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1.
Neurochem Int ; 175: 105723, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490486

RESUMO

Impaired olfactory function may be associated with the development of psychiatric disorders such as depression and anxiety; however, knowledge on the mechanisms underlying psychiatric disorders is incomplete. A reversible model of olfactory dysfunction, zinc sulfate (ZnSO4) nasal-treated mice, exhibit depression-like behavior accompanying olfactory dysfunction. Therefore, we investigated olfactory function and depression-like behaviors in ZnSO4-treated mice using the buried food finding test and tail suspension test, respectively; investigated the changes in the hippocampal microglial activity and neurogenesis in the dentate gyrus by immunohistochemistry; and evaluated the inflammation and microglial polarity related-proteins in the hippocampus using western blot study. On day 14 after treatment, ZnSO4-treated mice showed depression-like behavior in the tail suspension test and recovery of the olfactory function in the buried food finding test. In the hippocampus of ZnSO4-treated mice, expression levels of ionized calcium-binding adapter molecule 1 (Iba1), cluster of differentiation 40, inducible nitric oxide synthase, interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, cleaved caspase-3, as well as the number of Iba1-positive cells and cell body size increased, and arginase-1 expression and neurogenesis decreased. Except for the increased IL-6, these changes were prevented by a microglia activation inhibitor, minocycline. The findings suggest that neuroinflammation due to polarization of M1-type hippocampal microglia is involved in depression accompanied with olfactory dysfunction.


Assuntos
Depressão , Transtornos do Olfato , Humanos , Camundongos , Animais , Depressão/metabolismo , Microglia/metabolismo , Interleucina-6/metabolismo , Hipocampo/metabolismo
2.
Neurosci Lett ; 825: 137711, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38432356

RESUMO

The gut microbiota is associated with memory; however, the relationship between dysbiosis-induced memory deficits and hippocampal glutamatergic neurons remains unclear. In our study, a mouse dysbiosis model showed impaired memory-related behavior in the passive avoidance test; decreased expression levels of glutaminase, excitatory amino acid transporter (EAAT)1, EAAT2, vesicular glutamate transporter 2, synaptophysin, brain-derived neurotrophic factor, doublecortin, neuronal nuclear protein, glial fibrillary acidic protein, and S100ß; and decreased phosphorylation of N-methyl-D-aspartate receptor subunit 1, calmodulin-dependent protein kinase II, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 1, and cAMP response element-binding protein in the hippocampus. This suggests that dysbiosis-induced memory dysfunction is associated with the hippocampal glutamatergic nervous system.


Assuntos
Antibacterianos , Disbiose , Camundongos , Animais , Disbiose/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transportador 1 de Aminoácido Excitatório/metabolismo
3.
Laryngoscope Investig Otolaryngol ; 9(1): e1204, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362198

RESUMO

Objective: Patients lose their voice after laryngectomy for laryngeal cancer or aspiration prevention surgery for severe dysphagia. To assist such patients, we developed and verified the utility of a novel vocalization method using a device termed the voice retriever (VR), in which the sound source is placed in the mouth. Methods: We investigated the effectiveness of the VR in patients. The VR consists of a mouthpiece with a built-in speaker and a dedicated application that serves as the sound source. We compared the speech intelligibility and naturalness in normal participants using VR and an electrolarynx (EL) for the first time as well as the voice-related quality of life (V-RQOL) in patients with dysphonia before and after using the VR. Results: The VR produced significantly higher 100-syllable test scores as well as fluency, amount of additional noise, intonation, intelligibility and overall long reading test ratings in the first-time VR and EL users. Furthermore, the VR use significantly improved the V-RQOL of participants with dysphonia. Conclusion: Compared to EL, VR allows more effective speech improvement in participants without experience using an alternative vocalization method and improves the V-RQOL in patients with dysphonia. Level of Evidence: Step 4.

4.
J Am Chem Soc ; 146(4): 2419-2425, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38060439

RESUMO

In this work, we developed a nickel-catalyzed transfer hydrogenolysis of 1-aryloxy-3-amino-2-propanols, which is a model compound of an amine-cured bisphenol A (BPA)-based epoxy resin. Mechanistic investigation revealed that the hydroxy group acts as the hydrogen donor to generate α-aryloxy ketone, which undergoes an unprecedented remote-concerted oxidative addition of the C(sp3)-O bond as suggested by DFT calculation. Successful application of this method was demonstrated by the degradation of a diamine-cured BPA-based epoxy resin, in which BPA was directly recovered from the resin.

5.
Environ Microbiol Rep ; 16(1): e13221, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38037543

RESUMO

Denitrification in oxic environments occurs when a microorganism uses nitrogen oxides as terminal electron acceptors even though oxygen is available. While this phenomenon is well-established, its consequences on ecological and evolutionary processes remain poorly understood. We hypothesize here that denitrification in oxic environments can modify the accumulation profiles of nitrogen oxide intermediates with cascading effects on the evolutionary potentials of denitrifying microorganisms. To test this, we performed laboratory experiments with Paracoccus denitrificans and complemented them with individual-based computational modelling. We found that denitrification in low oxic environments significantly increases the accumulation of nitrite and nitric oxide. We further found that the increased accumulation of these intermediates has a negative effect on growth at low pH. Finally, we found that the increased negative effect at low pH increases the number of individuals that contribute to surface-associated growth. This increases the amount of genetic diversity that is preserved from the initial population, thus increasing the number of genetic targets for natural selection to act upon and resulting in higher evolutionary potentials. Together, our data highlight that denitrification in low oxic environments can affect the ecological processes and evolutionary potentials of denitrifying microorganisms by modifying the accumulation of nitrogen oxide intermediates.


Assuntos
Desnitrificação , Óxido Nítrico , Humanos , Nitritos , Óxido Nitroso , Nitrogênio
6.
Artigo em Inglês | MEDLINE | ID: mdl-38097062

RESUMO

The Japanese mitten crab Eriocheir japonica inhabits rivers throughout Japan and is being cultivated for food. To conduct aquaculture efficiently, it is crucial to comprehend the physiological functions of the target organisms. However, there is a lack of fundamental information on Japanese mitten crabs. In this study, hydrolases were extracted from the midgut glands of Japanese mitten crabs and their metabolic activities were analyzed. An enzyme with hydrolytic activity was discovered within the cytosol of the midgut gland. Western blot analysis also revealed that the Japanese mitten crab contains a hydrolase with cross-reactivity to human carboxylesterase 1 (hCES1) antibodies. The substrate specificity of the S9 fraction of the midgut gland was investigated and, interestingly, it was revealed that it reacts well with indomethacin phenyl ester and fluorescein diacetate, which are substrates of hCES2, not substrates of hCES1. Furthermore, this enzyme was observed to metabolize the ester derivative of astaxanthin, which is a red pigment inherent to the Japanese mitten crab. These findings underscore the significance the midgut gland in the Japanese mitten crab as an important organ for metabolizing both endogenous and exogenous ester-type compounds.


Assuntos
Braquiúros , Hidrolases , Humanos , Animais , Japão , Alimentos Marinhos , Rios , Ésteres
7.
Exp Neurol ; 373: 114671, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160982

RESUMO

Patients with inflammatory bowel disease, including ulcerative colitis (UC) and Crohn's disease, have a high incidence of psychiatric disorders, including depression and anxiety. However, the underlying pathogenic mechanism remains unknown. Dextran sulfate sodium (DSS)-treated mice, a model of UC, exhibit depressive-like behavior and reduced adenosine monophosphate-activated protein kinase (AMPK) activity, which regulates various physiological functions in the brain and gut. However, comprehensive studies on UC pathophysiology with co-occurring depression focused on brain-gut AMPK activity are lacking. Therefore, we aimed to investigate whether resveratrol (RES), an AMPK activator, prevented DSS-induced UC-like symptoms and depressive-like behavior. DSS treatment induced UC-like pathology and depressive-like behavior, as assessed via the tail suspension test. Moreover, western blotting and immunohistochemical studies revealed that DSS increased p-p70S6 kinase (Thr389), p62, tumor necrosis factor-α, interleukin (IL)-1ß, IL-18, NLR family pyrin domain containing 3 (NLRP3), cleaved caspase-1, cleaved Gasdermin-D (GSDMD), and cleaved caspase-3 expression levels in the rectum and hippocampus, and increased CD40, iNOS, and Kelch-like ECH-associated protein 1 expression levels, and the number of Iba1-positive cells in the hippocampus, and decreased p-AMPK and LC3II/I expression levels, and the number of NF-E2-related factor 2 (Nrf2)-positive cells, and reduced neurogenesis in the hippocampus. These changes were reversed by the RES administration. RES also enhanced PGC1α and SOD1 expression in the hippocampus of DSS-treated male mice. Moreover, NLRP3 staining was observed in the neurons and microglia, and cleaved GSDMD staining in neurons in the hippocampus of DSS-treated mice. Notably, RES prevented UC-like pathology and depressive-like behavior and enhancement of autophagy, decreased rectal and hippocampal inflammatory cytokines and inflammasome, and induced the Nrf2-PGC1α-SOD1 pathway in the hippocampus, resulting in neurogenesis in the hippocampal dentate gyrus. Our findings suggest that brain-gut AMPK activation may be an important therapeutic strategy in patients with UC and depression.


Assuntos
Colite Ulcerativa , Colite , Enterocolite , Humanos , Masculino , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Superóxido Dismutase-1/metabolismo , Encéfalo/metabolismo , Inflamassomos/metabolismo , Enterocolite/patologia , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/patologia , Modelos Animais de Doenças
8.
Spine Surg Relat Res ; 7(6): 526-532, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38084213

RESUMO

Introduction: Three-dimensional (3D) magnetic resonance imaging (MRI) is reportedly superior to two-dimensional (2D) MRI for diagnosing lumbar foraminal stenosis at L5-S1. In this study, we strictly distinguished the intra- and extraforaminal regions and compared the diagnostic reliability and accuracy of 2D and 3D MRI in each region. Methods: A total of 92 surgical cases of unilateral L5 radiculopathy were selected for imaging analysis, including 46 of foraminal stenosis at L5-S1 (Group F) and 46 of intraspinal canal stenosis at L4-5 (Group C) (48 men, 44 women; mean age, 66 years). The 2D and 3D MRI sets were assessed twice by two examiners. They were informed only of the laterality of the lesion in each case and asked to select among the following for each modality: "absence of foraminal stenosis," "intraforaminal stenosis," "extraforaminal stenosis," and "coincident intraforaminal and extraforaminal stenosis." The intra- and interobserver reliabilities were evaluated using kappa (κ) statistics for the intra- and extraforaminal regions and compared between 2D and 3D MRI. For each case, disagreements between examiners were resolved through discussion to obtain a diagnostic judgment for each modality. Subsequently, the final diagnosis of intra- and/or extraforaminal stenosis in Group F was made using multiple modalities and intraoperative findings. A comparison between 2D and 3D MRI in terms of diagnostic accuracy was performed for the intra- and extraforaminal regions. Results: No significant difference was observed in the κ statistics between 2D and 3D MRI for the intraforaminal region, whereas 3D MRI had significantly larger κ statistic than 2D MRI for the extraforaminal region. Ultimately, 3D MRI perfectly judged the extraforaminal region, whereas 2D MRI detected only 44.8% of the cases of extraforaminal stenosis. Conclusions: More than half of extraforaminal stenosis was overlooked by 2D MRI, suggesting that it is unreliable for diagnosing extraforaminal stenosis at L5-S1.

9.
Spine Surg Relat Res ; 7(5): 436-442, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37841035

RESUMO

Introduction: Imaging analysis of foraminal stenosis in the fifth lumbar (L5) nerve root remains to be a challenge because of the anatomical complexity of the lumbosacral transition. T2-weighted three-dimensional (3D) magnetic resonance images (MRI) have been dominantly used for diagnosis of lumbar foraminal stenosis, while the reliability of T1-weighted images (WI) has also been proven. In this study, we aim to compare the reliability and reproducibility of T1- and T2-weighted 3D MRI in diagnosing lumbar foraminal stenosis (LFS) of the L5 nerve root. Methods: In this study, 39 patients with unilateral L5 radiculopathy (20 had L4-L5 intracanal stenosis; 19 had L5-S foraminal stenosis) were enrolled, prospectively. T1- and T2-weighted 3D lumbar MRI were obtained from each patient. T1WI and T2WI were blinded and then separately reviewed twice by four examiners randomly. The examiners were instructed to answer the side of LFS or absence of LFS. The correct answer rate, sensitivity, specificity, and area under the curve were analyzed and compared between T1WI and T2WI. Also, intra- and interobserver agreements were calculated using kappa (κ)-statistics and compared in the same manner. Results: The average correct answer rate, sensitivity, specificity, and area under the curve of the T1WI/T2WI were 84.6%/80.1%, 82.9%/80.3%, 86.3%/81.3%, and 0.846/0.801, respectively. The intraobserver κ-values of the four examiners ranged from 0.692 to 0.916 (average: 0.762) and from 0.669 to 0.801 (average: 0.720) for T1WI and T2WI, respectively. The interobserver κ-values calculated in a round-robin manner (24 combinations in total) ranged from 0.544 to 0.790 (average: 0.657) and from 0.524 to 0.828 (average: 0.652), respectively. Conclusions: As per our findings, T1- and T2-weighted 3D MRI were determined to have nearly equivalent reliability and reproducibility in terms of diagnosing LFS of the L5 nerve root.

10.
J Spine Surg ; 9(3): 278-287, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37841796

RESUMO

Background: The highest incidence of lumbar foraminal stenosis (LFS) occurs in the L5-S1 segment and its anatomical features differ from those of other segments. Few previous reports have exhaustively assessed surgical outcomes after decompression surgery, limiting the materials to patients with LFS at the L5-S1 segment. We aimed to prospectively investigate instability and neurological improvement following our novel surgical technique for LFS at L5-S1, named "radical decompression" of the nerve root. Methods: Patients with foraminal stenosis at L5-S1 who underwent surgery using our technique were prospectively evaluated two years postoperatively. The Japanese Orthopaedic Association (JOA) score and the JOA Back Pain Evaluation Questionnaire (JOABPEQ) were evaluated preoperatively and two years postoperatively. The following radiological parameters at L5-S1 were measured: lateral translation, sagittal translation, the difference in sagittal translation (DST) between flexion and extension, disc wedging angle, lordotic angle, the difference in lordotic angle (DLA) between flexion and extension, and disc height. Pre- and postoperative data were compared using paired t-tests. In addition, the patients were classified into a disc group (Group D) and a non-disc group (Group ND) according to whether a discectomy was performed intraoperatively. Changes in each parameter before and after surgery were compared between the groups. Results: Twenty-eight patients were included in this analysis. The JOA scores improved in all patients. The mean preoperative and two-year postoperative JOA scores were 14.5±3.2 (range, 8-21) and 24.3±3.3 (range, 18-29), respectively (P<0.01). All JOABPEQ categories improved two years postoperatively (P<0.05). None of the patients underwent revision surgery. No significant changes were observed in any of the radiological parameters. No significant differences in the changes in each parameter before and after surgery were found between groups D and ND. Conclusions: Our surgical technique resulted in good neurological recovery and was associated with a low risk of postoperative segmental instability, regardless of additional discectomy.

11.
Acute Med Surg ; 10(1): e893, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37736501

RESUMO

Background: Continuous positive airway pressure (CPAP) therapy is an effective treatment for patients with severe heart failure, and certain guidelines recommend its early initiation. However, the current Japanese law strictly prohibits paramedics from administering this treatment. To demonstrate the efficacy and safety of prehospital administration of CPAP therapy, this study was conducted by the Yokohama Medical Control Council (Yokohama MC). Methods: The Yokohama MC established a protocol for CPAP treatment and dispatched Doctor Cars to attend to patients with severe respiratory failure. The Boussignac CPAP system was installed in all Yokohama Doctor Cars, including Workstation-type Doctor Cars and Hospital-type Doctor Cars. Data from this study were collected and recorded in the Yokohama City Doctor Car Registry system from October 2020 to January 2022. Results: The Doctor Car was dispatched 661 times, and CPAP therapy was administered to 13 patients in the prehospital field. It is important to note that the number of CPAP cases was lower than anticipated due to the coronavirus disease 2019 (COVID-19) pandemic, given concerns about aerosol production. When assessing changes over time in oxygen saturation (SpO2), the median (interquartile range), excluding missing values, was 89% (83%-93%) without oxygen, 95% (94%-99.3%) with oxygen, and 100% (97%-100%) with CPAP. The differences between these groups were statistically significant with a p-value of <0.0001. Respiratory distress was primarily attributed to heart failure in 10 patients (91%) and pneumothorax in 1 patient (9%). Notably, none of the patients' conditions worsened after the use of CPAP. Conclusion: We have detailed the administration of CPAP therapy in the prehospital field within a local city in Japan. To the best of our knowledge, this represents the inaugural report of a prospective observational study on the prehospital administration of CPAP therapy originating from Japan.

12.
Physiol Behav ; 271: 114348, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37709001

RESUMO

Post-stroke cognitive impairment (PSCI) of the complications after stroke has been shown to be involved in brain proinflammatory cytokines such as interleukin (IL)-1ß (IL-lß) and IL-18. In the present study, we examined using acetic acid-induced embolic cerebral infarct (ECI) mice whether post-stroke inflammasome activation is involved in the development of PSCI. In behavioral tests, long-term learning and memory assessed using the passive avoidance test were impaired after ECI. On the other hand, the impairment of short-term learning and memory assessed using the Y-maze test was not observed. Furthermore, the phosphorylated α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) at Ser 831 and Ser 845 protein was found to be significantly decreased in the dorsal hippocampus of ECI mice. In addition, the expression levels of ionized calcium-binding adapter protein 1 (Iba1), glial fibrillary acidic protein (GFAP), apoptosis-associated speck-like protein containing a caspase recruitment domain / target of methylation-induced silencing 1 (ASC/TMS1), Caspase-1, IL-1ß, IL-18 and tumor necrosis factor-α (TNF-α) were significantly increased in the dorsal hippocampus of ECI mice. These results indicate that development of PSCI after embolic cerebral infarction is due to a decrease in AMPA receptor subunit GluR1 at Ser831 and Ser845 through the inflammasome activation pathway in the dorsal hippocampus.

13.
Geriatr Gerontol Int ; 23(11): 788-794, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37735145

RESUMO

AIM: The present study examined the relationship between body mass index and the ability to perform the activities of daily living in patients with vertebral compression fractures. METHODS: A retrospective cohort analysis of patients aged >65 years hospitalized with a vertebral compression fracture was carried out using a nationwide database in Japan. Body mass index was categorized as underweight (<18.5 kg/m2 ), normal weight (18.5-22.9 kg/m2 ), overweight (23.0-27.4 kg/m2 ) and obese (≥27.5 kg/m2 ) according to the World Health Organization criteria for the Asia-Pacific region. The primary outcome was Barthel Index gain, namely, the change in the Barthel Index score at discharge from that at admission. Secondary outcomes were the length of hospital stay and readmission within 30 days of discharge. RESULTS: Among 41 423 participants, 24.5% were classified as underweight, excluding those with missing body mass index data. The underweight group had a significantly lower Barthel Index gain than the normal, overweight and obese groups (median 20 vs 25 vs 30 vs 30, respectively, P < 0.001). The underweight group also had longer hospital stays and higher 30-day readmission rates than the other groups. A multivariable analysis showed that being underweight was independently associated with a Barthel Index gain -3.63 points (95% confidence interval -4.58 to -2.68) lower than normal weight. Furthermore, being underweight was an independent variable affecting the length of hospital stay and readmission within 30 days (P < 0.001). CONCLUSIONS: In patients with vertebral compression fractures, being underweight leads to lower Barthel Index scores, longer hospital stays and increased readmissions within 30 days of discharge. Geriatr Gerontol Int 2023; 23: 788-794.


Assuntos
Fraturas por Compressão , Fraturas da Coluna Vertebral , Humanos , Índice de Massa Corporal , Fraturas por Compressão/complicações , Sobrepeso , Estudos Retrospectivos , Magreza/complicações , Magreza/epidemiologia , Atividades Cotidianas , Pacientes Internados , Japão/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/complicações , Obesidade/complicações , Obesidade/epidemiologia , Estudos de Coortes
14.
In Vivo ; 37(5): 2327-2333, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37652521

RESUMO

BACKGROUND/AIM: Diabetes mellitus is a risk for subsequent nephrogenic anemia due to accelerated decline in renal function, and the global diabetic population continues to grow exponentially. In clinical studies, sodium-glucose co-transporter 2 (SGLT2) inhibitors, one of the drugs used to treat diabetes, have recently attracted attention as anemia suppressors, but there is still lack of evidence on this matter. The present study aimed to investigate the effects of SGLT2 inhibitor administration on anemia suppression using hemoglobin (Hb) levels as an indicator. PATIENTS AND METHODS: We conducted a longitudinal study to evaluate and compare the changes in Hb levels in diabetes patients treated with SGLT2 inhibitors (n=48) and those treated with DPP-4 inhibitors (n=48). Study participants were stratified into sub-cohorts based on sex, and the Hb level trajectory in the participants was observed for 90 days. RESULTS: We evaluated the use of SGLT2 inhibitors as a prophylactic factor for the decline in Hb levels and compared it to that of DPP-4 inhibitors [odds ratio (OR)=3.40, 95% confidence interval (CI)=1.93-6.00]. Administration of SGLT2 inhibitors and DPP-4 inhibitors resulted in decline of 14.4±0.34 and 12.4±0.31 g/dl (p<0.001), respectively, in male Hb levels from baseline to 90 days. Notably, the prophylactic effect of SGLT2 inhibitors on the reduction in Hb levels was independent of renal function and sex. CONCLUSION: SGLT2 inhibitors prevent the reduction in Hb levels and exhibit anti-anemic effects.


Assuntos
Anemia , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos Longitudinais , Estudos Retrospectivos , Anemia/tratamento farmacológico , Hemoglobinas
15.
Biol Pharm Bull ; 46(7): 1027-1030, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37394635

RESUMO

Globin digest (GD) inhibits dietary hypertriglyceridemia; however, its effects on physical fatigue remain unknown. Therefore, this study aimed to investigate the potential anti-fatigue effects of GD. Repeated administration of GD and valine (Val)-Val-tyrosine (Tyr)-proline (Pro), a component of GD, for five days prevented the forced walking-induced decrease in locomotion. Furthermore, GD treatment reversed the forced walking-induced increase in blood lactate levels in mice and increased phosphorylated AMP-activated protein kinase (p-AMPK) in the soleus muscle, suggesting that the anti-fatigue effect of GD involves AMPK activation in the soleus muscle through reduced blood lactate.


Assuntos
Globinas , Hiperlipidemias , Camundongos , Animais , Globinas/metabolismo , Globinas/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Músculo Esquelético/metabolismo , Lactatos
16.
Int J Mol Sci ; 24(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37511321

RESUMO

The theory that an itch inhibits pain has been refuted; however, previous research did not investigate this theory for an interleukin-31 (IL-31)-induced itch. Previously, we have found that morphine-induced antinociception was partially reduced in IL-31 receptor A (IL-31RA)-deficient (IL-31RAKI) mice, indicating that IL-31RA may play an important role in morphine-induced peripheral antinociception. In the present study, we evaluated the effect of IL-31-induced analgesia on a 2,4,6-trinitrochlorobenzene (TNCB)-sensitized mice using a hot-plate test. This test evaluated the antinociceptive activity of morphine and non-steroidal anti-inflammatory drugs (NSAIDs). Repeated pretreatment with IL-31 showed significant antinociceptive action. Furthermore, its combination with morphine, but not with NSAIDs, increased the analgesic action. In contrast, treatment with TNCB and capsaicin decreased antinociception. Moreover, TNCB increased IL-31RA expression in the dorsal root ganglia at 24 h, whereas capsaicin inhibited it. The comparative action of several analgesics on TNCB or capsaicin was evaluated using a hot-plate test, which revealed that the antinociceptive activity was decreased or disappeared in response to capsaicin-induced pain in IL-31RAKI mice. These results indicate that the analgesic action of IL-31 involves the peripheral nervous system, which affects sensory nerves. These results provide a basis for developing novel analgesics using this mechanism.


Assuntos
Analgésicos , Capsaicina , Camundongos , Animais , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Morfina/farmacologia , Morfina/uso terapêutico , Dor/tratamento farmacológico , Dor/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Interleucinas/uso terapêutico
17.
Mol Brain ; 16(1): 52, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37312182

RESUMO

Angiotensin (Ang)-converting-enzyme (ACE) 2 converts Ang II into Ang (1-7), which in turn acts on MAS receptors (ACE2/Ang (1-7)/MAS receptors pathway). This pathway has neuroprotective properties, making it a potential therapeutic target for psychiatric disorders such as depression. Thus, we examined the effects of diminazene aceturate (DIZE), an ACE2 activator, on depressive-like behavior using behavioral, pharmacological, and biochemical assays. To determine whether DIZE or Ang (1-7) produce antidepressant-like effects, we measured the duration of immobility of mice in the tail suspension test following their intracerebroventricular administration. Next, we measured the levels of ACE2 activation in the cerebral cortex, prefrontal cortex, hippocampus, and amygdala after DIZE injection, and examined which cell types, including neurons, microglia, and astrocytes, express ACE2 in the hippocampus using immunofluorescence. Administration of DIZE or Ang (1-7) significantly shortened the duration of immobility time in the tail suspension test, while this effect was inhibited by the co-administration of the MAS receptor antagonist A779. DIZE activated ACE2 in the hippocampus. ACE2 was localized to neurons, astrocytes, and microglia in the hippocampus. In conclusion, these results suggest that DIZE may act on ACE2-positive cells in the hippocampus where it increases the activity of ACE2, thereby enhancing signaling of the ACE2/Ang (1-7)/MAS receptor pathway and resulting in antidepressant-like effects.


Assuntos
Enzima de Conversão de Angiotensina 2 , Antidepressivos , Animais , Camundongos , Tonsila do Cerebelo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Córtex Cerebral , Hipocampo
18.
Tohoku J Exp Med ; 260(4): 341-346, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37286520

RESUMO

Primary malignant lymphoma confinement to the cauda equina is rare. Only 14 cases of primary malignant lymphoma in the cauda equina have been reported. In these cases, the clinical features were similar to those of lumbar spinal canal stenosis (LSCS). This report describes a case of diffuse large B-cell lymphoma of the cauda equina that was diagnosed after decompression surgery for LSCS. An 80-year-old man presented with gait disturbance due to progressive muscle weakness in the lower extremities over the previous two months. He was diagnosed with LSCS, and decompression surgery was performed. However, the muscle weakness worsened after surgery; therefore, he was referred to our department. Plain magnetic resonance imaging (MRI) revealed swelling of the cauda equina. It demonstrated marked homogenous enhancement by gadolinium-diethylenetriamine pentaacetic acid. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) revealed diffuse accumulation of 18F-FDG in the cauda equina. These imaging findings were consistent with those of cauda equina lymphomas. To confirm the diagnosis, we performed an open biopsy of the cauda equina. Histological examination indicated diffuse large B-cell lymphoma. Considering the patient's age and activities of daily living, further treatment was not performed. The patient died four months after the first surgery. Rapid progression of muscle weakness, which cannot be prevented by decompression surgery, and swollen cauda equina on MRI may be signs of this disorder. Gadolinium-enhanced MRI, 18F-FDG PET, and histological investigation of the cauda equina should be performed for diagnosing primary malignant lymphoma of the cauda equina.


Assuntos
Cauda Equina , Linfoma Difuso de Grandes Células B , Estenose Espinal , Masculino , Humanos , Idoso de 80 Anos ou mais , Cauda Equina/diagnóstico por imagem , Cauda Equina/cirurgia , Cauda Equina/patologia , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Atividades Cotidianas , Fluordesoxiglucose F18 , Gadolínio , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/cirurgia , Debilidade Muscular/patologia , Descompressão , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia
19.
Commun Biol ; 6(1): 590, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-37296191

RESUMO

The coexistence of three sexual phenotypes (male, female and bisexual) in a single species, 'trioecy', is rarely found in diploid organisms such as flowering plants and invertebrates. However, trioecy in haploid organisms has only recently been reported in a green algal species, Pleodorina starrii. Here, we generated whole-genome data of the three sex phenotypes of P. starrii to reveal a reorganization of the ancestral sex-determining regions (SDRs) in the sex chromosomes: the male and bisexual phenotypes had the same "male SDR" with paralogous gene expansions of the male-determining gene MID, whereas the female phenotype had a "female SDR" with transposition of the female-specific gene FUS1 to autosomal regions. Although the male and bisexual sex phenotypes had the identical male SDR and harbored autosomal FUS1, MID and FUS1 expression during sexual reproduction differed between them. Thus, the coexistence of three sex phenotypes in P. starrii is possible.


Assuntos
Genoma , Cromossomos Sexuais , Haploidia , Reprodução/genética
20.
Front Surg ; 10: 1120069, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37114152

RESUMO

Background: Thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) remains one of the most difficult disorders to treat. The Ohtsuka procedure, extirpation, or anterior floating of the OPLL through a posterior approach, has shown great surgical outcomes after several modifications. However, these procedures are technically demanding and pose a significant risk of neurological deterioration. We have developed a novel modified Ohtsuka procedure in which removal or minimization of the OPLL mass is unnecessary; instead, the ventral dura mater is shifted anteriorly with the posterior part of the vertebral bodies and targeted OPLL. Surgical Procedure: First, pedicle screws were inserted at more than three spinal levels above and below the spinal level where pediculectomies were performed. After laminectomies and total pediculectomies, partial osteotomy of the posterior vertebra adjacent to the targeted OPLL was performed by using a curved air drill. Then, the PLL is completely resected at the cranial and caudal sites of the OPLL using special rongeurs or a threadwire saw with a diameter of 0.36 mm. The nerve roots were not resected during surgery. Methods: Eighteen patients (follow-up ≥1 year) treated with our modified Ohtsuka procedure were assessed clinically, including the Japanese Orthopaedic Association (JOA) score for thoracic myelopathy and radiographically. Results: The average follow-up period was 3.2 years (range, 1.3-6.1 years). The preoperative JOA score was 2.7 ± 1.7, which improved to 8.2 ± 1.8 at 1 year postoperatively; therefore, the recovery rate was 65.8 ± 19.8%. The CT scan at 1 year after surgery revealed the anterior shift of the OPLL averaged 3.1 ± 1.7 mm and the ossification-kyphosis angle of the anterior decompression site decreased at an average of 7.2 ± 6.8 degrees. Three patients demonstrated temporary neurological deterioration, all of whom completely recovered within 4 weeks postoperatively. Discussion: The concept of our modified Ohtsuka procedure is 1) not OPLL extirpation or minimization but only the creation of space between the OPLL and spinal cord by an anterior shift of the ventral dura mater, which is achieved by complete resection of the PLL at the cranial and caudal sites of the OPLL; and 2) no nerve roots are sacrificed to prevent ischemic spinal cord injury. This procedure is not technically demanding and safe and provides secure decompression for thoracic OPLL. The anterior shift of the OPLL was smaller than expected, but it resulted in a relatively good surgical outcome with a recovery rate ≥65%. Conclusion: Our modified Ohtsuka procedure is quite secure and is not technically demanding, with a recovery rate of 65.8%.

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