Vibratory stimulation enhances thyroid epithelial cell function.

The tissues of the body are routinely subjected to various forms of mechanical vibration, the frequency, amplitude, and duration of which can contribute both positively and negatively to human health. The vocal cords, which are in close proximity to the thyroid, may also supply the thyroid with important mechanical signals that modulate hormone production via mechanical vibrations from phonation. In order to explore the possibility that vibrational stimulation from vocalization can enhance thyroid epithelial cell function, FRTL-5 rat thyroid cells were subjected to either chemical stimulation with thyroid stimulating hormone (TSH), mechanical stimulation with physiological vibrations, or a combination of the two, all in a well-characterized, torsional rheometer-bioreactor. The FRTL-5 cells responded to mechanical stimulation with significantly (p<0.05) increased metabolic activity, significantly (p<0.05) increased ROS production, and increased gene expression of thyroglobulin and sodium-iodide symporter compared to un-stimulated controls, and showed an equivalent or greater response than TSH only stimulated cells. Furthermore, the combination of TSH and oscillatory motion produced a greater response than mechanical or chemical stimulation alone. Taken together, these results suggest that mechanical vibrations could provide stimulatory cues that help maintain thyroid function.

Blebbistatin-Loaded Poly(d,l-lactide-co-glycolide) Particles For Treating Arthrofibrosis.

Joint immobility is a debilitating complication of articular trauma that is characterized by thickening and stiffening of the joint capsule and the formation of fibrotic lesions inside joints. Capsule release surgery can temporarily restore mobility, but contraction often recurs due to the contractile activities of fibroblasts, which exert tension on the capsule ECM via nonmuscle myosin II. Based on these findings we hypothesized that blebbistatin, a drug that reversibly inhibits the activity of this protein, would relax ECM tension imposed by fibroblasts and reduce fibrosis. In this study, we characterized the effectiveness of blebbistatin as an anticontractile treatment. Given that sustained suppression of contractile activity may be required to achieve capsule release and reduce fibrosis, we compared the effects on fibroblast-mediated collagen ECM displacement of blebbistatin-loaded poly(lactide-co-gylcolide) (PLGA) particles versus bolus blebbistatin dosing. Time-lapse imaging of fluorescent microspheres embedded in collagen gels confirmed that PLGA/blebbistatin inhibited force generation and reduced both gel displacement and rate of displacement. In addition, collagen production at 10 days was significantly reduced. Taken together, these data indicate that blebbistatin-loaded PLGA particles can be used to inhibit fibroblast force-generation and reduce collagen production and lay the foundation for optimization of drug delivery technology for treating arthrofibrosis.

The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis.

Juvenile polyposis (JPS) is an autosomal dominant syndrome that predisposes individuals to develop gastrointestinal polyps and cancer. Germline point mutations in SMAD4 and BMPR1A have been identified as causing JPS in approximately 40-60% of patients, but few studies have looked at the rate of large deletions. In this study, we determined the overall prevalence of genetic changes of SMAD4 and BMPR1A by sequencing and by screening for larger deletions. DNA was extracted from 102 JPS probands, and each exon and intron-exon boundary of SMAD4 and BMPR1A were sequenced. Coding and non-coding exons of SMAD4 and BMPR1A were screened for deletions with multiplex ligation-dependent probe amplification (MLPA). By sequencing, 20 probands had point mutations of SMAD4 and 22 of BMPR1A. By MLPA, one proband had deletion of most of SMAD4, one of both BMPR1A and PTEN, one of the 5' end of BMPR1A, and another of the 5' end of SMAD4. The overall prevalence of SMAD4 and BMPR1A point mutations and deletions in JPS was 45% in the largest series of patients to date. Large deletions are less frequent in JPS patients, but represent other heritable causes of JPS, which should be screened for in pre-symptomatic genetic testing.

An extracellular α-L-arabinofuranosidase fromSclerotium rolfsii.

Activity of α-L-arabinofuranosidae (EC 3.2.1.55) ranged between 0.03 and 1.63 U/ml whenSclerotium rolfsii was grown in a synthetic medium containing different nitrogen and carbon sources. Agricultural and forest residues such as rice straw, corn cob, groundnut husk, and apple pomace were suitable substrates for enzyme production. Maximum activity, 4.2 U/ml, was with pre-treated corn cobs.