T Lymphocyte Exhaustion During Human and Experimental Visceral Leishmaniasis.

A key point of immunity against protozoan Leishmania parasites is the development of an optimal T cell response, which includes a low apoptotic rate, high proliferative activity and polyfunctionality. During acute infection, antigen-specific T cells recognize the pathogen resulting in pathogen control but not elimination, promoting the development and the maintenance of a population of circulating effector cells that mount rapid response quickly after re-exposure to the parasite. However, in the case of visceral disease, the functionality of specific T cells is lost during chronic infection, resulting in inferior effector functions, poor response to specific restimulation, and suboptimal homeostatic proliferation, a term referred to as T cell exhaustion. Multiple factors, including parasite load, infection duration and host immunity, affect T lymphocyte exhaustion. These factors contribute to antigen persistence by promoting inhibitory receptor expression and sustained production of soluble mediators, influencing suppressive cell function and the release of endogenous molecules into chronically inflamed tissue. Together, these signals encourage several changes, reprogramming cells into a quiescent state, which reflects disease progression to more severe forms, and development of acquired resistance to conventional drugs to treat the disease. These points are discussed in this review.

Effects of Polymerization Mode and Interaction with Hydroxyapatite on the Rate of pH Neutralization, Mechanical Properties, and Depth of Cure in Self-Adhesive Cements.

OBJECTIVE: The aim of the study was to evaluate the physicochemical properties of self-adhesive resin cements associated with hydroxyapatite (HAp) according to the polymerization activation. MATERIALS AND METHODS: Specimens of cements (PermaCem 2.0 [DMG]; MaxCem Elite [Kerr], and RelyX U200 [3M ESPE]) were distributed into three groups: activation mode; self-cured and dual-cured modes; and association or not with HAp powder mode. The pH neutralization was evaluated as a function of time. Flexural strength and elastic modulus were also tested (0.5 mm/min.). The depth of cure was also analyzed using the scraping test (ISO 4049). Infrared spectroscopy was also used to collect the spectra of specimens to evaluate the chemical bonds. Statistical comparisons were conducted at 5% of significance. RESULTS: The aggressiveness of the self-adhesive resin cements evaluated varied among the materials with a tendency for neutralization. Self-cure groups exhibited lower pH throughout the entire evaluation when compared with that of the dual-cure ones, irrespective of the addition of HAp. MaxCem Elite when photoactivated was the only cement influenced by the addition of the HAp in terms of mechanical properties. The self-adhesive cements tested presented equivalent depth of cure based on the ISO 4049 requirements, regardless of the evaluated factors. CONCLUSIONS: Based on the parameters evaluated, the results demonstrated that most of the self-adhesive cements remained unaltered or improved when mixed with HAp, regardless of the activation mode.

Synthesis and Characterizations of a Collagen-Rich Biomembrane with Potential for Tissue-Guided Regeneration.

OBJECTIVES: In this study, a collagen-rich biomembrane obtained from porcine -intestinal submucosa for application in guided bone regeneration was developed and characterized. Then, its biological and mechanical properties were compared with that of commercial products (GenDerm [Baumer], Lumina-Coat [Critéria], Surgitime PTFE [Bionnovation], and Surgidry Dental F [Technodry]). MATERIALS AND METHODS: The biomembrane was extracted from porcine intestinal submucosa. Scanning electron microscopy, spectroscopic dispersive energy, glycosaminoglycan quantification, and confocal microscopy by intrinsic fluorescence were used to evaluate the collagen structural patterns of the biomembrane. Mechanical tensile and deformation tests were also performed. STATISTICAL ANALYSIS: The results of the methods used for experimental membrane characterizations were compared with that obtained by the commercial membranes and statistically analyzed (significance of 5%). RESULTS: The collagen-rich biomembrane developed also exhibited a more organized, less porous collagen fibril network, with the presence of glycosaminoglycans. The experimental biomembrane exhibited mechanical properties, tensile strength, and deformation behavior with improved average stress/strain when compared with other commercial membranes tested. Benefits also include a structured, flexible, and -bioresorbable characteristics scaffold. CONCLUSIONS: The experimental collagen-rich membrane developed presents physical-chemical, molecular, and mechanical characteristics similar to or better than that of the commercial products tested, possibly allowing it to actively participating in the process of bone neoformation.

Design, Prins-cyclization reaction promoting diastereoselective synthesis of 10 new tetrahydropyran derivatives and in vivo antinociceptive evaluations.

We described in this article the very efficient 2,6-cis ou 2,4,6-cis diastereoselective synthesis (2 or 3 steps, 62-65% global yields) from Prins-cyclization reaction as synthetic key-step to tetrahydropyran rings construction of 10 new congeners compounds (3-12) designed from Naproxen structure. These tetrahydropyran derivatives were in vivo bioevaluated on antinociceptive effect in the acetic acid-induced abdominal writhing test, the tail-flick test, the rota-rod performance and open field tests. All new compounds showed greater antinociceptive activity compared to compound 1a, an analgesic tetrahydropyran derivative previously described by us. We can detach the high activity of tetrahydropyran derivative 10 which presented 87.5% inhibition (14% inhibition was presented by 1a) in the acetic acid-induced abdominal writhing test. Besides that the tail-flick tests indicate compounds 7 and 10 as the most actives. All these new compounds showed no toxicity in mice in all biologically studied models.

Micropropagation, antinociceptive and antioxidant activities of extracts of Verbena litoralis Kunth (Verbenaceae).

This work describes an efficient micropropagation protocol for Verbena litoralis and the study of the antinociceptive and antioxidant activities in extracts of this species. For the establishment in vitro, surface-sterilization procedures and PVPP showed high efficiency in fungal-bacterial contamination and phenol oxidation controls. Nodal segments cultivation in MS medium supplemented with 6-benzyladenine (7.5 µM)/α-naphthaleneacetic acid (NAA; 0.005 µM) induced multiple shoots. Elongated shoots were rooted with IAA (0.2 µM). Acclimatization rates were elevated and the plants showed the typical features of this species. The hexanic fraction (HF) of powdered leaves presented a radical scavenging activity with IC(50) = 169.3 µg mL(-1). HF showed a non-dose dependent analgesic activity in the writhing test; its antinociceptive activity in the hot plate test was restricted to 500 mg kg(-1), which is the highest dose. The results of this study showed the potential of tissue culture on conservation and large scale multiplication and confirmed the traditional folk medicine use of V. litoralis.

Effects of light intensity on the distribution of anthocyanins in Kalanchoe brasiliensis Camb. and Kalanchoe pinnata (Lamk.) Pers.

This paper compares two medicinal species of Kalanchoe, which are often used interchangeably by the population, regarding the distribution of anthocyanins under the influence of four luminosity levels for 6 months. For the morphoanatomical analysis, the 6th stem node of each plant was sectioned. Usual histochemical tests revealed the presence of anthocyanins by cross sections of the stems, petioles and leaf blades. The petioles and leaf blades were submitted to the extraction with acidified methanol, and the anthocyanins were quantified by spectrophotometric readings. At the macroscopic level, it was noticed for both species a higher presence of anthocyanins in stems and petioles of plants under full sunlight. The microscopy of K. brasiliensis stems evidenced the deposition of anthocyanins in the subjacent tissue to the epidermis and cortex, which increased with light intensity. In K. pinnata a subepidermal collenchyma was observed, which interfered in the visualization of anthocyanins. In petioles and leaf blades of K. brasiliensis the deposition of anthocyanins was peripheral, and in K. pinnata it was also throughout the cortex. The quantification of anthocyanins in petioles showed in 70% of light higher averages than in 25%, but in leaf blades there were no significant results. This study contributes to the pharmacognosy of Kalanchoe and it is sustained by the description of flavonoids as biological markers of the genus.

Clinical neurofunctional rehabilitation of a cat with spinal cord injury after hemilaminectomy and autologous stem cell transplantation.

Stem cell-based therapy has been investigated in a number of degenerative and traumatic diseases, including spinal cord injury. In the present study, we investigated the use of autologous mesenchymal stem cells in the functional rehabilitation of a domestic cat presenting a compressive L1-L5 fracture. Bone marrow cells collected by puncture of the iliac crest were cultured to obtain mesenchymal stem cells three weeks before surgery. Hemilaminectomy was performed, followed by injection of the mesenchymal stem cells in the injured area. Clinical evaluation of the animal prior to surgery showed absence of pain, muscular tonus, and panniculi reflexes. Seven days after surgery and cell transplantation the examination revealed a progressive recovery of the panniculus reflexes and of the responses to superficial and deep pain stimuli despite the low proprioceptive and hyperreflexic ataxic hind limbs. Physiotherapy protocols were applied for clinical rehabilitation after surgery. The cat's first steps, three-minute weight-bearing, and intestine and urinary bladder partial reestablishment were observed 75 days post-surgery. Our results indicate the therapeutic potential of mesenchymal stem cells in chronic spinal cord injuries.

Clinical Neurofunctional Rehabilitation of a Cat with Spinal Cord Injury after Hemilaminectomy and Autologous Stem Cell Transplantation

Stem cell-based therapy has been investigated in a number of degenerative and traumatic diseases, including spinal cord injury. In the present study, we investigated the use of autologous mesenchymal stem cells in the functional rehabilitation of a domestic cat presenting a compressive L1-L5 fracture. Bone marrow cells collected by puncture of the iliac crest were cultured to obtain mesenchymal stem cells three weeks before surgery. Hemilaminectomy was performed, followed by injection of the mesenchymal stem cells in the injured area. Clinical evaluation of the animal prior to surgery showed absence of pain, muscular tonus, and panniculi reflexes. Seven days after surgery and cell transplantation the examination revealed a progressive recovery of the panniculus reflexes and of the responses to superficial and deep pain stimuli despite the low proprioceptive and hyperreflexic ataxic hind limbs. Physiotherapy protocols were applied for clinical rehabilitation after surgery. The cat's first steps, three-minute weight-bearing, and intestine and urinary bladder partial reestablishment were observed 75 days post-surgery. Our results indicate the therapeutic potential of mesenchymal stem cells in chronic spinal cord injuries.

Soroprevalência de Maedi-Visna em ovinos na região de Araçatuba, SP / Occurrence of Maedi-visna in sheep from Araçatuba region - SP - Brazil

The seroprevalence of Maedi-Visna in sheep from Araçatuba region - SP, was determined and correlated to age, gender, breed, or sheep production systems. Blood samples were collected from 444 sheep, aging from two to 12 year-old. Both sexes and different breeds were sampled in 20 farms of this region. Physical examination was performed in all animals. Agar gel immunodiffusion test kit was used to diagnose in serum samples. Twelve animals, from five different farms, were AGID positive, yielding a seroprevalence of 2.7%, with no correlation among breed, gender, or sheep production systems and the detection of the disease. No animal considered positive for Maedi-Visna showed clinical signs compatible with Maedi-Visna.

Influence of light-curing sources on polymerization reaction kinetics of a restorative system.

PURPOSE: To determine the effect of using a variety of commercial light-curing units on polymerization of a dentin-bonding agent (Adper Single Bond) and of a resin composite (Filtek Z250). METHODS: Infrared (IR) spectra were obtained kinetically at one scan/second at 2 cm(-1) resolution for a period of 5 minutes and were analyzed for: maximum conversion rate (%/s), time into exposure when maximum rate occurred (seconds), conversion at maximum rate (%), and total conversion (%) at 300 seconds by comparison of aliphatic-to-aromatic absorption IR peak ratios, before and after polymerization. Light units used were: QTH 540 mW/cm2 (XL3000); LED 750 mW/cm2 (Elipar FreeLight 2); PAC 2,130 mW/cm2 (ARC II). Exposure followed manufacturers' recommendations: dentin bonding agent for 10 seconds, RC for 20 seconds (QTH), and 10 seconds (LED and PAC). Polymerization kinetics was evaluated at the bottom surface (2.5 mm thick) for the resin composite and as a thin film for the dentin bonding agent on the diamond surface of an attenuated total reflectance accessory in the IR spectrometer. Values (n = 5) were compared using ANOVA and Tukey's pairwise post-hoc test: pre-set alpha 0.05. RESULTS: PAC produced the highest total conversion and conversion rate for the resin composite (P < 0.05). Total conversion was lower for dentin bonding adhesive using PAC than with LED or QTH (P < 0.05). LED provided the highest proportion of conversion at the maximum rate with respect to conversion at 300 seconds for both materials. QTH demonstrated the lowest maximum rate value that occurred at a longer time into exposure (P < 0.05). Polymerization kinetic parameters varied greatly between the restorative materials as well as among light-curing unit types when compared to values observed when using a QTH light as control.

A new technique for assessing hybrid layer interfacial micromorphology and integrity: two-photon laser microscopy.

PURPOSE: This study describes a two-photon laser fluorescence microscopy technique developed to evaluate the interfacial micromorphology of the hybrid layer in bonded restorations. MATERIALS AND METHODS: Micropermeability of the hybrid layer was characterized by means of simultaneously contrasting a dye-containing adhesive with a differently colored dye placed into the pulp chamber and allowed to diffuse toward the different-colored hybrid layer. A fluorescent red dye (rhodamine B) was incorporated into a commercial dentin bonding agent. Class I preparations (margins in enamel) were made on extracted human third molars. The teeth were restored using conventional methods: bonding agent, composite, finishing, and polishing. An aqueous solution of a yellow/green dye (fluorescein) was then placed into the pulp chamber for 3 h, allowing time to diffuse toward the different-colored bonded interface. The teeth were then embedded, sectioned, and microscopically analyzed using two-photon laser microscopy at 40X magnification. RESULTS: Subsurface fluorescent imaging using this technique enabled interfacial micromorphology to be characterized at submicrometer resolution and provided high-contrast images. The quality of surrounding structures and potential presence of gaps were also precisely assessed. CONCLUSION: Two-photon laser microscopy provided high quality, high-resolution images of the bonded interface and surrounding areas, allowing accurate qualitative and quantitative analysis of the structure and integrity of the hybrid layer.

Factors affecting use of fluorescent agents in identification of resin-based polymers.

PURPOSE: The present study is a compilation of methodologies developed in order to evaluate the effects of addition of a fluorescent agent, rhodamine B, to resin-based materials. The intent of the work was to develop a systematic methodology that accounts for variables not shown to be of concern in past testing, but may significantly affect interpretation of the resulting images and material properties. MATERIALS AND METHODS: Different methodologies were specifically developed to evaluate factors affecting the use of the fluorescent agent rhodamine B in the identification of resin-based materials. The influence of dye concentration was evaluated with respect to adhesive polymerization reaction kinetics and bond strength of the resin into which the dye is added. The pH of the dye-solvent solution was also considered. Additionally, the mass and percentage of rhodamine B leached into different media over time was determined. RESULTS: It was demonstrated that a specific dye must be used with caution, and the concentration of a fluorescent agent is important with respect to both the conversion and bond strength of the resin to which the dye is added. An alcohol-based dye solution also produced an extremely high amount of dye leaching from polymerized specimens. The adhesive pH was not altered. CONCLUSION: The standardized methodology developed here to analyze restoration interfaces using a fluorescent dye can lessen the impact of variables when interpreting results.

Bond strength of resin-based restorations polymerized with different light-curing sources.

PURPOSE: To evaluate the influence of different light-curing units on microtensile bond strength of resin composite restorations. MATERIALS AND METHODS: Standardized Class I preparations (6.0 x 4.5 mm, 2.5 mm deep) were made in extracted human third molars after abrading the cusps. Resin was inserted in bulk using a 3M ESPE restorative system [Adper Single Bond (DBA)/ Filtek Z250 (RC)]. Both materials were polymerized using different light-curing units: QTH at 540 mW/cm(2) (XL 3000, 3M ESPE); LED at 750 mW/cm(2) (Elipar FreeLight2, 3M ESPE); PAC at 2130 mW/cm(2) (Arc Light II, Air Techniques). Nine different light combinations were developed to polymerize both DBA and RC: QTH/QTH; QTH/LED; QTH/PAC; LED/LED; LED/QTH; LED/PAC; PAC/PAC; PAC/QTH; PAC/LED. Restored teeth were stored in distilled water for 24 h at 37 degrees C and then sectioned, yielding stick-shaped specimens with a bonded area of approximately 0.9 mm(2). Specimens were assessed in a testing machine at a crosshead speed of 1 mm/min. The results were analyzed using two-way ANOVA and Tukey's test at a pre-set alpha = 0.05. RESULTS: The combinations PAC/QTH and QTH/QTH presented the highest bond strength values, and LED/QTH the lowest (p < 0.05). Significantly lower values were observed in combinations when the LED light was used to polymerize DBA compared to QTH and PAC lights, irrespective of the light source used to polymerize RC (p < 0.05). Same light combinations presented similar bond strength values. CONCLUSIONS: Different light sources influence restoration bond strength. Bond strength is more dependent on the light source used for DBA than for curing RC.

Use of fluorescent compounds in assessing bonded resin-based restorations: a literature review.

OBJECTIVES: This work reviews fundamental concepts involved with fluorescent imaging in the dental materials field. DATA: Fluorescent dyes have been widely used: incorporated into adhesive system components, placed in the pulp chamber and allowed to diffuse toward the restorative interface, as well as used as a visible tracer in microleakage tests. CONCLUSIONS: Although use of fluorescent imaging has substantially contributed to the existing knowledge base, there is no standardized methodology used, and as a result, interpretation of study results as well as comparison of results among studies remains questionable.

Evaluation of compatibility between different types of adhesives and dual-cured resin cement.

PURPOSE: The objective of this in vitro study was to evaluate the bonding compatibility between different adhesives and a dual-cured resin cement, using a conventional tensile bond test. MATERIALS AND METHODS: The adhesives used were: Prime & Bond (PB) (Dentsply) (PB), Scotchbond Multi Purpose (SB) (3M), and the activator Self Cure (SC) (Dentsply). The dual-curing resin cement used was Enforce (EF) (Dentsply). Six groups with five specimens in each were tested: G1: EF/PB/EF (light cured); G2: EF/SB/EF (light cured); G3: EF/PB+SC/EF (light cured); G4: EF/PB+SC/EF (only chemically cured); G5: EF/EF (light cured); G6: EF/EF (only chemically cured). The resin cement was applied in two stainless steel molds with a cone-shaped perforation measuring 4 mm in diameter and 1 mm in thickness, and the adhesive was applied between them. Ten minutes after specimens were cured, the tensile strength was measured in a universal testing machine at a crosshead speed of 0.5 mm/min. RESULTS: The mean values (MPa) +/- SD obtained in each experimental group were: G1: 1.4 +/- 0.2; G2: 1.3 +/- 0.2; G3: 1.2 +/- 0.4; G4: 0.8 +/- 0.2; G5: 1.2 +/- 0.1; G6: 0.7 +/- 0.1. The results were statistically evaluated using nonparametric Kruskal-Wallis and Dunn tests (p < or = 0.05). Statistically significant differences among groups were found only between G1 and G4, and G1 and G6. CONCLUSION: There was no incompatibility among the different adhesives used with dual-cured resin cement. The lowest tensile bond strength values occurred in the absence of photoactivation.

Fracture resistance of teeth directly and indirectly restored with composite resin and indirectly restored with ceramic materials.

PURPOSE: To evaluate the fracture resistance of teeth restored with direct and indirect restorations of composite resin and restored with indirect ceramic restorations. MATERIAL AND METHODS: Fifty-six maxillary premolar teeth were chosen and divided at random into seven equal groups; Group 1 (control): intact teeth; Group 2: MOD cavity preparations, 1/2 intercuspal distance, with rounded internal angles, convergent walls, unrestored; Group 3: MOD cavity preparations, 1/2 intercuspal distance, divergent walls; Group 4: same preparation as Group 2, restored with direct composite resin (Single Bond/Filtek Z250-3M); Group 5: same as Group 3, restored with indirect composite resin (Artglass/Single Bond/Rely X); Group 6: same as Group 3, restored with indirect composite resin (Targis/Single Bond/Rely X); Group 7: same as Group 3, restored with indirect ceramic restoration (Empress/Single Bond/Rely X). The specimens were subjected to a compressive axial loading in a Universal testing machine at 0.5 mm/minute by means of a steel bar (8 mm in diameter). RESULTS: The mean fracture strength obtained was: Group 1: 1.91 kN; Group 2: 1.06 kN; Group 3: 0.93 kN; Group 4: 1.45 kN; Group 5: 1.81 kN; Group 6: 1.81 kN; Group 7: 1.77 kN. The restored teeth with direct composite restoration increased the fracture resistance of Group 4 up to 76% of a level comparable with the intact teeth (Group 1). However, statistical analysis indicated no significant (P < 0.05) differences between Group 1 (intact teeth) and restored teeth groups, with direct restorations as well as indirect restorations. Both cavity preparation designs weakened the remaining tooth structure. These results demonstrated that a bonded indirect restoration could satisfactorily be an ideal option for restoring teeth weakened by wide cavity preparation.

Abscesso cerebelar por nocardia: relato de caso / Cerebellar abscess by Nocardia: a case report

A nocardiose do sistema nervoso central tem alcançado importante destaque no diagnóstico diferencial de patologias tumorais nos últimos anos pelo aumento da incidência de pacientes imunodeficiêntes (pacientes submetidos a quimioterapia, transplante de órgäos ou com a síndrome de imunodeficiência adquirida - SIDA. Os autores descrevem o caso de um paciente com SIDA que desenvolveu nocardiose cerebelar na sua forma tumoral. O paciente foi submetido a craniectomia de fossa posterior para diagnóstico e tratamento. Os achados de neuroimagem e patológicos bem como a conduta cirúrgica säo discutidos com base em revisäo da literatura

A study on the action of two calcium channel blockers (verapamil and flunarizine) upon an experimental model of tardive dyskinesia in rats

A discinesia tardia (DT) é complicaçäo decorrente do uso prolongado de neurolépticos. Até o presente, nenhum tratamento provou ser eficaz na DT. Evidências indiretas apontam para a açäo de drogas bloqueadoras de canais de cálcio (BCC) em algumas vias neurais. A açäo de duas dessas drogas, varapamil e flunarizina, foi testada em modelo experimental de DT em rato, neste estudo. O haloperidol foi administrado por 21 dias e induçäo de movimentos estereotipados era obtida no 24§ dia, com a injeçäo de apomorfina. As drogas BCC foram administradas por uma vez no 28§ dia (experimento agudo) e por 8 dias, após o 25§ dia (experimento crônico). A flunarizina näo induziu modificaçäo no padräo de estereotipia dos animais, mas o verapamil levou a aumento no experimento agudo e a diminuiçäo no experimento crônico. Estes achados indicam que as drogas BCC podem ter alguma açäo sobre a DT e que ensaios clínicos devem ser feitos para se comprovar se tal açäo ocorre no homem

Síndrome de Turcot: relato de dois casos / Turcot syndrome: report of 2 cases

Os autores descrevem dois pacientes com associaçäo de polipose intestinal e tumor do sistema nervoso central (síndrome de Turcot), discutindo aspectos clínicos, genéticos e terapêuticos