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1.
J Frailty Aging ; 12(3): 208-213, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37493381

RESUMO

BACKGROUND: In older people, frailty has been recognized as an important prognostic factor. However, only a few studies have focused on multidimensional frailty as a predictor of mortality and readmission among inpatients with pneumonia. OBJECTIVE: The present study aimed to assess the association between preadmission frailty and clinical outcomes after the hospitalization of older patients with pneumonia. DESIGN: Single-center, retrospective case-control study. SETTING: Acute phase hospital at Kobe, Japan. PARTICIPANTS: The present study included 654 consecutive older inpatients with pneumonia. MEASUREMENTS: Frailty status before admission was assessed using total Kihon Checklist (KCL) score, which has been used as a self-administered questionnaire to assess comprehensive frailty, including physical, social, and cognitive status. The primary outcome was a composited 6-month mortality and readmission after discharge. RESULTS: In total, 330 patients were analyzed (median age: 79 years, male: 70.4%, median total KCL score: 10 points), of which 68 were readmitted and 10 died within 6 months. After multivariate analysis, total KCL score was associated with a composited 6-month mortality and readmission (adjusted hazard ratio, 1.07; 95% confidence interval, 1.02-1.12; p = 0.006). The cutoff value for total KCL score determined by receiver operating characteristic curve analysis was 15 points (area under the curve = 0.610). The group with a total KCL score ≥ 15 points had significantly higher readmission or mortality rates than the groups with a total KCL score < 15 points (p < 0.001). CONCLUSIONS: Preadmission frailty status in older patients with pneumonia was an independent risk factor for readmission and survival after hospitalization.


Assuntos
Fragilidade , Pneumonia , Humanos , Masculino , Idoso , Fragilidade/diagnóstico , Idoso Fragilizado , Readmissão do Paciente , Estudos Retrospectivos , Estudos de Casos e Controles , Avaliação Geriátrica/métodos
2.
J Physiol Pharmacol ; 73(4)2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36696244

RESUMO

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic agents; however, it often causes intestinal mucositis with severe diarrhea. An efficient treatment strategy to reduce this side effect is lacking. Glutamate (Glu), a nonessential amino acid, is the most important energy source in the small intestine and has been shown to maintain intestinal morphology, barrier function, and antioxidative capacity. However, the effects of Glu on intestinal mucositis induced by chemotherapeutic agents have not been explored. This study aimed to demonstrate the alleviative effects of Glu on 5-FU-induced intestinal mucositis. Mucositis was induced in C57B/6N mice by intraperitoneal injection of 5-FU (50 mg/kg) for 6 days and assessed by histological and physiological analyses. Glu (500 or 1000 mg/kg) was orally administered as a pretreatment twice daily for 7 days before the initial treatment of 5-FU. Cellular proliferation and apoptosis were assessed using Ki-67 immunostaining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. Furthermore, fluorescein isothiocyanate-dextran infiltration was assessed to measure intestinal permeability. In vitro experiments using rat intestinal epithelial cells (IEC-6 cells) were performed to clarify the effect of Glu on 5-FU-induced barrier dysfunction. Glu alleviated 5-FU-induced intestinal mucositis by reducing villi shortening, enhancing cell proliferation, and suppressing apoptosis. It also alleviated the 5-FU-induced increased intestinal permeability. In vitro studies revealed significantly increased trans-epithelial electrical resistance (TEER) in Glu-pretreated IEC-6 cells compared to that in 5-FU-treated and control cells. In conclusion, the findings of this study provide evidence for the potential of Glu to protect against 5-FU-induced intestinal mucositis in patients with cancer.


Assuntos
Mucosite , Animais , Camundongos , Ratos , Antimetabólitos Antineoplásicos/toxicidade , Fluoruracila , Ácido Glutâmico/metabolismo , Mucosa Intestinal , Intestinos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/patologia
3.
Sci Adv ; 6(37)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917710

RESUMO

Understanding the precise atomic structure of ice surfaces is critical for revealing the mechanisms of physical and chemical phenomena at the surfaces, such as ice growth, melting, and chemical reactions. Nevertheless, no conclusive structure has been established. In this study, noncontact atomic force microscopy was used to address the characterization of the atomic structures of ice Ih(0001) and Ic(111) surfaces. The topmost hydrogen atoms are arranged with a short-range (2 × 2) order, independent of the ice thickness and growth substrates used. The electrostatic repulsion between non-hydrogen-bonded water molecules at the surface causes a reduction in the number of the topmost hydrogen atoms together with a distortion of the ideal honeycomb arrangement of water molecules, leading to a short-range-ordered surface reconstruction.

4.
J Dent Res ; 98(13): 1407-1417, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31746682

RESUMO

The field of neuroscience did not exist as such when the Journal of Dental Research was founded 100 y ago. It has emerged as an important scientific field relevant to dentistry in view of the many neurally based functions manifested in the orofacial area (e.g., pain, taste, chewing, swallowing, salivation). This article reviews many of the novel insights that have been gained through neuroscience research into the neural basis of these functions and their clinical relevance to the diagnosis and management of pain and sensorimotor disorders. These include the neural pathways and brain circuitry underlying each of these functions and the role of nonneural as well as neural processes and their "plasticity" in modulating these functions and allowing for adaptation to tissue injury and pain and for learning or rehabilitation of orofacial functions.


Assuntos
Odontologia/tendências , Neurociências/tendências , Humanos , Vias Neurais , Plasticidade Neuronal
6.
Oral Dis ; 24(6): 1093-1100, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29505690

RESUMO

OBJECTIVE: To examine whether transient receptor potential vanilloid 2 (TRPV2) contributes to the changes in intra-oral thermal and mechanical sensitivity following the incision of buccal mucosa. MATERIALS AND METHODS: Buccal mucosal pain threshold was measured after the incision. Changes in the number of TRPV2-immunoreactive (IR) trigeminal ganglion (TG) neurons which innervate the whisker pad skin and buccal mucosa, changes in the number of isolectin B4-negative/isolectin B4-positive TRPV2-IR TG neurons which innervate the whisker pad skin and the buccal mucosa, and the effect of peripheral TRPV2 antagonism on the pain threshold of incisional whisker pad skin and buccal mucosa were examined after these injuries. RESULTS: Buccal mucosal pain hypersensitivities were induced on day 3 following the incision. The total number of TRPV2-IR TG neurons and the number of isolectin B4-negative TRPV2-IR TG neurons which innervate the whisker pad skin and buccal mucosa were increased. Buccal mucosal TRPV2 antagonism completely suppressed the heat and mechanical hypersensitivities, but not cold hypersensitivity. TRPV2 antagonist administration to the incisional whisker pad skin only partially suppressed pain hypersensitivities. CONCLUSION: The increased expression of TRPV2 in peptidergic TG neurons innervating the incisional buccal mucosa is predominantly involved in buccal mucosal heat hyperalgesia and mechanical allodynia following buccal mucosal incision.


Assuntos
Dor/metabolismo , Canais de Cátion TRPV/fisiologia , Sensação Térmica , Tato , Animais , Masculino , Mucosa Bucal/cirurgia , Dor/etiologia , Limiar da Dor , Ratos , Ferida Cirúrgica/complicações , Canais de Cátion TRPV/metabolismo
7.
Clin Microbiol Infect ; 24(11): 1184-1189, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29408612

RESUMO

OBJECTIVES: To assess the effectiveness of short duration antimicrobial therapy for acute cholangitis with bacteraemia. METHODS: We conducted a retrospective cohort study of patients with acute bacteraemic cholangitis with successful biliary duct drainage at a single centre in Japan. We compared short-course antimicrobial therapy (SCT, ≤7 days) and long-course therapy (LCT, ≥8 days), with a primary outcome of 30-day mortality. We constructed logistic regression models for mortality and a composite outcome, including mortality, recurrence, recrudescence, new bacteraemia, liver abscess or other complications related to cholangitis. We also developed a propensity score for SCT with inverse probability weighting for both the primary outcome and the composite outcome. RESULTS: We identified 263 patients in our cohort; 86 (32.7%) patients received SCT and the remaining 177 (67.3%) received LCT. The median durations of SCT and LCT were 6 days (range 2-7 days) and 12 days (range 8-46 days), respectively. The 30-day mortalities of SCT and LCT were 4.7% (4/85) and 5.7% (10/176), respectively (p 1.00). Logistic regression analysis showed that the odds ratio of SCT for 30-day mortality and the composite outcome were 1.07 (95% CI 0.25-4.52, p 0.93) and 1.08 (95% CI 0.48-2.45, p 0.85), respectively. Propensity score analyses for both 30-day mortality and the composite outcome did not demonstrate a difference between SCT and LCT (p 0.65 and p 0.95, respectively). CONCLUSIONS: SCT with a median duration of 6 days did not have worse outcomes than LCT with a median duration of 12 days. Shortening the duration of antimicrobial therapy may be a reasonable option when treating acute bacteraemic cholangitis following successful biliary drainage.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Colangite/microbiologia , Colangite/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Estudos de Coortes , Drenagem , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
J Dent Res ; 97(4): 467-475, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29131694

RESUMO

Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1ß (IL-1ß) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation. The digastric muscle electromyogram (D-EMG) activity elicited by capsaicin administration into the maxillary second molar tooth pulp was analyzed to evaluate the noxious reflex and was significantly increased in rats with inflammation of the maxillary first molar (M1) versus rats injected with saline. A significant increase in the expression of connexin43 (Cx43), a gap junction containing protein, was observed in activated satellite glial cells surrounding second molar-innervating neurons in the TG after M1 pulpitis. Daily administration of Gap26, a Cx43 mimetic peptide and inhibitor, in the TG significantly suppressed the enhancement of capsaicin-induced D-EMG activity and the percentage of Fluoro-Gold (FG)-labeled cells encircled by glial fibrillary acid protein-immunoreactive (IR) + Cx43-IR cells after M1 pulp inflammation ( P < 0.01). The percentage of FG-labeled cells encircled by glial fibrillary acid protein-IR + IL-1ß-IR cells, IL-1 type I receptor-IR cells labeled with FG, and TRPV1-IR cells labeled with FG significantly increased after M1 pulp inflammation ( P < 0.01). Daily administration of IL-1ra, an IL-1 receptor antagonist, into the TG significantly reduced the enhancement of capsaicin-induced D-EMG activity and the percentage of TRPV1-IR neurons labeled with FG after M1 pulp inflammation ( P < 0.01). The present findings suggest that satellite glial cell is activated in the TG via activated gap junctions composed of Cx43 following tooth pulp inflammation, which leads to the hyperactivation of remote neurons via IL-1ß mechanisms and results in ectopic tooth pulp pain in the adjacent tooth.


Assuntos
Interleucina-1beta/farmacologia , Neuroglia/metabolismo , Neurônios/metabolismo , Pulpite/patologia , Gânglio Trigeminal/metabolismo , Animais , Capsaicina , Conexina 43/metabolismo , Eletromiografia , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Canais de Cátion TRPV/metabolismo
9.
Phys Chem Chem Phys ; 20(5): 2970-2975, 2018 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-28952630

RESUMO

Novel regioisomeric alkylated-naphthalene liquids were designed and synthesized. In the solvent-free liquid state, 1-alkyloxy regioisomers showed excimeric luminescence, whereas 2-alkyloxy analogues exhibited monomer-rich luminescence features. Correlations among the molecular structures and the photophysical, calorimetric, and rheological properties are presented, demonstrating the impact of regioisomerism on the alkylated-chromophore liquid systems.

10.
Int J Cosmet Sci ; 39(3): 275-283, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27731900

RESUMO

OBJECTIVE: Several studies have shown that a deterioration of skin properties, an impaired cutaneous microcirculatory function and an imbalance of autonomic nervous activity are observed in smokers and in patients with diabetes mellitus or Raynaud's phenomenon. These observations suggest that skin properties are associated with cutaneous microcirculatory function and autonomic nervous activity in pathological conditions. However, there is no published evidence to support the concept that these two functions have any relationship with skin properties even in healthy subjects. To investigate the hypothesis that these properties are related, we conducted a survey of healthy adult subjects to investigate the relationships between cutaneous microcirculatory function and autonomic nervous activity and skin properties. METHODS: The hydration of the stratum corneum and transepidermal water loss (TEWL) were investigated as skin properties, and the responsiveness of skin blood flow (SkBF) to local warming was examined as an index of cutaneous microcirculatory function in 19 healthy adult male subjects. Electrocardiograms were monitored for 24 h and heart rate variability was analysed considering low-frequency power (LF: 0.04-0.15 Hz), high-frequency power (HF: 0.15-0.40 Hz) and a ratio of low- to high-frequency power (LF/HF) as indices of autonomic nervous activity; HF is an index of parasympathetic activity, whereas LF/HF is an index of sympathovagal balance. The relationships between those indices were then analysed. RESULTS: A moderate negative correlation was found between TEWL and the relative maximum rate of increases in the responsiveness of SkBF on local warming. A moderate positive and a moderate negative correlation were observed between TEWL and LF/HF or HF, respectively. Moreover, a moderate negative and a moderate positive correlation were shown between the responsiveness of SkBF and LF/HF or HF, respectively. The hydration of the stratum corneum showed no correlations with any indices of microcirculation or autonomic nervous activity. CONCLUSION: These results indicate that skin barrier function, cutaneous microcirculatory function and autonomic nervous activity are mutually associated in healthy adults.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Água Corporal , Microcirculação , Pele/irrigação sanguínea , Adulto , Diabetes Mellitus/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Raynaud/fisiopatologia , Adulto Jovem
11.
J Dent Res ; 95(10): 1191-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27474258

RESUMO

It is well known that exposure to maternal separation (MS) in early life causes plastic changes in the nervous system in adulthood, occasionally resulting in ubiquitous chronic pain. However, the pathogenic mechanisms of pain hypersensitivity remain unclear. Here, the authors examined the involvement of corticosterone in orofacial mechanical hypersensitivity induced by MS. To establish a rat model of MS, pups were placed in isolated cages 180 min/d and kept in a temperature-controlled environment at 22 ± 2 °C for 14 d. Mechanical allodynia in the whisker pad skin in adulthood was induced by MS and was significantly suppressed by successive postnatal subcutaneous administration of the glucocorticoid receptor antagonist mifepristone. Corticosterone levels were increased in the serum of MS rats, and successive postnatal administration of subcutaneous corticosterone to naive rats induced mechanical allodynia in the whisker pad skin. The number of P2X3 receptor-immunoreactive (P2X3R-IR) trigeminal ganglion (TG) neurons innervating the whisker pad skin was significantly increased in MS rats and decreased following subcutaneous administration of mifepristone. The number of P2X3R-IR TG neurons innervating the whisker pad skin was also significantly increased following successive postnatal administration of subcutaneous corticosterone in naive rats. Moreover, the mechanical allodynia was suppressed 30 min after administration of the P2X3R antagonist A317491 to the whisker pad skin in MS rats. These findings suggest that the increase in P2X3R-IR TG neurons innervating the whisker pad skin via enhanced neonatal corticosterone signaling by MS plays an important role in orofacial mechanical allodynia in adulthood.


Assuntos
Dor Facial/patologia , Hiperalgesia/patologia , Privação Materna , Corticosteroides/sangue , Corticosteroides/farmacologia , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Dor Facial/metabolismo , Feminino , Hiperalgesia/metabolismo , Masculino , Mifepristona/farmacologia , Limiar da Dor , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P2X3/metabolismo , Gânglio Trigeminal/metabolismo , Gânglio Trigeminal/patologia , Vibrissas/inervação
12.
J Dent Res ; 95(10): 1176-82, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27151915

RESUMO

To elucidate if microglial P2Y12 receptor (P2Y12R) mechanisms are involved in the trigeminal spinal subnucleus caudalis (Vc; also known as the medullary dorsal horn) in intraoral cancer pain, we developed a rat model of tongue cancer pain. Squamous cell carcinoma (SCC) cells were inoculated into the tongue of rats; sham control rats received the vehicle instead. Nociceptive behavior was measured as the head-withdrawal reflex threshold (HWRT) to mechanical or heat stimulation applied to the tongue under light anesthesia. On day 14 after the SCC inoculation, activated microglia and P2Y12R expression were examined immunohistochemically in the Vc. The HWRT was also studied in SCC-inoculated rats with successive intra-cisterna magna (i.c.m.) administration of specific P2Y12R antagonist (MRS2395) or intraperitoneal administration of minocycline, a microglial activation inhibitor. Tongue cancer was histologically verified in SCC-inoculated rats, within which the HWRT to mechanical stimulation of the tongue was significantly decreased, as compared with that of vehicle-inoculated rats, although the HWRT to heat stimulation was not. Microglia was strongly activated on day 14, and the administration of MRS2395 or minocycline reversed associated nocifensive behavior and microglial activation in SCC-inoculated rats for 14 d. The activity of Vc wide dynamic range nociceptive neurons was also recorded electrophysiologically in SCC-inoculated and sham rats. Background activity and noxious mechanically evoked responses of wide dynamic range neurons were significantly increased in SCC-inoculated rats versus sham rats, and background activity and mechanically evoked responses were significantly suppressed following i.c.m. administration of MRS2395 in SCC-inoculated rats as compared with sham. The present findings suggest that SCC inoculation that produces tongue cancer results in strong activation of microglia via P2Y12 signaling in the Vc, in association with increased excitability of Vc nociceptive neurons, reflecting central sensitization and resulting in tongue mechanical allodynia.


Assuntos
Dor do Câncer/metabolismo , Carcinoma de Células Escamosas/metabolismo , Microglia/metabolismo , Neuralgia/metabolismo , Receptores Purinérgicos P2Y12/metabolismo , Neoplasias da Língua/metabolismo , Núcleo Espinal do Trigêmeo/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Imuno-Histoquímica , Masculino , Minociclina/farmacologia , Nociceptores/metabolismo , Ratos , Ratos Endogâmicos F344 , Transdução de Sinais , Valeratos/farmacologia
13.
Int J Tuberc Lung Dis ; 19(8): 918-20, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26162357

RESUMO

We conducted a retrospective comparative study of acid-fast bacilli (AFB) smear sensitivity according to time of specimen collection to assess whether three consecutive AFB smears collected in 1 day are useful when deciding to discontinue respiratory isolation of patients with pulmonary tuberculosis (TB). A total of 236 sputum specimens from 119 patients with pulmonary TB were used for the analysis. There was no statistical difference in AFB smear sensitivity of early-morning sputum and those collected later (P = 0.186). This may allow us to collect all specimens in a single day and discontinue respiratory isolation of TB patients earlier.


Assuntos
Isolamento de Pacientes , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Idoso , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Manejo de Espécimes , Fatores de Tempo
14.
J Dent Res ; 94(3): 446-54, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25576470

RESUMO

Thermal and mechanical hypersensitivity in the injured region is a common complication. Although it is well known clinically that thermal and mechanical sensitivity of the oral mucosa is different from that of the skin, the mechanisms underlying injured pain of the oral mucosa remain poorly understood. The transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) in primary afferent neurons are known to contribute to pathological pain. Therefore, we investigated whether TRPV1 and/or TRPA1 contribute to thermal and mechanical hypersensitivity following oral mucosa or whisker pad skin incision. Strong heat and mechanical and cold hypersensitivity was caused in the buccal mucosa and whisker pad skin following incisions. On day 3 after the incisions, the number of TRPV1-immunoreactive (IR) and TRPA1-IR trigeminal ganglion (TG) neurons innervating the buccal mucosa and whisker pad skin was significantly increased, and the number of TRPV1/TRPA1-IR TG neurons innervating whisker pad skin, but not the buccal mucosa, was significantly increased. Administration of the TRPV1 antagonist, SB366791, to the incised site produced a significant suppression of heat hyperalgesia in both the buccal mucosa and whisker pad skin, as well as mechanical allodynia in the whisker pad skin. Administration of the TRPA1 antagonist, HC-030031, to the incised site suppressed mechanical allodynia and cold hyperalgesia in both the buccal mucosa and whisker pad skin, as well as heat hyperalgesia in the whisker pad skin. These findings indicate that altered expressions of TRPV1 and TRPA1 in TG neurons are involved in thermal and mechanical hypersensitivity following the buccal mucosa and whisker pad skin incision. Moreover, diverse changes in the number of TRPV1 and TRPA1 coexpressed TG neurons in whisker pad skin-incised rats may contribute to the intracellular interactions of TRPV1 and TRPA1 associated with whisker pad skin incision, whereas TRPV1 and TRPA1 expression in individual TG neurons is involved in buccal mucosa-incised pain.


Assuntos
Dor Facial/fisiopatologia , Mucosa Bucal/lesões , Dor/fisiopatologia , Canais de Cátion TRPC/fisiologia , Canais de Cátion TRPV/fisiologia , Acetanilidas/farmacologia , Anilidas/farmacologia , Animais , Cinamatos/farmacologia , Temperatura Baixa , Eletromiografia/métodos , Temperatura Alta , Hiperalgesia/fisiopatologia , Masculino , Mucosa Bucal/inervação , Neurônios/citologia , Neurônios/fisiologia , Purinas/farmacologia , Ratos , Ratos Sprague-Dawley , Canal de Cátion TRPA1 , Canais de Cátion TRPC/análise , Canais de Cátion TRPC/antagonistas & inibidores , Canais de Cátion TRPV/análise , Canais de Cátion TRPV/antagonistas & inibidores , Gânglio Trigeminal/fisiopatologia , Vibrissas/lesões , Vibrissas/inervação
15.
Eur J Pain ; 19(9): 1258-66, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25523341

RESUMO

BACKGROUND: It is important to know the mechanisms underlying pain abnormalities associated with inferior alveolar nerve (IAN) regeneration in order to develop the appropriate treatment for orofacial neuropathic pain patients. However, peripheral mechanisms underlying orofacial pain abnormalities following IAN regeneration are not fully understood. METHODS: Head withdrawal threshold (HWT), jaw opening reflex (JOR) thresholds, single-fibre recordings of the regenerated mental nerve (MN) fibres, calcitonin gene-related peptide (CGRP), isolectin B4 (IB4), peripherin, neurofilament-200 (NF-200) and transient receptor potential vanilloid 1 (TRPV1) expression in trigeminal ganglion (TG) cells, and electron microscopic (EM) observations of the regenerated MN fibres were studied in MN- and IAN-transected (M-IANX) rats. RESULTS: HWT to mechanical or heat stimulation of the mental skin was significantly lower in M-IANX rats compared with sham rats. Mean conduction velocity of action potentials recorded from MN fibres (n = 124) was significantly slower in M-IANX rats compared with sham rats. The percentage of Fluoro-Gold (FG)-labelled CGRP-, peripherin- or TRPV1-immunoreactive (IR) cells was significantly larger in M-IANX rats compared with that of sham rats, whereas that of FG-labelled IB4- and NF-200-IR cells was significantly smaller in M-IANX rats compared with sham rats. Large-sized myelinated nerve fibres were rarely observed in M-IANX rats, whereas large-sized unmyelinated nerve fibres were frequently observed and were aggregated in the bundles at the distal portion of regenerated axons. CONCLUSIONS: These findings suggest that the demyelination of MN fibres following regeneration may be involved in peripheral sensitization, resulting in the orofacial neuropathic pain associated with trigeminal nerve injury.


Assuntos
Dor Facial , Nervo Mandibular , Fibras Nervosas , Regeneração Nervosa/fisiologia , Traumatismos do Nervo Trigêmeo , Vias Aferentes/metabolismo , Vias Aferentes/patologia , Vias Aferentes/fisiopatologia , Animais , Modelos Animais de Doenças , Dor Facial/etiologia , Dor Facial/metabolismo , Dor Facial/fisiopatologia , Masculino , Nervo Mandibular/metabolismo , Nervo Mandibular/patologia , Nervo Mandibular/fisiopatologia , Fibras Nervosas/metabolismo , Fibras Nervosas/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismos do Nervo Trigêmeo/complicações , Traumatismos do Nervo Trigêmeo/metabolismo , Traumatismos do Nervo Trigêmeo/patologia , Traumatismos do Nervo Trigêmeo/fisiopatologia
16.
J Dent Res ; 92(12): 1113-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24130220

RESUMO

Inferior alveolar nerve (IAN) injury induces persistent ectopic pain which spreads to a wide area in the orofacial region. Its exact mechanism remains unclear. We investigated the involvement of nitric oxide (NO) in relation to ectopic orofacial pain caused by IAN transection (IANX). We assessed the changes in mechanical sensitivity of the whisker pad skin following IANX, neuronal nitric oxide synthase (nNOS) expression in the trigeminal ganglion (TG), and the functional significance of NO in relation to the mechanical allodynia following intra-TG administration of a chemical precursor to NO and selective nNOS inhibitors. IANX induced mechanical allodynia, which was diminished by intra-TG administration of selective nNOS inhibitors. NO metabolites and nNOS immunoreactive neurons innervating the lower lip were also increased in the TG. Intra-TG administration of nNOS substrate induced the mechanical allodynia. The present findings suggest that NO released from TG neurons regulates the excitability of TG neurons innervating the whisker pad skin, and the enhancement of TG neuronal excitability may underlie ectopic mechanical allodynia.


Assuntos
Dor Facial/etiologia , Nervo Mandibular/fisiopatologia , Neuralgia/etiologia , Óxido Nítrico/fisiologia , Transdução de Sinais/fisiologia , Traumatismos do Nervo Trigêmeo/complicações , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Inibidores Enzimáticos/farmacologia , Precursores Enzimáticos/farmacologia , Hiperalgesia/etiologia , Indazóis/farmacologia , Lábio/inervação , Masculino , Nervo Mandibular/patologia , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Óxido Nítrico/análise , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/análise , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Limiar da Dor/fisiologia , Ratos , Ratos Sprague-Dawley , Limiar Sensorial/fisiologia , Transdução de Sinais/efeitos dos fármacos , Tato/fisiologia , Gânglio Trigeminal/efeitos dos fármacos , Gânglio Trigeminal/patologia
17.
Phys Rev Lett ; 111(1): 015001, 2013 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-23863005

RESUMO

We report the first observation of 3-30 MeV prolonged gamma-ray emission that was abruptly terminated by lightning. The gamma-ray detection was made during winter thunderstorms on December 30, 2010, by the Gamma-Ray Observation of Winter Thunderclouds experiment carried out in a coastal area along the Sea of Japan. The gamma-ray flux lasted for less than 3 min, continuously hardening closer to the lightning occurrence. The hardening at energies of 3-10 MeV energies was most prominent. The gamma-ray flux abruptly ceased less than 800 ms before the lightning flash that occurred over 5 km away from the experimental site. In addition, we observed a clear difference in the duration of the 3-10 MeV gamma rays and those >10 MeV, suggesting that the area of >10 MeV gamma-ray emission is considerably smaller than that of the lower-energy gamma rays. This work may give a manifestation that a local region emitting prolonged gamma rays connects with a distant region to initiate lightning.

18.
J Dent Res ; 92(5): 456-60, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23520364

RESUMO

The exact mechanism underlying chronic masseter muscle pain, a conspicuous symptom in temporomandibular disorder, remains unclear. We investigated whether expression of P2X3 receptor (P2X3R) is involved in mechanical hyperalgesia after contraction of masseter muscle (CMM). As compared with sham rats, the head-withdrawal threshold (HWT) to mechanical pressure stimulation of masseter muscle (MM) (but not after similar stimulation of facial skin) was significantly lower, and IL-1ß level was significantly higher, in CMM rats on day 7 after CMM. The mean percentage of FG-labeled P2X3R-positive neurons was significantly increased in TG following successive IL-1ß injections into the MM for 7 days. Successive administration of an IL-1ß receptor-antagonist into the MM attenuated the increase of P2X3-IR cells in the TG. ATP release from MM after 300-g pressure stimulation of MM was also significantly enhanced after CMM. Administration into MM of the selective P2X3,2/3 receptor antagonist A-317491 attenuated the decrement of HWT in CMM rats. A significant increase in HWT was also observed at 30 min after A-317491 (60 µg) injection in IL-1ß-injected rats. These findings suggest that P2X3R expression associated with enhanced IL-1ß expression and ATP release in MM has a possible important role in MM mechanical hyperalgesia after excessive muscular contraction.


Assuntos
Neuralgia Facial/metabolismo , Interleucina-1beta/metabolismo , Músculo Masseter/metabolismo , Contração Muscular/fisiologia , Receptores Purinérgicos P2X3/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Estimulação Elétrica , Neuralgia Facial/complicações , Neuralgia Facial/fisiopatologia , Hiperalgesia/complicações , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Músculo Masseter/fisiopatologia , Antagonistas do Receptor Purinérgico P2X/farmacocinética , Ratos , Ratos Sprague-Dawley , Tempo de Reação/fisiologia , Receptores de Interleucina/antagonistas & inibidores , Receptores Purinérgicos P2X3/efeitos dos fármacos , Síndrome da Disfunção da Articulação Temporomandibular/complicações , Síndrome da Disfunção da Articulação Temporomandibular/metabolismo , Síndrome da Disfunção da Articulação Temporomandibular/fisiopatologia
19.
J Dent Res ; 91(12): 1141-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23018815

RESUMO

Discomfort and pain encountered during orthodontic treatment are major problems for patients, but the details of the underlying neural processes and molecular mechanisms are not well-understood. Here we show that noxious tooth mechanical pressure induced by orthodontic elastics resulted in a rapid and transient activation of extracellular signal-regulated protein kinase (ERK) in the trigeminal spinal subnucleus interpolaris and caudalis transition zone (Vi/Vc), trigeminal spinal subnucleus caudalis (Vc), and upper cervical spinal cord (Vc/C2). The phosphorylated ERK (pERK) was observed in neurons but not in astroglia and microglia. Single-plane scanning analysis indicated that the pERK was localized to the nucleus of Vc neurons. In addition, the tooth mechanical pressure led to Fos expression in the pERK-positive Vc neurons that would be suppressed by intrathecal administration of an MEK1/2 inhibitor (PD98059). Taken together, these findings suggest that activation of the ERK signaling cascade following noxious mechanical pressure on the teeth regulates Fos expression in Vc neurons and may thereby contribute to pain associated with orthodontic treatment.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Técnicas de Movimentação Dentária , Núcleos do Trigêmeo/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Dor/metabolismo , Pressão , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Estresse Mecânico , Núcleos do Trigêmeo/citologia
20.
Acta Biol Hung ; 63(3): 389-98, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22963919

RESUMO

The effects of the mycotoxin patulin on the thermodynamics and kinetics of the transition of bovine serum albumin (BSA) in aqueous solution were studied by Differential Scanning Calorimetry and Photoluminescence methods. Results show that in the presence of patulin, the free enthalpy change during the transition of BSA was decreased by an average of ∼ 46 kJ/mol, the free energy change was decreased by ∼ 4 kJ/mol, and the activation energy fell from ∼ 1546 to ∼ 840 kJ/mol. These results indicate that the bioactivity of patulin is based on the kinetic rather than on the thermodynamic properties of the transition. This is the first evidence of the direct interaction of patulin with the free thiol-containing BSA, a process which could contribute to the adverse cyto- and genotoxic effects induced by patulin.


Assuntos
Patulina/química , Venenos/química , Desnaturação Proteica , Soroalbumina Bovina/química , Animais , Bovinos , Cinética , Termodinâmica
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