Preliminary safety assessment of CIGB-210, an investigational peptide for HIV infection.

Current human immunodeficiency virus treatments need to be periodically administered lifelong. In this study we assess the effect of repeated doses of an anti-HIV peptide drug candidate in C57BL6 strain. Two schemes of up to 15 administrations and one of 30, daily dosing for 5 days per week, all by the subcutaneous route were evaluated. Different dose concentrations of the peptide were assayed. CIGB-210 treated animals showed no symptoms or abnormal behavior as compared with placebo. All the animals gained weight during the study. Macroscopic evaluation showed no alterations in any of the organs studied. Microscopic analysis of the tissues did not show morphological changes in thymus, stomach, small and large intestines, kidney, brain, or cerebellum. The proliferative response of splenocytes and their capacity to secrete gamma interferon were not compromised by the repeated administration of CIGB-210. There were not statistically significant differences for any of the parameters evaluated during the study among treated and non-treated groups. We can conclude that CIGB-210 is well tolerated in C57BL6 mice in the dose concentration range explored and merits subsequent toxicological studies.

Synergic effect of anticancer peptide CIGB-552 and Cisplatin in lung cancer models.

BACKGROUND: The antitumor peptide CIGB-552 is a new targeted anticancer therapy which molecular mechanism is associated with the inhibition of the transcription factor NF-kB, mediated by COMMD1 protein stabilization. In this study, we examined the antiproliferative capacity of CIGB-552 in combination with chemotherapeutic agents in lung cancer models. METHODS AND RESULTS: We combined of CIGB-552 and the antineoplastic agent Cisplatin (CDDP) in concomitant and pre-treatment scenary in a dose matrix approach. This study was performed in the non-small cell lung cancer cell lines NCI-H460, A549 and in a mouse model of TC-1 lung cancer. Our results demonstrate a clear synergic effect between 37.5 µM of CIGB-552 and 5 µM of CDDP under concomitant scheme, on proliferation inhibition, cell cycle arrest, apoptosis induction and oxidative stress response. The effect of CIGB-552 (1 mg/kg) and CDDP (0.4 mg/kg) administrated as a combined therapy was demonstrated in vivo in a TC-1 mouse model where the combination achieved an effective antitumor response, without any deterioration signs or side effects. CONCLUSIONS: These findings demonstrate the efficacy of the concomitant combination of both drugs in preclinical studies and support the use of this therapy in clinical trials. This study is the first evidence of synergistic effect of the combination of  the antitumoral peptide CIGB-552 and CDDP.

Evaluation of Cell-Penetrating Peptides as Mucosal Immune Enhancers for Nasal Vaccination.

Cell-penetrating peptides (CPPs) have been evaluated as enhancers in drug delivery, their addition in medical formulations favors drug absorption allowing obtaining the pharmacological effect with lower doses. In vaccine formulations their inclusion has been also explored with interesting results. Currently mucosal vaccination constitutes a promising alternative with the main advantage of inducing both systemic and mucosal immune responses, which are crucial for control tumors and infections at mucosal tissues. In the present work the nasal immune-enhancing effect of four CPPs was evaluated in Balb/c mice. Animals were intranasally immunized with CPP and the recombinant hepatitis B surface protein (HBsAg) as model antigen. The antibody response in sera and mucosal tissue was measured by ELISA. The IFN-γ secretion response at spleen was also evaluated by ELISPOT and ELISA. Among the CPPs studied one novel peptide stand out by its ability to potentiate the humoral and cellular immune response against the co-administered antigen. Considering that the use of mucosal routes is a promising strategy in vaccination, which are gaining special relevance nowadays in the development of novel candidates against SARS-CoV-2 and other potential emerging respiratory virus, the searching and development of safe mucosal adjuvants constitute a current need.

Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis.

A peptide from the P0 acidic ribosomal protein (pP0) of ticks conjugated to keyhole limpet hemocyanin from Megathura crenulata has shown to be effective against different tick species when used in host vaccination. Turning this peptide into a commercial anti-tick vaccine will depend on finding the appropriate, technically and economically feasible way to present it to the host immune system. Two conjugates (p64K-Cys1pP0 and p64K-ßAla1pP0) were synthesized using the p64K carrier protein from Neisseria meningitidis produced in Escherichia coli, the same cross-linking reagent, and two analogues of pP0. The SDS-PAGE analysis of p64K-Cys1pP0 showed a heterogeneous conjugate compared to p64K-ßAla1pP0 that was detected as a protein band at 91kDa. The pP0/p64K ratio determined by MALDI-MS for p64K-Cys1pP0 ranged from 1 to 8, being 3-5 the predominant ratio, while in the case of p64K-ßAla1pP0 this ratio was 5-7. Cys1pP0 was partially linked to 35 out of 39 Lys residues and the N-terminal end, while ßAla1pP0 was mostly linked to the six free cysteine residues, to the N-terminal end, and, in a lesser extent, to Lys residues. The assignment of the conjugation sites and side reactions were based on the identification of type 2 peptides. Rabbit immunizations showed the best anti-pP0 titers and the highest efficacy against Rhipicephalus sanguineus ticks when the p64K-Cys1pP0 was used as vaccine antigen. The presence of high molecular mass aggregates observed in the SDS-PAGE analysis of p64K-Cys1pP0 could be responsible for a better immune response against pP0 and consequently for its better efficacy as an anti-tick vaccine. Graphical abstract.

A first-in-class, first-in-human, phase I trial of CIGB-552, a synthetic peptide targeting COMMD1 to inhibit the oncogenic activity of NF-κB in patients with advanced solid tumors.

CIGB-552 is a synthetic peptide that interacts with COMMD1 and upregulates its protein levels. The objectives of this phase I study were safety, pharmacokinetic profile, evaluation of the lymphocytes CD4+ and CD8+ and preliminary activity in patients with advanced tumors. A 3 + 3 dose-escalation design with seven dose levels was implemented. Patients were included until a grade 3 related adverse event occurred and the maximum tolerated dose was reached. The patients received subcutaneous administration of CIGB-552 three times per week for 2 weeks. Single-dose plasma pharmacokinetics was characterized at two dose levels, and tumor responses were classified by RECIST 1.1. Twenty-four patients received CIGB-552. Dose-limiting toxicity was associated with a transient grade 3 pruritic maculopapular rash at a dose of 7.0 mg. The maximum tolerated dose was defined as 4.7 mg. Ten patients were assessable for immunological status. Seven patients had significant changes in the ratio CD4/CD8 in response to CIGB-552 treatment; three patients did not modify the immunological status. Stable disease was observed in five patients, including two metastatic soft sarcomas. We conclude that CIGB-552 at dose 4.7 mg was well tolerated with no significant adverse events and appeared to provide some clinical benefits.

Monoclonal antibody against Nile tilapia (Oreochromis niloticus) IgM heavy chain: A valuable tool for detection and quantification of IgM and IgM+ cells.

Nile tilapia (Oreochromis niloticus) is a freshwater fish, which is extensively cultivated worldwide and constitutes one of the model species for the study of fish immunology. Monoclonal antibodies are very advantageous molecular tools for studying teleost immune system. Specifically, monoclonal antibodies that react with immunoglobulins are used successfully in the study of the humoral immune response of several fish species. In the present study, we produced and characterized a monoclonal antibody against tilapia IgM heavy chain using a peptide-based strategy. The peptide sequence was selected from the surface-exposed region between CH3-CH4 domains. The specificity of the polyclonal serum and the hybridoma culture supernatant obtained by immunization with the peptide conjugated to keyhole limpet hemocyanin were evaluated by western blotting, both showing reactivity against tilapia serum IgM. The purified mAb was able to recognize secreted IgM by western blotting and ELISA and membrane IgM by flow cytometry. We also demonstrated that the antibody doesn't cross-react with a recombinant IgT fragment. This tool allowed us to study for the first time the stimulation of mucosal immunity after Pituitary Adenylate Cyclase Activating Polypeptide administration. Overall, the results demonstrated the utility of this mAb to characterize humoral immune response in O. niloticus.

Autoantibodies against a novel citrullinated fibrinogen peptide related to smoking status, disease activity and therapeutic response to methotrexate in cuban patients with early rheumatoid arthritis.

Treatment recommendations of early rheumatoid arthritis (RA) suggest differential management of patients on the basis of prognostic factors. In this study we aimed to investigate the relationship between autoantibodies against a novel citrullinated fibrinogen peptide (anti-CFP), smoking status, clinical activity and therapeutic response in Cuban patients with early RA, receiving treatment with methotrexate in comparison to rheumatoid factor (RF), anti-cyclic citrullinated peptide of second generation (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV). A 6-month prospective observational study was performed in 60 early RA patients at baseline and 6 months after receiving methotrexate. Baseline and outcome measures included disease activity score of 28 joints (DAS 28), simplified disease activity index (SDAI), anti-CFP antibodies, RF, anti-CCP2 and anti-MCV. Therapeutic response was determined using 20/50/70 American College of Rheumatology (ACR) response rates. DAS28 (p < 0.0001), SDAI (p < 0.0001) as well as titres of anti-CFP (p = 0.0481), anti-CCP2 (p = 0.0082), RF IgM (p = 0.0187) and RF IgA (p = 0.0252) decreased under therapy. Multivariate analyses showed association of final anti-CFP values with sex and smoking status (p = 0.0296). It is of note that anti-CFP antibodies were one of predictors for DAS 28 (p = 0.0072) SDAI (p < 0.0001) and ACR response (p = 0.0003) in multivariate models. Anti-CFP antibodies decrease in correspondence with clinical improvement after 6-month therapy and are associated with sex and smoking status. Moreover, baseline anti-CFP antibodies, using in combination with sex, smoking status and autoantibodies (anti-CCP2, anti-MCV or RF) seems to have clinical relevance for predicting clinical activity and therapeutic response.

A competitive ELISA for the quantitative determination of the novel anti-HIV drug candidate CIGB-210 in biological fluids.

The synthetic peptide CIGB-210 is a promising anti-HIV drug candidate shown to inhibit HIV replication in MT4 cells at the nanomolar range by triggering the rearrangement of vimentin intermediate filaments. Sensitive and specific analytical methods are required for pharmacological studies of CIBG-210 in animals. In this study, we describe the development of a competitive ELISA for the quantitative determination of CIGB-210 using an anti-CIGB-210 hyperimmune serum. After optimization of all the steps, the assay exhibited a dynamic range from 11.87 to 0.0095 µg/mL. The intra-assay coefficient of variation (CV) was lower than or close to 5% for all the six concentrations of the calibrator, and the inter-assay CV was below 10% in five out of the six concentrations tested. No interference of either murine or human plasma was observed. The analyte was stable in plasma after five freeze-thaw cycles, while the hyperimmune serum maintained its binding capacity after 10 freeze-thaw cycles. Furthermore, the ELISA was able to detect the two main metabolites of CIGB-210, although with a tenfold decrease in sensitivity. Our results demonstrate the utility and feasibility of this analytical method for pharmacological experiments in animals as humans.

Characterization of low-abundance species in the active pharmaceutical ingredient of CIGB-300: A clinical-grade anticancer synthetic peptide.

CIGB-300 is a first-in-class synthetic peptide-based drug of 25 amino acids currently undergoing clinical trials in cancer patients. It contains an amidated disulfide cyclic undecapeptide fused to the TAT cell-penetrating peptide through a beta-alanine spacer. CIGB-300 inhibits the CK2-mediated phosphorylation leading to apoptosis of tumor cells in vitro, and in vivo in cancer patients. Despite the clinical development of CIGB-300, the characterization of peptide-related impurities present in the active pharmaceutical ingredient has not been reported earlier. In the decision tree of ICHQ3A(R2) guidelines, the daily doses intake, the abundance, and the identity of the peptide-related species are pivotal nodes that define actions to be taken (reporting, identification, and qualification). For this, purity was first assessed by reverse-phase chromatography (>97%) and low-abundance impurities (≤0.27%) were collected and identified by mass spectrometry. Most of the impurities were generated during peptide synthesis, the spontaneous air oxidation of the reduced peptide, and the lyophilization step. The most abundant impurity, with no biological activity, was the full-length peptide containing Met17 transformed into a sulfoxide residue. Interestingly, parallel and antiparallel dimers of CIGB-300 linked by 2 intermolecular disulfide bonds exhibited a higher antiproliferative activity than the CIGB-300 monomer. Likewise, very low abundance trimers and tetramers of CIGB-300 linked by disulfide bonds (≤0.01%) were also detected. Here we describe for the first time the presence of active dimeric species whose feasibility as novel CIGB-300 derived entities merits further investigation.

The first report of cases of pet dogs with naturally occurring cancer treated with the antitumor peptide CIGB-552.

The absence of an effective therapy against human solid tumors has fostered the development of promising antineoplastic therapeutic candidates, as the CIGB-552 peptide. This synthetic peptide has shown to be effective in reducing tumor size and increasing the lifespan in tumor-bearing mice. Therefore, this work was aimed to explore the safety profile and preliminary assessment of antitumor activity of the CIGB-552 peptide therapeutic candidate in a small population of dogs (n=9) having malignant spontaneously-arising solid tumors. The peptide was administered by subcutaneous (s.c.) route, at three dosage levels (0.075, 0.15 and 0.3mg/kg). The results showed no dose-limiting toxicities in any dogs. The antitumor activity observed in dogs receiving CIGB-552 was associated with the reduction in the tumor volume. Given the antitumor effects of CIGB-552 as mediated by COMMD1 protein, which function is highly conserved among eukaryotic organisms, and the similarities of canine and human types of cancer with respect to tumor biology, it is likely that CIGB-552 could demonstrate comparable anti-cancer activity in human patients. Synthetic peptide, COMMD1, Tumor, Dog, CIGB-552.

Development and validation of a bioanalytical method based on LC-MS/MS analysis for the quantitation of CIGB-814 peptide in plasma from Rheumatoid Arthritis patients.

CIGB-814, originally named as E18-3 APL1 or APL1 in preclinical experiments, is a novel therapeutic peptide candidate for Rheumatoid Arthritis (RA). It is an altered peptide ligand containing a novel CD4+ T-cell epitope of human heat shock protein 60 (83-109, MW 2988.38g/mol) with a mutation (D100→L) that increases its affinity for HLA-II type molecules associated to RA. A bioanalytical method, based on LC-MS/MS analysis, in the SRM mode was developed and fully validated to quantify this peptide in human plasma. An internal standard with the same amino acid sequence but labeled with three (13C615N2)-Lys residues was used for quantitation. The method provides a linear range from 1.5 to 48ng/mL (without matrix effect and carry over) and an accuracy and precision good enough for monitoring more than 80% of the AUC of the PK profile in a phase I clinical trial. The peptide was administered subcutaneously in three dose levels (1, 2.5 and 5mg) not normalized to the body weight of patients with RA. The low doses imposed an analytical challenge; however, a LLOQ of 1.5ng/mL enabled the PK analysis. The Cmax, reached at 0.5h, showed a great variability, that was most likely due to the non-normalized doses; the proposed mechanism for this peptide; and the variability between patients. A rapid clearance of this peptide (4-6h) is advantageous for an immunomodulatory drug, because the therapeutic schedule requires repeated dosages to restore peripheral tolerance.

The intrinsic antimicrobial activity of citric acid-coated manganese ferrite nanoparticles is enhanced after conjugation with the antifungal peptide Cm-p5.

Diseases caused by bacterial and fungal pathogens are among the major health problems in the world. Newer antimicrobial therapies based on novel molecules urgently need to be developed, and this includes the antimicrobial peptides. In spite of the potential of antimicrobial peptides, very few of them were able to be successfully developed into therapeutics. The major problems they present are molecule stability, toxicity in host cells, and production costs. A novel strategy to overcome these obstacles is conjugation to nanomaterial preparations. The antimicrobial activity of different types of nanoparticles has been previously demonstrated. Specifically, magnetic nanoparticles have been widely studied in biomedicine due to their physicochemical properties. The citric acid-modified manganese ferrite nanoparticles used in this study were characterized by high-resolution transmission electron microscopy, which confirmed the formation of nanocrystals of approximately 5 nm diameter. These nanoparticles were able to inhibit Candida albicans growth in vitro. The minimal inhibitory concentration was 250 µg/mL. However, the nanoparticles were not capable of inhibiting Gram-negative bacteria (Escherichia coli) or Gram-positive bacteria (Staphylococcus aureus). Finally, an antifungal peptide (Cm-p5) from the sea animal Cenchritis muricatus (Gastropoda: Littorinidae) was conjugated to the modified manganese ferrite nanoparticles. The antifungal activity of the conjugated nanoparticles was higher than their bulk counterparts, showing a minimal inhibitory concentration of 100 µg/mL. This conjugate proved to be nontoxic to a macrophage cell line at concentrations that showed antimicrobial activity.

Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model.

In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19-31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer.

Macrocyclization of Peptide Side Chains by the Ugi Reaction: Achieving Peptide Folding and Exocyclic N-Functionalization in One Shot.

The cyclization of peptide side chains has been traditionally used to either induce or stabilize secondary structures (ß-strands, helices, reverse turns) in short peptide sequences. So far, classic peptide coupling, nucleophilic substitution, olefin metathesis, and click reactions have been the methods of choice to fold synthetic peptides by means of macrocyclization. This article describes the utilization of the Ugi reaction for the side chain-to-side chain and side chain-to-termini macrocyclization of peptides, thus enabling not only access to stable folded structures but also the incorporation of exocyclic functionalities as N-substituents. Analysis of the NMR-derived structures revealed the formation of helical turns, ß-bulges, and α-turns in cyclic peptides cross-linked at i, i + 3 and i, i + 4 positions, proving the folding effect of the multicomponent Ugi macrocyclization. Molecular dynamics simulation provided further insights on the stability and molecular motion of the side chain cross-linked peptides.

High efficacy of a 20 amino acid peptide of the acidic ribosomal protein P0 against the cattle tick, Rhipicephalus microplus.

Current strategies to control cattle ticks use integrated control programs (ICP) that include vaccination. Reduction in the use of chemicals and in the cost of tick control, the delay or elimination of acaricide resistance and the decreasing of environmental pollution are the advantages of using these programs. This integrated program is potentially applicable to all genotypes of chemical resistant ticks. However, the problem here is to improve the efficacy of anti-tick vaccines. The P0 protein is a structural component of the ribosome of all organisms. We have identified an immunogenic region of ribosomal protein P0 from Rhipicephalus spp. ticks that is not very conserved compared to the orthologous protein in their hosts. A synthetic 20 amino acid peptide from this sequence was effective as a vaccine against Rhipicephalus sanguineus infestations in an immunization and challenge experiment using rabbits. In this paper, the same peptide used as vaccine against the cattle tick Rhipicephalus Boophilus microplus shows a significant diminution in the number of engorged females recovered, in the weight of females and the weight of egg masses. The number of eggs hatched was also significantly reduced for the vaccinated group, with an overall effectivity for the antigen pP0 of 96%. These results, together with the conserved sequence of the P0 peptide among ticks, suggest that this antigen could be a good broad spectrum vaccine candidate. It would be expected to be active against many species of ticks and thus has promise in an ICP for effective control of ticks and thereby to improve the efficiency and productivity of the livestock industry.

Bio-analytical method based on MALDI-MS analysis for the quantification of CIGB-300 anti-tumor peptide in human plasma.

A fully validated bio-analytical method based on Matrix-Assisted-Laser-Desorption/Ionization-Time of Flight Mass Spectrometry was developed for quantitation in human plasma of the anti-tumor peptide CIGB-300. An analog of this peptide acetylated at the N-terminal, was used as internal standard for absolute quantitation. Acid treatment allowed efficient precipitation of plasma proteins as well as high recovery (approximately 80%) of the intact peptide. No other chromatographic step was required for sample processing before MALDI-MS analysis. Spectra were acquired in linear positive ion mode to ensure maximum sensitivity. The lower limit of quantitation was established at 0.5 µg/mL, which is equivalent to 160 fmol peptide. The calibration curve was linear from 0.5 to 7.5 µg/mL, with R(2)>0.98, and permitted quantitation of highly concentrated samples evaluated by dilution integrity testing. All parameters assessed for five validation batches met the FDA guidelines for industry. The method was successfully applied to analysis of clinical samples obtained in a phase I clinical trial following intravenous administration of CIGB-300 at a dose of 1.6 mg/kg body weight. With the exception of Cmax and AUC, pharmacokinetic parameters were similar for ELISA and MALDI-MS methods.

Antitumor efficacy, pharmacokinetic and biodistribution studies of the anticancer peptide CIGB-552 in mouse models.

Accumulation of the COMMD1 protein as a druggable pharmacology event to target cancer cells has not been evaluated so far in cancer animal models. We have previously demonstrated that a second-generation peptide, with cell-penetrating capacity, termed CIGB-552, was able to induce apoptosis mediated by stabilization of COMMD1. Here, we explore the antitumor effect by subcutaneous administration of CIGB-552 in a therapeutic schedule. Outstandingly, a significant delay of tumor growth was observed at 0.2 and 0.7 mg/kg (p < 0.01) or 1.4 mg/kg (p < 0.001) after CIGB-552 administration in both syngeneic murine tumors and patient-derived xenograft models. Furthermore, we evidenced that (131)I-CIGB-552 peptide was actually accumulated in the tumors after administration by subcutaneous route. A typical serine-proteases degradation pattern for CIGB-552 in BALB/c mice serum was identified. Further, biological characterization of the main metabolites of the peptide CIGB-552 suggests that the cell-penetrating capacity plays an important role in the cytotoxic activity. This report is the first in describing the antitumor effect induced by systemic administration of a peptide that targets COMMD1 for stabilization. Moreover, our data reinforce the perspectives of CIGB-552 for cancer targeted therapy.

The Antitumor Peptide CIGB-552 Increases COMMD1 and Inhibits Growth of Human Lung Cancer Cells.

We have demonstrated that the peptide L-2 designed from an alanine scanning of the Limulus-derived LALF32-51 region is a potential candidate for the anticancer therapy and its cell-penetrating capacity is an associated useful property. By the modification in the primary structure of L-2, a second-generation peptide (CIGB-552) was developed. However, the molecular mechanism underlying its cytotoxic activity remains partially unknown. In this study, it was shown that CIGB-552 increases the levels of COMMD1, a protein involved in copper homeostasis, sodium transport, and the NF-κB signaling pathway. We found that CIGB-552 induces ubiquitination of RelA and inhibits the antiapoptotic activity regulated by NF-κB, whereas the knockdown of COMMD1 blocks this effect. We also found that CIGB-552 decreases the antioxidant capacity and induces the peroxidation of proteins and lipids in the tumor cells. Altogether, this study provides new insights into the mechanism of action of the peptide CIGB-552, which could be relevant in the design of future anticancer therapies.

Perfil epidemiológico, clínico y endoscópico de los pacientes con sintomatología anorrectal en el Hospital Nacional Arzobispo Loayza 2013 / Epidemiological, clinical and endoscopic profile of patients with anorectal symptoms in National Hospital Arzobispo Loayza 2013

INTRODUCCION: Las enfermedades anorrectales benignas son bastante comunes entre la población general; aunque la incidencia exacta se desconoce, se estima una prevalencia global de 3-7 por ciento en Estados Unidos. La mayoría de estas enfermedades afectan significativamente la calidad de vida del pacientes en nuestro medio no están claramente definidas las diferentes características de estas patologías, por lo tanto el objetivo de este estudio es conocer las características de este problema de Salud. OBJETIVO GENERAL: Determinar las características: epidemiológicas, clínicas, y endoscópicas de los pacientes con sintomatología anorrectal. METODOLOGIA: Estudio Descriptivo, Transversal, Prospectivo de Serie de Casos. Se realizaron 181 encuestas en pacientes que accedieron a la entrevista luego de ser evaluados en la sala de procedimientos de Endoscopia Digestiva Baja del Servicio de Gastroenterología del Hospital Nacional Arzobispo Loayza, en los meses de Mayo y Junio 2013, luego de la evaluación e indicación de procedimiento se aplicó la encuesta respectiva. RESULTADOS: La Rectorragia es el síntoma y signo predominante, siendo la edad promedio 49 años de edad, predominando el sexo femenino, la mayoría era instruido, con ocupación frecuente de actividades elementales: amas de casa, trabajadores de limpieza, estibadores y ambulante; un tercio de la población estudiada acude a la consulta médica entre 1 a 5 años después de iniciados sus molestias, siendo el Estreñimiento, la patología concomitante más frecuente. Las 5 primeras patologías anorrectales fueron Enfermedad Hemorroidal (64.09 por ciento), Pólipos en Recto (5.52 por ciento), Fisura anal (5.52 por ciento), Pólipos en Colon (4.97 por ciento) y Fístula anal (4.97 por ciento).

INTRODUCTION: Benign Anorectal diseases are quite common among the general population, although the exact incidence is unknown, the estimated overall prevalence of 3-7 per cent in the United State. Most of these diseases significantly affect the quality of life of patients, in our environment are not clearly defined the different characteristics of these diseases, therefore the aim of this study was to determine the characteristics of this health problem. GENERAL PURPOSE: To determine the characteristics: epidemiological, clinical, and endoscopic patients with Anorectal symptoms. METHODOLOGY: Descriptive, Cross, Prospective Case Series. 181 surveys were conducted in patients who agreed to the interview after being evaluated in the procedure room Lower Digestive Endoscopy Gastroenterology National Hospital Arzobispo Loayza in the months of May and June 2013, after evaluation procedure and indication respective survey was applied. RESULTS: Rectal bleeding is the predominant symptom and sign, the average age being 49 years of age, predominantly female, most were educated with basic activities common occupation: housewife, cleaning workers, dockers and itinerant, a third of the study population comes to the medical consultation between 1-5 years after his troubles started, with Constipation, the most common concomitant condition. The first 5 were Anorectal Pathology Hemorrhoidal Disease (64.09 per cent), polyps in Recto (5.52 per cent), anal fissure (5.52 per cent), colon polyps (4.97 per cent), and anal fistula (4.97 per cent).

A novel tick antigen shows high vaccine efficacy against the dog tick, Rhipicephalus sanguineus.

Ticks are acaridae ectoparasites that, while taking a blood meal, can transmit viruses, bacteria, protozoa and filarial nematodes, which cause a variety of human and animal illnesses. The use of chemical pesticides constitutes the primary measure for control of these ectoparasites. However, the intensive use of these chemicals has drawbacks such as the contamination of food, environmental pollution and development of resistance by ectoparasites. Vaccination is considered a promising alternative for controlling infestations by ectoparasites. Although emerging tick proteins have been identified recently, and have been proposed as potential targets for generating protective molecules, only a limited number of them have been evaluated in vaccine trials. More than 80 proteins are found in eukaryotic ribosomes. The protein P0 is essential for the assembly of the 60S ribosomal subunit. We have identified an immunogenic region of the ribosomal protein P0 from Rhipicephalus sp. ticks that is not very conserved compared to host P0. The efficacy of a 20 amino acid synthetic peptide from this sequence was assayed as a vaccine antigen against Rhipicephalus sanguineus infestations in an immunization and challenge experiment on rabbits. A remarkable diminution in the viability of newly molted nymphs from larvae fed on vaccinated rabbits was observed. The number of adults and the number of eggs hatching were significantly reduced, with an overall efficacy of 90%. Our results demonstrated that immunization with an immunogenic peptide of tick protein P0 greatly reduced survival of ticks, suggesting that it has promise as an effective tick control agent.