ZAGA Double Pedicle Palatal Flap for Soft Tissue Management in Zygomatic Surgery.

Oral rehabilitation of the atrophic maxilla using prostheses anchored on zygomatic implants is a well-documented process. To prevent the risk of sinusitis and or oro-antral communications, the placement of zygomatic implants with an externalized path has been proposed. In these cases where the sealing of the implant neck depends exclusively on a hemidesmosomal junction, there is a risk of dehiscence of the soft tissue. This can lead to esthetic problems, bone resorption, oro antral communication, cellulitis, and even orbital infection. To avoid soft tissue recession when implants are placed in a buccal position to the remaining ridge, different procedures have been proposed, the simplest being a good buccal coverage of the implant by keratinized tissue. In this technical note, we propose the use of a double pedicle palatal flap to increase the keratinized tissue buccal to the implant and, at the same time, to facilitate the incision closure by initial intention.

ITI consensus report on zygomatic implants: indications, evaluation of surgical techniques and long-term treatment outcomes.

OBJECTIVES: The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants. MATERIALS AND METHODS: Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds. RESULTS: A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants. CONCLUSIONS: Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36-141.6 months (3-11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient's perspective.

A modified Delphi consensus for rehabilitations anchored to zygomatic implants.

BACKGROUND: Studies on different surgical approaches have been published with excellent success rates for zygomatic implants. The same publications offer different results regarding the complications associated with the use of such implants. A consensus protocol on zygomatic implant interventions has yet to be documented. PURPOSE: To seek to establish a consensus at each step of treatment consisting of oral rehabilitation using zygomatic implant-anchored restorations, and to share the outcome of the process to serve as a basis for practitioners and researchers. MATERIALS AND METHODS: A wide variety of protocols were identified based on the results of a literature review conducted previously. All participants received the results of the systematic literature search. A modified Delphi process was used to establish a consensus protocol. Six sections were defined: Diagnosis and indications, Planning, Medication, Surgery, Prosthesis, and Follow-up. The first round of 17 open-ended questions was shared with 63 participants, all of whom were experts in zygomatic implant rehabilitation and part of the ZAGA Centers network. A total of 77 follow-up questions were then generated after analysis of the responses to the first 17 questions. RESULTS: Of the 63 experts enrolled, 48 responded to both rounds of questions. Consensus was determined based on the percentage of agreement: < 70% was considered "no consensus" and ≥ 70% was considered "consensus". A high level of consensus was reached. The sections with the lowest percentage of agreement were Medication and Surgery, where a consensus was reached for 67% of the questions. Of the questions included in the Follow-up section in both rounds, a consensus was reached for 80%. Overall, agreement was obtained on 71% of the topics. CONCLUSIONS: Use of the modified Delphi process led to the creation of the first consensus protocol for oral restorations anchored to zygomatic implants.

Evaluation of surgical techniques in survival rate and complications of zygomatic implants for the rehabilitation of the atrophic edentulous maxilla: a systematic review.

PURPOSE: To assess the outcome [zygomatic implant (ZI) survival] and complications of the original surgical technique (OST) and an Anatomy-Guided approach (AGA) in the placement of ZI in patients with severely atrophic maxillae. METHODS: Two independent reviewers conducted an electronic literature search from January 2000 to August 2022. The inclusion criteria were articles reporting at least five patients with severely atrophic edentulous maxilla undergoing placement OST and/or AGA, with a minimum of 6 months of follow-up. Number of patients, defect characteristics, number of ZI, implant details, surgical technique, survival rate, loading protocol, prosthetic rehabilitation, complications, and follow-up period were compared. RESULTS: Twenty-four studies comprised 2194 ZI in 918 patients with 41 failures. The ZI survival rate was 90.3-100% in OST and 90.4-100% in AGA. Probability of complications with ZI with OST was as follows: sinusitis, 9.53%; soft tissue infection, 7.50%; paresthesia, 10.78%; oroantral fistulas, 4.58%; and direct surgical complication, 6.91%. With AGA, the presenting complications were as follows: sinusitis, 4.39%; soft tissue infection, 4.35%; paresthesia, 0.55%; oroantral fistulas, 1.71%; and direct surgical complication, 1.60%. The prevalence of immediate loading protocol was 22.3% in OST and 89.6% in the AGA. Due to the heterogeneity of studies, statistical comparison was only possible after the descriptive analysis. CONCLUSIONS: Based on the current systematic review, placing ZI in severely atrophic edentulous maxillae rehabilitation with the OST and AGA is associated with a high implant survival rate and surgical complications within a minimum of 6 months follow-up. Complications, including sinusitis and soft tissue infection around the implant, are the most common. The utilization of immediate loading protocol is more observed in AGA than in OST.

Round and flat zygomatic implants: effectiveness after a 1-year follow-up non-interventional study.

INTRODUCTION: There are few zygomatic implants (ZI) designs available. The objective of this non-interventional study was to report the effectiveness of two new site-specific ZI, selected and placed following the zygoma anatomy-guided approach (ZAGA). MATERIALS AND METHODS: Consecutive patients presenting indications for rehabilitation using ZI were treated according to ZAGA Concept recommendations. Implants were immediately loaded following the manufacturer's instructions. Success criteria regarding prosthetic offset, rhino-sinus status, soft tissue condition, and implant stability were additionally used as outcome parameters. RESULTS: Twenty patients were followed for a period of 12 to 28 months (average 18.8 months). Ten received 2 ZI plus regular anterior implants; One received 3 ZI plus regular implants and nine received 4 ZI. In total, 59 ZI were placed, 34 (58%) Straumann ZAGA-Flat design, and 25 (42%) ZAGA-Round. Forty-nine percent of the sites were classified as ZAGA-4 type and 27% as ZAGA-2. Four patients (20%) presented discontinuities of the sinus-nose floor before surgery and 15 patients (75%) presented previous sinus opacities. All implants bar one reached more than 45 N.cm of insertion torque. No surgical complications were observed. After 1 year, the modified Lund-Mackay score was negative in 17 patients. Seventeen sites in 11 patients exhibited decreased opacity when pre-surgical imaging was compared to 1-year post-surgical CBCT. All implants and prostheses remained stable and in function. CONCLUSIONS: The study concluded 100% implant/prosthesis survival rates and low complication levels. Within the limitations of the sample and observation period, results suggest that even in cases of extremely resorbed maxillae (as per cases in this study), ZAGA-Flat and ZAGA-Round ZI are viable treatment options when restoring atrophic maxillae following the ZAGA protocol.

Vertical Bone Regeneration with Synthetic Biomimetic Calcium Phosphate onto the Calvaria of Rats.

IMPACT STATEMENT: This work reports a new bone substitute made of precipitated apatite crystals that resemble in composition and crystallinity to the mineral phase of bone. The bone regeneration capacity of this synthetic biomimetic calcium phosphate (SBCP) was studied by using an original model of vertical bone regeneration with cups on the calvaria of rats. After 4 weeks, a significantly higher bone growth was found with SBCP compared with deproteinized bovine bone matrix and empty controls. This rapid vertical bone regeneration indicated that this new biomaterial is particularly interesting for filling bone defects in oral surgery.

6-Hydroxydopamine lesions in the medial prefrontal cortex of rats exposed to a peak-interval procedure

Impaired temporal control is symptomatic of several neurological disorders; recently, it has been implicated in schizophrenia. An animal model of schizophrenia using 6-hydroxydopamine (6-OHDA) infused to the medial pre-frontal cortex (mPFC) was employed to examine its effects on temporal control. Twelve rats were trained on a peak-interval procedure (PIP) until stable patterns of behavior were obtained. Rats infused with 6-OHDA responded less during peak trials and their peak functions were flatter than sham rats. These results are consistent with similar studies with transgenic mice with increased striatal dopamine D2 receptor activity. Lesions in the mPFC decreased motivation to respond in a PIP. These effects may be considered analogous to negative symptoms of schizophrenia...

Novel water-soluble prodrugs of acyclovir cleavable by the dipeptidyl-peptidase IV (DPP IV/CD26) enzyme.

We herein report for the first time the successful use of the dipeptidyl peptidase IV (DPPIV/CD26) prodrug approach to guanine derivatives such as the antiviral acyclovir (ACV). The solution- and solid-phase synthesis of the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of acyclovir are reported. The synthesis of the demanding tetrapeptide amide prodrug of ACV 3 was first established in solution and successfully transferred onto solid support by using Ellman's dihydropyran (DHP) resin. In contrast with the valyl ester prodrug (valacyclovir, VACV), the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of ACV proved fully stable in PBS. Both prodrugs converted to VACV (for 4) or ACV (for 3) upon exposure to purified DPPIV/CD26 or human or bovine serum. Vildagliptin, a potent inhibitor of DPPIV/CD26 efficiently inhibited the DPPIV/CD26-catalysed hydrolysis reaction. Both amide and ester prodrugs of ACV showed pronounced anti-herpetic activity in cell culture and significantly improved the water solubility in comparison with the parent drug.

A proposed classification for zygomatic implant patient based on the zygoma anatomy guided approach (ZAGA): a cross-sectional survey.

PURPOSE: The aim of the present cross-sectional study was to propose a classification system based on a cross-sectional survey of zygomatic implant cases. MATERIALS AND METHODS: Cone beam computerised tomography (CBCT) postoperative images and clinical intra-surgery photographs of 200 sites corresponding to 100 patients, treated with a total of 198 zygomatic implants in the maxilla according to an anatomy-driven prosthetic approach, were reviewed with regard to anatomy and pathway of the zygomatic implant body. The patients were consecutively selected independently of the type of surgery performed, with the unique requirement of a post-surgical CBCT performed at the moment of selection. Of special interest was the morphology of the lateral sinus wall, residual alveolar crest and the zygomatic buttress. An attempt was made to divide the patients into groups, describing typical anatomies and implant pathways. RESULTS: Five basic skeletal forms of the zygomatic buttress-alveolar crest complex and subsequent implant pathways could be identified in a sample of 100 patients. Out of them, 62% were female and 38% male, with ages varying between 36 and 83 years (mean age 59.6, SD: 9.67). The five groups were classified as ZAGA 0 to 4 representing 15%, 49%, 20.5%, 9% and 6.5% of the studied sites, respectively. Intra-individual anatomical differences affecting the zygomatic buttress-alveolar crest complex was also found in 58% of the patients. CONCLUSIONS: Five typical anatomical and implant pathway situations could be identified. A classification system comprising five groups named ZAGA 0 to 4 is proposed. Anatomical intra-individual differences were also found in the 58% of the studied population. It is believed that the proposed classification system is useful for categorising zygomatic implant cases for therapy planning and for scientific follow-up purposes.

Neuropatía trigeminal idiopática en un poodle / Idiopathic trigeminal neuropathy in a poodle

Un poodle macho de siete años presenta un cuadro agudo de parálisis de la mandíbula (mandíbula caída), salivación y dificultad para la aprensión y masticación; no evidencia otra alteración de pares craneales. La biopsia muscular descarta una miositis de los músculos masticadores. El trastorno se resuelve totalmente a las tres semanas, confirmando el diagnóstico de neuropatía trigeminal idiopática.

A seven years old, male poodle is examined presenting acute mandibular paralysis (dropped jaw), drooling and difficulty for the apprehension and chewing; not evidence of an other alteration of cranial nerves. The muscular biopsy rules out a myositis of masticatory muscles. The disorder is resolved completely in 3 weeks confirming diagnosis of idiopathic trigeminal neuropathy.

Effects of Haloperidol on Responding Maintained with Food and Sucrose-Water / Efectos del Haloperidol en Respuestas Mantenidas con Comida y Agua Azucarada

La dopamina es un mediador del valor hedonico de los reforzadores. El haloperidol reduce el valor del reforzador, interfiriendo con la emisión de conductas operantes. Alternativamente, interferencias en la transmisión de dopamina no impiden que los animales consuman el alimento. Los reforzadores quedan intactos después de la administración del haloperidol. Exploramos esas posibilidades con dos tipos de reforzadores, comida y agua azucarada, entregados en programas múltiples de reforzamiento. La comida mantuvo un mayor número de presiones de palanca que el agua-azucarada. Las presiones de palanca y los reforzadores obtenidos disminuyeron con el incremento en la dosis de haloperidol. Las diferencias en presiones de palanca entre alimento y agua-azucarada se mantuvieron con el haloperidol. La administración subcutánea del haloperidol causó mayores decrementos en las presiones de palanca que la administración intraperitoneal, pero no necesariamente causó decrementos en los reforzadores obtenidos; con el haloperidol las ratas continuaron produciendo los dos tipos de reforzadores.

The hedonic value of reinforcers is mediated by dopamine. Accordingly, haloperidol diminishes the value of reinforcers, by interfering with the emission of operant behaviors. Alternatively, the interference of dopamine transmission does not prevent animals from eating food. Thus, reinforcers remain intact after the administration of haloperidol. We assessed these possibilities with eight Wistar rats and two types of reinforcers, food-pellets and sucrose-water, delivered under multiple reinforcement schedules. In general, lever presses maintained by food-pellets were higher than those maintained by sucrose-water. Haloperidol produced dose-related decreases in lever presses and obtained reinforcers. Different doses had no effect on the number of lever presses. Subcutaneous administrations of haloperidol produced higher decreases in lever presses than intra-peritoneal administrations. Decreases in lever pressing were not necessarily accompanied by substantial reductions in obtained food-pellets and sucrose-water reinforcers; under the effects of haloperidol rats continued to produce a considerable number of both types of reinforcers.

Application of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to different amine-containing drugs.

Here we explore the applicability of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to a variety of amine-containing drugs. Efficient procedures have been developed for the synthesis of dipeptide and tetrapeptide amide prodrugs including N-acylation protocols of the exocyclic amino function of cytidine and adenosine nucleosides. Our studies demonstrated that XaaPro dipeptides linked to a free amino group present on an aromatic ring or on a sugar entity are prodrugs that efficiently release the parent drug upon conversion by purified DPPIV/CD26 as well as soluble DPPIV/CD26 in bovine and human serum. Vildagliptin, a specific inhibitor of DPPIV/CD26, was able to completely block the hydrolysis of the prodrugs in the presence of purified CD26 but also in human and bovine serum. When the amino group is present on a pyrimidine or purine ring, the dipeptide derivatives are chemically unstable, whereas the tetrapeptide derivatives (i.e., ValProValPro or ValAlaValPro) were much more stable in solution and efficiently converted to the parent drug by the action of DPPIV/CD26. This DPPIV/CD26-directed prodrug technology can be useful to increase solubility of the parent drug molecules and/or to allow better formulation properties.

Immediate/Early loading of zygomatic implants: clinical experiences after 2 to 5 years of follow-up.

BACKGROUND: Conventional prosthetic treatment of the edentulous and resorbed maxilla with zygomatic implants is a lengthy procedure. Today, immediate/early loading is a clinical reality and it is possible that such protocols could be used also for zygomatic implants. PURPOSE: The aim of the present study is to report on the clinical outcomes of immediate/early loading of zygomatic implants for prosthetic rehabilitation of edentulous and severely resorbed maxillary cases. MATERIALS AND METHODS: A total of 47 zygomatic and 129 regular implants were placed in 25 consecutive patients with total (N = 23) or partial (N = 2) edentulism in the maxilla. The patients had less than 4 mm of available bone height and width distal to the canine pillars. Straight and angulated abutments and impression copings were attached to the implants during surgery. Impressions and bite registrations were made and 19 patients received a bridge within 24 hours and six patients were rehabilitated within 5 days. Screw-retained full arch restorations were used in 23 patients and cemented in 2 patients. The patients were instructed for a soft diet during 4 months. Follow-up controls were performed at 1, 4, and 12 months and thereafter annually. All patients were followed for at least 2 years and up to 5 years in function. RESULTS: All zygomatic implants were stable during the follow-up (cumulative survival rate 100%). One regular implant placed in the pterygoid plate failed after 52 months of loading (cumulative survival rate 99.2%). Apart from fracture of one abutment screw and of anterior teeth in five patients, no other complications were noted. CONCLUSIONS: Within the limitations of the present study, it is concluded that immediate/early loading is a viable treatment modality for prosthetic rehabilitation of the severely resorbed maxilla using zygomatic and conventional implants.

Efficient conversion of tetrapeptide-based TSAO prodrugs to the parent drug by dipeptidyl-peptidase IV (DPPIV/CD26).

A novel prodrug approach has been evaluated using the anti-HIV-active TSAO molecule as the prototype drug to prove the kinetics with purified enzyme and the principles of conversion to the parent compound in sera and cell culture. When a variety of tetrapeptidyl amide prodrugs of NAP-TSAO were synthesized and exposed to purified dipeptidyl-peptidase IV (DPPIV/CD26) as well as human and bovine sera, they are converted to the parent NAP-TSAO drug in two successive steps by both purified CD26 and human and bovine serum. The efficiency of conversion strongly depends on the nature of the amino acid that has to be cleaved-off from the prodrug molecule. The tetrapeptidyl prodrug 20 showed a more than 10-fold improved water-solubility in comparison to that of the parent compound NAP-TSAO. The antiviral activity of the prototype NAP-TSAO could also be modulated by introducing different tetrapeptide moieties on the molecule resulting, in some cases, in a superior antiviral potential in cell culture than the parent drug.

Design and discovery of a novel dipeptidyl-peptidase IV (CD26)-based prodrug approach.

Here we describe a novel type of enzyme-based prodrug approach in which a dipeptide moiety is linked to a nonpeptidic therapeutic drug through an amide bond which is specifically cleaved by the dipeptidyl-peptidase IV (DPP IV/CD26) enzyme activity present in plasma and on the surface of certain cells. DPP IV has high substrate selectivity for peptides with a proline (or an alanine) at the penultimate amino acid position at the N-terminus but tolerates a wide range of natural amino acids at the amino terminal end. A variety of dipeptidyl amide prodrugs of anti-HIV TSAO molecules were synthesized and evaluated for their ability to act as substrates for the enzyme. Our data revealed that DPP IV/CD26 can efficiently recognize such prodrugs as substrates, releasing the parent compound. Moreover, it is possible to modify the half-life and the lipophilicity of the prodrugs by changing the nature of the dipeptide. All conjugates have shown marked in vitro antiviral activities irrespective the the nature of the terminal and/or the penultimate amino acid moiety.

El paradigma de elección con barrera: evaluación del haloperidol con ocho alternativas de respuestas y dos requisitos de traslado / The barrier choice paradigm: assessing haloperidol with eight response alternatives and two travel requirements

La investigación ha mostrado que las mismas dosis de neurolépticos que suprimen la conducta de presionar una palanca para obtener un alimento preferido por el organismo, facilitan el consumo de otro alimento que no es el preferido pero que cuesta menos trabajo obtenerlo. Esto sugiere que los neurolépticos afectan las preferencias alimentarias del organismo en favor de alternativas que requieren menor esfuerzo

Producción de un anticuerpo de conejo anti-glóbulos rojos de carnero para utilizarlo en la valoración de la Actividad Hemolítica del Complemento (CH50) / Production of an anti-ram erythrocite rabbit antibody for use in haemolytic activity assessment of CH 50 complement

La valoración de la Actividad Hemolítica del Complemento (CH50) constituye un medio diagnóstico en el que se mide la capacidad de la vía clásica del complemento para lisar eritrocitos de carnero óptimamente sensibilizados con un anticuerpo anti-eritrocitos de carnero (hemolisina), cuya actividad esta en función de la cantidad y calidad de cada una de los componentes proteicos del complemento. Con el propósito de obtener una hemolisina capaz de sensibilizar adecuadamente a los eritrocitos de carnero, se sometieron a conejos adultos a inoculaciones repetidas y crecientes de antígeno de Forssman presentes en la superficie celular de los hematíes de carnero con lo cual se lograron inmunizar a los conejos contra este antígeno y obtener un anticuerpo en conejo contra eritrocitos de carnero, el cual fue titulado obteniéndose una dilución de 1:200 como título óptimo para la sensibilización de los eritrocitos de carnero, y su posterior utilización en la Valoración de la Actividad Hemolítica del Complemento.