Effect of rhizobium and gibberellin on the production of hydroponic green forage of red clover (Trifolium pratense L.) variety quiñequeli.

The purpose of the present investigation was to determine the effect of rhizobium and gibberellin on the production of hydroponic green forage from red clover (Trifolium pratense L.) variety quiñequeli, four variables were measured: plant height, biomass weight, grass weight and root weight. The treatments were T0: 0%, T1: 10%, T2: 20%, T3: 30% and T4: 40% of Rhizobium before germination and Gibberellin T0: 0g, T1: 2.4g; T2: 3.3g; T3: 4.3 and T4: 5.3g each treatment with 6 repetitions, three applications on days 5, 10, 15 and 20 of growth. Data were analyzed with DCA, ANOVA and DUNCAN's multiple comparisons test; the results obtained were: first measurement with rhizobium without gibberellin there were no statistical differences, second and third measurement with Gibberellin application did not present statistical differences and the fourth measurement presented statistical difference (α=0.05), average height of the plant with a mean of 12.82 cm, T4 was higher, in biomass a statistical difference was obtained with a mean of 3.056 kg, T3 was higher, weight of grass and root did not present statistical differences; concluding that the use of rhizobium and gibberellin could be a usable alternative in the production of hydroponic green fodder, to alleviate the problems of fodder scarcity in dry season, its use being recommended in high Andean livestock.

Human Menstrual Blood-Derived Mesenchymal Stem Cells as Potential Cell Carriers for Oncolytic Adenovirus.

Antitumor efficacy of systemically administered oncolytic adenoviruses (OAdv) is limited due to diverse factors such as liver sequestration, neutralizing interactions in blood, elimination by the immune system, and physical barriers in tumors. It is therefore of clinical relevance to improve OAdv bioavailability and tumor delivery. Among the variety of tumor-targeting strategies, the use of stem cells and specifically bone marrow-derived mesenchymal stem cells (BM-MSCs) is of particular interest due to their tumor tropism and immunomodulatory properties. Nonetheless, the invasive methods to obtain these cells, the low number of MSCs present in the bone marrow, and their restricted in vitro expansion represent major obstacles for their use in cancer treatments, pointing out the necessity to identify an alternative source of MSCs. Here, we have evaluated the use of menstrual blood-derived mesenchymal stem cells (MenSCs) as cell carriers for regional delivery of an OAdv in the tumor. Our results indicate that MenSCs can be isolated without invasive methods, they have an increased proliferation rate compared to BM-MSCs, and they can be efficiently infected with different serotype 5-based capsid-modified adenoviruses, leading to viral replication and release. In addition, our in vivo studies confirmed the tumor-homing properties of MenSCs after regional administration.

Adenovirus coxsackie adenovirus receptor-mediated binding to human erythrocytes does not preclude systemic transduction.

There is great skepticism in the capability of adenovirus vectors and oncolytic adenoviruses to reach specific organs or tumors upon systemic administration. Besides antibodies, the presence of CAR (coxsackie and adenovirus receptor) in human erythrocytes has been postulated to sequester CAR-binding adenoviruses, commonly used in gene therapy and oncolytic applications. The use of non-CAR-binding fibers or serotypes has been postulated to solve this limitation. Given the lack of integrins in erythrocytes and therefore of internalization of the CAR-bound virus, we hypothesized that the interaction of adenovirus type 5 (Ad5) with CAR in human erythrocytes could be reversible. In this work, we have studied the effects of Ad5 interaction with human erythrocytes via CAR. Although erythrocyte binding was observed, it did not reduce viral transduction of tumor cells in vitro after long-term incubations. Transplantation of human erythrocytes into nude mice did not reduce Ad5 extravasation and transduction of liver and human xenograft tumors after systemic administration. These findings indicate that despite human erythrocytes are able to bind to Ad5, this binding is reversible and does not prevent extravasation and organ transduction after systemic delivery. Thus, the poor bioavailability of systemically delivered CAR-binding adenoviruses in humans is likely due to other factors such as liver sequestration or neutralizing antibodies.

Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to enhance TAP-independent presentation and immunogenicity.

Oncolytic adenoviruses can promote immune responses against tumors by expressing and/or displaying tumor-associated antigens. However, the strong immunodominance of viral antigens mask responses against tumor epitopes. In addition, defects in major histocompatibility complex class I antigen presentation pathway such as the downregulation of the transporter-associated with antigen processing (TAP) are frequently associated with immune evasion of tumor cells. To promote the immunogenicity of exogenous epitopes in the context of an oncolytic adenovirus, we have taken advantage of the ER localization of the viral protein E3-19K. We have inserted tumor-associated epitopes after the N-terminal signal sequence for membrane insertion of this protein and flanked them with linkers cleavable by the protease furin to facilitate their TAP-independent presentation. This strategy allowed an enhanced presentation of the exogenous epitopes in TAP-deficient tumor cells in vitro and the generation of higher specific immune responses in vivo that were able to significantly control tumor growth.

iRGD tumor-penetrating peptide-modified oncolytic adenovirus shows enhanced tumor transduction, intratumoral dissemination and antitumor efficacy.

Endovenously administered oncolytic viruses extravasate and penetrate poorly into tumors. iRGD is a cyclic peptide that enhances tumor penetration when conjugated or coadministered with different types of molecules such as drugs, nanoparticles or phages. iRGD-mediated tumor penetration occurs in three steps: binding to αv-integrins on tumor vasculature or tumor cells, exposure by proteolysis of a C-terminal motif that binds to neuropilin-1 (NRP-1) and cell internalization. We have genetically inserted the iRGD peptide in the fiber C terminus of ICOVIR15K, an oncolytic tumor-retargeted adenovirus to increase its tumor penetration. In vitro, NRP-1 interaction improved binding and internalization of the virus in different cancer cells overexpressing integrins and NRP-1. However, such NRP-1-mediated internalization did not affect transduction or cytotoxicity. In vivo, iRGD did not change the normal organ transduction pattern, with liver and spleen as main targeted organs. In tumors, however, iRGD enhanced transduction and early adenovirus dissemination through the tumor mass leading to an improved antitumor efficacy.

Accuracy of imaging methods for detection of bone tissue invasion in patients with oral squamous cell carcinoma.

The objective of this review is to evaluate the diagnostic accuracy of imaging methods for detection of mandibular bone tissue invasion by squamous cell carcinoma (SCC). A systematic review was carried out of studies in MEDLINE, SciELO and Science Direct, published between 1960 and 2012, in English, Spanish or German, which compared detection of mandibular bone tissue invasion via different imaging tests against a histopathology reference standard. Sensitivity and specificity data were extracted from each study. The outcome measure was diagnostic accuracy. We found 338 articles, of which 5 fulfilled the inclusion criteria. Tests included were: CT (four articles), MRI (four articles), panoramic radiography (one article), positron emission tomography (PET)/CT (one article) and cone beam CT (CBCT) (one article). The quality of articles was low to moderate and the evidence showed that all tests have a high diagnostic accuracy for detection of mandibular bone tissue invasion by SCC, with sensitivity values of 94% (MRI), 91% (CBCT), 83% (CT) and 55% (panoramic radiography), and specificity values of 100% (CT, MRI, CBCT), 97% (PET/CT) and 91.7% (panoramic radiography). Available evidence is scarce and of only low to moderate quality. However, it is consistently shown that current imaging methods give a moderate to high diagnostic accuracy for the detection of mandibular bone tissue invasion by SCC. Recommendations are given for improving the quality of future reports, in particular provision of a detailed description of the patients' conditions, the imaging instrument and both imaging and histopathological invasion criteria.

Childhood Guillain-Barré syndrome in Paraguay, 1990 to 1991.

During 1990 to 1991, through a national surveillance program for poliomyelitis, the Paraguayan Ministry of Health received reports of 50 children with incident acute flaccid paralysis (< 15 years old). On the basis of established criteria, 37 were diagnosed with Guillain-Barré syndrome. The average annual incidence rate for 1990 to 1991 was 1.1/100,000 children. The clinical course was more benign than reported in other pediatric series. There were low rates of hospitalization (57%), respiratory compromise (8%), and intubation (5%). The overall severity, however, was similar to that described in previous reports, with a 3% case-fatality rate and an 81% total recovery rate at 12 months. Seventy-six percent of patients had symptom onset during January to April, the warmest months of the year. Thirty percent of patients had definite or possible exposure to organophosphate pesticides, and the peak use coincides with the peak incidence of Guillain-Barré syndrome. There was no correlation between occurrence of Guillain-Barré syndrome and prior immunization.

[Mandibular reconstruction after hemimandibulectomy. Report of a clinical case]. / Reconstrucción mandibular post hemimandibulectomia. Presentación caso clinico.

Reconstruction of the mandible with iliac crest bone graft has been reported since early 1900'S. The series go from one to 160 cases published. This article shows the way we approached de reconstruction of a patient who came with an hemimandibulectomy due to osteosarcoma.

Reconstrucción mandibular post hemimandibulectomia. Presentación caso clinico / [Mandibular reconstruction after hemimandibulectomy. Report of a clinical case]

Reconstruction of the mandible with iliac crest bone graft has been reported since early 1900’S. The series go from one to 160 cases published. This article shows the way we approached de reconstruction of a patient who came with an hemimandibulectomy due to osteosarcoma.

Reconstrucción mandibular post hemimandibulectomia. Presentación caso clinico. / [Mandibular reconstruction after hemimandibulectomy. Report of a clinical case]

Reconstruction of the mandible with iliac crest bone graft has been reported since early 1900S. The series go from one to 160 cases published. This article shows the way we approached de reconstruction of a patient who came with an hemimandibulectomy due to osteosarcoma.