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1.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732124

RESUMEN

Oxytocin, a significant pleiotropic neuropeptide, regulates psychological stress adaptation and social communication, as well as peripheral actions, such as uterine contraction and milk ejection. Recently, a Japanese Kampo medicine called Kamikihito (KKT) has been reported to stimulate oxytocin neurons to induce oxytocin secretion. Two-pore-domain potassium channels (K2P) regulate the resting potential of excitable cells, and their inhibition results in accelerated depolarization that elicits neuronal and endocrine cell activation. We assessed the effects of KKT and 14 of its components on a specific K2P, the potassium channel subfamily K member 2 (TREK-1), which is predominantly expressed in oxytocin neurons in the central nervous system (CNS). KKT inhibited the activity of TREK-1 induced via the channel activator ML335. Six of the 14 components of KKT inhibited TREK-1 activity. Additionally, we identified that 22 of the 41 compounds in the six components exhibited TREK-1 inhibitory effects. In summary, several compounds included in KKT partially activated oxytocin neurons by inhibiting TREK-1. The pharmacological effects of KKT, including antistress effects, may be partially mediated through the oxytocin pathway.


Asunto(s)
Neuronas , Oxitocina , Canales de Potasio de Dominio Poro en Tándem , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Canales de Potasio de Dominio Poro en Tándem/antagonistas & inhibidores , Oxitocina/farmacología , Oxitocina/metabolismo , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Animales , Humanos , Medicina Kampo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratones
2.
IJU Case Rep ; 7(3): 197-200, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38686072

RESUMEN

Introduction: CHARGE syndrome is a rare disorder that causes congenital abnormalities in multiple organs, including secondary hypogonadism. We report, herein, a unique case of CHARGE syndrome with both primary and secondary hypogonadism and discuss the possible causes and pathogenesis in this patient. Case presentation: A 15-year-old boy with delayed secondary sexual characteristics and non-palpable testes was referred to our hospital. Physical examination and detection of a chromodomain-helicase-deoxyribonucleic acid-binding protein 7 gene mutation confirmed CHARGE syndrome. Hormone stimulation tests suggested both primary and secondary hypogonadism. Laparoscopic bilateral orchiectomy was performed because of decreased testosterone production and atrophy in both testes. Pathological examination of the testes revealed maturation arrest, germ cell neoplasm in situ, and decreased expression of steroid synthase. Conclusion: This appears to be the first report of CHARGE syndrome with both primary and secondary hypogonadism demonstrated in endocrinological and histological examinations.

3.
Immun Inflamm Dis ; 12(4): e1252, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38652015

RESUMEN

We developed pulmonary emphysema and a type 2 airway inflammation overlap mouse model. The bronchoalveolar lavage (BAL) interleukin 13 (IL-13), IL-4, and IL-5 levels in the overlap model were higher than in the pulmonary emphysema model and lower than in the type 2 airway inflammation model, but IL-33 level in the lung was higher than in other models. IL-33 and interferon-γ (IFNγ) in lungs may control the severity of a type 2 airway inflammation in lung.


Asunto(s)
Modelos Animales de Enfermedad , Interleucina-33 , Enfisema Pulmonar , Animales , Interleucina-33/metabolismo , Ratones , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patología , Enfisema Pulmonar/etiología , Enfisema Pulmonar/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Pulmón/patología , Pulmón/inmunología , Pulmón/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Interferón gamma/metabolismo , Interferón gamma/inmunología , Ratones Endogámicos C57BL
4.
J Nat Med ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38587582

RESUMEN

The relative configuration of the epoxide functionality in pinofuranoxin A (1), α-alkylidene-ß-hydroxy-γ-methyl-γ-butyrolactone with trans-epoxy side chain isolated by Evidente et al. in 2021, was revised by DFT-based spectral reinvestigations and stereo-controlled synthesis. The present investigation demonstrates the difficulty of the configurational elucidation of the stereogenic centers on the conformationally flexible acyclic side-chains. Sharpless's enantioselective epoxidations and dihydroxylations were quite effective in the reinvestigations of the configurations. As our syntheses made all diastereomers available, these would be quite effective in the next structure-biological activity relationship studies.

5.
Proc Natl Acad Sci U S A ; 121(14): e2317254121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38551840

RESUMEN

Pv11 is the only animal cell line that, when preconditioned with a high concentration of trehalose, can be preserved in the dry state at room temperature for more than one year while retaining the ability to resume proliferation. This extreme desiccation tolerance is referred to as anhydrobiosis. Here, we identified a transporter that contributes to the recovery of Pv11 cells from anhydrobiosis. In general, the solute carrier 5 (SLC5)-type secondary active transporters cotransport Na+ and carbohydrates including glucose. The heterologous expression systems showed that the transporter belonging to the SLC5 family, whose expression increases upon rehydration, exhibits Na+-dependent trehalose transport activity. Therefore, we named it STRT1 (sodium-ion trehalose transporter 1). We report an SLC5 family member that transports a naturally occurring disaccharide, such as trehalose. Knockout of the Strt1 gene significantly reduced the viability of Pv11 cells upon rehydration after desiccation. During rehydration, when intracellular trehalose is no longer needed, Strt1-knockout cells released the disaccharide more slowly than the parental cell line. During rehydration, Pv11 cells became roughly spherical due to osmotic pressure changes, but then returned to their original spindle shape after about 30 min. Strt1-knockout cells, however, required about 50 min to adopt their normal morphology. STRT1 probably regulates intracellular osmolality by releasing unwanted intracellular trehalose with Na+, thereby facilitating the recovery of normal cell morphology during rehydration. STRT1 likely improves the viability of dried Pv11 cells by rapidly alleviating the significant physical stresses that arise during rehydration.


Asunto(s)
Chironomidae , Desecación , Animales , Trehalosa/metabolismo , Larva/metabolismo , Chironomidae/genética , Insectos/metabolismo , Línea Celular
6.
Artículo en Inglés | MEDLINE | ID: mdl-38407968

RESUMEN

Significance: Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) act as signaling molecules, regulating gene expression, enzyme activity, and physiological responses. However, excessive amounts of these molecular species can lead to deleterious effects, causing cellular damage and death. This dual nature of ROS, RNS, and RSS presents an intriguing conundrum that calls for a new paradigm. Recent Advances: Recent advancements in the study of photosynthesis have offered significant insights at the molecular level and with high temporal resolution into how the photosystem II oxygen-evolving complex manages to prevent harmful ROS production during the water-splitting process. These findings suggest that a dynamic spatiotemporal arrangement of redox reactions, coupled with strict regulation of proton transfer, is crucial for minimizing unnecessary ROS formation. Critical Issues: To better understand the multifaceted nature of these reactive molecular species in biology, it is worth considering a more holistic view that combines ecological and evolutionary perspectives on ROS, RNS, and RSS. By integrating spatiotemporal perspectives into global, cellular, and biochemical events, we discuss local pH or proton availability as a critical determinant associated with the generation and action of ROS, RNS, and RSS in biological systems. Future Directions: The concept of localized proton availability will not only help explain the multifaceted nature of these ubiquitous simple molecules in diverse systems but also provide a basis for new therapeutic strategies to manage and manipulate these reactive species in neural disorders, pathogenic diseases, and antiaging efforts.

7.
Cureus ; 16(1): e52981, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38406008

RESUMEN

A 66-year-old male presented with renal dysfunction. At the time of presentation, his serum creatinine (sCr) was 2.55 mg/dL, estimated glomerular filtration rate (eGFR) was 20.93 ml/min/1.73 m2, urinary red blood cell (RBC) was 30-49/high power field, and urine protein-creatinine ratio was 0.43 g/gCr. The patient had no urinalysis abnormalities or renal dysfunction within the year prior to presentation but had gross hematuria after the third and fourth coronavirus disease 2019 (COVID-19) vaccinations. Therefore, immunoglobulin A nephropathy (IgAN) was suspected and a percutaneous renal biopsy was performed. Renal pathology confirmed IgAN and interstitial nephritis and glucocorticoid therapy was initiated. Glucocorticoids improved renal function, and microscopic hematuria resolved. Although previous reports have shown that the COVID-19 vaccine induces various renal diseases, complications associated with these two renal diseases are rare. In this case, while IgAN was suspected based on episodes of gross hematuria after vaccination, renal biopsy confirmed it and also revealed interstitial nephritis.

8.
Intensive Care Med Exp ; 12(1): 13, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38361021

RESUMEN

BACKGROUND: ECPELLA, a combination of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and Impella, a percutaneous left ventricular (LV) assist device, has emerged as a novel therapeutic option in patients with severe cardiogenic shock (CS). Since multiple cardiovascular and pump factors influence the haemodynamic effects of ECPELLA, optimising ECPELLA management remains challenging. In this study, we conducted a comprehensive simulation study of ECPELLA haemodynamics. We also simulated global oxygen delivery (DO2) under ECPELLA in severe CS and acute respiratory failure as a first step to incorporate global DO2 into our developed cardiovascular simulation. METHODS AND RESULTS: Both the systemic and pulmonary circulations were modelled using a 5-element resistance‒capacitance network. The four ventricles were represented by time-varying elastances with unidirectional valves. In the scenarios of severe LV dysfunction, biventricular dysfunction with normal pulmonary vascular resistance (PVR, 0.8 Wood units), and biventricular dysfunction with high PVR (6.0 Wood units), we compared the changes in haemodynamics, pressure-volume relationship (PV loop), and global DO2 under different VA-ECMO flows and Impella support levels. RESULTS: In the simulation, ECPELLA improved total systemic flow with a minimising biventricular pressure-volume loop, indicating biventricular unloading in normal PVR conditions. Meanwhile, increased Impella support level in high PVR conditions rendered the LV-PV loop smaller and induced LV suction in ECPELLA support conditions. The general trend of global DO2 was followed by the changes in total systemic flow. The addition of veno-venous ECMO (VV-ECMO) augmented the global DO2 increment under ECPELLA total support conditions. CONCLUSIONS: The optimal ECPELLA support increased total systemic flow and achieved both biventricular unloading. The VV-ECMO effectively improves global DO2 in total ECPELLA support conditions.

9.
Am J Physiol Regul Integr Comp Physiol ; 326(3): R230-R241, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38223938

RESUMEN

Although body fluid volume control by the kidneys may be classified as a long-term arterial pressure (AP) control system, it does not necessarily follow that the urine flow (UF) response to changes in AP is slow. We quantified the dynamic characteristics of the UF response to short-term AP changes by changing mean AP between 60 mmHg and 100 mmHg every 10 s according to a binary white noise sequence in anesthetized rats (n = 8 animals). In a baro-on trial (the carotid sinus baroreflex was enabled), the UF response represented the combined synergistic effects of pressure diuresis (PD) and neurally mediated antidiuresis (NMA). In a baro-fix trial (the carotid sinus pressure was fixed at 100 mmHg), the UF response mainly reflected the effect of PD. The UF step response was quantified using the sum of two exponential decay functions. The fast and slow components had time constants of 6.5 ± 3.6 s and 102 ± 85 s (means ± SD), respectively, in the baro-on trial. Although the gain of the fast component did not differ between the two trials (0.49 ± 0.21 vs. 0.66 ± 0.22 µL·min-1·kg-1·mmHg-1), the gain of the slow component was greater in the baro-on than in the baro-fix trial (0.51 ± 0.14 vs. 0.09 ± 0.39 µL·min-1·kg-1·mmHg-1, P = 0.023). The magnitude of NMA relative to PD was calculated to be 32.2 ± 29.8%. In conclusion, NMA contributed to the slow component, and its magnitude was approximately one-third of that of the effect of PD.NEW & NOTEWORTHY We quantified short-term dynamic characteristics of the urine flow (UF) response to arterial pressure (AP) changes using white noise analysis. The UF step response approximated the sum of two exponential decay functions with time constants of ∼6.5 s and 102 s. The neurally mediated antidiuretic (NMA) effect contributed to the slow component of the UF step response, with the magnitude of approximately one-third of that of the pressure diuresis (PD) effect.


Asunto(s)
Presión Arterial , Barorreflejo , Animales , Ratas , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Arterias Carótidas , Diuresis
10.
J Artif Organs ; 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38190085

RESUMEN

There are no criteria for surgical mechanical circulatory system (MCS) selection for acute heart failure. Since 2021, we have utilized cardiopulmonary bypass system to assess patients' heart and lung condition to inform surgical MCS selection. we aimed to retrospectively analyze the outcomes of treatments administered using our protocol. We analyzed the data of 19 patients who underwent surgical MCS implantation. We compared patients' characteristics across the biventricular-assist device (BiVAD), central Y-Y extracorporeal membrane oxygenation (ECMO), central ECMO, and left VAD (LVAD) systems. Patients' diagnoses included fulminant myocarditis (47.4%), dilated cardiomyopathy (21.1%), acute myocardial infarction (15.8%), infarction from aortic dissection (5.3%), doxorubicin-related cardiomyopathy (5.3%), and tachycardia-induced myocarditis (5.3%). Eight patients (42.1%) underwent LVAD implantation, 1 (5.2%) underwent central ECMO, 4 (21.1%) underwent BiVAD implantation, and 6 (31.6%) underwent central Y-Y ECMO. 48 h after surgery, both the pulmonary arterial and right atrial pressures were effectively controlled, with median values being 19.0 mmHg and 9.0 mmHg, respectively. No patients transitioned from LVAD to BiVAD in the delayed period. Cerebrovascular events occurred in 21.1%. Successful weaning was achieved in 11 patients (57.9%), and 5 patients (26.3%) were converted to durable LVAD. Two-year cumulative survival was 84.2%. Our protocol showed good results for device selection in patients with heart failure, and device selection according to this protocol enabled good control of the pulmonary and systemic circulations.

11.
Intern Med ; 63(7): 985-988, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37558475

RESUMEN

Nivolumab plus ipilimumab is one of the first-line treatments for advanced non-small-cell lung cancer (NSCLC), but the safety and efficacy in patients on hemodialysis (HD) is unclear. We herein report a patient with NSCLC on HD in whom nivolumab and ipilimumab were initiated. We observed general deterioration and enlarged lesions, followed by a long-term response. The patient developed secondary hypoadrenocorticism, an immune-related adverse event that was easily controlled. Nivolumab plus ipilimumab can be used safely for patients with NSCLC on HD. Long-term effectiveness can be observed after initial progression, so we should carefully assess the response.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Nivolumab/uso terapéutico , Ipilimumab/uso terapéutico , Antígeno B7-H1 , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
12.
J Nutr Sci Vitaminol (Tokyo) ; 69(5): 357-369, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37940576

RESUMEN

Nonalcoholic steatohepatitis (NASH) can progress to hepatic fibrosis, and is associated with cardiovascular and liver-related mortality. To understand the pathogenesis of NASH, reliable animal models of the disease are useful. In animal studies, the animals are usually fasted overnight before biospecimens are taken, but little is known about the effects of fasting. Here, we investigated the impact of overnight fasting for approximately 9 to 17 h on glucose and lipid metabolism in a Sprague-Dawley (SD) rat model of diet-induced moderate and advanced NASH in comparison to normal SD rats. Our results revealed that in the moderate NASH model rats, the fasting duration did not affect glucose and lipid metabolism, the histopathological findings, or the hepatic mRNA expression levels of genes related to lipid metabolism, cholesterol metabolism, inflammation, fibrosis, and oxidative stress. In contrast, in the normal rats, significant fasting time-dependent reductions were observed in the epididymal fat pad weight and the hepatic mRNA expression levels of adipose differentiation-related protein and heme oxygenase-1. Moreover, in the advanced NASH model rats, a significant fasting time-dependent reduction and increase were observed in the serum insulin level and mRNA expression level of alpha-smooth muscle actin, respectively. Our present results suggest that the influence of the overnight fasting duration differs among the healthy condition, moderate NASH, and advanced NASH statuses. Further studies are needed in humans to determine the appropriate overnight fasting duration for the accurate evaluation of glucose and lipid metabolism in NASH patients.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratas , Animales , Enfermedad del Hígado Graso no Alcohólico/etiología , Ratas Sprague-Dawley , Glucosa/metabolismo , Metabolismo de los Lípidos , Dieta Alta en Grasa , Hígado/metabolismo , Cirrosis Hepática/patología , Ayuno , ARN Mensajero/metabolismo , Modelos Animales de Enfermedad
13.
IJU Case Rep ; 6(6): 465-467, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37928283

RESUMEN

Introduction: We report a case of bilateral neonatal testicular torsion, with an extravaginal and a contralateral intravaginal testicular torsion. Case presentation: A 5-day-old boy with bilateral scrotal swelling and palpable induration was diagnosed with bilateral neonatal testicular torsion by color Doppler ultrasonography. The right testis was black with 360-degree extravaginal torsion of the spermatic cord, and the left testis was brown with 90-degree intravaginal torsion. We repaired the torsion and incised the tunica albuginea to reduce intratesticular pressure. The left testis became pink in color, but the right testis remained unchanged. Based on the pathological findings of the intraoperative biopsy of tissue specimens from both testes, we performed a right orchiectomy and preserved the left testis. Conclusions: Our experience suggests that testicular color improvement after fasciotomy and pathological findings of intraoperative testicular biopsy may indicate testicular preservation.

14.
J Med Cases ; 14(9-10): 344-349, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37868329

RESUMEN

Anorexia nervosa is a psychiatric disorder that is often diagnosed in adolescents and young adults. Renal-related complications of anorexia nervosa include abnormal water metabolism, electrolyte abnormalities, and nephrocalcinosis, which may lead to irreversible renal damage. Furthermore, tubulointerstitial nephritis has been reported as a renal pathological feature of anorexia nervosa. Immunosuppressive therapy, such as with glucocorticoids, has been recommended for idiopathic interstitial nephritis treatment; however, the effectiveness of immunosuppressive therapy for interstitial nephritis in patients with anorexia nervosa remains unestablished. Here, we report a case of interstitial nephritis in a patient with anorexia nervosa whose renal function was successfully improved with glucocorticoid therapy. The patient was a 38-year-old woman who was referred for renal dysfunction (estimated glomerular filtration rate: 7.6 mL/min/1.73 m2). She had anorexia nervosa and repeated episodes of vomiting. Hypokalemia (K: 2.1 mEq/L) and metabolic alkalosis (HCO3-: 54.2 mEq/L) were observed. Fluid therapy and potassium supplementation did not improve renal function; therefore, a percutaneous renal biopsy was performed. The renal pathology results revealed interstitial fibrosis, inflammatory cell infiltration in the interstitium, and tubulitis, suggesting a diagnosis of tubulointerstitial nephritis. Glucocorticoid therapy improved the patient's renal function to an estimated glomerular filtration rate of 19.91 mL/min/1.73 m2, and the renal function remained stable thereafter. This case suggests that glucocorticoid therapy may be considered for the treatment of interstitial nephritis in patients with anorexia.

15.
Inflamm Regen ; 43(1): 48, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37814342

RESUMEN

BACKGROUND: The progression of liver fibrosis leads to portal hypertension and liver dysfunction. However, no antifibrotic agents have been approved for cirrhosis to date, making them an unmet medical need. Small extracellular vesicles (sEVs) of mesenchymal stem cells (MSCs) are among these candidate agents. In this study, we investigated the effects of sEVs of MSCs, analyzed their distribution in the liver post-administration, whether their effect was dose-dependent, and whether it was possible to collect a large number of sEVs. METHODS: sEVs expressing tdTomato were generated, and their uptake into constituent liver cells was observed in vitro, as well as their sites of uptake and cells in the liver using a mouse model of liver cirrhosis. The efficiency of sEV collection using tangential flow filtration (TFF) and changes in the therapeutic effects of sEVs in a volume-dependent manner were examined. RESULTS: The sEVs of MSCs accumulated mostly in macrophages in damaged areas of the liver. In addition, the therapeutic effect of sEVs was not necessarily dose-dependent, and it reached a plateau when the dosage exceeded a certain level. Furthermore, although ultracentrifugation was commonly used to collect sEVs for research purposes, we verified that TFF could be used for efficient sEV collection and that their effectiveness is not reduced. CONCLUSION: In this study, we identified some unknown aspects regarding the dynamics, collection, and capacity dependence of sEVs. Our results provide important fundamentals for the development of therapies using sEVs and hold potential implications for the therapeutic applications of sEV-based therapies for liver cirrhosis.

16.
J Physiol Sci ; 73(1): 20, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37704939

RESUMEN

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have exerted cardioprotective effects in clinical trials, but underlying mechanisms are not fully understood. As mitigating sympathetic overactivity is of major clinical concern in the mechanisms of heart failure treatments, we examined the effects of modulation of glucose handling on baroreflex-mediated sympathetic nerve activity and arterial pressure regulations in rats with chronic myocardial infarction (n = 9). Repeated 11-min step input sequences were used for an open-loop analysis of the carotid sinus baroreflex. An SGLT2 inhibitor, empagliflozin, was intravenously administered (10 mg/kg) after the second sequence. Neither the baroreflex neural nor peripheral arc significantly changed during the last observation period (seventh and eighth sequences) compared with the baseline period although urinary glucose excretion increased from near 0 (0.0089 ± 0.0011 mg min-1 kg-1) to 1.91 ± 0.25 mg min-1 kg-1. Hence, empagliflozin does not acutely modulate the baroreflex regulations of sympathetic nerve activity and arterial pressure in this rat model of chronic myocardial infarction.


Asunto(s)
Glucosa , Infarto del Miocardio , Animales , Ratas , Barorreflejo , Glucósidos/farmacología , Infarto del Miocardio/tratamiento farmacológico
17.
Exp Physiol ; 108(10): 1295-1307, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37658608

RESUMEN

Previous studies have demonstrated the beneficial effects of apple polyphenol (AP) intake on muscle endurance. Since mitochondria are critical for muscle endurance, we investigated mitochondrial enzyme activity, biogenesis, degradation and protein quality control. Twenty-four Wistar rats were randomly fed a 5% AP diet (5% AP group, n = 8), a 0.5% AP diet (0.5% AP group, n = 8), or a control diet (control group, n = 8). After a 4-week feeding period, the expression level of peroxisome proliferator-activated receptor γ coactivator-1α, a mitochondrial biosynthetic factor, did not increase, whereas that of transcription factor EB, another regulator of mitochondrial synthesis, significantly increased. Moreover, the mitochondrial count did not differ significantly between the groups. In contrast, mitophagy-related protein levels were significantly increased. The enzymatic activities of mitochondrial respiratory chain complexes II, III and IV were significantly higher in the AP intake group than in the control group. We conclude that AP feeding increases the activity of respiratory chain complex enzymes in rat skeletal muscles. Moreover, mitochondrial biosynthesis and degradation may have increased in AP-treated rats. NEW FINDINGS: What is the central question of this study? Does the administration of apple polyphenols (AP) affect mitochondrial respiratory chain complex enzyme activity, biogenesis, degradation and protein quality control in rat skeletal muscles? What is the main finding and its importance? AP feeding increases respiratory chain complex enzyme activity in rat skeletal muscle. Moreover, AP administration increases transcription factor EB activation, and mitophagy may be enhanced to promote degradation of dysfunctional mitochondria, but mitochondrial protein quality control was not affected.


Asunto(s)
Mitofagia , Músculo Esquelético , Ratas , Animales , Músculo Esquelético/fisiología , Transporte de Electrón , Ratas Wistar , Factores de Transcripción/metabolismo , Polifenoles/farmacología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo
18.
In Vivo ; 37(5): 2327-2333, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37652521

RESUMEN

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.


Asunto(s)
Anemia , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Masculino , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estudios Longitudinales , Estudios Retrospectivos , Anemia/tratamiento farmacológico , Hemoglobinas
19.
J Biomech ; 157: 111697, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37406603

RESUMEN

In the analysis of the shoulder complex, the sequential changes occurring in the sternoclavicular and acromioclavicular joints during active shoulder motion are challenging to track. This study aimed to investigate the in vivo sternoclavicular and acromioclavicular joint motions during active elevation, including the sequential changes in these joint spaces using upright four-dimensional computed tomography (4DCT). Bilateral shoulders of 12 healthy volunteers upright 4DCT were obtained during active elevation similar to a "hands up" motion. The sternoclavicular and acromioclavicular rotation angles, joint distances, and closest points on the clavicle relative to the thorax and scapula were evaluated during 10°-140° of humerothoracic elevation. During humerothoracic elevation, the clavicle elevated, retracted, and rotated posteriorly relative to the thorax, whereas the scapula rotated upwardly, internally, and posteriorly relative to the clavicle. All the sternoclavicular and acromioclavicular joint rotation angles were significantly different at ≥ 30°-50° of humerothoracic elevation compared with 10° of humerothoracic elevation. The mean sternoclavicular and acromioclavicular joint distances were 2.2 ± 1.1 mm and 1.6 ± 0.9 mm, respectively. The closest points were located on the anteroinferior part of the medial and lateral clavicle in the sternoclavicular and acromioclavicular joints, respectively. Significant differences were observed in the acromioclavicular joint distance and anterior/posterior movements of the closest points in the sternoclavicular and acromioclavicular joints compared with 10° of humerothoracic elevation. Our sternoclavicular and acromioclavicular closest point results indicate that the impingement tends to occur at the anteroinferior part of the medial and lateral aspects of the clavicle and may be related to osteoarthritis.


Asunto(s)
Articulación Acromioclavicular , Humanos , Articulación Acromioclavicular/diagnóstico por imagen , Tomografía Computarizada Cuatridimensional , Escápula/diagnóstico por imagen , Tórax , Clavícula/diagnóstico por imagen
20.
JGH Open ; 7(7): 504-508, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37496809

RESUMEN

Background and Aim: Percutaneous endoscopic gastrostomy (PEG) is often associated with early mortality. We therefore investigated factors associated with early death after PEG. Methods: The present study comprised patients who had undergone PEG between April 2014 and March 2020. Patients were divided into two groups: an early mortality group who died within 1 month of PEG, and a non-mortality group whose clinical course could be followed for more than 1 month after the procedure. Patient background, hematological data, and procedural duration were compared between groups. Results: Univariate analysis identified older age, high blood urea nitrogen (BUN), low prognostic nutritional index (PNI), and high controlling nutritional status (CONUT) score as factors associated with early death after PEG. In multivariate analysis, high CONUT score remained an independent prognostic factor (P = 0.0035). Conclusion: A high CONUT score may be a prognostic factor for early mortality after PEG.

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