TGF-ß signaling pathway in spinal cord injury: Mechanisms and therapeutic potential.

Spinal cord injury (SCI) is a highly disabling central nervous system injury with a complex pathological process, resulting in severe sensory and motor dysfunction. The current treatment modalities only alleviate its symptoms and cannot effectively intervene or treat its pathological process. Many studies have reported that the transforming growth factor (TGF)-ß signaling pathway plays an important role in neuronal differentiation, growth, survival, and axonal regeneration after central nervous system injury. Furthermore, the TGF-ß signaling pathway has a vital regulatory role in SCI pathophysiology and neural regeneration. Following SCI, regulation of the TGF-ß signaling pathway can suppress inflammation, reduce apoptosis, prevent glial scar formation, and promote neural regeneration. Due to its role in SCI, the TGF-ß signaling pathway could be a potential therapeutic target. This article reported the pathophysiology of SCI, the characteristics of the TGF-ß signaling pathway, the role of the TGF-ß signaling pathway in SCI, and the latest evidence for targeting the TGF-ß signaling pathway for treating SCI. In addition, the limitations and difficulties in TGF-ß signaling pathway research in SCI are discussed, and solutions are provided to address these potential challenges. We hope this will provide a reference for the TGF-ß signaling pathway and SCI research, offering a theoretical basis for targeted therapy of SCI.

Roles of pyroptosis in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD), the key pathological process in low back pain, is characterized by chronic inflammation and progressive cell death. Pyroptosis is a type of pro-inflammatory programmed necrosis mediated by inflammasomes that is dependent on the gasdermin family of proteins. An in-depth study of the pathological mechanisms of IDD has revealed that pyroptosis plays an important role in its occurrence and development. The molecular characteristics and activation signaling mechanisms of pyroptosis are reviewed in this paper. Moreover, the specific roles of pyroptosis in IDD pathology are outlined and various targeted drugs for its treatment are highlighted.

Intrathecal Injection of Botulinum Toxin Type A has an Analgesic Effect in Male Rats CCI Model by Inhibiting the Activation of Spinal P2X4R.

Purinergic receptor P2X4 (P2X4R) plays an essential role in neuropathic pain. However, the specific mechanism needs to be clarified. Botulinum toxin type A is a neurotoxin produced by Clostridium botulinum type A. This study found that intrathecal injection of botulinum toxin type A produced an excellent analgesic effect in a rat model of chronic constriction sciatic nerve injury and inhibited the activation of P2X4R, microglia, and astrocytes. The administration of a P2X4R activator can up-regulate the expression of P2X4R and eliminate the analgesic effect of intrathecal injection of botulinum toxin type A. In addition, we found that microglia and astrocytes in the spinal cord of rats injected with botulinum toxin type A were reactivated after administration of the P2X4R activator. Our results suggest that intrathecal injection of botulinum toxin type A has an analgesic effect in a rat model of chronic constriction sciatic nerve injury by inhibiting the activation of P2X4R in the spinal cord.

Effects of substrate topography on the regulation of human fibroblasts and capsule formation via modulating macrophage polarization.

The host-material interface is critical in determining the successful integration of medical devices into human tissue. The surface topography can regulate the fibrous capsule formation around implants through macrophage polarization, but the exact mechanism remains unclear. In this study, four types of microgrooves (10 or 50 µm in groove depths and 50 or 200 µm in groove widths) were fabricated on polydimethylsiloxane (PDMS) using lithography. The microgroove surfaces were characterized using the laser scanning confocal microscopy and fourier transform infrared spectroscopy. The effect of surface topography on macrophage phenotypes and conditioned medium (CM) collected from macrophages on human foreskin fibroblast 1 (HFF-1) were investigated. The result revealed that a deeper and narrower microgroove structure means a rougher surface. Macrophages tended to adhere and aggregate on group 50-50 surface (groove depths and widths of 50 µm). THP-1 cell polarized toward both inflammatory M1 and anti-inflammatory M2 macrophages on the surface of each group. Meanwhile, CM from macrophages culture on PDMS differentially up-regulated the proliferation, migration and fibrosis of HFF-1. Among them, the group 50-50 had the strongest promoting effect. In vivo, the inflammatory response and fibrotic capsule around the implants were observed at 1 week and 4 weeks. As time passed, the inflammatory response decreased, while the capsule thickness continued to increase. The rough material surface was more inclined to develop a severe fibrotic encapsulation. In conclusion, this finding further suggested a potential immunomodulatory effect of macrophages in mediating the fibrotic response to implants and facilitated the design of biomaterial interfaces for improving tissue integration.

In Vivo and In Vitro Fibroblasts' Behavior and Capsular Formation in Correlation with Smooth and Textured Silicone Surfaces.

BACKGROUND: As the most principal complication following breast augmentation with silicone breast implants, capsular contracture is greatly influenced by surface texture. However, there have long been widespread debates on the function of smooth or textured surface implants in reducing capsular contracture. MATERIALS AND METHODS: Three commercially available silicone breast implants with smooth and textured surfaces were subjected to surface characterization, and in vitro and in vivo assessments were then implemented to investigate the effect of these different surfaces on the biological behaviors of fibroblasts and capsular formation in rat models. RESULTS: Surface characterization demonstrated that all three samples were hydrophobic with distinct roughness values. Comparing the interactions of fibroblasts or tissues with different surfaces, we observed that as surface roughness increased, the adhesion and cell spreading of fibroblasts, the level of echogenicity, the density of collagen and α-SMA-positive immunoreactivity decreased, while the proliferation of fibroblasts and capsule thickness increased. CONCLUSIONS: Our findings elucidated that the effect of silicone implant surface texture on fibroblasts' behaviors and capsular formation was associated with variations in surface roughness, and the number of myofibroblasts may have a more significant influence on the process of contracture than capsule thickness in the early stage of capsular formation. These results highlight that targeting myofibroblasts may be wielded in the prevention and treatment strategies of capsular contracture clinically. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

FoxO3a depletion accelerates cutaneous wound healing by regulating epithelial­mesenchymal transition through ß­catenin activation.

The hysteresis of keratinocyte (KC) re­epithelialization is an important factor resulting in chronic wounds; however, the molecular mechanisms involved in this cellular response remain yet to be completely elucidated. The present study demonstrated the function of transcription factor Forkhead box O3a (FoxO3a) in KC growth and migration functional effects, resulting in restrained KC re­epithelialization during wound healing. In chronic wound tissue samples, the expression of FoxO3a was significantly increased when compared with the acute wound healing group (P<0.01). Overexpressing FoxO3a significantly inhibited, whereas silencing endogenous FoxO3a enhanced, the growth and migration of HaCaT cells in vitro. Further investigation revealed that FoxO3a negatively regulated matrix metalloproteinases 1 and 9, and increased the expression of tissue inhibitor of metalloproteinase 1. In addition, the upregulation of FoxO3a retarded, whereas the downregulation of FoxO3a accelerated, transforming growth factor­ß1­induced epithelial­mesenchymal transition in HaCaT cells. Mechanistically, the overexpression of FoxO3a inactivated ß­catenin signaling and markedly reduced the levels of nuclear ß­catenin. These results reveal a novel mechanism of FoxO3a in regulating KC re­epithelialization, and provide novel targets for the prevention and treatment of chronic wounds.

Autologous Vascularization: A Method to Enhance the Antibacterial Adhesion Properties of ePTFE.

BACKGROUND: Expanded polytetrafluoroethylene (ePTFE), an ideal bioimplant material, is commonly used in surgical repair to treat soft tissue defects and deformities. However, the main disadvantage of ePTFE is that its distinctive porous ultrastructure is prone to bacterial adhesion that gives rise to infection and chronic inflammation, resulting in functional failure. Herein, a potentially promising approach to ePTFE autologous vascularization (AV-ePTFE) in vivo was established and developed to enhance the material's antibacterial properties. METHODS: Hematoxylin and eosin (H&E) staining and visual observation were performed to validate the intensity of the inflammatory response and related histological changes in surgical wounds after AV-ePTFE implantation. In addition, the antibacterial activities of AV-ePTFE were assessed by an in vitro bacterial adhesion assay and scanning electron microscope observation. RESULTS: The optimal time point of AV-ePTFE was 12 weeks after implantation. AV-ePTFE relieved inflammation based on an inflammation grading evaluation and expedited wound healing. Furthermore, AV-ePTFE effectively reduced the number of bacterial adhesions, inhibited bacterial biofilm formation, and prevented the occurrence of infection. CONCLUSIONS: We conclude that autologous vascularization is an effective method to improve the antibacterial adhesion properties and biocompatibility of ePTFE after implantation and that it may have a significant effect on clinical application of future porous biomaterials.

Negative pressure wound therapy and split thickness skin graft aided in the healing of extensive perineum necrotizing fasciitis without faecal diversion: a case report.

BACKGROUND: Perineum necrotizing fasciitis, also known as Fournier gangrene (FG), is a rare but highly mortal infectious necrotizing fasciitis with or without involvement of the underlying muscle. Evidence exists that negative pressure wound therapy (NPWT) combined with a split thickness skin graft (STSG) can help to heal wounds with FG. However, when the wound spreads to the anal area, it can easily be contaminated by faeces, causing a more extensive wounds; thus, faecal diversion is considered. Here, we report a case of extensive perineum necrotizing fasciitis that spread to near the anus; NPWT combined with STSGs was used to help heal the wound without faecal diversion. CASE PRESENTATION: A 47-year-old male patient was admitted with extensive perineum fascia necrosis caused by Pseudomonas aeruginosa that rapidly spread to near the anus. After comprehensive therapy completed wound bed preparation, STSGs from the scalp were grafted to the wound, and NPWT was applied to improve STSGs survival and seal the anus without faecal diversion. After treatment, graft take was 95%, and the exposed testicular and residual wounds were repaired with a local skin flap. At discharge, the wound had decreased to two pea-sized areas. The patient received conventional moist gauze therapy to close the residual wound at the local hospital. A follow-up by telephone 1 month later showed that both wounds had healed and that the patient was satisfied with the outcome. CONCLUSION: NPWT use combined with STSGs to cover the whole wound and the anus without faecal diversion is a safe and effective method to help with wound healing and avoid contamination with excrement.

Biofunctionalization of silicone rubber with microgroove-patterned surface and carbon-ion implantation to enhance biocompatibility and reduce capsule formation.

PURPOSE: Silicone rubber implants have been widely used to repair soft tissue defects and deformities. However, poor biocompatibility can elicit capsule formation, usually resulting in prosthesis contracture and displacement in long-term usage. To overcome this problem, this study investigated the properties of silicone rubber materials with or without a microgroove-patterned surface and with or without carbon (C)-ion implantation. MATERIALS AND METHODS: Atomic force microscopy, X-ray photoelectron spectroscopy, and a water contact angle test were used to characterize surface morphology and physicochemical properties. Cytocompatibility was investigated by a cell adhesion experiment, immunofluorescence staining, a Cell Counting Kit-8 assay, and scanning electron microscopy in vitro. Histocompatibility was evaluated by studying the inflammatory response and fiber capsule formation that developed after subcutaneous implantation in rats for 7 days, 15 days, and 30 days in vivo. RESULTS: Parallel microgrooves were found on the surfaces of patterned silicone rubber (P-SR) and patterned C-ion-implanted silicone rubber (PC-SR). Irregular larger peaks and deeper valleys were present on the surface of silicone rubber implanted with C ions (C-SR). The silicone rubber surfaces with microgroove patterns had stable physical and chemical properties and exhibited moderate hydrophobicity. PC-SR exhibited moderately increased dermal fibroblast cell adhesion and growth, and its surface microstructure promoted orderly cell growth. Histocompatibility experiments on animals showed that both the anti-inflammatory and antifibrosis properties of PC-SR were slightly better than those of the other materials, and there was also a lower capsular contracture rate and less collagen deposition around implants made from PC-SR. CONCLUSION: Although the surface chemical properties, dermal fibroblast cell growth, and cell adhesion were not changed by microgroove pattern modification, a more orderly cell arrangement was obtained, leading to enhanced biocompatibility and reduced capsule formation. Thus, this approach to the modification of silicone rubber, in combination with C-ion implantation, should be considered for further investigation and application.

Complications from Nasolabial Fold Injection of Calcium Hydroxylapatite for Facial Soft-Tissue Augmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: Despite its increasing usage of facial applications, there is a paucity of objective data regarding calcium hydroxylapatite (CaHA). OBJECTIVES: To systematically evaluate the complications from CaHA injection for facial soft tissue augmentation. METHODS: Published studies on CaHA injection for facial soft tissue enhancement were identified through searches of the PubMed, EMBASE, and Cochrane Controlled Trial databases. Only randomized, controlled trials comparing CaHA injection to either placebo or an active comparator for facial cosmetic use were included. The outcome measures were the count (n) and frequency (%) of each complication, including edema (swelling), erythema (redness), ecchymosis (bruising), pain, pruritus (itching), hematomas, nodules, and extrusions. RESULTS: Four studies on nasolabial fold (NLF) injection of CaHA consisting of two subgroups were included: (i) a CaHA-lidocaine vs CaHA subgroup and (ii) a CaHA vs hyaluronic acid (HA) subgroup. The addition of lidocaine to CaHA therapy displayed no significant effect on edema (RR (95% CI): 1.07 (0.94-1.21), P = .311), erythema (RR (95% CI): 0.91 (0.66-1.24), P = .544), ecchymosis (RR (95% CI): 1.04 (0.71-1.52), P = .843), pain (RR (95% CI): 0.88 (0.58-1.33), P = .553), or pruritus (RR (95% CI): 0.82 (0.45-1.50), P = .515). There was no significant difference between CaHA vs HA for hematomas (RR (95% CI): 0.24 (0.01-4.31), P = .332) or nodules (RR (95% CI): 0.18 (0.01-6.62), P = .353). There was no significant publication bias detected in either subgroup (Begg's test P > 0.05). CONCLUSIONS: These findings support the addition of lidocaine to NLF injection of CaHA and suggest an equivalence between CaHA and HA with respect to hematoma and nodule formation. LEVEL OF EVIDENCE 2: Risk.

Hydroxyapatite-coated sillicone rubber enhanced cell adhesion and it may be through the interaction of EF1ß and γ-actin.

Silicone rubber (SR) is a common soft tissue filler material used in plastic surgery. However, it presents a poor surface for cellular adhesion and suffers from poor biocompatibility. In contrast, hydroxyapatite (HA), a prominent component of animal bone and teeth, can promote improved cell compatibility, but HA is an unsuitable filler material because of the brittleness in mechanism. In this study, using a simple and economical method, two sizes of HA was applied to coat on SR to counteract the poor biocompatibility of SR. Surface and mechanical properties of SR and HA/SRs confirmed that coating with HA changes the surface topology and material properties. Analysis of cell proliferation and adhesion as well as measurement of the expression levels of adhesion related molecules indicated that HA-coated SR significantly increased cell compatibility. Furthermore, mass spectrometry proved that the biocompatibility improvement may be related to elongation factor 1-beta (EF1ß)/γ-actin adjusted cytoskeletal rearrangement.

Osteopontin (OPN) is an important protein to mediate improvements in the biocompatibility of C ion-implanted silicone rubber.

Medical device implants are drawing increasing amounts of interest from modern medical practitioners. However, this attention is not evenly spread across all such devices; most of these implantable devices can cause adverse reactions such as inflammation, fibrosis, thrombosis, and infection. In this work, the biocompatibility of silicone rubber (SR) was improved through carbon (C) ion implantation. Scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) results confirmed that these newly generated carbon-implanted silicone rubbers (C-SRs) had large, irregular peaks and deep valleys on their surfaces. The water contact angle of the SR surface decreased significantly after C ion implantation. C ion implantation also changed the surface charge distribution, silicone oxygen rate, and chemical-element distribution of SR to favor cell attachment. The dermal fibroblasts cultured on the surface C-SR grew faster and showed more typical fibroblastic shapes. The expression levels of major adhesion proteins, including talin-1, zyxin, and vinculin, were significantly higher in dermal fibroblasts cultured on C-SR coated plates than in dermal fibroblasts cultured on SR. Those same dermal fibroblasts on C-SRs showed more pronounced adhesion and migration abilities. Osteopontin (OPN), a critical extracellular matrix (ECM) protein, was up-regulated and secreted from dermal fibroblasts cultured on C-SR. Matrix metalloproteinase-9 (MMP-9) activity was also increased. These cells were highly mobile and were able to adhere to surfaces, but these abilities were inhibited by the monoclonal antibody against OPN, or by shRNA-mediated MMP-9 knockdown. Together, these results suggest that C ion implantation significantly improves SR biocompatibility, and that OPN is important to promote cell adhesion to the C-SR surface.

Shaking stress aggravates burn-induced cardiovascular and renal disturbances in a rabbit model.

The aim of this study was to address the effects of shaking stress (a.k.a. physical agitation) on burn-induced remote organ injury and to evaluate the application of delayed fluid resuscitation to treat severe burns under shaking conditions. Healthy adult male rabbits, weighing 2.50±0.40 kg, were randomly assigned to the following groups: control group, burn group, and burn+shaking group. One half of burned animals received a 6-h delayed fluid resuscitation and the other half remained untreated. Cardiovascular hemodynamics and functional and pathological changes of the heart and kidney were examined. Compared to normal controls, untreated burned animals showed decreased hemodynamic parameters, increased serum lactic acid, and severe myocardial inflammation. The burn-induced hemodynamic abnormalities and cardiac injury were aggravated by shaking stress. Burn injury led to reduced urine volume, elevated serum creatinine and blood urea nitrogen, and formation of erythrocyte casts in renal tubules. Shaking stimulation worsened the burn-associated functional and pathological changes of the kidney. Fluid resuscitation markedly mitigated cardiac and renal injury in burned animals, and, to a lesser extent, in the presence of shaking stimulation. Shaking stimulation aggravates burn-induced cardiovascular and renal disturbances. Delayed fluid resuscitation attenuates cardiac and renal damages in burn injury under shaking conditions.

Protective effects of enalapril, an angiotensin-converting enzyme inhibitor, on multiple organ damage following scald injury in rats.

The aim of this study is to investigate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on multiple organ damage after scald injury. Healthy adult rats (half male and half female; 8-12 weeks old) were randomly assigned to the following treatments: sham operation, scald injury, and intraperitoneal enalapril (1, 2, and 4 mg/kg body weight) treatment after scalding. At 1, 12, and 24 H postscald, left ventricular and aortic hemodynamics were measured using a multichannel physiological recorder. Functional and pathological changes of the heart, liver, and kidney were examined by biochemical and histological methods. Compared with sham controls, untreated scalded animals showed decreased hemodynamic parameters and increased myocardial angiotensin II, serum creatine kinase heart isoenzyme, and serum cardiac troponin I and histopathological inflammation in the myocardium 12 H postscald. These hemodynamic, functional, and pathological changes were attenuated by 1 mg/kg enalapril. Enalapril reversed scald-induced elevations in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and blood creatinine 12 H postscald, and ameliorated focal necrosis in the liver and erythrocyte cast formation in renal tubules. However, higher doses of enalapril yielded less or no improvement in organ dysfunction. Enalapril at 1 mg/kg attenuates scald-induced multiple organ damage in rats.

Prompt myocardial damage contributes to hepatic, renal, and intestinal injuries soon after a severe burn in rats.

BACKGROUND: Ischemic/hypoxic myocardial damage and functional impairment of the myocardium occurs immediately after major burns. This experimental study investigated whether the prompt cardiac dysfunction initiates hepatic, renal, and intestinal injuries soon after a severe burn. METHODS: Wistar rats were randomized to a sham burn group, a burn group (subjected to 30% total body surface area third-degree burn) that was subdivided into two groups: a simple burn group, observed at 0.5 hour, 1 hour, 3 hours, 6 hours, 12 hours, 24 hours postburn and a group medicated with propranolol (a cardiac inhibitor), cedilanid (a cardiotonic agent), enalaprilat (an angiotensin converting enzyme inhibitor), and cedilanid plus enalaprilat injected at 0.5 hour postburn and observed at 6 hours later. Serum cardiac troponin I, total bile acid, beta2-microglobulin concentrations, and diamine oxidase activity were measured to reflect the severity of cardiac, hepatic, renal, and intestinal injuries that were confirmed by histopathologic observations. Cardiac function and organs' blood flow were also recorded. RESULTS: Histopathologic changes and serum cardiac troponin I increase occurred significantly earlier than the other organs, and the organ damage developments followed a similar pattern. Myocardial injury was significantly aggravated in rats treated with propranolol, with further decreases in myocardial function, blood flow to the liver, kidneys, and intestines significantly decreased, and injuries were aggravated. In contrast, these conditions were greatly improved in the rats treated with enalaprilat, cedilanid, or with both. CONCLUSION: The prompt cardiac dysfunction has some initiating effects on ischemic/hypoxic injury to organs such as the liver, kidneys, and intestines soon after a severe burn.

Role of serum amyloid P in skin graft survival and wound healing in burned patients receiving skin grafts.

BACKGROUND: Recent studies in animal models suggest that serum amyloid P (SAP) can affect burn wound healing. However, the role of SAP in a clinical setting remains unknown. METHODS: We enrolled 88 patients with third degree burn wounds. All the patients were candidates for auto-skin graft procedure using stamp skin graft. The complete graft healing time and the number of survived grafts were recorded. Serum SAP levels were assessed 1 day before operation. RESULTS: There was no significant difference in SAP level between controls and patients. There were no significant differences noted among the patients with different burn surface area. However, when the patients in each group were stratified by SAP levels, the mean complete healing time of grafted wound and the mean numbers of survived skin grafts were significantly different. Spearman's analyses showed that the serum SAP levels negatively correlated with the complete wound healing time and mean numbers of survived skin grafts. Logistic regression analysis showed that the serum SAP levels and mean numbers of survived skin grafts were potent independent factors contributing to wound healing. CONCLUSIONS: The results of this study suggest that the serum SAP levels may be an easy detected predictor for the healing of burn wounds.

[Influence of myocardial inhibition on injury to liver, kidney and intestine at early stage in rat with severe scald].

OBJECTIVE: To investigate the influence of myocardial inhibition on injury to liver, kidney and intestine and blood perfusion at early stage in rat with severe burn. METHODS: Thirty-two healthy male Wistar rats were enrolled in the study and randomly divided into sham scald, propranolol, scald control and scald + propranolol groups, with 8 rats in each group. After intraperitoneal injection of 10 g/L pentobarbital sodium for anesthesia, rats of the former two groups were sham scalded in a water bath of 37 degrees C for 18 s, while the latter two groups were inflicted with 30% TBSA full-thickness scald in a 97 degrees C water bath for 18 s. Rats were resuscitated with Ringer's lactate solution (4 mL x kg(-1) x 1% TBSA(-1), i. p.) following the Parkland formula 30 mins after the injury. At the same time, rats in propranolol and scald + propranolol groups received propranolol 0.75 mg/kg intravenously. After 6 hours, parameters of myocardiac mechanics (SBP, DBP, MAP, LVSP, LVEDP, +/- dp/dt max) were recorded by the multiple channel physiological signal collecting and processing system; blood flow of liver, kidney and intestine were detected with the laser doppler flowmetry; the serum contents of cTnI, TBA, beta2-MG and DAO were determined for reflecting injuries to the heart, liver, kidney and intestine, respectively. RESULTS: Myocardiac mechanics parameters, with the exception of LVEDP, were decreased in propranolol group as compared with those in sham group (P <.05). All myocardiac mechanics parameters in burn control group were lower than those in sham group and higher than those in burn + propranolol group (P < 0.05). Blood flow of organs showed similar changes in above-mentioned 3 groups (P < 0.05). Organ damages as shown in burn control group [cTnI (4.86 +/- 0.29) microg/L, TBA (83.6 +/- 18.2) micromol/L, beta2-MG (2.75 +/- 0.19) mg/L, DAO (1.45 +/- 0.09) x 10(3) U/L] were more serious than those in sham control group [cTnI (1.73 +/- 0.09) microg/L, TBA (24.5 +/- 2.4) micromol/L, beta2-MG (1.15 +/- 0.18) mg/L, DAO (0.87 +/- 0.13) x 10(3) U/L], and less serious than those in scald + propranolol group [cTnI 5.95 +/- 0.42 microg/L, TBA 125.8 +/- 21.3 micromol/L, beta2-MG 3.25 +/- 0.17 mg/L, DAO (1.83 +/- 0.13) x 10(3) U/L] (P < 0.05). CONCLUSIONS: Propranolol can aggravate injury to the liver, kidney and intestine at early stage in rat with severe burn, suggesting that "shock heart" may be one of initial factors in lowering blood flow to the organs, thus inducing injury to them.

[Effects of angiotensin (1-7) and enalaprilat on function of isolated rat heart perfused by burn serum].

OBJECTIVE: To investigate effects of angiotensin (1-7) [Ang (1-7)] and enalaprilat on function of isolated rat heart perfused by burn serum. METHODS: Eighty SD rats were used to prepare burn serum. Hearts of another 24 SD rats were isolated to reproduce Langendorff perfusion model. The rat hearts were divided into different groups with different perfusion fluids as K-H buffer group, K-H buffer containing 20% burn serum group (burn serum group), K-H buffer containing 20% burn serum and 2 microg/mL enalaprilat group (enalaprilat group), and K-H buffer containing 20% burn serum and 1 nmol/mL Ang (1-7) group [Ang(1-7) group]. The rat hearts were perfused for 30 mins with each of above-mentioned fluids in different groups. Then left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), +/- dp/dt max, coronary flow(CF), level of creatine kinase (CK) and lactate dehydrogenase (LDH) in respective coronary effluent were determined. RESULTS: Compared with LVSP (11.2 +/- 1.0 kPa, 1 kPa = 7.5 mm Hg), +dp/dt max (642 +/- 53 kPa/s), -dp/dt max (380 +/- 61 kPa/s) and CF level in K-H buffer group, CF, LVSP (5.9 +/- 0.8, 8.0 +/- 1.1, 8.9 +/- 1.3 kPa, respectively), +dp/dt max (275 +/- 37, 454 +/- 48, 479 +/- 63 kPa/s, respectively), -dp/dt max (135 +/- 35, 219 +/- 47, 277 +/- 58 kPa/s, respectively) of burn serum group, those levels in Ang (1-7) group, and enalaprilat group were decreased obviously (P < 0.05 or P < 0.01), but LVEDP, level of CK and LDH in coronary effluent were increased. Compared with those parameters in burn serum group, CF, LVSP, +/- dp/dt max of Ang (1-7) group and enalaprilat group were increased obviously (P < 0.05 or P < 0.01), and LVEDP, level of CK and LDH in coronary effluent were decreased obviously (P < 0.01). CONCLUSIONS: Ang (1-7) and enalaprilat can effectively improve left ventricular function of isolated rat heart perfused by burn serum and mitigate myocardial injury.

Mechanical and biological evaluations of beta-tricalcium phosphate/silicone rubber composite as a novel soft-tissue implant.

BACKGROUND: Although silicone rubber (SR) implants are most commonly used and effective for soft-tissue augmentation, they still have been implicated in many adverse reactions. To overcome this problem, a novel composite beta-tricalcium phosphate/silicone rubber (beta-TCP/SR) was prepared by adding beta-TCP into a SR matrix. This study was to evaluate its application potential by investigating the mechanical properties and biocompatibility of beta-TCP/SR. METHODS: Mechanical properties, including Shore A hardness and tensile strength, were evaluated with 3-mm-thick samples and a universal testing machine. Cytocompatibility tests were conducted in vitro using 0.2-mm-thick beta-TCP/SR samples by seeding fibroblasts onto different samples. Soft-tissue response to beta-TCP/SR and pull-out measurements were investigated 4 weeks and 24 weeks after implantation. RESULTS: The main mechanical properties were all significantly changed after mixing beta-TCP into the SR matrix, except for tearing strength. The cytocompatibility test showed enhanced adhesion and proliferation of fibroblasts onto beta-TCP/SR. Fibrous tissue ingrowth after resorption of beta-TCP was observed by in vivo histologic analysis. The peri-implant capsules in the beta-TCP/SR group were thinner than in the SR group 24 weeks after implantation. In a 24-week test, the maximum force required to pull out the beta-TCP/SR sheet was about six times greater than that needed for SR. CONCLUSION: Although some mechanical properties were significantly changed, the results of the cytocompatibility test and in vivo animal study still suggest that beta-TCP/SR may be more suitable as a soft-tissue implant than SR and has the potential to be used in plastic surgery.