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This study examined the controlled release of cetylpyridinium chloride (CPC) from a tissue conditioner (TC) containing CPC-montmorillonite (CPC-Mont), the associated antimicrobial activity, and oral mucosa irritation. The CPC release test was performed daily for 28 days in three test solutions: distilled water, 0.2 M NaCl, and 0.2 M HCl. The antimicrobial activities for 7, 14, 21, and 28 days against Candida albicans, Staphylococcus aureus, and Streptococcus mutans were assessed according to the JIS Z 2801/ISO 22196 standard. An oral mucosa irritation test was conducted using cheek pouches in five male hamsters according to the ISO 10993-10:2010 standard. The amount of CPC released each day and the cumulative amount released over 28 days (6.12 mg) were less than the daily safe maximum of sore throat medicines (8 mg). Additionally, TC with CPC-Mont could sustain antimicrobial activity against adherent bacteria for 14 days and has no oral mucosa irritation potential.

A 14-month-old male Armenian hamster ( Cricetulus migratorius) presented with a spontaneous, subcutaneous, firm mass (4.0 × 2.0 × 1.5 cm) on the ventral neck extending towards the cheek pouch causing multifocal small oral ulcerations. This animal was immunized subcutaneously on the dorsal neck for the development of monoclonal antibodies seven months before presentation. The animal was euthanized and necropsy was performed. Histopathology of the mass showed a well demarcated, multilobulated, unencapsulated, highly cellular, neoplastic mass composed of spindle cells arranged in interlacing streams and bundles, with a moderate amount of fibrovascular stroma. The neoplastic cells exhibited indistinct cell borders and a moderate to large amount of eosinophilic, fibrillar cytoplasm, marked anisocytosis and anisokaryosis, binucleated and multinucleated cells, and high mitotic rate. Based on the histomorphologic features of the mass, and the presence of renal tubular hyaline globules and myeloid hyperplasia in the bone marrow, a diagnosis of histiocytic sarcoma was made. The presumptive diagnosis was confirmed by immunohistochemistry, upon which the neoplastic cells showed strong immunoreactivity for the histiocytic cell markers Iba1 and CD11b. Histiocytic sarcomas have been reported in Syrian ( Mesocricetus auratus) and Siberian dwarf ( Phodopus sungorus) hamsters but, to our knowledge, the current report represents the first case of histiocytic sarcoma described in an Armenian hamster. It is plausible to consider the animal’s experimental immunization history and the development of the histiocytic sarcoma to be related. An association between adjuvanted vaccines and soft-tissue sarcomas has been described in cats and referred to as feline injection-site sarcomas.

Translational animal models for oral mucositis (OM) are necessary to simulate and assess the bioclinical effects and response in humans. These models should simulate high levels of radiation exposure that leads to oxidative stress and inflammatory‐initiated tissue changes. Hamster models have been extensively studied to observe pathological effects of radiation exposure and help in the development of effective treatments. To successfully evaluate the potential for treatment regimens with consistency and relevance, a radiation‐induced OM hamster model was developed using a clinical linear accelerator utilized by cancer patients daily. The dose exposure to the isolated, everted cheek pouch of a hamster, as well as the progression of injury, pro‐inflammatory marker, histological, and elasticity analyses of the buccal pouch were conducted to verify replicability and reproducibility of the injury model. The findings from this model demonstrated its ability to consistently induce injury and resolution over 28 days using an acute dose of 60 Gy. This model was developed to enhance clinical relevance when evaluating potential efficacious treatments and can now be utilized in efficacy studies to better evaluate developed therapeutics in a preclinical model that is easy to translate to clinical studies..

Background/Aim: A three-dimensional (3D) printed tracheostomy tube has potential application for patients who require a specialized tube. The aim of this study was to evaluate the characteristics of various 3D printing materials and determine their use in producing 3D-printed tracheostomy tube. Materials and Methods: Mechanical, chemical, and microbiological in vivo changes in the scaffolds were analyzed using a hamster cheek pouch (HCP) model. Results: The poly methyl methacylate (PMMA)-resin showed superior pre- and post-insertion mechanical properties and a relatively consistent lower biofilm formation compared with other scaffolds. PMMA-resin was successfully 3D-printed with dimensional accuracy without a support system. The use of a 3D-printed PMMA tracheostomy tube in a rabbit trachea showed no definite signs of infection, allergy or foreign body reaction. Conclusion: PMMA-resin can be proposed as an alternative for a 3D-printed tracheostomy tube material. In addition, we suggest HCPs as an in vivo model for evaluating indwelling medical devices.

Introduction: Cancer is a serious public health problem in many parts of the world; oral squamous cell carcinoma was the 11th most common malignant neoplasm in human papulation. The hamster cheek pouch carcinogenesis model is a well-known animal system that closely mimics the development of premalignant and malignant lesions in human oral cancer. The expressions of cancerization process in this model using DNA ploidy and S-phase fraction is the point of interest. Aim of the study: This research was carried out to study the analysis of DNA ploidy and S-phase fraction in relation to development of oral squamous cell carcinoma during hamster cheek pouches carcinogenesis process induced by DMBA. Material and methods: A total of 50 young gold Syrian hamsters distributed into groups as follows: 2 normal animals examined for the normal histology of the cheek pouch mucosa and 48 animals divided into; group I, as a control group (n= 12), in which pouches were painted with a heavy mineral oil only; group II, were painted with DMBA mixed in a heavy mineral oil (n=36). The examined animal tissue utilized for flow cytometry analysis to obtain DNA ploidy and S-phase fraction development during carcinogenesis process. Results: The flow cytometric analysis of DNA content demonstrated a significant role in carcinogenesis process in oral squamous cell carcinoma. Moreover, they provided a significant analysis in the proliferation and activity of the cancer cells as measured by the S-phase fraction activity.Conclusions: The combinatorial DNA content analysis involving general ploidy and S-phase fraction have potential for support in the early diagnosis; during the development of oral squamous cell carcinoma.

Boron neutron capture therapy (BNCT) is a targeted therapy, which consists of preferential accumulation of boron carriers in tumor followed by neutron irradiation. Each oral cancer patient has different risks of developing one or more carcinomas and/or oral mucositis induced after treatment. Our group proposed the hamster oral cancer model to study the efficacy of BNCT and associated mucositis. Translational studies are essential to the advancement of novel boron delivery agents and targeted strategies. Herein, we review our work in the hamster model in which we studied BNCT induced mucositis using three different cancerization protocols, mimicking three different clinical scenarios. The BNCT-induced mucositis increases with the aggressiveness of the carcinogenesis protocol employed, suggesting that the study of different oral cancer patient scenarios would help to develop personalized therapies.

Background Newly, chemo‐preventive technique might be a hopeful advancement in developing countries for treating cancers with the aid of toxic less natural based constituents. Malignancy urges to augment effectual chemo‐preventive agents that are look forward to suppress the tumours which may be stimulated by chewing and smoking of tobacco and over alcohol consumption related with the high prevalence of human oral cancer (OC) patients. Methods In the present research, we examined to assess antioxidants, lipid peroxidation (LPO) and detoxification enzymes levels of anticancer activity of mangiferin on 0.5% 7.12‐dimethylbenz[a]anthracene (DMBA) provoked hamster cheek pouch carcinoma (HCPC). OC on hamster buccal pouch (HBP) was incited by DMBA treatment for thrice per week for over 14 weeks. Results 100% well defined OC establishment with body weight (bw), tumour burden (TB), antioxidant, LPO and liver marker enzymes and also histological changes were observed on DMBA‐challenged buccal pouch carcinoma (BPC) in hamsters. Orally treated mangiferin at an effective dosage of 50 mg/kg bw, to DMBA painted hamsters were significantly averted the body weight, succession of tumour, the biochemical as well as histopathological changes. Conclusion Findings of this work clearly suggest that the anti‐carcinoma effect of mangiferin possesses the modulator effects on potent antioxidant, anti‐LPO and detoxification agents to expel the metabolites of malignant cells, on DMBA‐provoked BPC in hamsters., Orally treated mangiferin at an effective dosage of 50 mg/kg bw, to DMBA painted hamsters were significantly averted the body weight, succession of tumor, the biochemical as well as histopathological changes. Anti‐carcinoma effect of mangiferin possess the modulator effects on potent antioxidant, anti‐LPO and detoxification agents to expel the metabolites of malignant cells, on DMBA‐provoked BPC in hamsters.

Background. Cardiovascular disease (CVD) is the leading cause of death in Western civilizations. The type of fatty acid which makes up the diet is related to the cardiovascular morbimortality and the formation of atheromas. Populations with high consumption of oils and fats have a higher number of deaths from CVD. Purpose. In the present study, the objective was to comparatively analyze the microcirculatory effects of unrefined babassu oil with olive oil in microcirculation and liver of male hamsters of the species Mesocricetus auratus, checking the permeability to macromolecules after ischemia-reperfusion (I/R) without and with topical application of histamine 5 × 10−6 M. This is an experimental study, using as model the hamster’s cheek pouch, which was prepared for intravital microscopy. The hamsters were divided into seven groups and orally treated for 14 days, twice a day (at 8 AM and 4 PM), orally received treatments in the following doses: unrefined babassu oil (BO) 0.02 mL/dose (group BO-2), 0.06 mL/dose (group BO-6), and 0.18 mL/dose (BO-18 group); extra virgin olive oil (OI) 0.02 mL/dose (group OI-2), 0.06 mL/dose (group OI-6), and 0.18 mL/dose (OI-18 group); and mineral oil (MO) 0.18 mL/dose (MO-18 group). The observations were made on the 15th day on the hamsters’ cheek pouch; the increase of vascular permeability induced by I/R with and without histamine application was evaluated, and in the liver the biological material was collected aseptically then fixed in 10% buffered formalin. Results. Microcirculatory analyses showed a significant reduction in the number of leaks after I/R with and without the topical use of histamine in animals treated with unrefined BO 0.06 mL/dose (BO-6) and 0.18 mL/dose (BO-18) compared to animals treated with OI. The BO group (p<0.001) presented a dose-response relationship for decreasing leaks after I/R with and without topical use of histamine. Histological liver analyses showed no fat deposition changes in any of the treatment groups. Phytochemical analyses evidenced a chemical compound (C31H60NO8) in unrefined BO but not in OI. Conclusions. This experiment demonstrates the protective effect of unrefined BO on the microcirculatory system and its greater dose effect than that of OI. Finding a chemical compound (C31H60NO8) that is present in BO but not in OI opens the possibility of investigating whether this chemical compound was responsible for the protective effect on membrane permeability.

We demonstrate that structured illumination microscopy has the potential to enhance fluorescence lifetime imaging microscopy (FLIM) as an early detection method for oral squamous cell carcinoma. FLIM can be used to monitor or detect changes in the fluorescence lifetime of metabolic cofactors (e.g. NADH and FAD) associated with the onset of carcinogenesis. However, out of focus fluorescence often interferes with this lifetime measurement. Structured illumination fluorescence lifetime imaging (SI-FLIM) addresses this by providing depth-resolved lifetime measurements, and applied to oral mucosa, can localize the collected signal to the epithelium. In this study, the hamster model of oral carcinogenesis was used to evaluate SI-FLIM in premalignant and malignant oral mucosa. Cheek pouches were imaged in vivo and correlated to histopathological diagnoses. The potential of NADH fluorescence signal and lifetime, as measured by widefield FLIM and SI-FLIM, to differentiate dysplasia (pre-malignancy) from normal tissue was evaluated. ROC analysis was carried out with the task of discriminating between normal tissue and mild dysplasia, when changes in fluorescence characteristics are localized to the epithelium only. The results demonstrate that SI-FLIM (AUC = 0.83) is a significantly better (p-value = 0.031) marker for mild dysplasia when compared to widefield FLIM (AUC = 0.63).

A mouthwash formulation of rebamipide (REB) is commonly used to treat oral mucositis, however, this formulation does not provide sufficient treatment or prevention in cases of serious oral mucositis. To improve treatment, we attempted to design a hydrogel incorporating REB nanocrystals (R-NPs gel). The R-NPs gel was prepared by a bead mill method using carbopol hydrogel, methylcellulose and 2-hydroxypropyl-&beta, cyclodextrin, and another hydrogel incorporating REB microcrystals (R-MPs gel) was prepared following the same protocol but without the bead mill treatment. The REB particle size in the R-MPs gel was 0.15&ndash, 25 &mu, m, and while the REB particle size was 50&ndash, 180 nm in the R-NPs gel. Next, we investigated the therapeutic effect of REB nanocrystals on oral mucositis using a hamster model. Almost all of the REB was released as drug nanocrystals from the R-NPs gel, and the REB content in the cheek pouch of hamsters treated with R-NPs gel was significantly higher than that of hamsters treated with R-MPs gel. Further, treatment with REB hydrogels enhanced the healing of oral wounds in the hamsters. REB accumulation in the cheek pouch of hamsters treated with the R-NPs gel was prevented by an inhibitor of clathrin-dependent endocytosis (CME) (40 &mu, M dynasore). In conclusion, we designed an R-NPs gel and found that REB nanocrystals are taken up by tissues through CME, where they provide a persistent effect resulting in an enhancement of oral wound healing.

Oral mucositis is a common inflammatory complication among patients with cancer. This study evaluated the histopathological, stereological, and antioxidant markers of 2% eucalyptus extract in induced oral mucositis in male golden hamsters. In this animal study, oral mucositis was induced in 30 male golden hamsters by 5-FU (60 mg/kg) on days 0, 5, and 10 of the study. The cheek pouch was scratched with a sterile needle once daily on days 3 and 4. On days 14-17, 2% eucalyptus hydroalcoholic extract gel and Calendula officinalis extract gel groups were treated and then compared with a non-treated control group. The histopathological and stereological scores and the pouch content of malondialdehyde, as well as the activities of glutathione and myeloperoxidase in the pouch tissue, were evaluated. Histopathologic scores of oral mucositis were lower in the eucalyptus gel group than those of the calendula and control groups (p

In most cancer patients, chemotherapy-induced oral mucositis (OM) is a frequent side effect, leading to low quality of life and delay in therapy. The aim of this study was to evaluate the effects of Onchung-eum, a well-known herbal prescription in traditional medicine comprising 8 herbs that has long been used for skin diseases, on 5-fluorouracil (5-FU)–induced OM in human pharyngeal cells and golden Syrian hamsters. DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and reactive oxygen species production were measured in vitro. The effects of Onchung-eum on OM of hamster cheek pouches induced by 5-FU were evaluated histologically and using TUNEL assay. In addition, the expression of nuclear factor-κB, caspase-3, and pro-inflammatory cytokines were measured by immunoblotting and immunohistochemistry. Significantly increased cell viability was observed in the Onchung-eum–treated groups compared with the 5-FU–treated control group. In 500 and 1000 mg/kg Onchung-eum–treated groups, the damaged epithelial layers in the cheek pouches of hamsters were significantly recovered. Moreover, at all concentrations, cell death in the cheek pouches of hamsters in the Onchung-eum–treated groups significantly decreased. The expression of pro-inflammatory cytokines, nuclear factor-κB, and caspase-3 also significantly decreased in Onchung-eum–treated groups at 500 and 1000 mg/kg. In conclusion, this study revealed that Onchung-eum can be used to treat chemotherapy-induced OM. However, further studies are required to understand the underlying mechanisms.

There remain gaps in knowledge concerning how vascular morphology evolves during carcinogenesis. In this study, we imaged neovascularization by label-free dark-field microscopy of a 7,12-Dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch model of oral squamous cell carcinoma (SCC). Wavelength-dependent imaging revealed distinct vascular features at different imaging depths and vessel sizes. Vascular tortuosity increased significantly in high-risk lesions, whereas diameter decreased significantly in hyperplastic and SCC lesions. Large vessels preserved the same trends seen in the original images, whereas small vessels displayed different trends, with length and diameter increasing during carcinogenesis. On the basis of these data, we developed and validated a classification algorithm incorporating vascular features from different vessel masks. Receiver operator curves generated from the classification results demonstrated high accuracies in discriminating normal and hyperplasia from high-grade lesions (AUC > 0.94). Overall, these results provided automated imaging of vasculature in the earliest stages of carcinogenesis from which one can extract robust endpoints. The optical toolbox described here is simple, low-cost and portable, and can be used in a variety of health care and research settings for cancer prevention and pharmacology research. Cancer Res; 77(24); 7109–19. ©2017 AACR.

This study aimed to investigate the effects of aqueous cinnamon extract (ACE) on 7, 12-Dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch (HCP) mucosa. Sixty male Syrian hamsters were randomly divided into six equal groups. The hamsters of groups I, II and III received no treatment, DMBA and ACE respectively, for 16 weeks. Groups IV and V were handled as group II and concomitantly treated with ACE for the same period and additionally group V received ACE for other 16 weeks after the stoppage of DMBA application. Group VI hamsters were handled as group III and additionally received DMBA for other 16 weeks after the stoppage of ACE supplementation. Hamsters of each group were euthanized according to the experimental schedule. The buccal pouches were and prepared for H&E stain, PAS reagent, CD3 and PDGF immunohistochemical reactivity. All groups showed dysplastic changes with varying degrees except groups I and III. Deep invasive carcinomas were recorded in 90% of the samples of group II, 60% of group IV, 50% of group V and 40% of group VI. From the previous results, it can be concluded that ACE has the potentiality preventing oral cancer initiation better than inhibiting oral cancer progression.

Myogenic tone is an important feature of arterioles and resistance arteries, but the mechanisms responsible for this hallmark characteristic remain unclear. We used pharmacological inhibitors to compare the roles played by phospholipase C (PLC; 10 μM U73122), inositol 1,4,5-trisphosphate receptors (IP3Rs; 100 μM 2-aminoethoxydiphenylborane), protein kinase C (10 μM bisindolylmaleimide I), angiotensin II type 1 receptors (1 μM losartan), Rho kinase (10 nM−30 μM Y27632 or 300 nM H1152), stretch-activated ion channels (10 nM−1 μM Gd3+or 5 μM spider venom toxin GsMTx-4) and L-type voltage-gated Ca2+channels (0.3–100 μM diltiazem) in myogenic tone of cannulated, pressurized (80 cmH2O), second-order hamster cremaster or cheek pouch arterioles. Effective inhibition of either PLC or IP3Rs dilated cremaster arterioles, inhibited Ca2+waves, and reduced global Ca2+levels. In contrast, cheek pouch arterioles did not display Ca2+waves and inhibition of PLC or IP3Rs had no effect on myogenic tone or intracellular Ca2+levels. Inhibition of Rho kinase dilated both cheek pouch and cremaster arterioles with equal efficacy and potency but also reduced intracellular Ca2+signals in both arterioles. Similarly, inhibition of mechanosensitive ion channels with Gd2+or GsMTx-4 produced comparable dilation in both arterioles. Inhibition of L-type Ca2+channels with diltiazem was more effective in dilating cremaster (86 ± 5% dilation, n = 4) than cheek pouch arterioles (54 ± 4% dilation, n = 6, P < 0.05). Thus, there are substantial differences in the mechanisms underlying myogenic tone in hamster cremaster and cheek pouch arterioles. Regional heterogeneity in myogenic mechanisms could provide new targets for drug development to improve regional blood flow in a tissue-specific manner.NEW & NOTEWORTHY Regional heterogeneity in the mechanisms of pressure-induced myogenic tone implies that resistance vessels may be able to alter myogenic signaling pathways to adapt to their environment. A better understanding of the spectrum of myogenic mechanisms could provide new targets to treat diseases that affect resistance artery and arteriolar function.

While surgery is at the foundation of cancer treatment, its access is limited in low-income countries. Here, we describe development of a low-cost alternative therapy based on intratumoral ethanol injection suitable for resource-limited settings. Although ethanol-based tumor ablation is successful in treating hepatocellular carcinomas, the necessity for multiple treatments, injection of large fluid volumes, and decreased efficacy in treatment of non-capsulated tumors limit its applicability. To address these limitations, we investigated an enhanced ethanol ablation strategy to retain ethanol within the tumor through the addition of ethyl cellulose. This increases the viscosity of injected ethanol and forms an ethanol-based gel-phase upon exposure to the aqueous tumor environment. This technique was first optimized to maximize distribution volume, using tissue-simulating phantoms. Then, chemically-induced epithelial tumors in the hamster cheek pouch were treated. As controls, pure ethanol injections of either four times or one-fourth the tumor volume induced complete regression of 33% and 0% of tumors, respectively. In contrast, ethyl cellulose-ethanol injections of one-fourth the tumor volume induced complete regression in 100% of tumors. These results contribute to proof-of-concept for enhanced ethanol ablation as a novel and effective alternative to surgery for tumor treatment, with relevance to resource-limited settings.

Mucositis and dermatitis induced by anticancer agents are common complications of anticancer therapies. In this study, we evaluated the efficacy of Elental (Ajinomoto Pharmaceutical Ltd, Tokyo, Japan), an elemental diet with glutamine in the treatment of 5-fluorouracil (5-FU)-induced oral mucositis and dermatitis in vivo and tried to clarify the underlying mechanisms of its action. Oral mucositis and dermatitis was induced through a combination of 5-FU treatment and mild abrasion of the cheek pouch in hamsters and the dorsal skin in nude mice respectively. These animals received saline, dextrin or Elental suspension (18 kcal/100 g) by a gastric tube daily until sacrifice. Elental reduced oral mucositis and dermatitis more effectively than dextrin in the animal model. Moreover, growth facilitating effects of Elental on HaCaT cells were examined in vitro. MTT assay, wound healing assay, and migration assay revealed that Elental could enhance the growth, invasion, and migration ability of HaCaT. ELISA and Western blotting showed upregulated FGF2 in Elental-treated HaCaT. These findings suggest that Elental is effective for the treatment of mucositis and dermatitis, and may accelerate mucosal and skin recovery through FGF2 induction and reepithelization.

Dimethylbenza-a-anthracene (DMBA), is a potent carcinogen that has an immunosuppressive effect on hamsters. Nigella sativa whole oil (NSO) and thymoquinone (TQ), are phytochemicals that have an antioxidant and protective action on the hamster cheek pouch epithelium (HCPE/DMBA) carcinogenesis model. The aim is to find which of the two ingredients TQ & NSO has more immune-enhancing activity comparable with its protective and/or chemotherapeutic activity against the carcinogenic effect of DMBA on HCPE, through evaluation of different peripheral monocytes. Material &methods: NS whole oil (NSO), and thymoquinone (TQ) were given before-, with- or after DMBA painting the hamster’s left cheek pouch. Before each animal’s sacrificing, two ml of blood was drawn in a fine heparinized capillary tube to estimate the total WBCs, total lymphocytes, MID cells, and granulocyte’s count by an automatic count system (Cell-DYN1700).Blood results were statistically analyzed using One-way ANOVA test between groups for each phase followed by LSD (Least Square Difference) test for multiple comparisons between different phases. All pouches were surgically-excised and examined microscopically to compare the histopathologic changes of DMBA-painted pouches, NSO-and TQ-treated groups, with untreated pouches as well as pouches of the untreated group.Histopathologic results: the groups given each of the tested ingredients for 2 wks showed normal appearing thin epithelium, with slight hyper-keratinization as compared with untreated pouches. Severe epithelial dysplasia was seen after 6 wks of DMBA, but when NSO or TQ was given for 2wks followed by DMBA for 6wks, mild dysplasia was seen i.e. both have protective effect. When DMBA for 6wks was followed by NSO or TQ for 6wks mild dysplasia was recorded .i.e. both had a therapeutic effect through regressing severe dysplasia to mild dysplasia in 6 weeks. Mononuclear cells results: DMBA for 6wks resulted in statistically significant reduction in total WBCs &lymphocyte counts than control group, as well as when DMBA for 6wks was followed

The aim of the present study was to evaluate the efficacy and analgesic duration of single dose of phenylbutazone administered by oral transmukosal route immediately before induction of anesthesia in dogs undergoing elective ovariohysterectomy. Eight-teen sexually intact female dogs (weiging between 5 and 30 kg, and 1 to 7 yrs of age) referred for ovariohysterectomy procedure from a local shelter at regular intervals over 3 months were included in the study. The dogs were administered phenylbutazone on the basis of their respective treatment group (20 mg/kg via oral transmucosal administration) immediately before anesthetic induction. The syringe was placed in the cheek pouch of the dog, and phenylbutazone was slowly administered over a period of 1 to 3 minutes to ensure the drug did not drip out of the dog’s mouth, or was not swallowed by the dog. In control group, 0.9% NaCl was administered in the cheek pouch of the dog. Throughout the study, pre and postoperative pain was assessed at baseline (before induction of anesthesia) and then at 0.5, 1, 2, 3, 8, and 24 hrs after the surgery. Group oral transmucosal had significantly lower Glascow pain scores than the control group at the 0.5, 1, 2, 3, and 8 hour postoperative periods. In conclusion, a single dose of phenylbutazone administered via the oral transmucosal route before surgery may be particularly beneficial for acheiving reasonable perioperative analgesia, but not in postoperative period.

Aim: Determine the potential for cheek pouch buccal mucosa irritation in hamsters following administration of apomorphine hydrochloride film (APL-130277). Methods: Three studies were conducted with Syrian golden hamsters. (First study, four hamsters received APL-130277 three times a day [TID] for 7 days. Second study, four hamsters received APL-130277 once a day [QD] for days 1–3, twice a day [BID] for days 4–7 and TID for days 8–21. Third study, 32 hamsters received either a placebo strip or APL-130277-dosed TID for 28 days). For all the studies, the macroscopic appearance of the buccal cavities was evaluated throughout the study. In the third study, all animals were necropsied on day 29, and macroscopic and histopathological examinations were performed. Results: In the first and second studies, the buccal mucosa of the cheek pouch did not show any signs of irritation. In the third study, administration of APL-130277-dosed TID for 28 consecutive days did not result in observable local irritation of the buccal mucosa. Conclusion: In all the studies, APL-130277 produced no irritation of the cheek pouch buccal mucosa.

The aim of this study was to differentiate normal and scarred hamster cheek pouch samples by applying a quantitative image analysis technique for determining collagen fiber direction and density in second-harmonic generation microscopy images. This paper presents a collagen tissue analysis of scarred cheek pouches of four adult male Golden Syrian hamsters as an animal model for vocal fold scarring. One cheek pouch was scarred using an electrocautery unit and the other cheek was used as a control for each hamster. A home-built upright microscope and a compact ultrafast fiber laser were used to acquire depth resolved epi-collected second-harmonic generation images of collagen fibers. To quantify the average fiber direction and fiber density in each image, we applied two-dimensional Fourier analysis and intensity thresholding at five different locations for each control and scarred tissue sample, respectively. The resultant depth-resolved average fiber direction variance for scarred hamster cheek pouches (0.61 ± 0.03) was significantly lower (p

Oral mucositis (OM) is one of the main side effects of the head and neck cancer treatment, particularly radiotherapy and/or chemotherapy. OM is characterized by ulcers, erythema, dysphagia, xerostomia, and increased susceptibility to opportunistic infections. In the perspective of finding pharmacological therapies to prevent inflammation and ulceration of OM, the investigation of the pleiotropic effect of commercial drugs is needed, among them gliclazide, an antidiabetic drug. This study aimed to evaluate the effect of gliclazide in an experimental OM model induced by 5-fluorouracil. Male hamsters were pre-treated with oral gliclazide (1, 5, or 10 mg/kg) for 10 days. Cheek pouch samples were subjected to histopathological and immunohistochemical analysis (COX2, iNOS, MMP-2, NFκB P65, GPx) and imunofluorescence (P-selectin). IL-1β and TNF-α levels, Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were investigated by ultraviolet-visible spectroscopy analysis. NFκB NLS P50 protein levels were analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg showed presence of erythema, no evidence of erosion, and absence of mucosal ulceration with a score of 1 (1–2) (p < 0.01). Histopathological data for the group treated with gliclazide 10 mg/kg showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage, edema, ulcers and abscesses with a score of 1 (1–1) (p < 0.01). Treatment with gliclazide 10 mg/kg reduced MPO activity (p < 0.001), MDA levels (p < 0.001) and NFκB NLS P50 (p < 0.05) protein levels, resulting in low immunostaining to Cox-2, iNOS (p < 0.05), NFκB P65 (p < 0.05), and negative immunoreaction to MMP-2 (p < 0.001). However, it appeared that for Gpx1, the staining was restored in the GLI 10-FUT group compared with 5FUT/saline (p < 0.05). Immunofluorescence revealed decreased levels of P-selectin (p < 0.001) after treatment with gliclazide 10 mg/kg (p < 0.05). In summary, gliclazide accelerated mucosal recovery and reduced oxidative stress and inflammation in the 5-FU-induced OM in hamsters.

This study aims to investigate the immunomodulatory effect of anthocyanins (ANTs) from Oryza sativa L. extracts on 5-fluorouracil (5-FU)-induced oral mucositis, using a rat model and oral keratinocytes. ANTs were detected by high-performance liquid chromatography (HPLC)-electrospray ionization mass spectrometry. Animals were randomly given varying doses of ANT-rich extract treatment (500 mg/kg and 1000 mg/kg) in the absence or presence of 5-FU-induced mucositis. Buccal mucosae were photographed and scored for macroscopic analysis and incisional biopsies of cheek pouches were collected for microscopic examination of oral mucositis. 5-FU caused marked hemorrhage, extensive ulcerations and abscesses compared to non-treated animals with slight erythema. Histologically, a loss of collagen bundles and inflammatory cell infiltrates was observed. After 29 days of ANT treatment, lesions resolved, and abundant collagen fibers were evident in the lamina propria. Buccal mucosa of 5-FU-injected rats showed increased Nuclear factor-kappa B (NF-κB) p50 and p65 in oral keratinocytes. The administration of ANT reduced NF-κB-positive cells in 5-FU rats (p &lt, 0.001) compared to the non-treatment group. In oral keratinocytes, ANT treatment significantly restored 5‑FU‑induced growth inhibition and impaired the nuclear accumulation of NF-κB p50 and p65. Our study demonstrated that ANT from Oryza sativa L. exhibited effective anti-inflammatory properties against 5-FU-induced oral mucositis by inhibiting NF-κB activation.

Hesperidin (Hsp), the so-called vitamin P, is an abundant flavonoid in citrus fruits and exerts many biological functions, including antioxidative, anti-inflammatory and anticarcinogenic activities. However, Hsp is not adequately soluble in aqueous solutions and not absorbed well through the intestinal tract. α-glucosyl hesperidin (Hsp-G) is a derivative of Hsp with enhanced water-solubility, while it retains the natural biological functions of Hsp. In this study, the biological functions of Hsp-G on oral stomatitis were examined. Hsp-G exhibited scavenging activity towards hydroxyl radical and superoxide anion radical. Oral stomatitis areas were significantly smaller in hamsters administered Hsp-G than in the non-administered group. Increases in thiobarbituric acid reactive substances, expressed as malondialdehyde equivalents, levels were significantly inhibited by the pre-treatment with Hsp-G prior to the administration of 5-fluorouracil. Hsp-G had no effect on anti-tumour activity in human oral squamous carcinoma cells. Therefore, Hsp-G may serve as a functional food ingredient to ameliorate the symptoms of oral stomatitis.

Objectives: The purpose of this study is to evaluate the optimum conditions for oral mucosal irritation testing using the buccal pouch of hamsters. Methods: Test materials were applied to the buccal pouch of seven-week old male Syrian hamsters (SLC, Japan) four times at one-hour intervals and macroscopic changes were examined at 24 hours after final treatment. After sacrifice, the buccal pouches were removed and prepared for histopathological evaluation. In order to set the exposure time, we performed exposure tests of 5, 12, 18 and 23 minutes using sodium lauryl sulfate (SLS) 1% and set the treatment volume from the test results at 2, 3, or 4 ml treatment using SLS 1%, Triton X-100 1% and ethanol. After setting the experimental conditions, seven groups of materials [sodium lauryl sulfate (SLS) (1%), Triton X-100 (1%), hydrogen peroxide (3%), ethanol (100%), chlorhexidine (0.2%, 2%), phosphate buffer saline (PBS)] were assessed. Results: Experimental conditions of material exposure time were fixed as 18 minutes from the exposure tests of 5, 12, 18 or 23 min using sodium lauryl sulfate (SLS) 1%. Treated volume was set as 4 ml per each pouch from the test results of 2, 3, or 4 ml treatments using SLS 1%, Triton X-100 1% and ethanol. The results in terms of irritation degree were in the order of sodium lauryl sulfate (SLS) (1%) > Triton X-100 (1%) hydrogen peroxide (3%) > ethanol (100%) chlorhexidine (0.2%, 2%) > phosphate buffer saline (PBS). Conclusion: From this study, suitable conditions for hamster mucosal irritation testing were suggested and this method was verified through materials commonly used on oral mucosal membranes.

The antineoplastic properties of the NSAID sulindac have long been studied. The purpose of this study was to explore sulindac's in vivo effects on oral squamous cell carcinoma (SCC) oncogenesis using the hamster cheek pouch oral carcinogenesis model (HOCM). Thirty Syrian golden hamsters were divided into three experimental and two control groups (n = 6 each). The animals' right buccal pouches were treated with carcinogen for 9 weeks in one experimental and one control group and for 14 weeks in all other three groups. The animals of two experimental groups received sulindac from the 1st week and those of the third experimental group from the 10th week. After the end of carcinogenesis, treated buccal pouches were removed and examined. In animals treated with carcinogen for 14 weeks, development of oral SCC and tumor volume were significantly lower in animals that received sulindac from the first week of the experiment. Oral SCC developing in animals that received sulindac were more frequently well differentiated compared with the control group. In animals treated with carcinogen for 9 weeks, the animals that received sulindac developed lower grade of epithelial dysplasia. Proliferation index Ki-67 and positivity for the antiapoptotic molecule survivin were lower in the animals that received sulindac. Treatment with sulindac appears to delays the progression of oral premalignant lesions to oral SCC in the HOCM, also resulting in smaller and better differentiated tumors. These in vivo antineoplastic effects may be related to sulindac's ability to decrease cell proliferation and to prevent survivin expression. Cancer Prev Res; 8(7); 642–9. ©2015 AACR.

Fil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica. Departamento de Radiobiología; Argentina Fil: Pozzi, Emiliano C. C. Comisión Nacional de Energía Atómica. Departamento de Investigación y Producción de Reactores; Argentina Fil: Thorp, S. I. Comisión Nacional de Energía Atómica. Departamento de Instrumentación y Control; Argentina Fil: Curotto, P. Comisión Nacional de Energía Atómica. Departamento de Investigación y Producción de Reactores; Argentina Fil: Medina, Vanina A. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Laboratorio de Radioisotopos; Argentina Fil: Medina, Vanina A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina Fil: Fil: Medina, Vanina A. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Martinel Lamas, Diego José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Laboratorio de Radioisotopos; Argentina Fil: Martinel Lamas, Diego José. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina Fil: Rivera, Elena S. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Laboratorio de Radioisotopos; Argentina Fil: Garabalino, M. A. Comisión Nacional de Energía Atómica. Departamento de Radiobiología; Argentina Fil: Farías, R. O. Comisión Nacional de Energía Atómica. Departamento de Tecnología y Aplicación de Aceleradores; Argentina Fil: González, S. J. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: González, S. J. Comisión Nacional de Energía Atómica. Departamento de Tecnología y Aplicación de Aceleradores; Argentina Fil: Heber, Elisa M. Comisión Nacional de Energía Atómica. Departamento de Radiobiología; Argentina Fil: Itoiz, María E. Comisión Nacional de Energía Atómica. Departamento de Radiobiología; Argentina Fil: Itoiz, María E. Universidad de Buenos Aires. Facultad de Odontología. Departamento de Patología Oral; Argentina Fil: Aromando, Romina F. Universidad de Buenos Aires. Facultad de Odontología. Departamento de Patología Oral; Argentina Fil: Nigg, David W. Idaho National Laboratory; Estados Unidos Fil: Trivillin, Verónica A. Comisión Nacional de Energía Atómica. Departamento de Radiobiología; Argentina Fil: Trivillin, Verónica A. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Schwint, Amanda E. Comisión Nacional de Energía Atómica. Departamento de Radiobiología; Argentina Fil: Schwint, Amanda E. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Abstract: OBJECTIVES: Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit longterm tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCTinduced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients’ treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue. MATERIALS AND METHODS: Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh: histamine 5 mg kg 1 ; Hislow: histamine 1 mg kg 1 ; and JNJ7777120: 10 mg kg 1 . RESULTS: Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs CONTROL: 55%; Hishigh: 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration. Conclusion: Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer.

This study evaluated the ability of lyophilized strawberries to prevent 7,12-dimethylbenz[α]anthracene (DMBA)-induced tumor development in hamster cheek pouch. The experimental diet containing 5% strawberries was given to hamsters during or after DMBA treatment, or throughout the entire bioassay. Our data indicate that tumor incidence, multiplicity, volume and histologic grade of oral precancerous lesions were reduced in animals fed the experimental diet compared to those fed the control diet. We chemically identified and quantified the main phytochemicals by high performance liquid chromatography/tandem mass spectrometry. Fourteen quantified compounds were classified to three categories: anthocyanins (48.8%, w/w of the phenolics), ellagitannin/ellagic acid/ellagic acid derivates (42.9%) and flavonols (8.3%). We further elucidated the molecular mechanisms underlying preventive activities of strawberries. Our mechanistic studies show that strawberries suppress cell proliferation, angiogenesis and oncogenic signaling. Moreover, feeding 5% strawberries also significantly decreased arachidonic acid metabolism and formation of 8-hydroxydeoxyguanosine. These observations suggest that strawberries inhibit DMBA-induced oral cancer in hamsters through suppression of multiple oncogenic events, and thus may serve as alterative agents for oral cancer prevention in humans.

Background: Recombinant human bone morphogenetic protein 2 (rhBMP - 2) regulates several functions within human cells, including invasion, adhesion, differentiation, proliferation, and programmed death. The intercellular role of this protein in cancer progression has been extensively investigated in recent studies. Alterations in β - catenin could also promote cancer progression throughout the Wnt/β - catenin signaling pathway. The present study aimed to evaluate the effect of rhBMP - 2 on the expression and localization of β - catenin in the induced oral squamous cell carcinoma (OSCC) in the buccal pouches of golden Syrian hamsters. Methods: Buccal cavities of 57 hamsters were scrubbed by 5% 7,12 - dimethylbenz[a]anthracene (DMBA) three times per week for 3.5 months. In addition, the animals in the test group (n = 29) were injected with 0.25 µg of rhBMP-on days one, seven, and 49 of the study, and biopsies were extracted afterwards. The expression of β - catenin was immunohistochemically studied in the affected tissues. Results: Membranous β - catenin expression was observed in 71.1% of the cells in the animals in the test group and 64.8% of the control subjects. However, no significant difference was observed between the study groups (P > 0.05). Moreover, nuclear β - catenin expression was detected in 39.1% and 23.6% of the cells in the test and control groups, respectively with a significant difference in this regard (P < 0.05). Conclusions: According to the results, rhBMP - 2 increased the nuclear localization of β - catenin in the OSCC and activated the Wnt/β - catenin signaling pathway. However, evidence is scarce on the increased invasiveness due to the loss of β - catenin membranous expression.

Purpose: To evaluate the effects of red propolis on cheek pouch angiogenesis in a hamster new model sponge implant. Methods: Forty eight animals divided into eight groups. (Groups I-IV), the animals were treated for 15 days before and 10 days after sponge implantation. (Groups V-VIII), the animals were treated for 10 days after sponge implantation (GI and GV: red propolis 100 mg/kg, GII and GVI: celecoxib 20 mg/kg, GIII and GVII: 1% gum arabic 5 mL/kg, GIV and GVIII: distilled water 5 mL/kg). On the 11th day of implantation, the animals were anesthetized for stereoscopic microscopic imaging and morphometric quantification of angiogenesis (SQAN), followed by histopathological evaluation (H&E). Results: In the SQAN analysis, no significant difference was found between the groups. However, on histology, propolis was found reduce the population of mastocytes in the qualitative analyses (p = 0,013) in the quantitative analyses to reduce the number of blood vessels (p = 0,007), and increase the macrophage count (p = 0,001). Conclusion: Red propolis inhibited inflammatory angiogenesis when administered before andcontinuously after sponge implant, and was shown to have immunomodulating effects on inflammatory cells (mastocytes and macrophages) in a new sponge implant hamster model.

No Abstract

Spondias mombin has been used in folk medicine to treat inflammation in the oral cavity. This study aimed to evaluate the antioxidant and anti-inflammatory activity of S. mombin extract in an oral mucositis experimental model.Male hamsters were orally pre-treated with hydroethanolic extract of S. mombin leaves (HESM) (50, 100, or 200 mg/kg) for ten days. Cheek pouch samples were subjected to macroscopic, histopathological and immunohistochemical analysis (Cox-2, iNOS, NF-kB p50 NLS and MMP-2). IL-1β and TNF-α levels were analyzed by ELISA immunoassay, and Superoxide dismutase estimative (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were submitted to spectroscopy analysis.The group treated with HESM at a dose of 200 mg/kg showed the best healing effect, showing no evidence of ulceration in the macroscopic analysis (p 0.05). Histopathological analysis showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage and edema score of 1 (1-1) (p 0.05), as well as a large amount of collagen fibers and a lower immunoexpression of Cox-2, iNOS, NF-kB p50 NLS and MMP-2. Decrease in SOD (p 0.05), MDA (p0.001), IL-1β (p 0.05), and TNF-α levels (p 0.001), with an increase in GSH (p 0.01) levels.HESM (200 mg/kg) reduced oxidative stress and inflammation in the 5-fluorouracil-induced oral mucositis in hamsters.

To determine whether the potential effects on liver and kidney caused by dental alloys could be reduced or terminated by the removal of nickel-chromium (Ni-Cr) alloy, cobalt-chromium (Co-Cr) alloy, and commercially pure titanium (CP-Ti), they were placed in the cheek pouches of Syrian hamsters according to ISO 10993-10. Then, the peak/plateau and end times of trace metals in the blood were determined with or without the removal of the dental alloys. Based on these time points, the trace metals and their effects on liver and kidney were examined. We found that trace metals released from these dental alloys and titanium were accumulated transiently in the blood, liver, and kidney but had no effect on the histopathology of the liver or kidney. Although the functions of the liver and kidney were compromised, the function of these tissues seemed to be clinically acceptable compared to those in control Syrian hamsters. In addition, the apoptotic effect on renal cells was terminated by removing the Ni-Cr and Co-Cr alloys, and that on hepatocytes was also eliminated by removing the Ni-Cr alloy. In contrast, the effect of the Co-Cr alloy on hepatocytes was temporary and recovered by itself. Taken together, Ni- and Co-based dental alloys and titanium have no effect on the histopathology or function of liver and kidney. Moreover, Ni-Cr and Co-Cr alloys induce transient trace metal accumulation and apoptotic effects in liver and kidney, which can be reduced or terminated by the removal of the alloys, while CP-Ti shows favorable biocompatibility.

Objective To evaluate the preclinical efficacy of topical administration of freeze-dried black raspberries (BRBs) to inhibit the progression of premalignant oral lesions and modulate biomarkers of cancer development in high at-risk mucosa (HARM). Study Design Hamster cheek pouches (HCPs) were treated with carcinogen for 6 weeks to initiate a HARM microenvironment. Subsequently, right HCPs were topically administered a BRB suspension in short-term or long-term studies. After 12 weeks, squamous cell carcinoma (SCC) multiplicity, SCC incidence, and cell proliferation rates were evaluated. mRNA expression was measured in short-term treated pouches for selected oral cancer biomarkers. Results SCC multiplicity (−41.3%), tumor incidence (−37.1%), and proliferation rate (−6.9%) were reduced in HCPs receiving BRBs. Topical BRBs correlated with an increase in RB1 expression in developing oral lesions. Conclusions Topical BRBs inhibit SCC development when targeted to HARM tissues. These results support the translational role of BRBs to prevent oral cancer development in humans.

The application of boron neutron capture therapy (BNCT) mediated by liposomes containing 10B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70–88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70–88%. Fil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica; Argentina Fil: Hawthorne, M. Frederick. University of Missouri; Estados Unidos Fil: Kueffer, Peter J.. University of Missouri; Estados Unidos Fil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica; Argentina Fil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; Argentina Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Maitz, Charles A.. University of Missouri; Estados Unidos Fil: Jalisatgi, Satish S.. University of Missouri; Estados Unidos Fil: Nigg, David W.. Idaho National Laboratory; Estados Unidos Fil: Curotto, Paula. Comisión Nacional de Energía Atómica; Argentina Fil: Trivillin, Verónica Andrea. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Ischemia/reperfusion (I/R) injury can occur in consequence of myocardial infarction, stroke and multiple organ failure, the most prevalent cause of death in critically ill patients. I/R injury encompass impairment of endothelial dependent relaxation, increase in macromolecular permeability and leukocyte-endothelium interactions. Polyunsaturated fatty acids (n-3 PUFA), such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) found in fish oil have several anti-inflammatory properties and their potential benefits against I/R injury were investigated using the hamster cheek pouch preparation before and after ischemia. Before the experiments, hamsters were treated orally with saline, olive oil, fish oil and triacylglycerol (TAG) and ethyl ester (EE) forms of EPA and DHA at different daily doses for 14 days. Fish oil restored the arteriolar diameter to pre ischemic values during reperfusion. At onset and during reperfusion, Fish oil and DHA TAG significantly reduced the number of rolling leukocytes compared to saline and olive oil treatments. Fish oil, EPA TAG and DHA TAG significantly prevented the rise on leukocyte adhesion compared to saline. Fish oil (44.83 ± 3.02 leaks/cm(2)), EPA TAG (31.67 ± 2.65 leaks/cm(2)), DHA TAG (41.14 ± 3.63 leaks/cm(2)), and EPA EE (30.63 ± 2.25 leaks/cm(2)), but not DHA EE (73.17 ± 2.82 leaks/cm(2)) prevented the increase in macromolecular permeability compared to saline and olive oil (134.80 ± 1.49 and 121.00 ± 4.93 leaks/cm(2), respectively). On the basis of our findings, we may conclude that consumption of n-3 polyunsaturated fatty acids, especially in the triacylglycerol form, could be a promising therapy to prevent microvascular damage induced by ischemia/reperfusion and its consequent clinical sequelae.

The goal of this study was to evaluate the biocompatibility of newly developed Zr61Ti2Cu25Al12 metallic glass (denoted ZT1) and its parallel material, commercially pure titanium (CP-Ti), as dental implants. To this end, we evaluated their cytotoxicity in vitro using human umbilical vein endothelial cells (HUVECs) and in vivo by performing an oral mucosa irritation test in hamsters. Specifically, cytotoxicity was determined in HUVECs by evaluating their cell morphology using scanning electron microscopy (SEM) and their cell viability using CCK-8 assays. Moreover, we examined the mRNA levels of vascular endothelial growth factor and von Willebrand factor by quantitative PCR (qPCR). In the early stages of proliferation and differentiation, no differences were observed between HUVECs inoculated on ZT1 compared to those on CP-Ti. However, in the later stages of proliferation and differentiation, the HUVECs inoculated on ZT1 were significantly better than the cells cultured on CP-Ti. In the oral mucosa irritation test, we sutured sample discs into the cheek pouch of hamsters. After 2, 3, and 4weeks, we harvested the corresponding mucosal tissues, stained them with hematoxylin and eosin, obtained blood samples for biochemical analysis, and finally, observed the topography of the sample discs by SEM. Immunohistochemistry and hematology analyses showed no differences in the biocompatibility of ZT1 and CP-Ti, and neither of these compounds caused irritation of the mucosa. In addition, SEM images showed that no pitting occurred on the sample discs. Together, these data indicate that ZT1 may be a good candidate for dental implants and should be further studied.

BACKGROUND: We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (Seq-BNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. MATERIAL AND METHODS: Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (Th+ Seq-BNCT) or Seq-Beam Only (Th+ Seq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. RESULTS: Th+ Seq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. CONCLUSION: Th+ Seq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control. Fil: Molinari, Ana Julia. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; Argentina Fil: Portu, Agustina Mariana. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Saint Martin, María Laura Gisela. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina Fil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina Fil: Bortolussi, Silva. Università degli studi di Pavia; Italia Fil: Itoiz, María Elina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Aromando, Romina Flavia. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Anatomía Patológica; Argentina Fil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina Fil: Altieri, Saverio. Università degli studi di Pavia; Italia Fil: Trivillin, Verónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina Fil: Schwint, Amanda Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentina

OBJECTIVES: Estrogen has been shown to play an important protective role in non-reproductive systems, such as the cardiovascular system. Our aim was to observe gender differences in vivo with regard to the increase in macromolecular permeability and leukocyte-endothelium interaction induced by ischemia/reperfusion as well as in microvascular reactivity to vasoactive substances using the hamster cheek pouch preparation. METHODS: Thirty-six male and 36 female hamsters, 21 weeks old, were selected for this study, and their cheek pouches were prepared for intravital microscopy. An increase in the macromolecular permeability of post-capillary venules was quantified as a leakage of intravenously injected fluorescein-labeled dextran, and the leukocyte-endothelium interaction was measured as the number of fluorescent rolling leukocytes or leukocytes adherent to the venular wall, labeled with rhodamin G, during reperfusion after 30 min of local ischemia. For microvascular reactivity, the mean internal diameter of arterioles was evaluated after the topical application of different concentrations of two vasoconstrictors, phenylephrine (α1-agonist) and endothelin-1, and two vasodilators, acetylcholine (endothelial-dependent) and sodium nitroprusside (endothelial-independent). RESULTS: The increase in macromolecular permeability induced by ischemia/reperfusion was significantly lower in females compared with males [19 (17-22) leaks/cm2 vs. 124 (123-128) leaks/cm2, respectively, p

Single-walled carbon nanotubes synthesized with iron (Fe-SWCNT) or gadolinium (Gd-SWCNT) show promise as high performance multimodal contrast and drug-delivery agents. Our purpose was to evaluate potential vasoactive effects of SWCNT. Stable aqueous solutions of Fe-SWCNTs or Gd-SWCNTs were made using the biocompatible amphiphilic polymer N-(carbonyl-methoxypolyethyleneglycol 2000)-1,2-distearoylsn-glycero-3- phosphoethanolamine (PEG-DSPE). Both aggregated and non-aggregated (sonicated) formulations were tested. The initial vasoactivity of the formulations and their potential for inducing pro-inflammatory endothelial dysfunction were investigated in the hamster cheek pouch and murine cremaster muscle intravital microscopy models. These models provide an assay to test several formulations/dosages in a paired fashion. Abluminal exposure to small arterioles exposes both endothelial and vascular smooth muscle cells. Using abluminal exposures of dosages that would approximate the first pass of an i.v. bolus injection, both Fe-SWCNTs and Gd-SWCNTs were immediately vasoactive. Aggregated formulations induced dilation and non-aggregated formulations induced constriction in both hamsters and mice. Endothelial dysfunction was evident after exposure to either aggregated or non-aggregated forms. General loss of dilator capability was seen after exposure to non-aggregated but not aggregated forms. Thus concentrations mimicking bolus dosing of PEG-DSPE coated SWCNT induce both acute and chronic vascular responses.

The present study aimed to evaluate the efficacy of krypton laser photodynamic therapy (PDT) with PsD-007 for the treatment of oral mucosa dysplasia in 9,10-dimethyl-1,2-benzanthracene (DMBA)-treated hamsters. A DMBA-induced hamster cheek pouch model of precancerous lesions was created and the resultant 25 hamsters were divided into five groups. The right side was treated with PDT and the left side was used as the positive control. Following systemic anesthesia, an incision was made in the groin area to expose the femoral vein. PsD-007 was administered intravenously through the femoral vein. Various doses of photosensitizer were used to treat groups A–E. Subsequent to closing the incision, the right side of the buccal mucosa was irradiated with light using the krypton laser at a wavelength of 413 nm, a power density of 150 mW/cm2 and an irradiation time of 20 min. At six weeks post-surgery, the response was analyzed using histological examinations of the buccal pouch mucosa. A total of 24 hamsters completed the six-week observation period, as one hamster from group C died in the second week following the PDT. Of all 24 irradiated sides, 15 formed normal mucosal tissues and nine demonstrated mild dysplasia. Of the total control sides, six developed moderate dysplasia, five developed severe dysplasia and 13 progressed to carcinoma in situ or squamous cell carcinoma (SCC). The results revealed a significant difference between the two sides (P10 mg/kg, there was no statistical difference (P>0.05). PsD-007-mediated krypton laser PDT is effective for the treatment of oral mucosa dysplasia in hamsters.

Objective: The aim of this study was to evaluate the effect of boron on 5-fluorouracil (5-FU)-induced oral mucositis in rats. Materials and Methods: Sixty-four male Wistar albino rats were injected with 5-FU on days 1 and 3. The right cheek pouch mucosa was scratched with the tip of an 18-G needle, dragged twice in a linear movement, on days 3 and 5. The animals were randomly divided into two groups of 32: boron group (BG) and control group (CG). Rats in the CG did not receive any treatment, whereas the others were fed boron (3 mg·kg -1·day -1 ) by gavage. The animals were sacrificed on day 3 (n = 8), 6 (n = 8), 9 (n = 8), and 12 (n = 8), and the cheek pouch was removed for histopathological analysis. Results: On day 3, both groups showed necrosis and active inflammation, but the inflammation was mild in CG and moderate in BG. On day 6, both BG and CG showed necrosis; in the CG, there was moderate inflammation, and in the BG, there was severe inflammation and granulation tissue around the necrotic area. On day 9, re-epithelization began in both groups, and there were no differences between groups. Re-epithelization was complete in both groups on day 12. Conclusion: We found no beneficial effect of boron in healing oral mucositis. Additional research is warranted to elucidate the pathogenic inflammatory mechanisms involved in mucositis and the prophylactic and therapeutic roles of antioxidants.

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new “B2” configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in “B1” experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94–96%) than in control (16%) and BO groups (9–38%), and did not differ significantly from the “B1” results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control. Fil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Longhino, Juan. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina Fil: Boggio, Esteban. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina Fil: Medina, Vanina Araceli. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina Fil: Martinel Lamas, Diego José. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina Fil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina Fil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina Fil: Itoiz, María Elina. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Aromando, Romina Flavia. Universidad de Buenos Aires. Facultad de Odontología; Argentina Fil: Nigg, David W.. Idaho National Laboratory; Estados Unidos Fil: Trivillin, Verónica Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina Fil: Schwint, Amanda Elena. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina