Efficacy of the Vaccine Candidate Based on the P0 Peptide against Dermacentor nitens and Ixodes ricinus Ticks.

The control of ticks through vaccination offers a sustainable alternative to the use of chemicals that cause contamination and the selection of resistant tick strains. However, only a limited number of anti-tick vaccines have reached commercial realization. In this sense, an antigen effective against different tick species is a desirable target for developing such vaccines. A peptide derived from the tick P0 protein (pP0) conjugated to a carrier protein has been demonstrated to be effective against the Rhipicephalus microplus, Rhipicephalus sanguineus, and Amblyomma mixtum tick species. The aim of this work was to assess the efficacy of this peptide when conjugated to the Bm86 protein against Dermacentor nitens and Ixodes ricinus ticks. An RNAi experiment using P0 dsRNA from I. ricinus showed a dramatic reduction in the feeding of injected female ticks on guinea pigs. In the follow-up vaccination experiments, rabbits were immunized with the pP0-Bm86 conjugate and challenged simultaneously with larvae, nymphs, and the adults of I. ricinus ticks. In the same way, horses were immunized with the pP0-Bm86 conjugate and challenged with D. nitens larva. The pP0-Bm86 conjugate showed efficacies of 63% and 55% against I. ricinus and D. nitens ticks, respectively. These results, combined with previous reports of efficacy for this conjugate, show the promising potential for its development as a broad-spectrum anti-tick vaccine.

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.

Insuficiencia mitral severa asintomática: a propósito de un caso / Severe asymptomatic mitral regurgitation: About a case

La insuficiencia mitral es una afección común que incide generalmente en 2 porceinto de la población, el prolapso valvular es el hallazgo más frecuente por la elongación o ruptura de las cuerdas tendinosas lo que ocasiona disímiles grados de regurgitación durante la contracción ventricular. A pesar de ello, la evaluación clínica de los pacientes asintomáticos con insuficiencia mitral severa, permanece en controversia y es motivo de debate entre los principales expertos. Se presentó un caso de insuficiencia mitral severa asintomática por rotura de cuerda tendinosa, al cual se le realizó sustitución valvular mitral debido al grado de deterioro del aparato valvular y sub-valvular, se logró buen resultado en el seguimiento(AU)

Mitral failure is a common disease that generally affects 2 percent of the population. The valvular prolapse is the most frequent finding due to elongation or rupture of tendinous cords that brings about different levels of regurgitation during the ventricular contraction. Despite the above-mentioned, the clinical evaluation of asymptomatic severe mitral failure patients remains controversial and is very much debated among outstanding experts. A case of asymptomatic severe mitral failure caused by rupture of the tendinous cord was presented. The mitral valve was replaced because the valvular and subvalvular systems were much deteriorated. The follow-up of the patient showed good results(AU)

Insuficiencia mitral severa asintomática: a propósito de un caso / Severe asymptomatic mitral regurgitation: About a case

La insuficiencia mitral es una afección común que incide generalmente en 2 porceinto de la población, el prolapso valvular es el hallazgo más frecuente por la elongación o ruptura de las cuerdas tendinosas lo que ocasiona disímiles grados de regurgitación durante la contracción ventricular. A pesar de ello, la evaluación clínica de los pacientes asintomáticos con insuficiencia mitral severa, permanece en controversia y es motivo de debate entre los principales expertos. Se presentó un caso de insuficiencia mitral severa asintomática por rotura de cuerda tendinosa, al cual se le realizó sustitución valvular mitral debido al grado de deterioro del aparato valvular y sub-valvular, se logró buen resultado en el seguimiento

Mitral failure is a common disease that generally affects 2 percent of the population. The valvular prolapse is the most frequent finding due to elongation or rupture of tendinous cords that brings about different levels of regurgitation during the ventricular contraction. Despite the above-mentioned, the clinical evaluation of asymptomatic severe mitral failure patients remains controversial and is very much debated among outstanding experts. A case of asymptomatic severe mitral failure caused by rupture of the tendinous cord was presented. The mitral valve was replaced because the valvular and subvalvular systems were much deteriorated. The follow-up of the patient showed good results

Transcrestal sinus lift and implant placementusing the sinus balloon technique

Objective: A description is made of transcrestal sinus lift using the sinus balloon technique, evaluating the bone height achieved and implant success one year after prosthetic loading. Material and method: Between January and July 2007, transcrestal sinus lift using the sinus balloon technique for dental implant placement was carried out in 6 patients. A panoramic X-ray study and maxillary computed tomography scan were carried out before the operation, in order to discard possible sinus pathology. During the intervention, the integrity of the sinus membrane was evaluated using a Medi Pack Pal endoscope (Farol Store and Co., Tuttlingen, Germany), and the intraoperative complications were analyzed. The dental implants were placed in the same surgical step in the presence of 3 mm or more of residual bone. Following the operation, panoramic X-rays were used to assess the bone height gained. One year after prosthetic loading, the implant success rate was determined based on the criteria of Buser. Results: One patient was excluded due to Schneider’s membrane perforation as confirmed by endoscopy. Transcrestalsinus lift was carried out in 5 males with a mean age of 41.6 years (range 27-51), without antecedents of sinus disease. There were no intraoperative complications. In four patients the implants were placed simultaneous to sinus lift, while in another case implant placement was postponed due to insufficient remaining bone height. The mean gain in height after the operation was 8.7 mm. One year after prosthetic loading, the implant success rate was 100% (AU)

Transcrestal sinus lift and implant placement using the sinus balloon technique.

OBJECTIVE: A description is made of transcrestal sinus lift using the sinus balloon technique, evaluating the bone height achieved and implant success one year after prosthetic loading. MATERIAL AND METHOD: Between January and July 2007, transcrestal sinus lift using the sinus balloon technique for dental implant placement was carried out in 6 patients. A panoramic X-ray study and maxillary computed tomography scan were carried out before the operation, in order to discard possible sinus pathology. During the intervention, the integrity of the sinus membrane was evaluated using a Medi Pack Pal endoscope (Farol Store and Co., Tuttlingen, Germany), and the intraoperative complications were analyzed. The dental implants were placed in the same surgical step in the presence of 3 mm or more of residual bone. Following the operation, panoramic X-rays were used to assess the bone height gained. One year after prosthetic loading, the implant success rate was determined based on the criteria of Buser. RESULTS: One patient was excluded due to Schneider's membrane perforation as confirmed by endoscopy. Transcrestal sinus lift was carried out in 5 males with a mean age of 41.6 years (range 27-51), without antecedents of sinus disease. There were no intraoperative complications. In four patients the implants were placed simultaneous to sinus lift, while in another case implant placement was postponed due to insufficient remaining bone height. The mean gain in height after the operation was 8.7 mm. One year after prosthetic loading, the implant success rate was 100%. CONCLUSIONS: Transcrestal sinus lift using the sinus balloon technique is a minimally invasive procedure. In 5 patients the bone height gained proved sufficient to allow implant placement even in the presence of 3 mm of residual bone.

Hemodynamic and ventilatory changes during implant surgerywith intravenous conscious sedation

Purpose: This study was conducted to determine the hemodynamic and ventilatory changes during implant surgerywith intravenous conscious sedation, and whether preoperative anxiety, gender or age influence these parameters.Patients and Methods: A prospective study carried out between May 2004 and February 2007, on 102 patientstreated with dental implants under local anesthesia and conscious intravenous sedation. Patients completed aquestionnaire prior to surgery to evaluate preoperative dental anxiety using Corah’s scale. The hemodynamic andventilatory changes were evaluated by monitoring systolic pressure (SP), diastolic pressure (DP), heart rate (HR)and oxygen saturation (SaO2). These values were collected at 5 points during surgery; before commencing theoperation (baseline value), during local anesthetic injection, at the moment of incision and raising of a mucoperiostealflap, during implant placement, and finally at suturing. Intravenous conscious sedation was administeredbetween baseline value and injection of the local anesthetic.Results: The highest SP and DP were recorded at baseline and at suturing. The highest HR was recorded at themoment of incision and raising of the mucoperiosteal flap; the lowest SaO2 was recorded at local anesthetic injection.There was no relationship between hemodynamic and ventilatory values and preoperative anxiety or gender.A greater age was associated with higher SP and lower SaO2, these differences being statistically significant.Conclusions: Most of the cardiovascular and ventilatory changes induced by the implant surgery with intravenousconscious sedation were within normal ranges. The results indicate that midazolam with fentanyl do not produceimportant hemodynamic and ventilatory changes, being a good association for intravenous conscious sedation indental implant surgery (AU)

Hemodynamic and ventilatory changes during implant surgery with intravenous conscious sedation.

PURPOSE: This study was conducted to determine the hemodynamic and ventilatory changes during implant surgery with intravenous conscious sedation, and whether preoperative anxiety, gender or age influence these parameters. PATIENTS AND METHODS: A prospective study carried out between May 2004 and February 2007, on 102 patients treated with dental implants under local anesthesia and conscious intravenous sedation. Patients completed a questionnaire prior to surgery to evaluate preoperative dental anxiety using Corah's scale. The hemodynamic and ventilatory changes were evaluated by monitoring systolic pressure (SP), diastolic pressure (DP), heart rate (HR) and oxygen saturation (SaO2). These values were collected at 5 points during surgery; before commencing the operation (baseline value), during local anesthetic injection, at the moment of incision and raising of a mucoperiosteal flap, during implant placement, and finally at suturing. Intravenous conscious sedation was administered between baseline value and injection of the local anesthetic. RESULTS: The highest SP and DP were recorded at baseline and at suturing. The highest HR was recorded at the moment of incision and raising of the mucoperiosteal flap; the lowest SaO2 was recorded at local anesthetic injection. There was no relationship between hemodynamic and ventilatory values and preoperative anxiety or gender. A greater age was associated with higher SP and lower SaO2, these differences being statistically significant. CONCLUSIONS: Most of the cardiovascular and ventilatory changes induced by the implant surgery with intravenous conscious sedation were within normal ranges. The results indicate that midazolam with fentanyl do not produce important hemodynamic and ventilatory changes, being a good association for intravenous conscious sedation in dental implant surgery.