Supra-arcuate free fascial MS-TRAM, a modified technique to reduce donor site morbidity in obese population-comparative study.

BACKGROUND: Abdomen-based free flaps represent the gold standard option in the armamentarium of breast reconstruction. The natural evolution to more preservation with less invasive forms of these flaps has been driven by both patient and surgeon satisfaction. Nevertheless, obese patients are challenging due to the increased risk of compromised flap perfusion and donor site morbidity. This challenge is compounded by the prevalence of obesity worldwide, resulting in more free abdominal flaps being performed for breast reconstruction in obese patients. The authors present the outcomes of a modified supra-arcuate fascial muscle-sparing transverse rectus abdominus myocutaneous (FMS-TRAM) technique compared to standard muscle-sparing transverse rectus abdominus myocutaneous (MS-TRAM) technique to reduce the donor site morbidity while providing a well-vascularized large volume of autologous tissue. METHODS: A retrospective comparative data analysis was conducted at two centers: Cairo University Hospitals, Egypt, and University Hospitals Birmingham, United Kingdom. Standard MS-TRAM was performed in 65 patients between 2008 and 2011 (Group 1) versus 275 patients between 2011 and 2020 (Group 2) who underwent FMS-TRAM. The modified technique involved limiting the fascial incision to above or at the level of the arcuate line to preserve the integrity of the anterior rectus sheath caudally. All patients included were of the obese population (BMI≥30 kg/m2 ) and underwent unilateral post-mastectomy reconstruction. Patient demographics, comorbidities, operative details, and outcomes focusing on donor site morbidity and flap complications were recorded and compared between the two groups. RESULTS: The median age and BMI for Group 1 were 43 and 32, respectively. While for Group 2, they were 47 and 33, respectively. Flap weight ranged from 560 to 1470 g (Mean 705) for Group 1, while Group 2 ranged from 510 to 1560 (mean 715). The majority (280/340 [82%]) of the patients in both groups received radiotherapy. 7.7% of Group 1 were smokers, while in Group 2 it was 4.7%. The percentage of delayed versus immediate reconstruction in Group 1 was 60%/40%, while in Group 2, it was 43%/56%. The incidence of fat necrosis, partial necrosis, and total necrosis was 7.6%.1.5%, and 3%, respectively, for Group 1 and 8%, 1.4%, and 2.6%, respectively, for Group 2. The two-tailed p-value demonstrated a significant statistical difference (p < 0.00001) in donor site morbidity between both groups, with more bulge 20% (13/65) and hernia 1.5% (2/65) occurrence in Group 1 versus 1.9% (5/275) and 0.7% (2/275) in Group 2 respectively, over a follow-up period ranging from 24 to 60 months (mean 32). CONCLUSION: FMS-TRAM flaps are safe, robust, and reliable with less donor site morbidity while maintaining optimal flap perfusion for large volume flaps in obese patients with excellent, durable outcomes. It should be considered a valuable tool in the reconstructive armamentarium of breast reconstruction.

No-Drain Single Incision Liposuction Pull-Through Technique for Gynecomastia.

BACKGROUND: Several different methods have been proposed for treatment of gynecomastia, depending on the amount of breast enlargement and skin redundancy. The liposuction pull-through technique has been proposed as an efficacious treatment for many gynecomastia cases. This work aims to study the outcome of this technique when applied as an outpatient procedure, without the use of drains and through a single incision. METHODS: Fifty-two patients with bilateral gynecomastia without significant skin excess were included in this study. The liposuction pull-through technique was performed through a single incision just above the inframammary fold and without the use of drains. Patients were followed up for 6 months. RESULTS: The proposed technique was able to treat the gynecomastia in all patients, with a revision rate of 1.9% to remove residual glandular tissues. There were no seromas, hematomas, nipple distortion, permanent affection of nipple sensation or wound healing problems. CONCLUSION: The liposuction pull-through technique is an effective treatment for gynecomastia without significant skin redundancy. It combines the benefits of the direct excision of glandular tissues, with the minimally invasive nature of liposuction. Performing the procedure through a single incision without the use of drains and without general anesthesia is a safe alternative. LEVEL OF EVIDENCE IV: 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 http://www.springer.com/00266 .

Evaluating current functional airway surgery during rhinoplasty: a survey of the American Society of Plastic Surgeons.

BACKGROUND: Despite numerous reports outlining technical modifications in rhinoplasty, few publications discuss the importance of the perioperative assessment and surgical management of the nasal airway. This study's objective is to increase awareness regarding the functional aspects of rhinoplasty surgery and to encourage surgeons to incorporate functional airway management into their rhinoplasty practice. METHODS: A web-based survey was given to all members of the American Society of Plastic Surgeons (ASPS). Survey results were analysed to determine if surgeons' experience, annual rhinoplasty volume, or postgraduate training affected their results. The relationship between surgeon satisfaction with the outcome of the airway management and the frequency of performing an inferior turbinate reduction was investigated. RESULTS: Of the 4,383 listed ASPS members, 671 (21%) completed the web-based survey. Surgeons who performed a preoperative internal nasal exam were more satisfied with their results (p = 0.016) and report lower rates of postoperative nasal airway obstruction (p = 0.054). Inferior turbinate reduction did correlate to postoperative satisfaction with the nasal airway (p < 0.001). Overall, 85% of respondents were satisfied with their management of the nasal airway and 87% of respondents agreed that there is a need for more instructional courses on this topic. CONCLUSION: There is considerable variation in the results and techniques of assessment and treatment of the nasal airway. Rhinoplasty volume and inferior turbinate reduction are associated with surgeon satisfaction of management of the nasal airway. Functional airway considerations should be incorporated into routine rhinoplasty training, assessment, and treatment. 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.

Enhancement of mechanical properties, microstructure, and antimicrobial activities of zein films cross-linked using succinic anhydride, eugenol, and citric Acid.

Zein constitutes about half of the endosperm proteins in corn. Recently, attempts have been made to utilize zein for food coatings and biodegradable materials, which require better physical properties, using chemical modification of zein. In this study, zein proteins were modified using citric acid, succinic anhydride, and eugenol as natural cross-linking agents in the wet state. The cross-linkers were added either separately or combined in increment concentrations (0.1, 0.2, 0.3, and 0.4%). The effects of those agents on the mechanical properties, microstructure, optical properties, infrared (IR) spectroscopy, and antibacterial activities of zein were investigated. The addition of cross-linking agents promoted changes in the arrangement of groups in zein film-forming particles. Regarding the film properties, incorporation of cross-linking agents into zein films prepared in ethanol resulted in two- to three-fold increases in tensile strength (TS) values. According to the Fourier-transform infrared (FTIR) spectra and Hunter parameters there were no remarkable changes in the structure and color of zein films. Transparency of zein films was decreased differentially according to the type and cross-linker concentration. The mechanical and optical properties of zein films were closely related to their microstructure. All cross-linked films showed remarkable antibacterial activities against Bacillus cereus ATCC 49064 and Salmonella enterica ATCC 25566. Food spoilage and pathogenic bacteria were affected in a film-dependent manner. Our experimental results show that even with partial cross-linking the mechanical properties and antipathogen activities of zein films were significantly improved, which would be useful for various industrial applications.

Protective role of probiotic lactic acid bacteria against dietary fumonisin B1-induced toxicity and DNA-fragmentation in sprague-dawley rats.

The genus Fusarium, especially F. verticillioides and F. proliferatum, has been found in several agricultural products worldwide, especially in maize. Regardless the occurrence of symptoms, the presence of Fusarium in maize constitutes an imminent risk due to its ability to produce fumonisins, mycotoxins with proven carcinogenic effect on rats, swine, and equines and already classified as possible carcinogens to humans. The toxicity of incremental levels of fumonisin B1 (FB1), that is, 50, 100, and 200 mg FB1/kg diet, and the role of Lactobacillus delbrueckii subsp. lactis DSM 20076 (LL) and Pediococcus acidilactici NNRL B-5627 (PA) supplementation in counteracting the FB1 effects in intoxicated rats were monitored over a period of 4 weeks. Effects on the feed intake and body weight gain were noticed. A significant (p ≤ 0.05) increase in the level of liver and kidney functions markers and DNA fragmentation was also noticed in rat groups T100 and T200. The lactic acid bacteria (LAB) supplementation could bring back the normal serum biochemical parameters in rats fed on fumonisin B1-contaminated diets (T50 and T100) compared to FB1-treated groups. In rats of high-dosage dietary groups supplemented with LAB (T200-LL and T200-PA), the supplementation reduced the serum activity levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine by 11.3, 11.9, 32, and 20%, respectively. DNA fragmentations were observed in the rat group treated with 200 mg FB1 after 3 weeks, while fragmentation was noticed in treated groups with 100 and 200 mg FB1 after 4 weeks. No DNA fragmentation was apparent in FB1-treated rats co-administered the LL or PA strain. These results suggest that in male rats consuming diets containing FB1, there is a time- and dose-dependent increase in serum enzyme activities and DNA lesions. Moreover, Lb. delbrueckii subsp. lactis (LL) and P. acidilactici (PA) strains have a protective effect against antigenotoxicity and precancerous lesions.

Activation of the insulin-like growth factor-1 receptor alters p27 regulation by the epidermal growth factor receptor in oral squamous carcinoma cells.

BACKGROUND: Although oral squamous cell carcinomas (OSCCs) commonly overexpress the epidermal growth factor receptor (EGFR), EGFR tyrosine kinase inhibitors (TKIs) exhibit poor efficacy clinically. Activation of the insulin-like growth factor-1 receptor (IGF1R) induces resistance of OSCC cells to EGFR-TKIs in vitro. This study seeks to evaluate the changes in cell cycle status in OSCC cells in response to gefitinib and IGF1R activation. METHODS: SCC-25 OSCC cells were used for in vitro analyses. RESULTS: Gefitinib caused a 50% reduction in S-phase population, and IGF1R activation caused a 2.8-fold increase; combined treatment yielded a baseline S-phase population. Gefitinib treatment increased the cyclin-dependent kinase inhibitor p27, and this was not abrogated by IGF1R activation. pT157-p27 was noted by immunoblot to be decreased on gefitinib treatment, but this was reversed with IGF1R activation. T157 phosphorylation contributes to cytoplasmic localization of p27 where it can promote cell proliferation and cell motility. Using both subcellular fractionation and immunofluorescence microscopy techniques, IGF1R stimulation was noted to increase the relative cytoplasmic localization of p27; this persisted when combined with gefitinib. CONCLUSIONS: IGF1R activation partially reverses the cell cycle arrest caused by gefitinib in OSCC cells. While IGF1R stimulation does not eliminate the gefitinib-induced increase in total p27, its phosphorylation state and subcellular localization are altered. This may contribute to the ability of the IGF1R to rescue OSCC cells from EGFR-TKI treatment and may have important implications for the use of p27 as a biomarker of cell cycle arrest and response to therapy.

Heat shock proteins in oncology: diagnostic biomarkers or therapeutic targets?

Heat shock proteins (HSP) are a family of proteins induced in cells exposed to different insults. This induction of HSPs allows cells to survive stress conditions. Mammalian HSPs have been classified into six families according to their molecular size: HSP100, HSP90, HSP70, HSP60, HSP40 and small HSPs (15 to 30kDa) including HSP27. These proteins act as molecular chaperones either helping in the refolding of misfolded proteins or assisting in their elimination if they become irreversibly damaged. In recent years, proteomic studies have characterized several different HSPs in various tumor types which may be putative clinical biomarkers or molecular targets for cancer therapy. This has led to the development of a series of molecules capable of inhibiting HSPs. Numerous studies speculated that over-expression of HSP is in part responsible for resistance to many anti-tumor agents and chemotherapeutics. Hence, from a pharmacological point of view, the co-administration of HSP inhibitors together with other anti-tumor agents is of major importance in overcoming therapeutic resistance. In this review, we provide an overview of the current status of HSPs in autoimmune, cardiovascular, and neurodegenerative diseases with special emphasis on cancer.

Development of Lepidium sativum Extracts/PVA Electrospun Nanofibers as Wound Healing Dressing.

Lepidium sativum L. (Garden cress/Hab El Rashad) (Ls), family Brassicaceae, has considerable importance in traditional medicine worldwide because of its antioxidant and anti-inflammatory activities. Ls fruits were used in Ayurvedic medicines as a useful drug for injuries, skin, and eye diseases. The aim of this study was to examine the effectiveness of the total ethanol extract (TEE) and polysaccharide (Poly) of Ls seeds loaded on poly(vinyl alcohol) (PVA) nanofibers (NFs) as a wound healing dressing and to correlate the activity with the constituents of each. TEE and Poly were phytochemically analyzed qualitatively and quantitatively. Qualitative analysis proved the presence of phenolic acids, flavonoids, tannins, sterols, triterpenes, and mucilage. Meanwhile, quantitative determinations were carried out spectrophotometrically for total phenolic and total flavonoid contents. High-performance liquid chromatography (HPLC) for TEE identified 15 phenolic acids and flavonoid compounds, with gallic acid and catechin as the majors. Separation, purification, and identification of the major compounds were achieved through a Puriflash system, column Sephadex LH20, and spectroscopic data (1H, 13C NMR, and UV). Eight compounds (gallic acid, catechin, rutin, kaempferol-3-O-rutinoside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, quercetin, and kaempferol) were obtained. Gas-liquid chromatography (GLC) analysis for Poly identified 11 compounds, with galactose being the main. The antioxidant activity for both extracts was measured by three different methods based on different mechanisms: 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing ability of plasma (FRAP), and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS). TEE has the highest effectiveness as an antioxidant agent with IC50 82.6 ± 8.35 µg/mL for DPPH and 772.47 and 758.92 µM Trolox equivalent/mg extract for FRAP and ABTS, respectively. The PVA nanofibers (NFs) for each sample were fabricated by electrospinning. The fabricated NFs were characterized by SEM and Fourier transform infrared spectroscopy (FTIR); the results revealed successful encapsulation of TEE and Poly in the prepared NFs. Moreover, the swelling index of TEE in the prepared NFs shows that it is the most appropriate for use as a wound dressing. Cytotoxicity studies indicated a high cell viability with IC50 216 µg/mL and 1750 µg/mL for TEE and Poly, respectively. Moreover, the results revealed that nanofibers possess higher cell viability compared to solutions with the same sample quantities: 9-folds for TEE and 4-folds for Poly of amount 400 µg. The in vitro wound healing test showed that the TEE nanofibers performed better than Poly nanofibers in accelerating wound healing, with 90% for TEE, more than that for the Poly extract (82%), after 48 h. These findings implied that the incorporation of TEE in PVA nanofibers was more efficient than incorporation of Poly in improving the biological activity in wound healing. In conclusion, the TEE and polysaccharides of L. sativum L seed are ideal candidates for nanofibrous wound dressings. Furthermore, the contents of phenolic acids and flavonoids in TEE, which have potential antioxidant activity, make the TEE of L. sativum more favorable for wound healing dressing.

Evaluating Flinders Technology Associates card for transporting bacterial isolates and retrieval of bacterial DNA after various storage conditions.

BACKGROUND AND AIM: Flinders Technology Associates (FTA) cards simplify sample storage, transport, and extraction by reducing cost and time for diagnosis. This study evaluated the FTA suitability for safe transport and storage of Gram-positive and Gram-negative bacterial cells of animal origin on its liquid culture form and from organ impression smears (tissues) under the same routine condition of microbiological laboratory along with detecting their nucleic acid over different storage conditions. MATERIALS AND METHODS: Increase in bacterial count from 104 to 107 (colony-forming units/mL) of 78 isolates representing seven bacterial species was applied onto cards. FTA cards were grouped and inoculated by these bacteria and then stored at different conditions of 24-27°C, 4°C, and -20°C for 24 h, for 2 weeks, for 1 and 3 month storage, respectively. Bacteriological examination was done, after which bacterial DNA was identified using specific primers for each bacterial type and detected by polymerase chain reaction (PCR). RESULTS: The total percentage of recovered bacteria from FTA cards was 66.7% at 24-27°C for 24 h, the detection limit was 100% in Gram-positive species, while it was 57.4% in Gram-negative ones. Regarding viable cell detection from organ impression smears, it was successful under the previous conditions. No live bacterial cells were observed by bacteriological isolation rather than only at 24-27°C for 24 h storage. All bacterial DNA were sufficiently confirmed by the PCR technique at different conditions. CONCLUSION: Overall, the FTA card method was observed to be a valid tool for nucleic acid purification for bacteria of animal origin in the form of culture or organ smears regardless of its Gram type and is used for a short time only 24 h for storage and transport of live bacteria specifically Gram-positive type. Moreover, the bacterial nucleic acid was intact after storage in -20°C for 3 months and was PCR amplifiable.

Antitumor effect of insulin-like growth factor-1 receptor inhibition in head and neck squamous cell carcinoma.

OBJECTIVES: The insulin-like growth factor-1 receptor (IGF1R) has been implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC), and small molecule tyrosine kinase inhibitors (TKIs) of IGF1R activity may have anticancer activity. Therefore, the relationship between survival and IGF1R expression was assessed for oral cavity (OC) cancer, and the antitumor effects of two IGF1R-TKIs, OSI-906 and BMS-754807, were evaluated in HNSCC cell lines in vitro. METHODS: Clinical outcome data and tissue microarray immunohistochemistry were used to generate IGF1R expression-specific survival curves. Immunoblot, alamarBlue proliferation assay, trypan blue exclusion viability test, clonogenic assay, flow cytometry, and reverse phase protein array (RPPA) were used to evaluate in vitro responses to IGF1R-TKIs. RESULTS: For patients with stage III/IV OCSCC, higher IGF1R expression was associated with poorer overall 5-year survival (P = 0.029). Both BMS-754807 and OSI-906 caused dose-dependent inhibition of IGF1R and Akt phosphorylation and inhibited proliferation; BMS-754807 was more potent than OSI-906. Both drugs reduced HNSCC cell viability; only OSI-906 was able to eliminate all viable cells at 10 µM. The two drugs similarly inhibited clonogenic cell survival. At 1 µM, only BMS-754807 caused a fourfold increase in the basal apoptotic rate. RPPA demonstrated broad effects of both drugs on canonical IGF1R signaling pathways and also inhibition of human epidermal growth factor receptor-3 (HER3), Src, paxillin, and ezrin phosphorylation. CONCLUSION: OSI-906 and BMS-754807 inhibit IGF1R activity in HNSCC cell lines with reduction in prosurvival and proliferative signaling and with concomitant antiproliferative and proapoptotic effects. Such antagonists may have utility as adjuvants to existing therapies for HNSCC. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1470-1478, 2020.

Teucrium Polium Plant Extract Provokes Substantial Cytotoxicity at the Early Stage of Embryonic Development.

The aim of this study is to explore the outcome of Teucrium polium (TP) medicinal plant consumption on the early stage of fetal development. We used the chicken embryo at 3 days of incubation as a model to evaluate the effect of TP plant extract during embryogenesis. In addition, quantitative polymerase chain reaction (qPCR) was applied to explore the expression of six genes related to cell proliferation, apoptosis, sur-vival, angiogenesis, and migration. Our data revealed that TP exposure inhibits angiogenesis of the chicken embryo and its chorioallantoic membrane. In addition, we found that TP extract significantly harms the normal development of the embryos since around 95% of TP-exposed embryos died after 1-3 days of treatment. Macroscopic examination did not show any anomalies in these embryos. However, qPCR analysis of activation transcription factor-3, B-cell lymphoma-2, caspase 8, inhibin subunit beta A, vascular endothelial growth factor-C, and Cadherin-6 type-2 genes revealed that these genes are considerably deregulated in heart and brain tissues from TP-exposed embryos in comparison with their matched tissues from unexposed ones. Our study implies that TP plant can have very toxic effects on the early stage of the embryo. Therefore, it is important to alert expectant women to avoid the use of this medicinal plant during pregnancy.

Fracture Resistance of Tilted Premolars Restored with Different Post-Core Systems.

AIMS AND OBJECTIVE: To assess the effect of root tilt on the fracture resistance and failure pattern of endodontically-treated premolars restored with different post-core systems. MATERIALS AND METHODS: Ninety endodontically-treated premolars were mounted in acrylic blocks with 0°, 12°, and 24° axial root tilt. Teeth in each group were restored in three subgroups with cast post-core, readymade metal posts and composite cores, and fiber post and composite cores. Crowns of all teeth were prepared coinciding with the long axis of the acrylic blocks to receive all-ceramic crowns. All restored teeth were stressed to record the maximum load at failure and the associated failure pattern. The collected data were statistically analyzed using two-way ANOVA, Tukey's, and Kruskal-Wallis tests at α = 0.05 on past software to detect any differences between subgroups. RESULTS: Analysis of the collected data indicated significant differences between the tested subgroups (ANOVA, P = 3.86). Further analysis showed significant difference between all test subgroups and the control (Tukey's, P < 0.05). In general, teeth with 0° tilt seemed more resistant to fracture than the tilted ones. For all groups, teeth restored with fiber post and composite cores (SG3) were more resistant to fracture compared to other post-core systems (SG1 and SG2) (Tukey's, P < 0.05). The root fracture was the most commonly seen mode of failure. CONCLUSIONS: Root tilting usually affects the fracture resistance of teeth restored with post-core systems. The fiber post and composite cores seemed to be the best choice to restore teeth with different root tilting possibilities.

Nanoimmunoassay to Detect Responses in Head and Neck Cancer: Feasibility in a Mouse Model.

OBJECTIVE: To demonstrate the feasibility of detecting and quantifying extracellular signal-related kinase (ERK) phosphorylation status using nanoimmunoassay (NIA). STUDY DESIGN: Analyses using Cal27, SCC25, and OSC19 head and neck squamous carcinoma cell lines in vitro and in a murine xenograft model. SUBJECTS AND METHODS: NIA and immunoblot were performed on whole-cell lysates, tumor lysates, and fine-needle aspirate biopsies to detect ERK phosphorylation states. RESULTS: Using NIA, all 6 isoforms of ERK1/2, including nonphosphorylated, monophosphorylated, and diphosphorylated species, could be reliably detected, distinguished, and quantified in a single assay using a single antibody. In vitro treatment of Cal27 cells with the epidermal growth factor receptor inhibitor gefitinib abolished phospho-ERK detection by immunoblot but resulted in residual detectable species by NIA. Residual phospho-ERK in gefitinib-treated cells could be further reduced by the addition of the insulin-like growth factor 1 receptor inhibitor OSI-906; this correlated with an additional decrease in proliferation over gefitinib alone. In a pilot study of 4 murine xenograft tumors, NIA performed on tumor lysates and fine-needle aspirate biopsies demonstrated altered ERK profiles after 2 days of gefitinib treatment compared with untreated mice. CONCLUSION: NIA offers a novel approach to quantitating the activation state of signaling molecules such as ERK in nanoscale in vitro and in vivo samples across a wide dynamic range. As such, it has potential to provide molecular diagnostic information before, during, and after treatment using a minimally invasive technique. Further study is warranted to determine its utility in assessing signaling proteins as biomolecular outcome predictors in clinical trials.

Nicotine enhances proliferation, migration, and radioresistance of human malignant glioma cells through EGFR activation.

It has been suggested that continued tobacco use during radiation therapy contributes to maintenance of neoplastic growth despite treatment with radiation. Nicotine is a cigarette component that is an established risk factor for many diseases, neoplastic and otherwise. The hypothesis of this work is that nicotine promotes the proliferation, migration, and radioresistance of human malignant glioma cells. The effect of nicotine on cellular proliferation, migration, signaling, and radiation sensitivity were evaluated for malignant glioma U87 and GBM12 cells by use of the AlamarBlue, scratch healing, and clonogenic survival assays. Signal transduction was assessed by immunoblotting for activated EGFR, ERK, and AKT. At concentrations comparable with those found in chronic smokers, nicotine induced malignant glioma cell migration, growth, colony formation, and radioresistance. Nicotine increased phosphorylation of EGFR(tyr992), AKT(ser473), and ERK. These molecular effects were reduced by pharmacological inhibitors of EGFR, PI3K, and MEK. It was therefore concluded that nicotine stimulates the malignant behavior of glioma cells in vitro by activation of the EGFR and downstream AKT and ERK pathways.

Subcutaneous administration of D-luciferin is an effective alternative to intraperitoneal injection in bioluminescence imaging of xenograft tumors in nude mice.

Currently, intraperitoneal (IP) injection of D-luciferin is the preferred method of providing substrate for bioluminescent imaging (BLI); however it has a failure rate of 3-10% due to accidental intestinal injection. The present study evaluates the quality of BLI after subcutaneous (SC) injection of D-luciferin and demonstrates the effectiveness of SC injection in anatomically disparate tumor models. Mice bearing luciferase-expressing tumors underwent BLI after SC or IP injection of D-luciferin. The average time to maximal luminescence was 6 min (range 5-9 min) after SC injection and 8 min (range 5-8 min) after IP injection. Within 7 minutes of injection, SC and IP routes yielded similar luminescence in subcutaneous, intracranial, tongue, and lung xenograft tumor models. In a model of combined subcutaneous and intracranial xenografts, SC injection resulted in proportional luminescence at all sites, confirming that preferential delivery of substrate does not occur. While tumors were occasionally not visualized with IP injection, all tumors were visualized reliably with SC injection. Thus, SC injection of D-luciferin is a convenient and effective alternative to IP injection for BLI in nude mice. It may be a preferable approach, particularly for tumors with weaker signals and/or when greater precision is required.

The Influence of Hypoxia and pH on Bioluminescence Imaging of Luciferase-Transfected Tumor Cells and Xenografts.

Bioluminescence imaging (BLI) is a relatively new noninvasive technology used for quantitative assessment of tumor growth and therapeutic effect in living animal models. BLI involves the generation of light by luciferase-expressing cells following administration of the substrate luciferin in the presence of oxygen and ATP. In the present study, the effects of hypoxia, hypoperfusion, and pH on BLI signal (BLS) intensity were evaluated in vitro using cultured cells and in vivo using a xenograft model in nude mice. The intensity of the BLS was significantly reduced in the presence of acute and chronic hypoxia. Changes in cell density, viability, and pH also affected BLS. Although BLI is a convenient non-invasive tool for tumor assessment, these factors should be considered when interpreting BLS intensity, especially in solid tumors that could be hypoxic due to rapid growth, inadequate blood supply, and/or treatment.

The submental flap for oral cavity reconstruction: extended indications and technical refinements.

BACKGROUND AND PURPOSE: The submental flap is gaining popularity as a simple technique for reconstruction of small to moderate size defects of the oral cavity. However, its role in composite defects involving the jaw is not clearly defined. Indeed, controversy exists about the flap's interference with an oncologically sound neck dissection PATIENTS AND METHODS: A total of 21 patients with oral cavity cancers over a three year period were included. All patients underwent surgical resection and immediate reconstruction with submental flap except one patient who had delayed reconstruction with reversed flap. The flap was used for reconstruction of intra-oral soft tissue defect in 13 patients and composite defects in 8 patients. RESULTS: Of 21 patients 12 were males and 9 were females, age ranged from 32 to 83 years. The primary tumor sites included buccal mucosa (7), tongue (4), alveolar margin (3), floor of mouth (5) and lip (2). Eventually in this study, we adopted completing the neck dissection first before flap harvest. Complete flap loss occurred in 2 whereas 3 patients had partial flap loss. Follow up ranged from 3 to 44 months, one patient died from metastatic disease. Four patients developed neck recurrences. CONCLUSION: The submental flap is a valid option for reconstruction of intra-oral soft tissue as well as composite oral defects particularly in elderly patients. However, oncologically sound neck dissection should be assured.

Autohydrolysed Tilapia nilotica Fish Viscera as a Peptone Source in Bacteriocin Production.

Fish processing generates large amounts of solid and liquid wastes. Many different by-products have been produced from fish processing wastes. Studies on solubilization of Bolti fish (Tilapia nilotica) viscera by endogenous enzymes at different pHs are described. Hydrolysis reactions were conducted with freshly thawed viscera utilizing an initial temperature gradient and terminated at various time points by heat inactivation of the enzymes. Various peptones obtained from hydrolysed visceral homogenates of Bolti fish residues showed their suitability for promoting the growth of lactic acid bacteria (mainly Lactobacillus sake Lb 706), microorganisms with particularly complex nutritional requirements especially peptidic sources. The assay of several treatments with L. sakei Lb 706, producer of the bacteriocin sakacin A, demonstrated that optimum conditions for biomass and bacteriocin production only imply a brief autohydrolysis at room temperature. The results showed that the Bolti fish hydrolysates gave remarkable results to those found in costly commercial media, specifically recommended for culturing and large-scale production of lactic acid bacteria.

Semisynthetic studies on the manzamine alkaloids.

Chemical transformation studies were conducted on (-)-8-hydroxymanzamine A ( 1), (-)-manzamine F ( 2), manzamine A ( 3), and (+)-8-hydroxymanzamine A ( 4), isolated from Indo-Pacific Acanthostrongylophora sponges. Thirteen new semisynthetic manzamine derivatives, including four Delta (34,35) manzamines ( 5, 6, 8, and 9) and the unprecedented manzamine derivative 17, are reported. The potent in vitro activities of the obtained semisynthetic manzamines against activated brain microglia and the AIDS opportunistic infection pathogen Mycobacterium tuberculosis are presented.