Current Pharmaceutical Biotechnology - Volume 14, Issue 9, 2013

Oral lesions that manifest as ulcer lesions are quite common and can cause discomfort to the patient. Searching for drugs to accelerate the healing of these lesions is nonstop process. Bixin is a molecule found in annatto (urucum) seeds and is considered a viable therapeutic option to treat such lesions due to its anti-inflammatory, anti-oxidant, and healing properties. Therefore, the present study aimed to evaluate the effect of the bixin solution in the ulcer healing process in the oral mucosa of rats. Ulcers were induced with punches of 0.5 cm in the middle of the dorsum of the tongue of 64 Wistar rats. The animals were randomly divided into 8 groups, in which 4 groups were treated with saline solution, while the other 4 were treated with the bixin solution. The animals were sacrificed in the periods 2, 7, 14, and 21 days after the beginning of the treatment. The species were histologically processed and stained with hematoxylin/eosin and picrosirius. Fibroblasts, reepithelialization, and wound contraction could be observed, as could the quantification of neutrophils, macrophages, plasma cells, lymphocytes, and mature and immature collagen. On the seventh day, the experimental group, when compared to the control group, presented a higher proliferation of fibroblasts, more advanced reepithelialization, and a higher contraction in the wounds. A reduction in the average number of neutrophils in the experimental group, when compared to the control group, could be observed in all periods (p=0.000). Up to two days, the total collagen area was higher (p=0.044) in the experimental group (4139.60±3047.51than in the control group (1564.81±918.47). The deposition of mature collagen, on the 14^th day, was higher (p=0.048) in the experimental group (5802.40±3578.18) than in the control group (1737.26±1439.97). The results found in the present study indicate that the bixin solution inhibits the acute inflammatory response with a minor average number of neutrophils and accelerates reepithelialization, wound contraction and collagen maturation, thus illustrating that this solution does in fact represent an important adjuvant in the treatment of ulcers.

The world’s population, areas intended for the production of bio-mass and bio-fuels and the food demand of mankind are on a continuous ascending trend. In this context, an increased efficiency in obtaining large and steady productions, in compliance with the requirements of sustainable development of the agricultural eco-system, is a priority. To be effective, the seed treatment will fulfill the following requirements: shall disinfect and protect the seeds against the pests and pathogen agents found in the soil, shall ensure the system protection, shall not pollute the soil, water and environment, shall have no remnant effect onto the environment and onto the crops and shall be bio-degradable, easy to transport and to use. This paper aims at presenting new collagen based materials for cereal seed treatment, which generates an increase of the quality and protection indicators for treated seeds. Creation of a new and advanced technology for treatment of cereal seeds, by using pesticide-collagen hydrolysate mixes has the objectives of increasing seed quality indexes; reducing pesticide consumption, which will in turn decrease environmental pollution and the cost of treatment for cereal seeds; achieving a better management of resources; reducing production expenses while preserving the environment. The technologies developed for protein raw material processing and characteristics of collagen hydrolysates with bioactive properties are presented. The future route for ecological treatment of seeds is the use of microencapsulated plant extracts (thyme and cinnamon essential oils) with insecticidal and antifungal properties in a shell made using collagen hydrolysate.

Argentinean juices have been studied for their antihypertensive activity, the inhibition of bacteria biofilm formation and the effect on the viability of wine yeast. The influence of phenolic compounds on these activities was evaluated. These studies are the first step for the development of a new type of wine that includes grape must supplement with fruit juices with antihypertensive effect. All juices posses a high antihypertensive activity, higher than 50%. Strawberry juices and eureka lemon showed the highest activity, whereas clarified juices posses the lowest activity. All studied juices produce a high inhibition of bacteria biofilm formation, and the strawberry, orange and mandarin varieties not affect the growth or viability of yeast. Our results permit to conclude that it could be possible the use of these juices in a new type of wine or as a source of new antihypertensive agents for pharmaceutical industry.

Oenococcus oeni is a lactic acid bacterium involved in winemaking where it generally carries out the malolactic fermentation converting the wine's malic acid into lactic acid. In this work were used the strain m of Oenococcus oeni. The culture was inoculated at 108 Log CFU/mL in a synthetic wine medium (SW) supplemented with a fraction of high molecular weight constituted by proteins and polypeptides (FPP) obtained from Cabernet Sauvignon and Syrah wines from Colalao del Valle, Tucumán, Argentine. In presence of FPP, O. oeni maintains viability after 48 h incubation time and release an extracellular proteolytic activity. Therefore, a release peptides of 1.247 and 1.373 mg N/L at 48 h of incubation time was detected in SW supplemented with FPP from Cabernet Sauvignon and Syrah wines respectively. Concomitantly with the maximum peptide release, the “in vitro” biological activities were increased. The released peptides from Cabernet Sauvignon wine enables the increase in the ferric reducing antioxidant power (FRAP) capacity, the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), and the inhibition of angiotensin I-converting enzyme (ACEI activity) in 392.8 μmol FeSO4/L, 9.7% and 63.9%, respectively. In presence of FPP of Syrah wine, the released peptides increases in 156.5 μmol FeSO4/L, 5.5% and 13.8% the FRAP, DPPH and ACEI activities, respectively. The utilization of Oenococcus oeni m to carry out the malolactic fermentation would contribute to enhance the beneficial biological activities of the final product and provide an additional value to regional wines.

Six cultivars of safflower which were (PI-387820, PI-251978, PI-170274, PI-387821, PI-386174 and Thori-78) grown in net house of NIAB under salinity (10 ds m-1) and drought (60% field capacity) conditions and compared to their oxidative damage and antioxidative responses. Plant samples (leaves) were collected for the determination of malonidialdehyde (MDA), antioxidative enzymes (catalase, ascorbate peroxidase, glutathione reductase, and peroxidase), proline, and photosynthetic pigments. Salinity and drought decreased the chlorophyll a and b contents but a decrease in chlorophyll a and b was less in safflower variety (THORI-78) which could be a useful marker for selecting a stress tolerant variety. Both stresses considerable increases the accumulation of proline in PI-251978, PI-170274, PI-387821, PI-386174 and THORI-78 varieties of safflower whereas the proline accumulation did not appear to be an essential part of the protection mechanism against salinity and drought in variety PI-387820. Enzyme activity measurements revealed that THORI-78 can tolerate salinity and drought stress well by increasing the activity of catalase and APX enzymes whereas variety PI- 386174 showed increased activity of glutathione reductase enzyme under salinity and drought and appear to be very crucial antioxidative defenses during intense stress conditions. The results indicate that the photosynthetic pigments, proline and activities of the enzymes are important mechanism for the stress tolerance in safflower plant and can be considered as genetic improvement for the plant in salinity and drought soil conditions.

Cyanobacteria are an important source of structurally bioactive metabolites, with cytotoxic, antiviral, anticancer, antimitotic, antimicrobial, specific enzyme inhibition and immunosuppressive activities. This study focused on the antitumor and antimicrobial activities of intra and extracellular cyanobacterial extracts. A total of 411 cyanobacterial strains were screened for antimicrobial activity using a subset of pathogenic bacteria as target. The in vitro antitumor assays were performed with extracts of 24 strains tested against two murine cancer cell lines (colon carcinoma CT-26 and lung cancer 3LL). Intracellular extracts inhibited 49 and 35% of Gram-negative and Gram-positive pathogenic bacterial growth, respectively. Furthermore, the methanolic intracellular extract of Cylindrospermopsis raciborskii CYP011K and Nostoc sp. CENA69 showed inhibitory activity against the cancer cell lines. The extracellular extract from Fischerella sp. CENA213 and M. aeruginosa NPJB-1 exhibited inhibitory activity against 3LL lung cancer cells at 0.8 μg ml-1 and Oxynema sp. CENA135, Cyanobium sp. CENA154, M. aeruginosa NPJB-1 and M. aeruginosa NPLJ-4 presented inhibitory activity against CT26 colon cancer cells at 0.8 μg ml-1. Other extracts were able to inhibit 3LL cell-growth at higher concentrations (20 μg ml-1) such as Nostoc sp. CENA67, Cyanobium sp. CENA154 and M. aeruginosa NPLJ-4, while CT26 cells were inhibited at the same concentration by Nostoc sp. CENA67 and Fischerella sp. CENA213. These extracts presented very low inhibitory activity on human peripheral blood lymphocytes. The results showed that some cyanobacterial strains are a rich source of natural products with potential for pharmacological and biotechnological applications.

The effect of mixed inoculums of VAM (Vesicular Arbuscular Mycorrhizas) fungi on seed growth and photosynthetic apparatus in green house was monitored. The plants were watered daily with tap water. Plants were cultivated in natural environment in mid of March (2011). A direct relation between root length and water contents suggests a defense mechanism of MP (microrihzal plants) against the fungal stress. It was also supported by the fact that the leaf area of MP was much greater as compared to the NMP (non microrihzal plants) with elevated concentration of all chlorophyllus pigments in 30 days. An increase in the surface area of the leaf and concentration of the pigments, may be for an acceleration in absorption of CO2 for reduction of it into glucose through oxidation of water molecule. The non-significant decline in glucose contents support the above hypothesis of rapid redox reaction mechanism which was established to overcome the stress. The positive effects of mycorrhizal which were already mentioned in the literature were reported in this article in relations of survival strategies of the plant, adapted in stress conditions. An increase in the chlorophyll contents (30 d) and leaf area of plants possibly attributed with absorption of solar radiation for the protection of plants. It was also supported by the higher concentration of carotenoids (30 d) that may have an additional function of regulation of certain developmental responses and screening of light to save the plants from stress conditions.

The outstanding physiological functions of glucagon-like peptide-1 make it a promising drug candidate for blood glucose regulation in type 2 diabetes. However, the short half-life of GLP-1 limited its widely clinical utility due to the rapid degradation by dipeptidyl peptidase IV (DPP-IV) and renal clearance. Therefore, stabilisation of glucagon-like peptide-1 is critical for the use of this peptide in drug development. Scientists in pharmaceutical companies have contributed in years to obtain long-acting or sustained GLP-1 derivatives which are reviewed in this report.

Bone marrow stroma is damaged by chemotherapy and irradiation protocol. Bone marrow microenvironment supports haematopoiesis and comprises Mesenchymal Stem Cells (MSCs). Coinfusion of MSCs with hematopoietic stem cells (HSC) improves engraftment and accelerates haematopoietic recovery. Stroma-derived factor-1 (SDF-1) is a chemotactic factor which plays a crucial role in stem cell transplantation by enhancing the ability of HSC to engraft. In this study expression of SDF-1 in bone marrow MSCs and the level of Colony Forming Unit Fibroblast (CFU-F) were evaluated in 8 patients with Acute Myeloid leukemia (AML). Evaluation was done at diagnosis and after induction/consolidation chemotherapy before the onset of haematopoietic stem cell transplantation (HSCT). CFU-F frequency increases from diagnosis to remission. Nevertheless level of stromal derived factor-1 (SDF-1) transcripts in bone marrow MSCs of patients with AML stays low. Considering the role of SDF-1 in the homing of HSC, the consequences of SDF-1 deficiency observed in this study might be deleterious on the engraftment after HSCT and haematopoietic recovery. The whole result of this clinical study is an argument for MSC infusion to restore a normal level of SDF1 in the bone marrow microenvironment that could reduce hematopoietic toxicity of chemotherapy and improve HSC engraftment after HSCT.

Acute promyelocytic leukemia(APL), a specific characteristic of t(15;17) chromosome translocation, represents 5% to 15% of cases of acute nonlymphocytic leukemia. An alternative approach is to consider retinoic acid(all-trans RA, ATRA or 13-cis RA or 9-cis RA) plus chemotherapy or RA plus As2O3 regimens as now novel therapy. Molecular gene analyses are conclusive in vivo evidence that oncogenic PML/RARa plays a crucial role in APL leukemogenesis. As a novel approach to APL treatment, one possible the action of RA, A consense sequence (5'-TCAGGTCATGACCTGA-3') has been postulated for the thyroid hormone (TRE) and retinoic acid responsive element (RARE) containing half palindromes, which located in the promoter region of target genes. High dose (100-fold) of RA-RARE-PML/RARa complex in intracellular localization appears to relieve repressor from DNA binding, including corepressors N-CoR, SMRT and HDACs, release PML/RARa- mediated transcriptional repression, and release histone deacetylase activity from PMLRARa. The resulting PML/RARa oncoprotein proteolytic degradation through the autophagy-lysosome pathway and the ubiquitin SUMO-proteasome system (UPS), as well as caspase 3 (cleavage site Asp522 within a-helics region of PML component of the fusion protein) or neutrophil elastase, or lysosomal protease enzyme induction. PML protein relocalizes into the wild-type nuclear body (PML-NB) configuration or/and wild-type RARa upregulated. An effect to relieve the blockade (inhibition) of PML/RARA-mediated RA dependent promyelocytic differentiation, and retinoic acid in APL therapy (see Figure in the full text, George Zhu, 1991). Here, like v-erbA, PML/RARa is a (strong) transcriptional repressor of the RA receptor (RAR) complex, and PML/RARa fusion receptor gene act as conditional oncogenic receptor (translocated chimeric retinoic acid a signaling) or oncogenic PML/RARa may participate in leukemogenesis of APL through blocking RA-mediated promyelocytic differentiation. This is first described in eukaryotes.

In this study induction of neoplasm in thyroid gland of one postoperative patient with breast cancer was conducted by marine algae (also seaweed, sargassum), which is presented here. A 41-year-old women was diagnosed as her right breast cancer complicated with lymph node metastasis in her right axilla on February, 1999. In June 19, 1999 she was given the combination chemotherapy of vincristine, cyclophosphamide, 5-Fluorouracil and cinobufacini drugs due to two lymph nodes on her right superclavicular following radical mastectomy. During chemotherapy she was also taken the adjuvant treatment of traditional medicine. Traditional medicine consisted of seaweed plant drugs (containing iodine 362400ug/kg). As to intermittent maintance treatment the total dosage of seaweed herb was at least exceeded 500gram. Induction of thyroid tumor (thumb size) was found in June, 2001. A thyroidectomy due to thyroma was successfully performed. Histologically there revealed thyroid tissue without the evidence of metastasis of breast cancer. She had a 5-year survivor. The data indicated oncogenic function of some traditional herbs, and further experience of traditional medicine in treating thyroid disease especially in thyroid cancer.