Chemo-immunotherapy by nanoliposomal epacadostat and docetaxel combination to IDO1 inhibition and tumor microenvironment suppression.

The over-activation of tryptophan (Trp) metabolism to kynurenine (Kyn) catalyzed by Indoleamine 2,3-dioxygenase-1 (IDO1) enzyme, is one of the main metabolic pathways involved in tumor microenvironment (TME) immune escape and cancer treatment failure. The most efficient of IDO1 inhibitors is Epacadostat (EPA). Since monotherapy with single-agent IDO1 inhibitor regimen has led to an insufficient anti-tumor activity, we examined the efficacy of simultaneous treatment by Liposomal epacadostat (Lip-EPA) as a potent IDO inhibitor, in combination with docetaxel (DTX) as a complement immunogenic cell death (ICD) agent against B16F10 model. First, the in vitro combination index (CI) of epacadostat (EPA) and DTX was investigated by using the unified theory. Then, the in vivo efficacy of the combination therapy was assessed. Results indicated the synergestic cytotoxic effect of the combination on B16F10 compared to normal fibroblast cells (NIH). The immune profiling demonstrated a significant increase in the percentage of infiltrated T lymphocytes and IFN-γ release, a significant decrease in the percentage of regulatory T cells (Treg) population and the subsequent low levels of IL-10 generation in mice treated with Lip-EPA + DTX. Further, a significant tumor growth delay (TGD = 69.15 %) and an increased life span (ILS > 47.83 %) was observed with the combination strategy. Histopathology analysis revealed a remarkable increase in the Trp concentration following combination treatment, while Kyn levels significantly decreased. Results showed that the nano-liposomal form of IDO1 inhibitor in combination with chemotherapy could significantly improve the imunity response and dominate the tumor immuno-suppressive micro-environment, which merits further investigations.

Comparison of oral candidiasis characteristics in head-and-neck cancer patients before and during radiotherapy.

Background: Patients undergoing head-and-neck radiotherapy are susceptible to Candida colonization and infection. This study aimed to identify oral Candida species type (ST), colony count (CC), and oropharyngeal candidiasis (OPC) in head-and-neck cancer patients, undergoing radiotherapy, before and 2 weeks after radiation. Materials and Methods: In this quasi-experimental study, head-and-neck cancer patients undergoing radiotherapy (up to 6000 cGy) were recruited. Samples were taken before and 2 weeks after radiation therapy (RT). CC was assigned using Sabouraud dextrose agar culture medium and morphological studies were performed to confirm OPC. For identification, polymerase chain reaction-restriction fragment length polymorphism was performed. Data were analyzed using Chi-square-test and kappa coefficient. P < 0.05 was considered statistically significant. Results: Twenty-one of 33 patients were Candida positive. The detected fungal species included Candida albicans (60%), Candida tropicalis (22%), Candida glabrata (9%), and other species (9%). Following RT, OPC and CC changed significantly (P = 0.003 and P = 0.001, respectively), whereas ST did not significantly change (P = 0.081). Two new species (Candida krusei and Candida parapsilosis) were detected after the intervention. The OPC, CC, and ST changes after RT were not significantly related to malignancy site or radiation dose (P > 0.05). Conclusion: The present study showed that OPC, CC, and ST were not related to the malignancy site. Following RT, OPC and CC changed significantly, while ST showed no significant change. The radiation dose and malignancy site had no effects on the OPC, CC, or ST alterations following RT.

Oral health-related quality of life in erosive/ulcerative oral lichen planus patients.

Background: Oral lichen planus (OLP) is a chronic oral mucosal disease. It can manifest as severe erosive/ulcerative oral lesions, causing pain and discomfort. Oral health-related quality of life (OHRQoL) may be deteriorated due to the patient's symptoms. The aim of this study was to evaluate OHRQoL and its relation to oral pain in erosive/ulcerative OLP patients. Materials and Methods: In this cross-sectional study, patients with erosive/ulcerative OLP filled out Chronic oral mucosal disease questionnaire (COMDQ). Meanwhile, they recorded their oral pain through Visual analog scale (VAS). The Pearson's correlation coefficient was used to analyze the relationship between COMDQ score and VAS (IBM SPSS Statistics). P < 0.05 was considered statistically significant. Results: Sixty patients participated in the present study; 51 (85%) were women and 9 (15%) were men. The mean age of participants was 50 ± 14.5 years. The mean score of COMDQ was 47.44 (±18.21). The mean VAS score was 4.5 (±2.4). COMDQ total and all domain scores were significantly correlated with VAS (P < 0.05), except for the "Patient support" domain (P = 0.63). Conclusion: In patients with erosive/ulcerative OLP, there was a significant correlation between oral pain and COMDQ total score, as well as its physical, social, and emotional domains. It seems that COMDQ can be a complementary tool for assessing treatment outcomes in OLP patients.

The effectiveness of olibanum orally disintegrating tablet in the treatment of oral aphthous ulcers: A randomized, double-blind, placebo-controlled clinical trial.

Background: Boswellia serrata oleo-gum-resin (frankincense; olibanum) has anti-inflammatory, analgesic, and antimicrobial effects. This study aimed to evaluate the clinical effectiveness of frankincense extract in the treatment of oral aphthous ulcers. Materials and Methods: In a randomized, double-blind, placebo-controlled clinical trial, patients with aphthous ulcers were randomly assigned to either experimental (Frankincense extract) or placebo groups to use orally disintegrating tablets (ODT) of frankincense and placebo, respectively, four times a day for 3 days. The size of aphthous ulcers and the pain severity by visual analogue scale were recorded at days 0, 2, and 4 and compared between the groups. Results: Twenty-five patients in each group completed the study. Olibanum extract ODT significantly reduced the ulcer size on the second (P < 0.001) and fourth (P < 0.001) days as well as the pain score on the second (P = 0.002) and fourth (P < 0.001) days of the intervention compared to placebo. Furthermore, at the end of the intervention, the number of patients with complete ulcer healing and pain relief in the experimental group was significantly more than the placebo group (5 vs. 0, P = 0.02; and 11 vs. 0, P < 0.001, respectively). Conclusion: Taking olibanum extract ODTs reduces the ulcer size and pain severity and accelerates the healing process in the oral aphthous lesions.

Evaluation of the efficacy of Echinacea on clinical indices of Erosive Oral Lichen Planus: A randomized double-blind clinical trial.

Background: Oral lichen planus (OLP) is a chronic immune-mediated mucocutaneous disorder, with an unknown etiology. Since, both pain and discomfort are observed in patients with the erosive type, many drugs have been studied to alleviate pain and clinical symptoms. The present study aimed to assess the effectiveness of systemic Echinacea on clinical indices of OLP. Materials and Methods: In this randomized, double-blind, placebo-controlled trial, 70 patients with erosive OLP were randomly divided into two groups, and each was treated with Echinacea tablets or placebo, 3 times a day, for 35 days. In addition, betamethasone lotion (0.1%) or nystatin (100,000 units) mouthwash were used by patients. The pain severity (visual analog scale [VAS]), lesion size, and the number of lesions were assessed at baseline and on days 10, 25, and 35 after study initiation. Finally, the obtained data were analyzed by statistical software, and Mann-Whitney test, Wilcoxon test, KaplanMeier, Chi-squared, and paired t-test. Results: The VAS scores in the Echinacea group were significantly reduced at each visit compared to the placebo group (P < 0.001). We observed a significant difference between the two groups (P < 0.01). Conclusion: We showed that Echinacea is an effective and complementary therapy for OLP. Furthermore, in short-term usage, Echinacea is almost completely tolerable.

Sphingomyelin liposome bearing whole Leishmania lysate antigens induce strong Th2 immune response in BALB/c mice.

OBJECTIVES: Whole Leishmania lysate antigens (WLL) has been shown to be effective to tackle leishmaniasis in murine models. Although liposomes can be considered as promising vaccines, the activity of phospholipase-A (PLA) in WLL, breeds difficulties to preparing stable liposomal WLL. One strategy to overcome this shortcoming is to use lipids such as sphingomyelin (SM) which is resistant against PLA. This study aim is formulating stable SM liposomes containing WLL and comparing their adjuvant effects with another first generation vaccine , i.e. solube Leishmania Antigen (SLA) liposomes in BALB/c mice. MATERIALS AND METHODS: BALB/c mice were immunized subcutaneously, three times with 2-week intervals, with Empty-liposome (E-lipo), Particulate WLL, Liposome-WLL, Liposome-SLA and control Buffer, three times every 2-week. Protection was assessed through measuring the swollen footpads and the load of parasites in the spleen. Other factors were used to assess the response of immune system by means of IgG subclasses, IL-4 and IFN-γ levels and intracellular cytokine assay in cultured splenocytes. RESULTS: Although liposomal WLL were stable in terms of physicochemical properties, mice received Liposome-WLL did not reduce footpad swelling. The load of parasites in spleen and levels of IL-4- were also higher compared to other immunized groups. In terms of IgG isotypes, no considerable difference observed in mice received Liposome-WLL or other formulations. CONCLUSION: Liposome-WLL could be a suitable vaccine delivery system when a Th2 response is desired. Also, further studies are warranted to fully understand the role of sphingomyelin in inducing an immune response.

Preparation of nanoliposomes containing HER2/neu (P5+435) peptide and evaluation of their immune responses and anti-tumoral effects as a prophylactic vaccine against breast cancer.

HER2/neu is an immunogenic protein inducing both humoral and cell-mediated immune responses. The antigen-specific cytotoxic T lymphocytes (CTLs) are the main effector immune cells in the anti-tumor immunity. To induce an effective CTL specific response against P5+435 single peptide derived from rat HER2/neu oncogene, we used a liposome delivery vehicle. In vivo enhancement of liposome stability and intracytoplasmic delivery of peptides are the main strategies which elevate the liposome-mediated drug delivery. Liposomes containing high transition temperature phospholipids, such as DSPC, are stable with prolonged in vivo circulation and more accessibility to the immune system. Incorporation of DOPE phospholipid results in the effective delivery of peptide into the cytoplasm via the endocytotic pathway. To this end, the P5+435 peptide was linked to Maleimide-PEG2000-DSPE and coupled on the surface of nanoliposomes containing DSPC: DSPG: Cholesterol with/without DOPE. We observed that mice vaccinated with Lip-DOPE-P5+435 formulation had the highest number of IFN-γ- producing CTLs with the highest cytotoxic activity that consequently led to significantly smallest tumor size and prolonged survival rate in the TUBO mice model. In conclusion, our study indicated that the liposomal form of P5+435 peptide containing DOPE can be regarded as a promising prophylactic anti-cancer vaccine to generate potent antigen-specific immunity.

A Phospholipase-A Activity in Soluble Leishmania Antigens Causes Instability of Liposomes.

AIM: This study aimed to investigate the existence of phospholipase-A (PLA) activity in Soluble L. major Antigens (SLA) because of no reports for it so far. Liposomes were used as sensors to evaluate PLA activity. OBJECTIVES: Liposomal SLA consisting of Egg Phosphatidylcholine (EPC) or Sphingomyelin (SM) were prepared by two different methods in different pH or temperatures and characterized by Dynamic Light Scattering (DLS) and Thin Layer Chromatography (TLC). METHODS: Lipid hydrolysis led to the disruption of EPC liposomal SLA in both methods but the Film Method (FM) produced more stable liposomes than the Detergent Removal Method (DRM). RESULT: The preparation of EPC liposomal SLA at pH 6 via FM protected liposomes from hydrolysis to some extent for a short time. EPC liposomes but not SM liposomes were disrupted in the presence of SLA. CONCLUSION: Therefore, a phospholipid without ester bond such as SM should be utilized in liposome formulations containing PLA as an encapsulating protein.

Effect of combined exercise training on pentraxins and pro- inflammatory cytokines in people with multiple sclerosis as a function of disability status.

OBJECTIVES: There is some evidence for beneficial effects of exercise on cytokines in people with multiple sclerosis (MS), but it is unclear if such effects differ by disability status (i.e., stage of the disease). This study investigated the effect of combined exercise training on pentraxins and pro- inflammatory cytokines in people with multiple sclerosis as a function of disability status. METHODS: This randomized control trial included 94 women with MS who were randomly assigned into exercise or control conditions with randomization stratified by Expanded Disability Status Scale (EDSS) scores of low (EDSS < 4.5), moderate (4.5 ≤ EDSS ≤ 6), or high (EDSS ≥ 6.5) disability. The exercise program lasted 12 weeks and comprised resistance, endurance, Pilates, balance and stretch exercises performed? days/week; the control condition involved a waitlist control. We measured resting levels of inflammatory factors, functional capacity, and lipid profile before and after the 12-week intervention period. RESULTS: Combined exercise training significantly decreased hs-CRP (p = 0.029) and IL-6 (p = 0.001) and increased PTX-3 (p = 0.001) and IFN-Æ´ (p = 0.001), but there was no significant change in Fibrin D-dimer (FDD) (p = 0.876) compared with control, and those effects were independent of disability status. 1RM for lat pull-down, knee extension, and seated row and 6MWT (i.e., walking further) significantly increased and TUG performance significantly decreased (i.e., faster performance) (all, p < 0.001) after combined exercise compared with control, and this too was independent of disability status. CONCLUSIONS: Exercise may stimulate anti-inflammatory effects in MS, and this is generally not influenced by disability status. Exercise training may be an adjuvant for disease-modifying therapy among people with MS, and such effects might not be moderated by disability status.

The framework for developing nursing specialist roles in the health care system of Iran.

BACKGROUND: A key step to the development of a roadmap for developing nursing specialist roles is to create its framework based on the immediate context. PURPOSE: This study aimed to create the framework for developing nursing specialist roles in the health care system of Iran. METHODS: This was a descriptive qualitative study. A purposeful sample of 81 nursing and nonnursing experts was recruited. The directed content analysis approach was used for data analysis. FINDINGS: The framework for developing nursing specialist roles in the health care system include eight main categories. These categories are role titles, prioritization of the necessary specialties, the necessary competencies of nurses at specialist level, the scope of nursing specialist practice, expected authorizations, requirements for role development, and its barriers and facilitators. DISCUSSION: Creating a context-based framework for nursing specialist role development based on the characteristics of each country is recommended.

Development of a topical liposomal formulation of Amphotericin B for the treatment of cutaneous leishmaniasis.

BACKGROUND: Currently, there is no topical treatment available for any form of cutaneous leishmaniasis (CL) in most of the endemic areas. The aim of the current study was to develop a topical nano-liposomal Amphotericin B (AmB) for the treatment of CL. METHODOLOGY/PRINCIPAL FINDINGS: Liposomes containing 0.1, 0.2 and 0.4% AmB (Lip-AmB) were formulated and characterized for the size, entrapment efficiency, long term stability, and skin penetration properties using Franz diffusion cells. Liposomes diameters were around 100 nm with no change during more than 20 months' storage either at 4 °C or at room temperature. Franz diffusion cells studies showed that almost 4% of the applied formulations penetrated across the skin and the highest skin retention (73.92%) observed with Lip-AmB 0.4%. The median effective doses (ED50), the doses of AmB required to kill 50% of L. major amastigotes were 0.151, 0.151, and 0.0856 (µg/mL) in Lip-AmB 0.1, 0.2, 0.4%, respectively. Lip-AmB 0.4% caused 80% reduction in fluorescence intensity of GFP+ L. tropica infected macrophages at 5 µg/mL of AmB concentration. Topical Lip-AmB was applied twice a day for 4 weeks to the skin of BALB/c mice to treat lesions caused by L. major. Results showed the superiority of Lip-AmB 0.4% compared to Lip-AmB 0.2 and 0.1%. The parasite was completely cleared from the skin site of infection and spleens at week 8 and 12 post-infection in mice treated with Lip-AmB 0.4%. The results suggest that topical Lip-AmB 0.4% may be a useful tool in the treatment of CL and merits further investigation.

P435 HER2/neu-derived peptide conjugated to liposomes containing DOPE as an effective prophylactic vaccine formulation for breast cancer.

The present study was aimed to develop an effective nanoliposomal vaccine delivery system with P435 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The nanoliposome formulation composed of DSPC/DSPG/Chol/DOPE and monophosphoryl lipid A was used as an adjuvant. Liposomal formulations were prepared and their physical properties were characterized. Anti-tumoral efficacy of formulations was evaluated by immunization of tumor-bearing BALB/c mice and the generated immune response was studied by using ELISpot and flow cytometry analysis. The results of the study demonstrated Lip + DOPE + P535 formulation caused the lowest tumor size and the longest survival time in TUBO mice model and could make it a promising candidate in developing effective vaccines against HER2-positive breast cancers.

Preparation of nanoliposomes linked to HER2/neu-derived (P5) peptide containing MPL adjuvant as vaccine against breast cancer.

The study was aimed at evaluating antitumor and immunomodulatory effects of liposomal vaccine composed of P5 human epidermal growth factor receptor 2 (HER2)/neu-derived peptide coupled to the surface of high-temperature nanoliposomes containing distearoylphosphocholine:distearoylphosphoglycerol:Chol:dioleoylphosphatidylethanolamine (DOPE) comprising monophosphoryl lipid A (MPL) adjuvant in HER2/neu overexpressing the breast cancer model. BALB/c mice bearing TUBO carcinoma were subcutaneously immunized with formulations containing 10 µg P5 peptide and 25 µg MPL three times with 2-week intervals. To determine immuno responses in immunized mice, the amount of released interferon-γ and IL-4 were measured by the enzyme-linked immunospot method and the flow cytometric analysis on the isolated splenocytes. The results demonstrated that tumor-bearing mice immunized with Lip/DOPE/MPL/P5 formulation had the most released interferon-γ and the highest cytotoxic T lymphocyte responses that led to the lowest tumor size and the longest survival time than those of other formulations. The results achieved by Lip/DOPE/MPL/P5 formulation could make it a suitable candidate to induce effective antigen-specific tumor immunity against breast cancer.

The relationship between ethical conflict and nurses' personal and organisational characteristics.

INTRODUCTION: Critical care nurses work in a complex and stressful environment with diverse norms, values, interactions, and relationships. Therefore, they inevitably experience some levels of ethical conflict. AIM: The aim of this study is to analyze the relationship of ethical conflict with personal and organizational characteristics among critical care nurses. METHODS: This descriptive-correlational study was conducted in 2017 on a random sample of 216 critical care nurses. Participants were recruited through stratified random sampling. Data collection tools were a demographic and professional characteristics questionnaire, the Ethical Conflict in Nursing Questionnaire-Critical Care Version, and the Organizational and Managerial Factors Questionnaire. The data were analyzed using the SPSS software (v. 22.0). ETHICAL CONSIDERATIONS: All participants were informed about the study's aim and were assured that participation in and withdrawal from the study would be voluntary. FINDINGS: The mean score of exposure to ethical conflict was 201.91 ± 80.38. The highest-scored conflict-inducing clinical situation was "working with professionally incompetent nurses or nurse assistants." Married nurses, nurses with official employment, nurses with master's degree, and nurses with the history of attending ethics education programs had significantly higher exposure to ethical conflict than the other nurses (p < 0.05). The significant predictors of exposure to ethical conflict were marital status, educational status, reward system, organizational culture, manager's conduct, and organizational structure and regulations (p < 0.05). These predictors accounted for 37.2% of the total variance of exposure to ethical conflict. CONCLUSION: Critical care nurses experience moderate levels of exposure to ethical conflict. A wide range of personal and organizational factors can contribute to such exposure, the most significant of which is the professional incompetence of nursing colleagues, nurse assistants, and physicians. Therefore, many improvements at personal and organizational levels are needed to reduce critical care nurses' exposure to ethical conflict.

Prevalence of oral mucosal status in resident and non-resident nursing home in Isfahan city, Iran: a comparative cross-sectional study / Prevalência da condição da mucosa oral em idosos residente em casas de repouso ou não residente, na cidade de Isfahan, Irã: um estudo transversal comparativo

Objective: The aim of this study was to evaluate the oral mucosal status of residents nursing home and non-resident in Isfahan, Iran and compare them with each other. Material and Methods: This was a cross-sectional study comparing 281 elderly in two groups: 141 resident and 140 non-residents nursing homes in Isfahan, Iran. The selection of nursing home and all of elderly was randomly. The nonresidents elderly were randomly selected from the public places adjacent to the nursing home. Persons were examining and the relevant information recorded in a checklists. Data were analyzed by SPSS version 24 using t-test, chi square, MannWhitney, Fisher exact test. (α =0/05). Results: The sample of the case was 281 people, including 135 males (48%) and 146 females (52%). Of all the subjects 153 patients (54.4%) had at least one oral lesion, 78 (55.3%) in resident nursing home and 75 (53.6%) in non-resident. There was no significant difference between two groups based on Chi-Square test (P>0/05). In this study, 25 different types of lesions were recorded, the most common lesion in all participants was epulis fissuratum (12.1%). Conclusion: The results showed that the prevalence of mucosal lesions is high in the elderly living in the centers and in the non-resident. Therefore, maintaining dentures is necessary to prevent and control lesions. (AU)

Objetivos: O objetivo deste estudo foi avaliar a condição da mucosa oral de residentes em casas de repouso e não residentes em Isfahan, Irã, e compará-los entre si. Material e Métodos: Estudo transversal que comparou 281 idosos em dois grupos: 141 casas de repouso residentes e 140 não residentes em em casas de repouso na cidade de Isfahan, Irã. A seleção da casa de repouso de idosos e todos os idosos envolvidos foi aleatória. Os idosos não residentes foram selecionados aleatoriamente nos locais públicos adjacentes ao lar de idosos. As pessoas foram examinadas e as informações relevantes registradas. Os dados foram analisados pelo SPSS versão 24, utilizando o teste t, Qui-quadrado, Mann-Whitney, teste exato de Fisher (α = 0/05). Resultados: A amostra do estudo constou de 281 pessoas, incluindo 135 homens (48%) e 146 mulheres (52%). Do total geral, 153 pacientes (54,4%) apresentaram pelo menos uma lesão oral, sendo 78 (55,3%) em idosos residentes na casa de repouso e 75 (53,6%) em idosos não-residentes. Não houve diferença significativa entre os dois grupos com base no teste do Quiquadrado (p>0.05). Neste estudo, foram registrados 25 tipos diferentes de lesões, sendo que a lesão mais comum em todos os participantes foi a epulis fissuratum (12,1%). Conclusão: Os resultados mostraram que a prevalência de lesões nas mucosas é alta nos idosos residentes nas casas de repouso e também em não residentes. Portanto, a manutenção da prótese é necessária para prevenir e controlar as lesões. (AU)

A study on the role of cholesterol and phosphatidylcholine in various features of liposomal doxorubicin: From liposomal preparation to therapy.

The lipid membrane composition defines the physical and pharmacological characteristics of liposomal drugs, and it can be tailored to meet the desired drug delivery needs. The current study is aimed to provide a sharper understanding of the lipid composition effect on doxorubicin (DOX) delivery kinetics, using cholesterol and phosphatidylcholine lipids (PCs) with different acyl chains in liposomal DOX formulations. The PCs were distearoyl (DSPC), dipalmitoyl (DPPC), dimyristoyl (DMPC) and egg-derived PC (EPC), either alone or in combination with cholesterol. Several characteristics were monitored, including DOX loading capacity of liposomes, DOX release in phosphate buffered saline (PBS), PBS/human plasma including buffy coat and human blood, cell uptake, as well as in vivo distribution and therapeutic effects in BALB/c mice bearing C26 colon carcinoma. Addition of cholesterol to liposomal formulation enhanced the particle size stability of the liposomes and the DOX-to-lipid ratio. EPC-liposomes and EPC/Cholesterol-liposomes showed few distinctive features. Overall, cholesterol decreased DOX release from the liposomes, and longer saturated fatty acyl chains in PC decreased DOX release and side-effects and increased the anti-tumor effects of liposomal DOX.

Effect of Herbal Echinacea on Recurrent Minor Oral Aphthous Ulcer.

BACKGROUND: The oral aphthous is a common oral ulcer with intense pain and there is no treatment for it, yet. Echinacea is an herbal medicine that moderated the immune system. OBJECTIVE: The aim of this study was to investigate the effects of Echinacea on the treatment of aphthous ulcer. METHODS: 50 patients with minor aphthous participated in our study. 25 patients take 3 tablets in a day for five weeks (case group) and 25 patients didn't take any tablets (control group). The patients were monitored for one month before taking the tablets for six months. During this period, the number of lesions, complete improvement of ulcers, recurrence rate and intensity of pain were considered in each month. Finally, the Friedman and ANOVA tests used to analyze the obtained data. RESULT: Our study showed a significant difference between a number of lesions during six-month in case and control groups (p>0.001). In this way, we observed that the number of lesions was decreased significantly after six months in the case group. Hence, ANOVA analysis showed a significant decrease between each month for the intensity of pain (p=0.025), complete improvement (p<0.001) and recurrence rate (p=0.026). CONCLUSION: In conclusion, we showed that Echinacea tablets as an herbal medicine have positive effects on a number of lesions, intensity of pain, complete improvement and recurrence rate in patients with recurrent minor aphthous ulcers.

Injury to skeletal muscle of mice following acute and sub-acute pregabalin exposure.

OBJECTIVES: Pregabalin (PGB) is a new antiepileptic drug that has received FDA approval for patient who suffers from central neuropathic pain, partial seizures, generalized anxiety disorder, fibromyalgia and sleep disorders. This study was undertaken to evaluate the possible adverse effects of PGB on the muscular system of mice. MATERIALS AND METHODS: To evaluate the effect of PGB on skeletal muscle, the animals were exposed to a single dose of 1, 2 or 5 g /kg or daily doses of 20, 40 or 80 mg/kg for 21 days, intraperitoneally (IP). Twaenty-four hr after the last drug administration, all animals were sacrificed. The level of fast-twitch skeletal muscle troponin I and CK-MM activity were evaluated in blood as an indicator of muscle injury. Skeletal muscle pathological findings were also reported as scores ranging from 1 to 3 based on the observed lesion. RESULTS: In the acute and sub-acute toxicity assay IP injection of PGB significantly increased the activity and levels of CK-MM and fsTnI compared to the control group. Sub-acute exposure to PGB caused damages that include muscle atrophy, infiltration of inflammatory cells and cell degeneration. CONCLUSION: PGB administration especially in long term care causes muscle atrophy with infiltration of inflammatory cells and cell degeneration. The fsTnI and CK-MM are reliable markers in PGB-related muscle injury. The exact mechanisms behind the muscular damage are unclear and necessitate further investigations.

Stimulation of Tumor-Specific Immunity by p5 HER-2/neu Generated Peptide Encapsulated in Nano-liposomes with High Phase Transition Temperature Phospholipids.

BACKGROUND: The aim of this study is to evaluate the possible advantages of liposomes with high transition temperature (Tm) in the function of a vaccine for P5 HER2/neu-generated peptide and its adjuvant action to elicit CD8+ T cell response and its efficacy in TUBO in vivo tumor mice model, which over expresses the HER2/neu oncogene. P5, a hydrophobic peptide, was encapsulated in the nanoliposomes consisting of DSPC/DSPG/Chol(Tm 54°C) with a chaotropic loading system via 7M urea and described by size, zeta potential, encapsulation efficiency, and the structural stability of SDS-PAGE. METHODS: We immunized the mice for three times subcutaneously based on a two-week intervals using encapsulated peptide in the nanoliposomes, empty liposome, P5 in PBS, and PBS. Enzyme-linked immunospot assay, cytotoxicity test, and flow cytometric studies followed by the size of tumor and survival time measurements, which were done in TUBO tumor mice version. RESULTS: Findings of ELISpot and flow cytometric analysis showed that immunization with Lip-p5 nanoliposomes has enhanced the antigen-specific IFN-γ response of CD8+ T cells and induced CTL response, which resulted in a smaller tumor and longer survival time. In addition to increase in amounts of IFN-γ-CD8+ T cells in a group, which was immunized with Lip-P5, our findings also revealed a Th1 shift in the group immunized with an empty liposome with reduced frequencies of IL-4-producing cells and increase of IFN-γ-producing cells. CONCLUSION: The results indicated that simple liposomes consisting of phospholipids with high transition temperature could be an effective vaccine vehicle for tumor-associated antigens for inducing cell mediate immunity.

Assessment of IgG Antibodies Against HSV1, HSV2, CMV and EBV in Patients with Pemphigus Vulgaris Versus Healthy People.

OBJECTIVES: Regarding the implication of viruses particularly herpes in pemphigus vulgaris, we sought to assess and compare the level of immunoglobulin G (IgG) antibodies against herpes simplex virus types 1 and 2 (HSV1 and HSV2), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with pemphigus vulgaris and healthy people. MATERIALS AND METHODS: In this cross-sectional study, 25 patients with pemphigus vulgaris and 27 healthy individuals comprised the experimental and control groups, respectively. Serum samples were taken from both groups; the levels of IgG antibodies against HSV1, HSV2, CMV and EBV were measured using ELISA. RESULTS: Immunoglobulin G titer was higher for all four viruses in the patient group in comparison to the control group. This difference was significant for anti-EBV (P= 0.005), anti-CMV (P=0.0001) and anti-HSV2 (P=0.001) but not significant for anti-HSV1 (P= 0.36). CONCLUSION: Viruses including EBV, CMV, and HSV2 probably play a role in the pathogenesis of pemphigus in addition to the effects of genetics, toxins and other predisposing factors. In this study, no statistically significant relationship was observed between HSV1 and pemphigus vulgaris, which was probably due to the high titer of anti-HSV1 IgG in healthy individuals in the community. More studies must be done in this regard.