Chemokines and chemokine receptors coordinate the inflammatory immune response in human cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) includes different clinical manifestations displaying diverse intensities of dermal Inflammatory infiltrate Diffuse CL (DCL) cases are hyporesponsive and lesions show very few lymphocytes and a predominance of macrophages In contrast localized CL (LCL) cases are responsive to leishmanial antigen and lesions exhibit granulocytes and mononuclear cell infiltration in the early phases changing to a pattern with numerous lymphocytes and macrophages later in the lesion Therefore different chemokines may affect the predominance of cell infiltration in distinct clinical manifestations In lesions from LCL patients we examined by flow cytometry the presence of different chemokines and their receptors in T cells and we verified a higher expression of CXCR3 in the early stages of LCL (less than 30 days of infection) and a higher expression of CCR4 in the late stages of disease (more than 60 days of infection) We also observed a higher frequency of T cells producing IL-10 in the late stage of LCL Using immunohistochemistry we observed a higher expression of CCL7 CCL17 in lesions from late LCL as well as CCR4 suggesting a preferential recruitment of regulatory T cells in the late LCL Comparing lesions from LCL and DCL patients we observed a higher frequency of CCL7 in DCL lesions These results point out the Importance of the chemokines defining the different types of cells recruited to the site of the infection which could be related to the outcome of infection as well as the clinical form observed (C) 2010 American Society for Histocompatibility and Immunogenetics Published by Elsevier Inc All rights reserved

Anesthetic efficacy of inferior alveolar nerve block plus buccal infiltration or periodontal ligament injections with articaine in patients with irreversible pulpitis in the mandibular first molar

Objective. We compared the anesthetic efficacy of inferior alveolar nerve block (IANB) plus buccal infiltration (BI) and IANB plus periodontal ligament (PDL) articaine injections in patients with irreversible pulpitis in the mandibular first molar. Study design. Fifty-seven volunteers, patients with irreversible pulpitis in the mandibular first molar admitted to the Department of Stomatology, Second Affiliated Hospital, Sun Yat-Sen University, randomly received conventional IANB, containing 1.7 mL 4% articaine/HCl with 1:100,000 epinephrine, plus either BI or PDL injections containing 0.4 mL articaine/HCl with 1: 100,000 epinephrine. The patients recorded the pain of the injections and endodontic access on a Heft-Parker visual analog scale (VAS). Results. According to the VAS scores, all patients experienced no or mild pain with BI and PDL injections after the application of IANB. Anesthetic success occurred in 81.48% for IANB plus BI (IANB/BI) compared with 83.33% for IANB plus PDL injection (IANB/PDL injection). None of the observed differences between the 2 groups was significant (P > .05). Conclusion. Both injection combinations resulted in high anesthetic success in patients with irreversible pulpitis in the mandibular first molar. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:e89-e93)

Diagnosis and treatment of odontogenic cutaneous sinus tracts of endodontic origin: three case studies

To describe three cases of extraoral sinus tracts, related to infected teeth, which were initially misdiagnosed as skin lesions and inappropriately treated. The extraoral sinus tracts were initially misdiagnosed as skin lesions. Dermatological surgery was performed and antibiotics prescribed but the lesions did not resolve. Then, a dental cause was sought, and identified. Endodontic intervention resulted in resolution of the problem, confirming the initial misdiagnosis. center dot Dermatologists and other medical practitioners should be aware that dental extraoral sinus tracts can be confused with skin lesions. center dot A dental aetiology, as part of a differential diagnosis, should be kept in mind with oro-facial skin lesions. center dot If an extraoral sinus tract is of endodontic origin, then elimination of infection through effective endodontic treatment will lead to resolution of the sinus tract. center dot Early correct diagnosis can prevent unnecessary and ineffective antibiotic therapy and/or surgical intervention.

Interfacial evaluation of experimentally weakened roots restored with adhesive materials and fibre posts: An SEM analysis

Objectives: To evaluate the bonding interface in experimentally weakened roots reinforced with adhesive restorative materials and quartz fibre posts, varying the light-exposure time of the composite resin used for root reinforcement. Methods: Twelve extracted human maxillary incisors teeth were used. The crowns were removed and the roots were endodontically treated. After post space preparation, the roots were assigned to four groups. The thickness of the root dentine was reduced and adhesively restored with composite resin light-activated through a translucent fibre post for either 40 s (group 1), 80 s (group 2) or 120 s (group 3). In the case of control (group 4), the roots were not weakened. One day after post cementation, the specimens were sectioned transversally in three slices and processed for scanning electron microscopic analysis to observe bonding interface formation, quality of the hybrid layer and density of resin tags using a four-step scale method. Results: Formation of a hybrid layer and resin tags were evident in all groups. There was no statistically (p > 0.05) significant difference between the regions analysed in each group (Friedman test) and between groups in each section depth (Kruskal-Wallis test). Furthermore, comparison of the flared/reinforced groups showed that the different time;; used for composite resin cure did not affect the results significantly (Kruskal-Wallis test, p = 0.2139). Conclusions: Different light-exposure times used for composite resin polymerisation during root canal reinforcement did not affect significantly the formation and quality of the dentine/adhesive/composite resin bonding interface. (C) 2008 Elsevier Ltd. All rights reserved.

Effects of light exposure time on composite resin hardness after root reinforcement using translucent fibre post

Objectives: The purpose of this in vitro study was to evaluate the Vickers hardness (VHN) of a Light Core (Bisco) composite resin after root reinforcement, according to the light exposure time, region of intracanal reinforcement and lateral distance from the light-transmitting fibre post. Methods: Forty-five 17-mm long roots were used. Twenty-four hours after obturation, the root canals were emptied to a depth of 12 mm and the root dentine was artificially flared to produce a 1 mm space between the fibre post and the canal walls. The roots were bulk restored with the composite resin, which was photoactivated through the post for 40 s (G1, control), 80 s (G2) or 120 s (G3). Twenty-four hours after post-cementation, the specimens were sectioned transversely into three slices at depths of 2, 6 and 10 mm, corresponding to the coronal, middle and apical regions of the reinforced root. Composite VHN was measured as the average of three indentations (100 g/15 s) in each region at lateral distances of 50, 200 and 350 mu m from the cement/post-interface. Results: Three-way analysis of variance (alpha = 0.05) indicated that the factors time, region and distance influenced the hardness and that the interaction time x region was statistically significant (p = 0.0193). Tukey`s test showed that the mean VHN values for G1 (76.37 +/- 8.58) and G2 (74.89 +/- 6.28) differed significantly from that for G3 (79.5 +/- 5.18). Conclusions: Composite resin hardness was significantly lower in deeper regions of root reinforcement and in lateral areas distant from the post. Overall, a light exposure time of 120 s provided higher composite hardness than the shorter times (40 and 80 s). (C) 2008 Elsevier Ltd. All rights reserved.

Temporal relationship between the auditory brainstem response and focal responses of auditory nerve root and cochlear nucleus during development in the tammar wallaby (Macropus eugenii)

Thirty-two pouch-young tammar wallabies were used to discover the generators of the auditory brainstem response (ABR) during development by the use of simultaneous ABR and focal brainstem recordings. A click response from the auditory nerve root (ANR) in the wallaby was recorded from postnatal day (PND) 101, when no central auditory station was functional, and coincided with the ABR, a simple positive wave. The response of the cochlear nucleus (CN) was detected from PND 110, when the ABR had developed 1 positive and 1 negative peak. The dominant component of the focal ANR response, the N-1 wave, coincided with the first half of the ABR P wave, and that of the focal CN response, the N-1 wave, coincided with the later two thirds. In older animals, the ANR response coincided with the ABR's N-1, wave, while the CN response coincided with the ABR's P-2, N-2 and P-3 waves, with its contribution to the ABR P-2 dominant. The protracted development of the marsupial auditory system which facilitated these correlations makes the tammar wallaby a particularly suitable model. Copyright (C) 2001 S. Karger AG, Basel.

Neural influences on sprint running - Training adaptations and acute responses

Performance in sprint exercise is determined by the ability to accelerate, the magnitude of maximal velocity and the ability to maintain velocity against the onset of fatigue. These factors are strongly influenced by metabolic and anthropometric components. Improved temporal sequencing of muscle activation and/or improved fast twitch fibre recruitment may contribute to superior sprint performance. Speed of impulse transmission along the motor axon may also have implications on sprint performance. Nerve conduction velocity (NCV) has been shown to increase in response to a period of sprint training. However, it is difficult to determine if increased NCV is likely to contribute to improved sprint performance. An increase in motoneuron excitability, as measured by the Hoffman reflex (H-reflex), has been reported to produce a more powerful muscular contraction, hence maximising motoneuron excitability would be expected to benefit sprint performance. Motoneuron excitability can be raised acutely by an appropriate stimulus with obvious implications for sprint performance. However, at rest reflex has been reported to be lower in athletes trained for explosive events compared with endurance-trained athletes. This may be caused by the relatively high, fast twitch fibre percentage and the consequent high activation thresholds of such motor units in power-trained populations. In contrast, stretch reflexes appear to be enhanced in sprint athletes possibly because of increased muscle spindle sensitivity as a result of sprint training. With muscle in a contracted state, however, there is evidence to suggest greater reflex potentiation among both sprint and resistance-trained populations compared with controls. Again this may be indicative of the predominant types of motor units in these populations, but may also mean an enhanced reflex contribution to force production during running in sprint-trained athletes. Fatigue of neural origin both during and following sprint exercise has implications with respect to optimising training frequency and volume. Research suggests athletes are unable to maintain maximal firing frequencies for the full duration of, for example, a 100m sprint. Fatigue after a single training session may also have a neural manifestation with some athletes unable to voluntarily fully activate muscle or experiencing stretch reflex inhibition after heavy training. This may occur in conjunction with muscle damage. Research investigating the neural influences on sprint performance is limited. Further longitudinal research is necessary to improve our understanding of neural factors that contribute to training-induced improvements in sprint performance.

Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signaling pathways

We show here that the neurotrophin nerve growth factor (NGF), which has been shown to be a mitogen for breast cancer cells, also stimulates cell survival through a distinct signaling pathway. Breast cancer cell lines (MCF-7, T47-D, BT-20, and MDA-MB-231) were found to express both types of NGF receptors: p140(trkA) and p75(NTR). The two other tyrosine kinase receptors for neurotrophins, TrkB and TrkC, were not expressed. The mitogenic effect of NGF on breast cancer cells required the tyrosine kinase activity of p140(trkA) as well as the mitogen-activated protein kinase (MAPK) cascade, but was independent of p75(NTR). I, contrast, the anti-apoptotic effect of NGF (studied using the ceramide analogue C2) required p75(NTR) as well as the activation of the transcription factor NF-kB, but neither p140(trkA) nor MAPK was necessary. Other neurotrophins (BDNF, NT-3, NT-4/5) also induced cell survival, although not proliferation, emphasizing the importance of p75(NTR) in NGF-mediated survival. Both the pharmacological NF-KB inhibitor SN50, and cell transfection with IkBm, resulted in a diminution of NGF anti-apoptotic effect. These data show that two distinct signaling pathways are required for NGF activity and confirm the roles played by p75(NTR) and NF-kappaB in the activation of the survival pathway in breast cancer cells.

Transport of endosomal early antigen I in the rat sciatic nerve and location in cultured neurons

Early endosomal antigen I (EEAI) is known to be a marker of early endosomes and in cultured hippocampal neurons it preferentially localizes to the dendritic but not the axonal compartment. We show in cultured dorsal root ganglia and superior cervical ganglia neurons that EEAI localizes to the cell bodies and the neurites of both sensory and sympathetic neurons. We then show in vivo using a ligated rat sciatic nerve that EEAI significantly accumulates on the proximal side and not on the distal side of the ligation. This suggests that EEAI is transported in the anterograde direction in axons either as part of the homeostatic process or to the nerve ligation site in response to nerve injury. NeuroReport 12:281-284 (C) 2001 Lippincott Williams & Wilkins.

On a possible mechanism for peripheral nerve stimulation during magnetic resonance imaging scans

When patients undergo a magnetic resonance imaging scan, they are subject to both strong static and temporal magnetic fields. The temporal fields are designed to vary at each point in the region being imaged. This is achieved by the use of gradient coils. However, when the gradient coils are switched very rapidly, the strongly time-varying magnetic fields produced can be responsible for stimulating nerves in the peripheral regions of the body. This paper gives a somewhat novel explanation for this phenomenon. The physical mechanism suggested is supported by an illustrative theoretical calculation.

Nuclear PTEN expression and clinicopathologic features in a population-based series of primary cutaneous melanoma

Germline mutations of the PTEN tumor-suppressor gene, on 10q23, cause Cowden syndrome, an inherited hamartoma syndrome with a high risk of breast, thyroid and endometrial carcinomas and, some suggest, melanoma. To date, most studies which strongly implicate PTEN in the etiology of sporadic melanomas have depended on cell lines, short-term tumor cultures and noncultured metastatic melanomas. The only study which reports PTEN protein expression in melanoma focuses on cytoplasmic expression, mainly in metastatic samples. To determine how PTEN contributes to the etiology or the progression of primary cutaneous melanoma, we examined cytoplasmic and nuclear PTEN expression against clinical and pathologic features in a population-based sample of 150 individuals with incident primary cutaneous melanoma. Among 92 evaluable samples, 30 had no or decreased cytoplasmic PTEN protein expression and the remaining 62 had normal PTEN expression. In contrast, 84 tumors had no or decreased nuclear expression and 8 had normal nuclear PTEN expression. None of the clinical features studied, such as Clark's level and Breslow thickness or sun exposure, were associated with cytoplasmic PTEN expressional levels. An association with loss of nuclear PTEN expression was indicated for anatomical site (p = 0.06) and mitotic index (p = 0.02). There was also an association for melanomas to either not express nuclear PTEN or to express p53 alone, rather than both simultaneously (p = 0.02). In contrast with metastatic melanoma, where we have shown previously that almost two-thirds of tumors have some PTEN inactivation, only one-third of primary melanomas had PTEN silencing. This suggests that PTEN inactivation is a late event likely related to melanoma progression rather than initiation. Taken together with our previous observations in thyroid and islet cell tumors, our data suggest that nuclear-cytoplasmic partitioning of PTEN might also play a role in melanoma progression. (C) 2002 Wiley-Liss, Inc.

The adult ventral nerve cord as a phylogenetic character in brachyceran Diptera

Insect ganglia are often composed of fused segmental units or neuromeres. We estimated the evolution of the ventral nerve cord (VNC) in higher Diptera by comparing the patterns of neuromere fusion among 33 families of the Brachycera. Variation within families is uncommon, and VNC architecture does not appear to be influenced by body shape. The outgroup pattern, seen in lower Diptera, is fusion of neuromeres belonging to thoracic segments 1 and 2 (T1 and T2), and fusion of neuromeres derived from T3 and abdominal segment 1 (A1). In the abdomen, neuromeres A7-10 are fused into the terminal abdominal ganglion (TAG). Increased neuromere fusion is a feature of the Brachycera. No brachyceran shows less fusion than the outgroups. We established six pattern elements; (1) fusion of T1 and T2, (2) fusion of T3 and A1, (3) fusion of the T1/T2 andT3/A1 ganglia, (4) increase in the number of neuromeres comprising the TAG, (5) anteriorward fusion of abdominal neuromeres, and (6) the complete fusion of thoracic and abdominal neuromeres into a synganglion. States 1 and 2 are present in the outgroup lower Diptera, and state 3 in the Xylophagomorpha, Stratiomyomorpha, Tabanomorpha and Cyclorrhapha. State 4 is a feature of all Eremoneura. State 5 is present in Cyclorrhapha only, and state 6, fusion into a synganglion, has evolved at least 4 times in the Eremoneura. Synapomorphies are provided for the Cyclorrhapha and Muscoidea, and a grouping of three basal brachyceran infraorders Xylophagomorpha, Stratiomyomorpha and Tabanomorpha. The patterns of fusion suggest that VNC architecture has evolved irreversibly, in accordance with Dollo's law.