoc, Propionibacterium and Streptococcus species induced anti-inflammatory IL-10 production, although quantitative differences between the bacteria were observed. S. thermophilus was able to induce IL-12 production, while the production of IL-12 induced by other bacteria remained at a low level. The highest anti-inflammatory potential was seen with bifidobacteria, as evidenced by high IL-10/IL-12 induction ratios. All studied non-pathogenic bacteria were able to stimulate the expression of suppressor of cytokine signalling (SOCS) 3 that controls the expression of proinflammatory cytokine genes. Lactobacillus and Streptococcus species induced SOCS3 mRNA expression directly in the absence of protein synthesis and indirectly via bacteria-induced IL-10 production, as demonstrated by experiments with cycloheximide (CHX) and anti-IL-10 antibodies, respectively. The mitogen-activated protein kinase (MAPK) p38 signalling pathway played a key role in bacteria-induced SOCS3 gene expression. Enhanced IL-10 production and SOCS3 gene expression induced by live non-pathogenic Lactobacillus and Streptococcus is also likely to contribute to their immunoregulatory effects in vivo.     

Expression of cellular fibronectin and tenascin in the rabbit cornea after excimer laser photorefractive keratectomy: a 12 month study.

An indirect immunohistochemical technique was used to monitor the expression of cellular fibronectin (cFN) and tenascin (TN) in the rabbit cornea after photorefractive keratectomy (PRK) in a 1 year follow up study. Rabbits received a 5.0 D myopic PRK, and were killed 3 days, 1, 3, 6, or 12 months after the operation. In most corneas, secondary epithelial defects appeared after the primary healing (mean 6.3 (SD 1.2) days). Corneal haze appeared a few weeks after PRK and was observed throughout the follow up. Three days after wounding an immunoreaction for cFN was observed as a bright narrow subepithelial line, but no immunoreaction for TN could be seen in the anterior third of the corneal stroma. However, at 1-6 months a similar location of immunoreactions for both cFN and TN was observed. Both were found in the anterior stroma at depths of 30-50 microns. At 12 months, only a trace of cFN immunoreaction but no TN immunoreaction could be discerned. Our results suggest that subepithelial scar tissue contains both cFN and TN up to 12 months.     

An investigation into the relationship between soft tissue body composition and bone mineral density in a young adult twin sample

The purpose of this study was to investigate the relationship of fat mass (FM) and lean mass (LM) with bone mineral density (BMD) independent of genetic effects. We also assessed the extent to which genetic and environmental influences explain the associations between these phenotypes. Body composition and BMD were measured using dual‐energy X‐ray absorptiometry in 57 monozygotic and 92 same‐sex dizygotic twin pairs, aged 23 to 31 years, chosen to represent a wide range of intrapair differences in body mass index (BMI; 0 to 15.2 kg/m²). Heritability estimates were adjusted for height and gender. In multiple linear regression analysis, intrapair differences in both FM and LM were independently associated with intrapair differences in BMD at most skeletal sites after adjustment for gender and differences in height. Within monozygotic and dizygotic pairs, LM was a significantly stronger predictor of whole‐body BMD than FM (p < .01). Additive genetic factors explained 87% [95% confidence interval (CI) 80%–91%), 81% (95% CI 70%–88%), and 61% (95% CI 41%–75%) of the variation in whole‐body BMD, LM, and FM, respectively. Additive genetic factors also accounted for 69% to 88% of the covariance between LM and BMD and for 42% to 72% of the covariance between FM and BMD depending on the skeletal site. The genetic correlation between LM and whole‐body BMD (r_g = 0.46, 95% CI 0.32–0.58) was greater than that of FM and whole‐body BMD (r_g = 0.25, 95% CI 0.05–0.42). In conclusion, our data indicate that peak BMD is influenced by acquired body weight as well as genetic factors. In young adulthood, LM and BMD may have more genes in common than do FM and BMD. © 2011 American Society for Bone and Mineral Research.     

Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy

BACKGROUND: Autoantibodies to glutamic acid decarboxylase (GAD-A) are present in type 1 diabetes and stiff man syndrome (SMS), and have also been reported in cerebellar ataxia. Epilepsy was present in 4 of 19 patients with SMS and GAD-A, implying that epilepsy sometimes is associated with anti-GAD autoimmunity. METHODS: The authors investigated the prevalence of GAD-A in patients with therapy-resistant localization-related epilepsy (n = 51) and generalized epilepsy (n = 49) by a radiobinding assay. The positive samples were confirmed by immunohistochemistry and immunoblotting of recombinant human GAD65. RESULTS: GAD-A were found in eight patients with localization-related epilepsy, whereas none of the patients with generalized epilepsy, other neurologic disorders (n = 38), or the control subjects (n = 48) had GAD-A. Two patients had high levels of GAD-A, similar to SMS, whereas six patients had significantly lower titers, characteristic of type 1 diabetes. The two patients with high levels of GAD-A had GAD-A both in serum and CSF by immunohistochemistry and immunoblotting. Both of them had longstanding therapy-resistant temporal lobe epilepsy but did not have diabetes. One had a history of autoimmune disease, whereas the other had serologic evidence of multiple autoantibodies without any clinical signs of autoimmune disease. CONCLUSIONS: GAD autoimmunity may be associated with refractory localization-related epilepsy.     

A locus for autosomal dominant keratoconus: linkage to 16q22.3-q23.1 in Finnish families

PURPOSE: The estimated world-wide prevalence of keratoconus is 50 to 230 per 100,000 in the general population. Sporadic keratoconus is the leading cause of corneal transplantation surgery in Western countries. Positive family history has been reported in 6% to 8% of patients. The purpose of this study was to map the disease locus in 20 Finnish families with autosomal dominant keratoconus, each family having two or more affected members and with no other associated genetic disease. METHODS: DNA was extracted from blood samples, collected from 42 affected and 34 unaffected family members. Genomic DNA from patients and their parents, was typed for alleles of 292 polymorphic markers. A genome-wide screening was performed to localize the disease gene. Fluorescent markers were amplified by polymerase chain reaction and separated on an automated sequencer. Allele sizes were assigned to each family member, after which LOD scores were calculated. RESULTS: The disease locus was mapped to chromosome 16q, between the markers D16S2624 and D16S3090, with a maximum parametric multipoint LOD score of 4.10 and corresponding nonparametric score of 3.27 (NPL, P = 0.00006). Evidence from 20 families provided support for the linkage, consistent with a single locus for familial autosomal dominant keratoconus without heterogeneity. CONCLUSIONS: This study is the first genome-wide linkage study to map the keratoconus gene. The results suggest that the causative gene in keratoconus is located within the 16q22.3-q23.1 chromosomal region.     

Efficacy of cold gel for soft tissue injuries: a prospective randomized double-blinded trial

BACKGROUND: The use of cold treatment to limit edema, decrease pain, and induce effective muscle relaxation in soft tissue injuries is widespread. PURPOSE: To compare the efficacy of a novel cold gel with that of a placebo gel in patients with a soft tissue injury. STUDY DESIGN: Prospective randomized double-blinded controlled study. METHODS: Seventy-four patients with sports-related soft tissue injury were randomly assigned to active cold gel (Ice Power) or placebo gel groups. The gel was applied four times daily on the skin for 14 days. Clinical assessment was made after 7, 14, and 28 days with use of visual analog scale ratings. RESULTS: Pain scores decreased from 59 to 30 during the first week, to 14 by the second, and to 7 by the end of study in the cold gel group. In the placebo group, pain scores decreased from 58 to 45, 26, and 13, respectively (significant difference). Patient satisfaction with treatment was 71 in the cold gel group and 44 in the placebo group (significant difference). Disability decreased significantly more rapidly in the cold gel group. CONCLUSIONS: Cold gel therapy provided an effective and safe treatment for sports-related soft tissue injuries.