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ImT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing

World Journal of Vaccines 2012年第4期2卷 182-188页

作者： Alejandro D. montaner Analia De Nichilo Juan m. Rodriguez Andres Hernando-Insua Juan Fló Ricardo A. Lopez Verónica Sierra Claudio Paolazzi Oscar Larghi David L. Horn Jorge Zorzopulos fernanda Elias David Horn LLC Doylestown PA USA. Immunotech S.A. Buenos Aires Argentina Instituto de Investigaciones Biomédicas Fundación Pablo Cassará Buenos Aires Argentina Instituto San Jorge Bagó Buenos Aires Argentina Instituto San Jorge Bagó Buenos Aires Argentina. nstituto de Investigaciones Biomédicas Fundación Pablo Cassará Buenos Aires Argentina

Background: Rabies virus infection causes encephalitis, which is almost always fatal. Vaccination can be extremely effective at preventing disease but is prohibitively costly. Vaccine formulations allowing dose-sparing and fewer inoculations with faster antibody response would be extremely desirable. ImT504, an immunostimulatory non-CpG oligo-deoxynucleotide, is a highly potent vaccine adjuvant. methods: Human and rat antibody measurements, and rat chal-lenge studies were performed. Results: In rats, highly effective immune responses with ImT504 were observed even after diluting vaccine up to 1/625. In highly lethal, live intracerebral rabies challenge studies, protection occurred even with extremely dilute vaccine plus ImT504. In humans, antibody titers developed faster and were significantly higher with ImT504-adjuvanted diluted vaccine vs non-adjuvanted vaccine (full strength or diluted). All five administered ImT504-adjuvanted diluted vaccine reached protective antibodies (≥0.5 IU/ml) after the second injection. After the third injection, individuals receiving ImT504-adjuvanted diluted vaccine reached levels approximately 10 times higher than controls (m ± SEm: 31.0 ± 10.9 vs 3.40 ± 0.99 IU/ml). Conclusions: These data suggest that ImT504 may allow fewer inoculations, highly significant dose-sparing of vaccine, rapid antibody production and protection from rabies. Extensive clinical studies are necessary to confirm if the use of ImT504 will permit significantly greater access to highly effective life-saving rabies vaccines.

关键词： ImT504 Adjuvant Rabies Vaccine Human Animal

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Antitumor Effect of Cationic INKKI Peptide from Bovine β-Casein on melanoma B16F10

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Journal of Cancer Therapy 2012年第4期3卷 237-244页

作者： Ricardo Alexandre Azevedo Adilson Kleber Ferreira Aline Vivian Vatti Auada Kerly fernanda mesquita Pasqualoto Rafael marques-Porto Durvanei Augusto maria Ivo Lebrun Butantan Institute Biochemistry and Biophysical Laboratory Sao Paulo Brazil

Cationic peptide with the sequence INKKI 41-45 was isolated from bovine β-casein after tryptic hydrolysis and synthetized. The aim of this work was to evaluate the antiproliferative activity in vitro and antitumor effect in animal model. The in vitro cytotoxicity was evaluated on B16F10 melanoma cells by mTT assay. Detection of apoptosis was measured using the annexin V/PI double staining and cell cycle analysis performed flow cytometry. Caspase-3 activity was analyzed with substrate specific fluorogenic DEVD-mCA. In vivo, antitumor activity was evaluated in B16F10 melanoma tumor-bearing C57BL/6J mice. The animals were treated with 55 mg/kg INKKI administered into peritumoral region, while control group received saline solution. The following antitumor parameters were examined: tumor volume, number of metastases, tumor delayed time, tumor doubling time. Histological analyses were performed with H & E staining. The results showed that INKKI induced dose-response cytotoxicity selective for B16F10 melanoma cells (IC50 1.7 μm) and did not present cytotoxic effects for FN1 fibroblast cells. INKKI-induced apoptosis detected trough of annexin V/PI assay and it was accompanied with an increase of sub-G1 apoptotic fractions and significant increase of caspase-3 cleavage. The tumor-bearing mice treated with INKKI showed a significant reduction in tumor volume of 72.62% and decreased of metastasis number loci. In addition, INKKI caused a significant delay in tumor growth and prolonged the tumor doubling time. Histological analysis revealed an increased of necrosis areas and reduction of tumor cells in tumor treated with INKKI, it was a many hallmark of its antitumor effects observed from in vivo experiments. In conclusion, we show that INKKI is a peptide that could be considered a new putative candidate development to anticancer therapy drug.

关键词： β-Casein Peptide Apoptosis metastasis Tumor Growth melanoma

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Optimization of the Protocol for the in VitroCultivation of Piper aduncumL.

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American Journal of Plant Sciences 2014年第23期5卷 3474-3482页

作者： Samia Torres Silva fernanda Ventorim Pacheco Ivan Caldeira Almeida Alvarenga José Eduardo Brasil Pereira Pinto Suzan Kelly Vilela Bertolucci Cibelly Pereira Ferreira Department of Agriculture Federal University of Lavras Lavras Brazil

Piper aduncum L. (Piperaceae) has great potential for economic exploration because of the proven use of its essential oil in the agriculture and in the human health. A technique that improves its propagation, as the tissue culture, becomes necessary. Some parameters must be determined for the successful cultivation in vitro. Thus, this study aimed to determine the salts concentration of mS medium, temperature, luminosity and light quality for in vitro culture of this species. The following treatments were conducted: 1/4mS, 1/2mS, mS and 2mS;20℃, 25℃, 30℃ and 35℃;monochromatic blue, red and white lights and the combination of red and blue, using light emitting diodes (LEDs);luminosities of 17, 37, 48 and 73 μmol·m-2·s-1 obtained with cool white fluorescent lamp. After 35 days, the treatments were analyzed. To determine the salts concentration of mS, the variables were evaluated: number of shoots, leaves and roots, length and width of leaves, length and dry mass of root and shoots and percentage of death by necrosis. To the plantlets under different temperatures, length and dry mass of shoot and root, number of shoots, number, length and width of leaves and survival and rooting percentages were measured. The plantlets that were maintained under different luminosities were evaluated for length of shoot and root, dry mass of leaf and root. To evaluate the growth under the LEDs, the length and dry mass of shoot and root, number of shoots and roots, percentage of rooting and sprouting were assessed. The medium 1/4mS and the medium 1/2mS showed better responses for number and length of root, leaf width and shoot length. The temperature 25℃ provided the highest number of leaves, length of shoot and root, root dry mass and rooting percentage. The luminosity 73 μmol·m-2·s-1 provided higher values in length of root and dry mass of leaf and root. The red LED provided plantlets with greater growth. Thus, for the in vitro cultivation of Piper aduncum, 1/4mS, environment temperatu

关键词： Tissue Culture LEDs monkey Pepper

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Lasertherapy as A Strategy for Treatment Healing under Caloric Restriction – Study in Rats

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Journal of Pharmacy and Pharmacology 2018年第7期6卷 647-658页

作者： Leandro C. moscardi Talita P. Espíndola Amanda A. Ferreira Naiara Alves maria Esméria C. Amaral Andréa A. Aro Rodrigo A. Dalia marcelo A. m. Esquisatto fernanda A. S. mendonca Gláucia m. T. Santos Thiago A. m. Andrade Graduate Program in Biomedical Sciences of the Hermínio Ometto University Center UNIARARAS Araras So Paulo 13607-339 Brazilc

Complications in the healing process are challenging, especially in clinical situations of caloric restriction （CR）. The lasertherapy becomes an important strategy that aids the repair, especially in CR. Thus, it is important to investigate the InGaAlP-660 nm laser as an strategy to repair cutaneous wounds in rats submitted to 30% of CR and to understand the tissue repair in clinical situations of CR. Thirty-six male Wistar rats were used, of which half were fed with 30% less ration, and half with ad libitum diet, for 21 days. Then, punch lesions of 1.5 cm in diameter were made on the animals backs, which were divided into： NR （no-restricted）, R （restricted）-both before lesion; C （control）, RC （restricted-control）, L （laser）, RL （restricted-laser）-after lesion. Samples of the skin/lesion/scar were collected on the 2nd, 7th and 14th days post-injury for histological, biochemical and molecular analyses. The R group showed reduction of body mass, epidermal/dermal thickness, inflammation, angiogenesis, fibroplasia and collagenesis. The RL group showed control of inflammation, oxidative damage and increase of antioxidants than RC, which probably favored angiogenesis, collagenesis and reepithelialization, similar to C and L. Thus, 30% of CR impaired the skin （before lesion）. In the lesion, lasertherapy has shown to be effective in tissue repair mainly in CR status, being thus, the laser clinically important strategy to tissue repair in critical situations of caloric restriction.

关键词： Wound healing skin caloric restriction wound treatment therapeutic strategy lasertherapy

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Photodynamic Therapy for medication-Related Osteonecrosis of the Jaws: A Case Report

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International Journal of Clinical medicine 2016年第12期7卷 824-828页

作者： mônica Simões Israel Sarah Aparecida Antero Gisele Cuba Riche Giulianna Lima Pinheiro mayara Leonel Duarte meira fernanda Vieira Heimlich Wagner Pinto das Chagas Nathália de Almeida Freire maria Eliza Barbosa Ramos Rosemiro de menezes maciel School of Dentistry Rio de Janeiro State University Rio de Janeiro Brazil

medication-related osteonecrosis of the jaws (mRONJ) is a relatively new disease. mARX reported first cases in 2003. mRONJ relates to oral and parenteral bisphosphonates as well as to the so-called target cancer therapies but the list of medications only grows. Although mRONJ is a relatively rare condition, it can be associated to significant morbidity with feeding limitations and intense pain. more severe cases can lead to potentially life-threatening infections. Every patient initiating bisphosphonate and/or target cancer therapy must visit a dentist before starting medication because preventive measures for mRONJ are much more effective compared to surgical management of the lesions. Surgical resolution can be especially difficult to obtain in the coexistence of certain complication factors like wider bone exposures, history of nitrogen containing bisphosphonates use (mainly zolendronate) and immunodeficiency. Recently, researchers have given attention to laser therapy associated to photosensitive agents as a possible option to management of some mRONJ lesions. Our case report demonstrates the use of photodynamic therapy in a denosumab related lesion in the mandible. It seems that denosumab related lesions are more amenable to treatment and total resolution because of the marked differences between its chemical and metabolic characteristics when compared to bisphosphonates.

关键词： Laser Phototherapy Osteonecrosis Jaws Denosumab

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Production, Detection and Cross-Reactivity of Anti-Polysaccharide Antibodies from Environmental Fungi

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Advances in Bioscience and Biotechnology 2014年第10期5卷 815-822页

作者： Rafael Andrade menolli Thais Soprani Ayala Pablo Rodrigo da Rosa Claudia Rejane Lima de macedo Costa Erica fernanda Osaku Rosiane G. mello Zibetti Centro de Ciências médicas e Farmacêuticas Universidade Estadual do Oeste do Paraná Cascavel Brasil Centro de Ciências Biológicas e da Saúde Universidade Estadual do Oeste do Paraná Cascavel Brasil Faculdades Pequeno Príncipe Curitiba Brasil

The diagnosis of Invasive Fungal Disease (IFD) is difficult because the sensitivity of conventional culture and cytology methods for the detection of Aspergillus is poor, and because serological methods exhibit cross-reactivity with environmental fungi. Fungal polysaccharides are of particular interest in the serologic diagnosis of IFD, especially galactomannan (Gm) and glucan, which have been recognized as useful tools for the diagnosis of fungal infections. Further investigation into polysaccharide antibody cross-reactivity is important in improving diagnostic tests. Our aim was to verify the production of antibodies against fungal antigens in mice immunized with exopolysaccharides (EPS) obtained from three fungal species (Aspergillus terreus, Paecilomyces variotii and Curvularia brachyspora). ELISA assays were performed to evaluate homologous and heterologous reactions and showed anti-polysaccharide antibodies production. EPS from A. terreus was immunogenic enough to immunize the animal and lead to antibody production against this EPS. In addition, no cross-reactivity was observed with EPS obtained from P. variotii and C. brachyspora. The EPS from P. variotii did not exhibit good immunogenicity, whereas EPS from C. brachyspora showed good immunogenicity, and heterologous reactions were detected on the ELISA assays performed using the EPS from this species. The results indicate that immunization can occur for environmental fungal polysaccharides, generating antibodies may be interfere in serological diagnosis that are based on detection of fungal polysaccharides, mainly glucans and galactomannans.

关键词： Exopolysaccharides Environmental Fungi Immunization

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Effects of microselective Neurotomy on Focal Spasticity and Description of the Surgical Technique

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Open Journal of modern Neurosurgery 2021年第3期11卷 144-156页

作者： Sergio A. Sacchettoni Joyce Bolaños Napoleon Torres Juan P. Abud Penelope mantilla Luis Salazar maria-fernanda Vargas Julio Rodriguez-Wulff Randy Balladares Ricardo Gomez Service of Neurosurgery Hospital Vargas de Caracas Caracas Venezuela Service of Neurosurgery Centro Medico Docente La Trinidad Caracas Venezuela Neurological Unit “NeuroQX” Centro Médico Integra Caracas Venezuela Université Grenoble Alpes Grenoble France

We studied the microselective neurotomy (mSN) and its advantages to alleviate disabling spasticity. The best indication for mSN is focal spasticity. We performed 298 mSN, 87 nerves on the upper limb, 211 nerves on the lower limb) in 68 patients. The initial causes were: stroke, cranial trauma, postoperative complications and multiple sclerosis. mSN procedures were performed on the median nerve (n = 40) for wrist and finger flexion;musculo-cutaneus nerve (n = 38) for elbow flexion;ulnaris nerve (n = 9) for cubital deviation of the hand;gastrocnemius nerve (n = 98) and soleus nerve (n = 49) for equinus foot, tibial posterior nerve (n = 45) for varus foot, and fascicles (or bundles) of the flexor digitorum for “claw” toes (n = 19). The main preoperative test to identify the responsible nerve was a neuromuscular block with local anesthesia (lidocaine or bupivacaine) injected into the site of the nerve connecting the spastic muscle. During surgery, the identified nerve was exposed and its epineurium opened. Nerve bundles were teased apart into individual rootlets and a number of rootlets cut were previously planned, according to the spasticity. Follow-up was performed for up to 10 years, with a mean period of 29 months. Results demonstrated a reduction of limb spasticity of 2 to 3 points: modified Ashworth scale (mAS). Pain and clonus were also diminished in the affected limb. In some cases, voluntary movement was once again possible. mSN is a useful alternative in those cases of focal spasticity where physiotherapy and nerve block with botulinum toxin or phenol no longer produce satisfactory results.

关键词： Focal Spasticity microselective Neurotomy Neurosurgery of Spasticity

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A Reliable method to Quantify Trimethoprim and Sulfamethoxazole in Plasma of Children by HPLC with Application in Pharmacokinetic Studies

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American Journal of Analytical Chemistry 2019年第7期10卷 247-253页

作者： Alejandra Toledo Ló pez Hugo Juá rez Olguí n Ismael Lares-Asseff fernanda Reyes Gonzá lez Radames Alemon medina Gabriela Pé rez Guillé Francisca Trujillo Jimenez Laboratory of Pharmacology Instituto Nacional de Pediatr&#237 a Mexico City Mexico Centro de Investigació n Interdisciplinario para el Desarrollo Integral Regional Durango Mexico

Aim: To develop a simple and sensitive high-performance liquid chromatography method to determine plasmatic levels of trimethoprim/sulfamethoxazole in paediatric population. method: Chromatographic separation was carried out using a reverse phase column with detection ultraviolet at a wavelength of 225 nm. The mobile phase consists of phosphate buffer 0.1 m, acetonitrile and methanol, (65:20:15) with a flow of 1.0 ml/min. Results: Calibration curve was linear over the concentration range for trimethoprim of 0.25 to 5 μg/ml and 5 to 100 μg/ml for sulfamethoxazole. Precision were found to be within 15% for both compounds. The detection limits and quantifications for trimethoprim/sulfamethoxazole were 0.2 - 0.25 μg/ml and 3 - 5 μg/ml respectively. Conclusions: The developed method was applied for the quantification of both compounds in plasma samples of two patients resulting concentrations within the therapeutic ranges. The method is convenient for pharmacokinetic studies.

关键词： Children Liquid Chromatography Phase Reverse Pharmacokinetics

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Clinical Trial Demonstrates Efficacy of Transcranial Direct Current Stimulation (tDCS) in Improving Pain management from Post-Laminectomy Syndrome

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Pain Studies and Treatment 2023年第4期11卷 27-42页

作者： marilia Capuço Oliveira fernanda menezes de Faria Gerardo maria de Araújo Filho Ana Carolina Gonçalves Olmos Demosthenes Santana Silva Junior Camila Souza Alves Cosmo Department of Neurological Sciences Psyquiatry and Medical Psychology Faculdade de Medicina de S&#227o José do Rio Preto S&#227o Paulo Brazil

Chronic pain, a multidimensional experience affecting individuals’ sensory, cognitive, and emotional aspects, significantly impacts their quality of life. Post-laminectomy syndrome, a condition characterized by persistent back pain following spinal surgery, often leads to disability and increased healthcare utilization. methods: This randomized, controlled, blind clinical trial aimed to investigate the efficacy of Transcranial Direct Current Stimulation (tDCS) in managing pain from post-laminectomy syndrome in patients. Twenty-four participants were assigned to three groups: sham stimulation, active stimulation over primary motor cortex (m1), or stimulation over dorsolateral prefrontal cortex (DLPFC). Stimulation was administered for five consecutive days, 20 minutes per session, using a current of 1.5 mA through 25 cm2 electrodes. Pain intensity was assessed using Visual Analog Scale (VAS) before, during, and after intervention. Results: An ANOVA model demonstrates significant reduction in pain intensity compared to baseline in VAS, (F(7, 285) = 12.292;p 0.001;Power = 1.000;η2p = 0.534), in tDCS applied to m1, after five days of intervention. After stimulation, a significant improvement was observed in WHOQoL-Bref Quality of life item 1 (p = 0.04), considering statistical significant difference p 0.05. Correlation between the variables: quality of life, depression, anxiety and pain also demonstrates reduction in depression and anxiety according to Beck’s Depression and Anxiety Inventories (BDI and BAI), p 0.05. This effect was not observed in DLPFC stimulation group. Patients who believed they received active stimulation, in sham group, demonstrated potential for effective blinding. Conclusion: The tDCS applied to primary motor cortex effectively improved pain management and psychiatry symptoms in post-laminectomy syndrome patients. The technique’s low cost, ease of use, and high tolerability make it a promising adjuvant therapy for chronic pain conditio

关键词： Non-Invasive Neuromodulation Transcranial Direct Current Stimulation Post-Laminectomy Syndrome Chronic Pain

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Agronomic and Energetic Potential of Biomass Sorghum Genotypes

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American Journal of Plant Sciences 2015年第11期6卷 1862-1873页

作者： fernanda maria Rodrigues Castro Adriano Teodoro Bruzi José Airton Rodrigues Nunes Rafael Augusto Costa Parrella Gabrielle maria Romeiro Lombardi Carlos Juliano Brant Albuquerque maurício Lopes Agriculture Department Federal University of Lavras Lavras Brazil Biology Department Federal University of Lavras Lavras Brazil Embrapa maize and Sorghum Sete Lagoas Brazil Epamig Uberlandia Brazil

The biomass sorghum [Sorghum bicolor (L.) moench], is an interesting crop considering the necessity to invest in alternative sources to generate renewable energy. The objective of this experiment was to identify sorghum biomass genotypes with greatest agronomic and energetic potential, and verify if there is phenotypic association between agronomic and technological properties in the hybrids. The study was conducted in three cities of the minas Gerais State, Brazil (Lavras, Uberlandia and Sete Lagoas). It was evaluated 16 genotypes of sorghum biomass, being 14 of them sensitive hybrids to photoperiod and two cultivars, as control, insensitive to photoperiod. The experimental design was a triple lattice 4 × 4, with plots formed by four linear rows of 5.0 m. The morphoagronomic characteristics evaluated for the three environments were: days to flowering (FLOW), plant height (PH), number of stems (NS) and green matter production (GmP). In the experiment conducted in Lavras, also it was evaluated the agronomic traits: stem diameter (SD) and dry matter production (DmP) besides the technological traits: higher heating value (HHV), crude fiber (CF), neutral detergent fiber (NDF) and acid detergent fiber (ADF). The genotype × environment interaction was significant for all traits. The hybrids had superior performance compared to the control genotypes. Biomass sorghum hybrids, sensitive to photoperiod, when compared with commercial hybrids of forage sorghum, insensitive to photoperiod, had an average production of 34 t ha-1 dry matter with 62% humidity and higher heating value of 4.400 Kcal/Kg. There was no phenotypic correlation between agronomic and technological characters evaluated.

关键词： Sorghum bicolor Bioenergy Alternative Source Phenotypic Correlation

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