Comparison of mechanical properties and host tissue response to OviTex™ and Strattice™ surgical meshes

Hernia - This study compared the in vitro/benchtop and in vivo mechanical properties and host biologic response to ovine rumen-derived/polymer mesh hybrid OviTex™ with porcine-derived...     

Ectopic bone formation of human bone morphogenetic protein-2 gene transfected goat bone marrow-derived mesenchymal stem cells in nude mice

onemorphogenetic proteins (BMPs)haveapowerfulcapacitytoelicitnewboneformation .ThereareseveraldeliverymethodsofBMPsintreatingbonedefects ,oneofwhichisgenetherapy .Retrovirus,adenovirusandadeno associatedvirushavebeenutilizedtodeliverBMPgene .1,2 Sincethedirectuseofthesevectorshasseveraldisadvantages ,wehavedevelopedexvivo genetherapytechniquewhichinvolvestheisolationandcultivationofautologousbonemarrow derivedmesenchymalstemcells (MSCs) ,transfectionofthecellsinvitroandimplantationofthesec…     

Quantitative analysis of distribution and fate of human lung cancer emboli labeled with 125I-5-iodo-2′-deoxyuridine in nude mice

The chemical and radio toxicity of ¹²⁵-5-iodo-2-deoxyuridine (¹²⁵IUDR) on 870127T human lung cancer (HLC) cells grown in tissue cultures and the quantitative analysis of the distribution and fate of ¹²⁵IUDR-labeled 870127T HLC cells in nude mice were evaluated. After 870127T HLC cells were plated and ¹²⁵IUDR was added to the dishes at levels ranging from 0.1 µCi/ml to 5.0 µCi/ml of media, the growth rate of the cells for 24h was similar to that of non-labeled cells. Nude mice were given intravenous injections of ¹²⁵IUDR labeled 870127T HLC cells and killed at various intervals ranging from 5 min to 24 h after injection. Organs were collected, processed, and monitored. The lung contained most of the tumor cells at all intervals and the number of tumor cells in the lung decreased gradually post-injection. The tumor cells died rapidly, and only about 1.5% of all cell survived after 24 h post-injection. This study confirmed that very few surviving tumor cells are needed to cause metastasis.     

Use of Bioglue™ to seal a difficult to treat air leak in a complicated empyema patient

Surgical sealants have been used in thoracic surgery in an effort to reduce air leak duration, intercostal drain duration, length of stay and complications. They are instilled over a defect usually treated with other means. We herein present the technique of controlling a difficult to treat defect by directly instilling Bioglue? alone into a crater, caused during empyema Video-assisted thoracic surgery in a 50-year-old patient with a trapped lung. This deep crater had caused a significant air leak rendering intraoperative ventilation challenging. After instillation, the dependent lung was kept blocked. With this technique, the Bioglue? polymerized and the air leak was dramatically decreased making ventilation and eventually extubation of the patient feasible. Instillation of Bioglue? directly into a large lung defect could be a choice of action to decrease complicated air leaks, otherwise impossible to treat with other means, in patients with trapped lung.     

Mechanism of the immunosuppressive effect in vivo of novel immunosuppressive drug β-SQAG9, which inhibits the response of the CD62L T-cell subset

Introduction

We synthesized sulfo-glycolipid, β-SQAG9 (designate □ β-SQAG9 liposome, because it efficiently forms a liposome structure) that possessed immunosuppressive effects such as inhibition of T-cell responses in human allogeneic MLR and skin allograft survival in rats, and bound to CD62L (L-selectin) in vitro. In this study, we further investigated the immunosuppressive mechanism in vivo by β-SQAG9 liposome in a skin-allografted rat model.

Methods

ACI rats (RT1^a) were grafted skin of LEW rats (RT1¹) treated with PBS or β-SQAG9 liposome IV once a day for 7 days. Subsequently, we investigated the population of T cells and CD62L⁺ T-cell subset in the spleen, axillary lymph nodes (ALNs), and peripheral blood of skin-allografted rats by two-color flow cytometry.

Results

Five of 11 (45.5%) rats that were treated with 50 mg/kg β-SQAG9 liposome showed graft survival and another showed moderate rejection in graft. The CD62L⁺ T-cell subset population in ALNs of β-SQAG9 liposome-treated rats decreased in a dose-dependent manner. No significant difference in the T-cell population was observed between the β-SQAG9 and control groups. These data suggest that β-SQAG9 could bind to the CD62L⁺ T-cell subset in vivo as well as in vitro and affect T-cell migration, which might lead to T-cell tolerance in vivo.     

Acceleration of wound repair by curcumin in the excision wound of mice exposed to different doses of fractionated γ radiation

Fractionated irradiation (IR) before or after surgery of malignant tumours causes a high frequency of wound healing complications. Our aim was to investigate the effect of curcumin (CUM) on the healing of deep excision wound of mice exposed to fractionated IR by mimicking clinical conditions. A full-thickness dermal excision wound was created on the shaved dorsum of mice that were orally administered or not with 100 mg of CUM per kilogram body weight before partial body exposure to 10, 20 or 40 Gy given as 2 Gy/day for 5, 10 or 20 days. The wound contraction was determined periodically by capturing video images of the wound from day 1 until complete healing of wounds. Fractionated IR caused a dose-dependent delay in the wound contraction and prolonged wound healing time, whereas CUM administration before fractionated IR caused a significant elevation in the wound contraction and reduced mean wound healing time. Fractionated IR reduced the synthesis of collagen, deoxyribonucleic acid (DNA) and nitric oxide (NO) at different post-IR times and treatment of mice with CUM before IR elevated the synthesis of collagen, DNA and NO significantly. Histological examination showed a reduction in the collagen deposition, fibroblast and vascular densities after fractionated IR, whereas CUM pre-treatment inhibited this decline significantly. Our study shows that CUM pre-treatment accelerated healing of irradiated wound and could be a substantial therapeutic strategy in the management of irradiated wounds.     

Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.     

Predicting response to bacillus Calmette-Guérin (BCG) in patients with carcinoma in situ of the bladder

PurposeCurrently, there is no reliable tool to predict response to intravesical bacillus Calmette-Guérin (BCG). Based on the fact that BCG is a Th1-polarizing immunotherapy, we attempt to correlate the pretreatment immunologic tumor microenvironment (Th1 or Th2) with response to therapy.Materials and methodsBladder cancer patients with initial diagnosis of carcinoma in situ (Tis) were stratified based on their response to BCG treatment. A total of 38 patients met inclusion criteria (20 patients who responded and 18 patients who did not respond). Immunohistochemical (IHC) methods known to assess the type of immunologic microenvironment (Th1 vs. Th2) were performed on tumor tissue obtained at initial biopsy/resection: the level of tumor eosinophil infiltration and degranulation (Th2 response); the number of tumor-infiltrating GATA-3⁺ (Th2-polarized) lymphocytes; and the number of tumor-infiltrating T-bet⁺ (Th1-polarized) lymphocytes. Results obtained from these metrics were correlated with response to treatment with BCG immunotherapy.ResultsThe IHC metrics of the tumor immune microenvironment prior to BCG treatment were each statistically significant predictors of responders (R) vs. nonresponders (NR). Eosinophil infiltration and degranulation was higher for R vs. NR: 1.02±0.17 vs. 0.5±0.12 (P = 0.01) and 1.1±0.15 vs. 0.56±0.15 (P = 0.04), respectively. Ratio of GATA-3⁺ (Th2-polarized) lymphocytes to T-bet⁺ (Th1-polarized) lymphocytes was higher for R vs. NR: 4.85±0.94 vs. 0.98±0.19 (P<0.001). The 3 markers were combined to create a Th2 signature biomarker, which was a statistically significant (P<0.0001) predictor of R vs. NR. All IHC markers demonstrated that a preexisting Th1 immunologic environment within the tumor was predictive of BCG failure.ConclusionThe Th1 vs. Th2 polarization of bladder tumor immune microenvironment prior to treatment with BCG represents a prognostic metric of response to therapy. If a patient has a preexisting Th1 immunologic response within the tumor, there is no value in using a therapy intended to create a Th1 immunologic response. An algorithm integrating 3 IHC methods provided a sensitive and specific technique that may become a useful tool for pathologists and urologists to predict response to BCG in patients with carcinoma in situ of the bladder.     

The response of 0steoblasts to parathyroid hormone (PTH 1–34) in vitro

Morphological study of osteoblasts of the endocranial aspect of the rat calvarium showed that they responded to the 1–34 fragment of parathyroid hormone in exactly the same way as to parathyroid extract : thus, the osteoblasts become elongated and aligned parallel to one another and to the collagen in the most superficial layer of the bone matrix. Fluctuations in PTH levels may conceivably relate to the lamellar texture of mature bone.     

The dose–response effect of insulin sensitivity on albuminuria in children according to diabetes type

Background

Insulin resistance is associated with microalbuminuria among youth with diabetes mellitus. We sought to determine the dose–response effect of insulin sensitivity (IS) on the magnitude of albuminuria and whether there is a threshold below which urine albumin excretion increases.

Methods

These analyses included participants from the SEARCH for Diabetes in Youth Study with incident diabetes who completed a baseline study visit (n?=?2988). We estimated IS using a validated equation incorporating waist circumference, HbA1C, and fasting serum triglycerides. Multivariate regression analyses were performed to assess the effect of IS on urine albumin creatinine ratio (UACR), stratified by diabetes type. The IS threshold was then determined using segmented regressions within each diabetes type and incorporated into the multivariate model.

Results

There was an association between IS and UACR in type 2 diabetes only (beta?=??0.39; p?<?0.001). There was strong statistical evidence for a threshold effect of IS score on UACR in the group of youth with type 2 (beta?=?0.40; p?<?0.001) but not type 1 diabetes (p?=?0.3).

Conclusions

In cross-sectional analyses, there is a negative association between IS and UACR in youth with type 2 but not type 1 diabetes, and this association likely includes a threshold effect of IS on UACR.