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Biologic Effects (biologic + effects)
Selected AbstractsA Review of the Biologic Effects, Clinical Efficacy, and Safety of Silicone Elastomer Sheeting for Hypertrophic and Keloid Scar Treatment and ManagementDERMATOLOGIC SURGERY, Issue 11 2007BRIAN BERMAN MD Silicone elastomer sheeting is a medical device used to prevent the development of and improve the appearance and feel of hypertrophic and keloid scars. The precise mechanism of action of silicone elastomer sheeting has not been defined, but clinical trials report that this device is safe and effective for the treatment and prevention of hypertrophic and keloid scars if worn over the scar for 12 to 24 hours per day for at least 2 to 3 months. Some of the silicone elastomer sheeting products currently on the market are durable and adhere well to the skin. These products are an attractive treatment option because of their ease of use and low risk of adverse effects compared to other treatments, such as surgical excision, intralesional corticosteroid injections, pressure therapy, radiation, laser treatment, and cryotherapy. Additional controlled clinical trials with large patient populations may provide further evidence for the efficacy of silicone elastomer sheeting in the treatment and prevention of hypertrophic and keloid scars. The purpose of this article is to review the literature on silicone elastomer sheeting products and to discuss their clinical application in the treatment and prevention of hypertrophic and keloid scars. [source] Low-dose TNF-, protects against hepatic ischemia-reperfusion injury in mice: Implications for preconditioningHEPATOLOGY, Issue 1 2003Narci Teoh Tumor necrosis factor , (TNF-,) is implicated in the pathogenesis of hepatic ischemia reperfusion injury but can also prime hepatocytes to enter the cell cycle. Ischemic preconditioning protects against ischemia-reperfusion (IR) liver injury and is associated with activation of nuclear factor ,B (NF-,B) and cell cycle entry. We examined the pattern of TNF-, release during hepatic IR in the presence or absence of ischemic preconditioning, and we tested whether a single low-dose injection of TNF could mimic the biologic effects of ischemic preconditioning. In naïve mice, hepatic and plasma levels of TNF-, rose during hepatic ischemia, reaching high levels after 90 minutes; values remained elevated during reperfusion until 44 hours. Following the ischemic preconditioning stimulus, there was an early rise in hepatic and serum TNF-, levels, but, during a second prolonged ischemic interval peak, TNF-, values were lower than in naïve mice and declined to negligible levels by 2 hours reperfusion. An injection with 1 ,g or 5 ,g/kg body weight TNF-, 30 minutes prior to hepatic IR substantially reduced liver injury determined by liver histology and serum alanine aminotransferase (ALT) levels. As in ischemic preconditioning, TNF-, pretreatment activated NF-,B DNA binding, STAT3, cyclin D1, cyclin-dependent kinase 4 (cdk4) expression, and cell cycle entry, determined by proliferating cell nuclear antigen (PCNA) staining of hepatocyte nuclei. In conclusion, the hepatoprotective effects of "preconditioning" can be simulated by TNF-, injection, which has identical downstream effects on cell cycle entry. We propose that transient increases in TNF-, levels may substitute for, as well as, mediate the hepatoprotective effects of ischemic preconditioning against hepatic IR injury. [source] Emerging targets and novel strategies in the treatment of AIDS-related Kaposi's sarcoma: Bidirectional translational scienceJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006Bruce J. Dezube Through the mentorship process, Dr. Arthur Pardee emphasized the critical importance of bidirectional translational research,not only advancing drug development from bench to bedside, but also bringing back precious clinical material to the laboratory to assess the biologic effects of therapeutic agents on their targets. This mini-review focuses on the signal transduction pathways of Kaposi's sarcoma (KS) and on how the knowledge of such pathways has led to the rational development of molecularly targeted pathogenesis-driven therapies. Acquired immune deficiency syndrome (AIDS) related-KS results from co-infection with human immunodeficiency virus and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8), which leads to the development of an angiogenic-inflammatory state that is critical in the pathogenesis of KS. KS is driven by KSHV/HHV8-specific pathways, which include viral G protein-coupled receptor (vGPCR), viral interleukin-6 (vIL-6), and viral chemokine homologues. In addition, cellular growth/angiogenic pathways, such as vascular endothelial growth factor (VEGF), insulin-like growth factor, platelet-derived growth factor (PDGF), angiopoietin and matrix metalloproteinases (MMPs) are "pirated" by KSHV/HHV8. As a very tangible example of how translational research has led to a marked improvement in patient outcome, the signal transduction inhibitor imatinib (a tyrosine kinase inhibitor of c-kit and PDGF) was administered to patients with KS whose tumors were serially biopsied. Not only did the patients' tumors regress, but also the regression was correlated with the inhibition of PDGF receptor (PDGFR) in the biopsy samples. Recent and future clinical trials of molecularly targeted therapy for the treatment of KS are a prelude to a shift in the paradigm of how KS is managed. J. Cell. Physiol. 209: 659,662, 2006. © 2006 Wiley-Liss, Inc. [source] Double-Blind Placebo-Controlled Trial of Adjuvant Pamidronate with Palliative Radiotherapy and Intravenous Doxorubicin for Canine Appendicular Osteosarcoma Bone PainJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2009T.M. Fan Background: Canine osteosarcoma (OSA) causes focal malignant osteolysis leading to severe pain. Despite the documented efficacy of radiotherapy or IV aminobisphosphonates for managing cancer bone pain, their potential combined therapeutic value has not been reported in OSA-bearing dogs. Hypothesis: Pamidronate combined with standardized palliative therapy will improve pain control and bone biologic effects in OSA-bearing dogs. Animals: Fifty dogs with appendicular OSA treated with standardized palliative therapy and either pamidronate or sterile saline. Methods: Randomized, prospective, double-blinded, placebo-controlled study. Treatment responses for dogs receiving standardized palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were serially evaluated for changes in subjective pain scores, urine N-telopeptide (NTx) excretion, primary tumor relative bone mineral density (rBMD), and computerized pressure platform gait analysis. Results: Median duration of subjective pain relief for dogs treated with adjuvant pamidronate or placebo was 76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate [11/26] and placebo [9/24]) of dogs experienced durable analgesia, defined by pain alleviation ,112 days. For patients achieving durable pain control, dogs treated with pamidronate achieved greater reductions in NTx excretion and larger increases in rBMD compared with placebo controls. Changes in peak vertical force assessed by computerized pressure platform gait analysis correlated with pain alleviation in OSA-bearing dogs. Conclusions and Clinical Importance: Combining pamidronate with standardized palliative therapy is safe, but does not clearly improve pain alleviation. However, in dogs achieving durable pain control, adjuvant pamidronate appears to decrease focal bone resorption in the local tumor microenvironment. [source] Nitric oxide in wound-healingMICROSURGERY, Issue 5 2005Jeff S. Isenberg M.D., M.P.H. Modulation of the complex process of wound-healing remains a surgical challenge. Little improvement beyond controlling infection, gentle tissue handling, and debridement of necrotic tissue has been had in the modern era. However, increasing appreciation of the process from a biomolecular perspective offers the potential for making significant strides in wound modulation. The bioactive molecule nitric oxide was found to have wide-ranging impact on cellular activities, including the cellular responses engendered by wound healing. Current research suggests that nitric oxide and several nitric oxide donors can exert biologic effects, although the particular net responses of cells contributing to wound repair are context-dependent. © 2005 Wiley-Liss, Inc. Microsurgery 25:442,451, 2005. [source] Intradiscal Electrothermal Coagulation and Percutaneous Neuromodulation Therapy in the Treatment of Discogenic Low Back PainPAIN PRACTICE, Issue 3 2005Dima Rozen MD Abstract: Low back pain (LBP) is a major physical and socioeconomic entity. A significant percentage of LBP is attributable to internal disc disruption. The management of internal disc disruption has traditionally been limited to either conservative treatment or spinal fusion. Intradiscal electrothermal coagulation (IDET) and percutaneous neuromodulation therapy (PNT) are now being performed as an alternative to these therapies. Scientific data regarding the pathophysiology, biologic effects, and clinical results are relatively scarce. Early biomechanical and histologic investigations into the effects of IDET are conflicting. However, in early prospective human trials, IDET seems to provide some benefit with little risk. PNT represents a new less invasive technique for the treatment of discogenic pain, but limited research is available to determine long-term clinical efficacy. IDET and PNT are potentially beneficial treatments for internal disc disruption in carefully selected patients as an alternative to spinal fusion. More basic science and clinical research with long-term follow-up evaluation is necessary. [source] MULTIDISCIPLINARY PAIN ABSTRACTS: 39PAIN PRACTICE, Issue 1 2004Article first published online: 15 MAR 200 A literature review was conducted to review the anatomy, pathophysiology, diagnosis, procedure, and clinical results of intradiscal electrothermal therapy (IDET). Low back pain is a major physical and socioeconomic entity. A significant percentage of low back pain is attributable to internal disc disruption. The management of internal disc disruption has traditionally been limited to either conservative treatment or spinal fusion. IDET has been performed as an alternative to these therapies. The available literature was reviewed. Scientific data regarding the pathophysiology, biologic effects, and clinical results are relatively scarce. Early biomechanical and histologic investigations into the effects of IDET are conflicting. However, in early prospective human trials, IDET seems to provide some benefit with little risk. It was concluded that IDET is a potentially beneficial treatment for internal disc disruption in carefully selected patients as an alternative to spinal fusion. More basic science and clinical research with long-term follow-up evaluation is necessary. [source] Phase I study of decitabine with doxorubicin and cyclophosphamide in children with neuroblastoma and other solid tumors: A children's oncology group study,,PEDIATRIC BLOOD & CANCER, Issue 4 2010MRCP, Rani E. George MD Abstract Background Demethylating agents may alter the expression of genes involved in chemotherapy resistance. We conducted a phase I trial to determine the toxicity and molecular effects of the demethylating agent, decitabine, followed by doxorubicin and cyclophosphamide in children with refractory solid tumors. Procedure Stratum A included children with any solid tumor; Stratum B included neuroblastoma patients only. Patients received a 1-hr decitabine infusion for 7 days, followed by doxorubicin (45,mg/m2) and cyclophosphamide (1,g/m2) on day 7. Pharmacokinetic studies were performed after the first dose of decitabine. Biological studies included methylation and gene expression analyses of caspase-8, MAGE-1 and fetal hemoglobin (HbF), and expression profiling of pre- and post-treatment peripheral blood and bone marrow cells. Results The maximum-tolerated dose of decitabine was 5,mg/m2/day for 7 days. Dose-limiting toxicities at 10,mg/m2/day were neutropenia and thrombocytopenia. Decitabine exhibited rapid clearance from plasma. Three of 9 patients in Stratum A and 4/12 patients in Stratum B had stable disease for ,4 months. Sustained MAGE-1 demethylation and increased HbF expression were observed in the majority of patients post-treatment (12/20 and 14/16, respectively). Caspase-8 promoter demethylation and gene expression were seen in 2/7 bone marrow samples. Differentially expressed genes were identified by microarray analysis. Conclusion Low-dose decitabine when combined with doxorubicin/cyclophosphamide has tolerable toxicity in children. However, doses of decitabine capable of producing clinically relevant biologic effects were not well tolerated with this combination. Alternative strategies of combining demethylating agents with non-cytotoxic, biologically targeted agents such as histone deactelyase inhibitors should be explored. Pediatr Blood Cancer. 2010;55:629,638. © 2010 Wiley-Liss, Inc. [source] ErbB receptor dimerization, localization, and co-localization in mouse lung type II epithelial cells,PEDIATRIC PULMONOLOGY, Issue 12 2006Katja Zscheppang MSc Abstract ErbB receptors are crucial for embryonic neuronal and cardiac development. ErbB receptor ligands neuregulin (NRG) and epidermal growth factor (EGF) play a major role in the developing lung, specifically in mesenchymal induced fetal surfactant synthesis by type II epithelial cells. Different erbB receptor ligands cause diverse biologic effects by stimulating specific erbB-dimers. It is not known how dimerization, cellular localization, and co-localization of erbB dimers are regulated in type II epithelial cells. We hypothesized that erbB receptors have a distinct dimerization, localization, and co-localization pattern in type II cells. In mouse type II epithelial cells, which express all four erbB receptors, erbB1 and erbB4 were the preferred dimerization partners. These dimerization patterns were ligand independent. Confocal microscopy showed these transmembrane receptors exhibited a strong nuclear localization. In non-stimulated cells, both erbB1 and erbB2 were predominantly localized to the nucleus and less intensely to the cytoplasm. However, erbB1 was mainly found in the nucleoli, whereas erbB2 spared the nucleolar region. ErbB3 was exclusively located in the nucleoli. ErbB4 was diffusely located in nucleus and cytoplasm, and like erbB2 spared the nucleolar region. Short stimulation with either EGF or NRG led to a more pronounced nuclear staining for erbB1, erbB2, and erbB4. All four receptors co-localized with each other after stimulation, but with varying intensity. The two known stimulators of fetal surfactant synthesis, NRG and NRG-containing fibroblast conditioned medium, changed cellular localization of the dimerization partners erbB4 and erbB2 in a distinct fashion. We conclude that erbB receptors have a receptor-specific localization and dimerization pattern in type II epithelial cells. Pediatr Pulmonol. 2006; 41:1205,1212. © 2006 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Lipopolysaccharide Alters the Vaginal Electrical Resistance in Cycling and Pregnant MiceAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009Varkha Agrawal Problem, Lipopolysaccharide (LPS) has been postulated to exert harmful biologic effects during pregnancy. The objective of present investigation is to measure the vaginal electrical resistance (VER) in LPS-treated normal cycling and pregnant female mice. Method of study, Minimum dose (MD) of LPS (250 ,g/kg body weight) was injected in pregnant female mice through i.p. route on day 0.5 of pregnancy. VER was measured during different phases of reproductive cycle in female mice, which were pre-exposed to LPS and in untreated cycling female mice. VER was also measured in control pregnant female mice (saline-treated mice) through whole pregnancy and LPS-treated female mice in early stages of pregnancy. Results, Vaginal electrical resistance was significantly higher during proestrous or early estrous stage as compared with any other stages of reproductive cycle in mouse. One peak of VER was observed during peri-implantation period of pregnancy in control female mice. The significant differences in the pattern of VER were found between LPS-treated and control female mice during peri-implantation period of pregnancy, and between cycling female mice, which were pre-exposed to LPS and untreated cycling female mice during proestrus. Conclusion, The presented results demonstrate, for the first time, that LPS exposure during pregnancy may be determined by measuring VER in mothers without any adverse effect on ongoing pregnancy and may help in refining the assisted reproduction techniques. [source] Insulin-Like Growth Factor-1 Restores Erectile Function in Aged Rats: Modulation the Integrity of Smooth Muscle and Nitric Oxide-Cyclic Guanosine Monophosphate Signaling ActivityTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2008Xiao-Yong Pu MD ABSTRACT Introduction., Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks. Aim., To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat. Main Outcome Measures., Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined. Methods., Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N = 10), IGF-1 1 µg/kg (N = 10) and IGF-1 10 µg/kg treatment group (N = 10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3,,5,-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed. Results., After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 µg/kg and the IGF-1 10 µg/kg group compared with the vehicle-only group at 4 and 8 weeks (P < 0.05). Masson's trichrom staining showed the percentage of cavernosal smooth muscle was increased in IGF-1 treatment group. IGF-1 increased e-NOS expression. NOS activities and cGMP concentrations were also significantly increased in IGF-1 treatment rats. Conclusions., IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways. Pu, X-Y, Wang X-H, Gao W-C, Yang Z-H, and Li S-L. Insulin-like growth factor-1 restores erectile function in aged rats: Modulation the integrity of smooth muscle and nitric oxide-cyclic guanosine monophosphate signaling activity. J Sex Med 2008;5:1345,1354. [source] Intravenous immunoglobulin and salicylate differentially modulate pathogenic processes leading to vascular damage in a model of Kawasaki diseaseARTHRITIS & RHEUMATISM, Issue 7 2009Andrew C. Lau Objective Kawasaki disease (KD) is a multisystem vasculitis affecting children and is characterized by immune activation in the acute stage of disease. Systemic inflammation eventually subsides, although coronary arteritis persists, resulting in aneurysm formation. KD is the leading cause of acquired heart disease among children in North America. Accepted treatment guidelines include high-dose intravenous immunoglobulin (IVIG) and aspirin in the acute phase. Although this therapy is effective, the cellular and molecular mechanisms involved are not clear. The aim of this study was to examine the effect of IVIG and salicylate at each stage of disease development. Methods Using a murine model of KD, we established and validated several in vitro techniques to reflect 3 key steps involved in disease pathogenesis, as follows: thymidine incorporation to evaluate T cell activation, enzyme-linked immunosorbent assay to measure tumor necrosis factor , (TNF,) production, and real-time polymerase chain reaction to examine TNF,-mediated expression of matrix metalloproteinase 9 (MMP-9). Results At therapeutic concentrations, IVIG, but not salicylate, effectively reduced the immune response leading to TNF, expression. Unexpectedly, pharmacologic doses of salicylate were not able to inhibit TNF, production and in fact enhanced its production. Neither drug directly regulated MMP-9 expression but did so only indirectly via modulating TNF,. TNF, activity was a prerequisite for local expression of MMP-9 at the coronary artery. Conclusion Therapeutic concentrations of IVIG and salicylate differentially modulate the expression of TNF, and its downstream effects. Further dissection of the biologic effects of aspirin in acute KD is necessary for the rational design of therapy. [source] Important role of interleukin-3 in the early phase of collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 5 2009Hilke Brühl Objective Activation of basophils contributes to memory immune responses and results in exacerbation of collagen-induced arthritis (CIA). We undertook the present study to analyze the production and biologic effects of interleukin-3 (IL-3), a strong activator of basophils, in CIA. Methods Arthritis was induced by immunization with type II collagen. Mice were treated with blocking monoclonal antibodies against IL-3 or with recombinant IL-3. Clinical scoring, histologic analysis, fluorescence-activated cell sorter analysis, enzyme-linked immunosorbent assay, and cell culturing were performed to assess disease activity and IL-3 production. Results IL-3 was produced in large quantities by collagen-specific CD4+ T cells in the spleen and was present in the synovial tissue during onset of arthritis, but was down-regulated in paws with severe inflammation. Blockade of IL-3 during the time of arthritis onset resulted in profound improvement of the disease, with reductions in synovial leukocyte and cytokine levels, peripheral blood basophil levels, and anticollagen antibody titers. Blockade of IL-3 during the late phase of arthritis had no beneficial effect. Administration of recombinant IL-3 during onset of arthritis induced a marked exacerbation of the disease, with increased peripheral blood basophil and plasma IL-6 levels and increased titers of anticollagen antibody. In studies of the regulation of IL-3 expression in CD4+ T cells, IL-6 and IL-4 suppressed the release of IL-3 by activated CD4+ T cells, whereas lipopolysaccharide and CpG DNA up-regulated IL-3 secretion in activated CD4+ T cells by acting on costimulatory cells. Conclusion Taken together, the present results demonstrate for the first time that IL-3 has an important role in the early phase of CIA. [source] | ||||||||||