Photothermal cancer therapy by gold-ferrite nanocomposite and near-infrared laser in animal model

Surface plasmon resonance effect of gold nanostructures makes them good candidates for photothermal therapy (PTT) application. Herein, gold-ferrite nanocomposite (GFNC) was synthesized and characterized as a photothermal agent in PTT. The aim of this study was to investigate the effect of GFNC upon laser irradiation on treatment of cancer in mice bearing melanoma cancer. Thirty mice received 1.5?×?10⁶ B16/F10 cells subcutaneously. After 1 week, the mice bearing solid tumor were divided into four groups: control group (without any treatment), laser group (received laser irradiation without GFNC injection), GFNC group (only received intratumorally GFNC), and GFNC?+?laser group (received intratumorally GFNC upon laser irradiation). In GFNC?+?laser group, 200 μL of fluid, 1.3?×?10^?7 mol L^?1 gold nanoparticles, was injected intratumorally and immediately the site of tumor was exposed to continuous wave diode laser beam (808 nm, 1.6 W cm^?2) for 15 min. All mice but four were euthanized 24 h after treatment to compare the necrotic surface area histologically by using measuring graticule. Statistical analyses revealed significant differences in necrosis extent for GFNC?+?laser group, compared to other groups. Four subjects (control group and GFNC?+?laser group, two mice each) were kept for longitudinal study. Histological analyses and tumor volume measurements of the four subjects indicated that tumor in GFNC?+?laser group was controlled appropriately. It was concluded that combining an 808-nm laser at a power density of 1.6 W cm^?2 with GFNC has a destruction effect in melanoma cancer cells in an animal model.     

NIR laser pointer for in vivo photothermal therapy of murine LM3 tumor using intratumoral China ink as a photothermal agent

The photothermal effect is one of the most promising photonic procedures currently under development to successfully treat several clinical disorders, none the least some kinds of cancer. At present, this field is undergoing a renewed interest due to advances in both photothermal materials and better-suited light sources. However, scientific studies in this area are sometimes hampered by the relative unavailability of state-of-art materials or the complexity of setting up a dedicated optical facility. Here, we present a simple and affordable approach to do research in the photothermal field that relies on a commercial NIR laser pointer and a readily available everyday pigment: China ink. A proof-of-concept study is presented in which mice bearing intradermal LM3 mammary adenocarcinoma tumors were successfully treated in vivo employing China ink and the laser pointer. TUNEL and Ki-67 post-treatment tissue assessment clearly indicates the deleterious action of the photothermal treatment on the tumor. Therefore, the feasibility of this simple approach has been demonstrated, which may inspire other groups to implement simple procedures to further explore the photothermal effect.     

Evaluation of palatal snoring surgery in an animal model.

OBJECTIVE: We introduce an animal model to reproduce and measure palatal snoring and to assess the effectiveness of cautery-assisted palatal stiffening operation and injection snoreplasty versus a control (no palatal intervention) on treatment of palatal flutter snoring.Study design and setting An anesthetized laboratory canine model uses 2 simultaneous temporary tracheotomies. An inferior tracheotomy is cannulated with an endotracheal tube for ventilation. A superior tracheotomy is cannulated with a tube passed cephalad and seated in the hypopharynx. Negative pressure applied to the upper tube leads to partial collapse of the upper airway with palatal fluttering, and the anesthetized dog snores. Videostroboscopy records palatal flutter frequency before and after surgical intervention. Preoperative and postoperative palatal assessments are made on 15 beagles. RESULTS: Cautery-assisted palatal stiffening operation and injection snoreplasty objectively stiffen the canine soft palate with diminished snoring compared with controls.Conclusion and significance We provide a reproducible animal model to experimentally measure new interventions to treat palatal flutter snoring.     

康复治疗对创伤后膝关节僵直活动度及肌肉组织的影响

[目的]探讨康复治疗对大鼠创伤后膝关节僵直关节活动度的影响及股四头肌组织的病理学变化。[方法]选取32只9周龄,雄性SD大鼠。建立膝关节僵直模型后,随机分为两组,即对照组和康复组。取不同时间点测量膝关节活动度变化,并取股四头肌进行病理学检查。[结果](1)12周后,康复组膝关节活动度有明显改善,两组比较,差异有统计学意义(P<0.05)。(2)12周后,康复组股四头肌病理学检查显示,肌肉细胞逐渐恢复正常形态,两组比较,差异明显。[结论]膝关节创伤后造成僵直,康复治疗有助于关节活动度及肌肉组织恢复,直至正常。     

Gold-coated magnetic nanoparticle as a nanotheranostic agent for magnetic resonance imaging and photothermal therapy of cancer

Because of their great scientific and technological potentials, iron oxide nanoparticles (IONPs) have been the focus of extensive investigations in biomedicine over the past decade. Additionally, the surface plasmon resonance effect of gold nanoparticles (AuNPs) makes them a good candidate for photothermal therapy applications. The unique properties of both IONPs (magnetic) and AuNPs (surface plasmon resonance) may lead to the development of a multi-modal nanoplatform to be used as a magnetic resonance imaging (MRI) contrast agent and as a nanoheater for photothermal therapy. Herein, core–shell gold-coated IONPs (Au@IONPs) were synthesized and investigated as an MRI contrast agent and as a light-responsive agent for cancer photothermal therapy.The synthesized Au@IONPs were characterized by UV–visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. The transverse relaxivity (r ₂) of the Au@IONPs was measured using a 3-T clinical MRI scanner. Through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of the Au@IONs was examined on a KB cell line, derived from the epidermal carcinoma of a human mouth. Moreover, the photothermal effects of Au@IONPs in the presence of a laser beam (λ = 808 nm; 6.3 W/cm²; 5 min) were studied.The results show that the Au@IONPs are spherical with a hydrodynamic size of 33 nm. A transverse relaxivity of 95 mM^?1 S^?1 was measured for the synthesized Au@IONPs. It is evident from the MTT results that no significant cytotoxicity in KB cells occurs with Au@IONPs. Additionally, no significant cell damage induced by the laser is observed. Following the photothermal treatment using Au@IONPs, approximately 70% cell death is achieved. It is found that cell lethality depended strongly on incubation period and the Au@IONP concentration.The data highlight the potential of Au@IONPs as a dual-function MRI contrast agent and photosensitizer for cancer photothermal therapy.     

Identification of in vitro parameters predictive of graft function: a study in an animal model of islet transplantation

The quality of human islets is one of the factors decisive for the success of human islet transplantation. Several parameters have been proposed to characterize islet quality, but none of them has been able to predict the fate of a transplant. The aim of our study was to correlate a panel of in vitro parameters for islet viability with their in vivo function after transplantation in nude mice. Islets were obtained after enzymatic digestion of a human pancreas; they were purified from exocrine tissue using a continuous-density gradient. Two aliquots of islets (1000 and 2000 islets) were transplanted under the kidney capsule of diabetic nude mice. The animals were followed for 1 month with repeated measurements of blood glucose and body weight. One month after transplantation, mice were killed and their graft harvested for histologic analysis. In parallel we studied in vitro islet viability with propidium iodide and fura-2, their insulin content, their purity, and their insulin response to glucose upon static incubation. Ten islet preparations were transplanted: 3 out of 10 preparations did not restore normoglycemia; 4 out of 10 normalized glycemia only in mice receiving 2000 islets, and 3 out of 10 fully restore normoglycemia in all mice. The purity of preparations (R(2) = 0.63 and 0.85, respectively, with 1000 and 2000 islets) and the insulin content (R(2) = 0.75 with 2000 IE) correlated with transplant success. These data show that purity of islet preparations and their insulin content should be useful parameters for the selection of islet preparations for transplant purposes.     

Evaluation of an animal model for teaching fibreoptic tracheal intubation

Twenty-seven anaesthesia faculty, fellows and residents compared a standard intubating mannequin and an anaesthetized pig as models for teaching fibreoptic tracheal intubation. When likened to the clinical situation, the anatomic characteristics of the pig airway were rated as significantly more realistic than the airway characteristics of the mannequin with the exception of the appearance of the epiglottis. In addition, the overall score for the pig model was significantly higher than the score for the mannequin and 26 of 27 evaluators rated the anaesthetized pig as the more effective teaching model. We conclude that an anaesthetized, spontaneously breathing pig is a valid model for teaching fibreoptic endotracheal intubation.     

Escharotomy using an enzymatic debridement agent for treating experimental burn-induced compartment syndrome in an animal model

BACKGROUND: In patients with deep circumferential burns, adequate resolution of burn-induced compartment syndrome (BICS) is achieved by surgical escharotomy. Surgical escharotomy is traumatic, may cause considerable blood loss, does nothing toward debridement of the burn wound, and entails possible morbidity and complications. Debridase is a Bromelain derived enzymatic preparation capable of lysing the burn eschar within 4 hours, obviating the need for surgical debridement. It has an affinity to burned necrotic tissue and does not damage healthy skin. In our clinical assessment of the Debridase efficacy, we found in several cases of deep burns of the limbs that the measured IC pressure subsided after 2-4 hours of Debridase application and none of the enzymatic escharotomy treated patients suffering from circumferential burns developed BICS. To confirm these observations we conducted this controlled study. AIM: to assess the efficacy of Debridase for treating BICS in an animal model. MATERIALS AND METHODS: A model for BICS was developed by making circumferential burns to pig legs and monitoring the anterior compartment the legs. BICS was induced in the legs of 5 pigs, 20 legs. 10 legs were treated with Debridase and 10 served as nontreated controls, treated by surgical escharotomy at the conclusion of the experiment. RESULTS: Debridase reduced BICS within 30 minutes from application. Debridase was as effective as a standard surgical escharotomy. CONCLUSION: Escharectomy using an effective enzymatic debriding agent is potentially an adequate, simple, fast and effective procedure to treat BICS, it has the added benefit of burn debridement without surgical escharotomy.     

Tonometry as a predictor of inadequate splanchnic perfusion in an intra-abdominal hypertension animal model

Background

The gastrointestinal system is the most sensitive to the presence of intra-abdominal hypertension. We aimed to assess the early prognostic value of gastric air tonometry as a predictor of inadequate splanchnic perfusion and determine its relation with abdominal perfusion pressure (APP).

Methods

Twenty-five Large White swine were used for this study. A control group and two study groups were included, in which intra-abdominal pressure (IAP) was elevated with Co₂ to 20 and 30 mmHg during 5 h. We measured the intramucosal gastric pH (pHim) and determined gastric luminal PCO₂ (PgCO₂) and PgCO₂gap (gastric luminal CO₂–arterial CO₂) to evaluate gastric acidity. APP was indirectly obtained through IAP and mean arterial pressure. Additionally, histopathologic samples of small intestine were obtained and analyzed.

Results

pHim showed a decrease in IAP groups, with statistical significance in the 30 mmHg group, 90 min after stabilization period (P < 0.01). Serum lactate showed delayed alteration when compared with pHim, with significant increase, 180 min after stabilization (P < 0.05). The values of PgCO₂ and PCO₂gap were increased in IAP groups, being statistically significant in the 30 mmHg group, 120 and 150 min, respectively, after stabilization. In increased IAP groups, there was a time progressive decrease of APP, with statistically significant differences observed between groups at 20 min (P < 0.001). The histopathology study revealed parenchymal injury of the intestine at 30 mmHg.

Conclusions

Tonometry is sensitive to the increase in IAP and relates to the reduction of APP generated by splanchnic hypoperfusion.     

Comparison of oxidized porous silicon with bare porous silicon as a photothermal agent for cancer cell destruction based on in vitro cell test results

In the systematic administration of cancer, cancer markers are normally used to help the therapeutic agents access the cancer cells spontaneously. Therefore, it is essential to functionalize the surface of porous silicon (pSi) for cancer markers to attach well to pSi in systematic administration because most cancer markers does not attach easily to pSi. The thermal oxidation of pSi is adopted most widely as a surface functionalization technique for pSi. This study examined the photothermal properties and cancer cell-killing ability of oxidized pSi (pSiO). The temperature measurement and in vitro cell tests including the annexin V-fluorescein isothiocyanate (FITC) apoptosis assay tests, MTT assay tests, and Trypan blue cell death assay tests were performed to compare the photothermal properties and the cytotoxic effect of pSiO with those of pSi in combination with an 808-nm NIR laser. pSiO showed lower photothermal properties and a lower cell-death rate than bare pSi. On the other hand, the pSiO treatment used in combination with an NIR laser treatment showed a cytotoxic effect high enough to kill a considerable portion of the cancer cells.     

Evaluation of intraoperative nerve-monitoring during insertion of an iliosacral implant in an animal model

BACKGROUND: The use of continuous electromyographic and somatosensory-evoked-potential monitoring systems has been advocated to assist in avoiding nerve-root injury during operations on the pelvic ring. More recently, it was suggested that stimulus-evoked electromyographic monitoring may further decrease the risk of iatrogenic nerve-root injury during posterior pelvic fixation by enabling the surgeon to determine the actual distance of an implant from a nerve root. The purpose of the current study was to evaluate the relative efficacy of these three methods of monitoring for minimizing the risk of neural injury during the placement of iliosacral implants. METHODS: While the function of the first sacral nerve root was monitored with the use of stimulus-evoked electromyographic, continuous electromyographic, and somatosensory-evoked-potential monitoring techniques, a 2.0-millimeter stainless-steel Kirschner wire was progressively inserted, guided by a high-speed computerized tomographic scanner, into the first sacral body of seventeen hemipelves in nine dogs. The end point was contact with the nerve as demonstrated by the computerized tomographic images. It was expected that this end point would be heralded by a burst of spontaneous electromyographic activity and an abnormal somatosensory-evoked-potential signal. Anatomical dissection at the completion of the study documented the final position of the Kirschner wire. RESULTS: Anatomical dissection demonstrated compression or penetration of the nerve root in sixteen of the seventeen specimens. A spontaneous burst of electromyographic activity was not recorded for any specimen on continuous electromyographic monitoring; this finding was significantly different from what had been expected (p<0.001). Because of technical problems, somatosensory evoked potentials could be recorded for only twelve hemipelves that had nerve-root compression or penetration, and abnormal somatosensory evoked potentials were recorded for only one of the twelve; this finding was significantly different from what had been expected (p<0.001). A total of 113 stimulus-evoked electromyographic data points were obtained. The correlation coefficient for the relationship between the current threshold recorded with stimulus-evoked electromyographic monitoring and the distance of the wire from the nerve was 0.801 (p<0.001). The actual measured current thresholds were of an observed proportion not different from what had been expected (p = 0.48). CONCLUSIONS: Continuous electromyographic and somatosensory-evoked-potential monitoring techniques failed to indicate contact with the nerve root reliably in this animal model. However, stimulus-evoked electromyographic monitoring consistently provided reliable information indicating the proximity of the implant to the nerve root.     

Evaluation of tissue oxygen measurements for flap monitoring in an animal model

Tissue oxygen tension (p (ti)O (2)) measurements are common in neurosurgery but uncommon in plastic surgery. We examined this technique as a monitoring method with probe placement in the subcutaneous tissue and addressed the importance of probe placement. Myocutaneous flaps were raised in an animal model and p (ti)O (2) measurements performed at different levels in the subcutaneous fat. Flap artery and vein were occluded until a 50% p (ti)O (2) reduction had occurred (T (1/2)). We found no significant effect of depth ( P > 0.10) on the level of p (ti)O (2). T (1/2)(arterial) was 7.2 minutes and T (1/2)(venous) was 18 minutes. We found no significant relation between intitial levels of p (ti)O (2) and T (1/2). Location of the probe and absolute p (ti)O (2) value is of little relevance for flap monitoring. It is the relative change in p (ti)O (2) that is important. The p (ti)O (2) technique is well suited for monitoring in the subcutaneous tissue and is highly sensitive to changes in both arterial and venous blood flow.