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1.
J Exp Biol ; 227(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38442390

RESUMO

Air-breathing vertebrates exhibit cardiovascular responses to diving including heart rate reduction (diving bradycardia). Field studies on aquatic mammals and birds have shown that the intensity of bradycardia can vary depending on diving behaviour, such as the depth of dives and dive duration. However, in aquatic reptiles, the variation in heart rate during deep dives under natural conditions has not been fully investigated. In this study, we released five loggerhead sea turtles (Caretta caretta) outfitted with recorders into the sea and recorded their electrocardiogram, depth, water temperature and longitudinal acceleration. After 3 days, the recorders automatically detached from the turtles. The heart rate signals were detected from the electrodes placed on the surface of the plastron. The mean (±s.d.) heart rate of 12.8±4.1 beats min-1 during dives was significantly lower than that of 20.9±4.1 beats min-1 during surface periods. Heart rate during dives varied with dive depth, although it remained lower than that at the surface. When the turtle dived deeper than 140 m, despite the relatively high flipper stroke rate (approximately 19 strokes min-1), the heart rate dropped rapidly to approximately 2 beats min-1 temporarily. The minimum instantaneous heart rate during dives was lower at deeper dive depths. Our results indicate that loggerhead sea turtles show variations in the intensity of diving bradycardia depending on their diving behaviour, similar to that shown by marine mammals and birds.


Assuntos
Caniformia , Tartarugas , Animais , Bradicardia , Frequência Cardíaca , Aceleração , Cetáceos
2.
Elife ; 122023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37814539

RESUMO

The relationship between the environment and marine animal small-scale behavior is not fully understood. This is largely due to the difficulty in obtaining environmental datasets with a high spatiotemporal precision. The problem is particularly pertinent in assessing the influence of environmental factors in rapid, high energy-consuming behavior such as seabird take-off. To fill the gaps in the existing environmental datasets, we employed novel techniques using animal-borne sensors with motion records to estimate wind and ocean wave parameters and evaluated their influence on wandering albatross take-off patterns. Measurements revealed that wind speed and wave heights experienced by wandering albatrosses during take-off ranged from 0.7 to 15.4 m/s and 1.6 to 6.4 m, respectively. The four indices measured (flapping number, frequency, sea surface running speed, and duration) also varied with the environmental conditions (e.g., flapping number varied from 0 to over 20). Importantly, take-off was easier under higher wave conditions than under lower wave conditions at a constant wind speed, and take-off effort increased only when both wind and waves were gentle. Our data suggest that both ocean waves and winds play important roles for albatross take-off and advances our current understanding of albatross flight mechanisms.


Wandering albatrosses are large seabirds with one of the most impressive wingspans found in the animal kingdom. While they spend most of their time efficiently gliding above the waves, they do have to regularly land on sea to snatch their prey. To resume flight, the birds turn into the wind and flap their wings as they run on the surface of the ocean; this causes their heart to beat three to four times faster than normal. In contrast, flying barely leads to a change in pulse rate compared to rest. As for many other marine birds, sea take-offs therefore represent one of the major energy costs that albatrosses face when out foraging. Scientists have long assumed that the amount of effort required for this manoeuvre depends on factors such as wind speed and, potentially, the height of the waves. However, this is difficult to establish for sure because direct information about the environment that a bird faces as it takes off is rarely available. Often, the best that researchers can do is to reconstruct this data based on global weather patterns, ocean climatic models or evidence collected from nearby locations. To address this problem, Uesaka et al. devised innovative ways to use data from animal-borne sensors. They equipped 44 albatrosses with these instruments and recorded over 1,500 hours of foraging sea trips. Wind parameters such as speed and direction were estimated based on the animals' flying paths, and wave height calculated from their floating motion. Sensor data also gave an insight into the energy cost of each take-off, which was estimated based on four parameters (running duration, running speed, number of wing flaps, and flapping frequency). The analyses confirmed that albatrosses take off into a headwind, with stronger winds reducing the amount of effort required. However, wave height also had a profound impact, suggesting that this parameter should be included in future studies. Overall, the birds flapped their wings less and ran on the surface of the water for shorter amounts of time when the wind was strong, or the waves were high. Even with weak winds, take offs were easier when waves were taller, and they were most costly when both the sea and wind were calm. The work by Uesaka et al. helps to capture how environmental factors influence the energy balance of albatrosses and other marine birds. As ocean weather patterns become more volatile and extreme climate events more frequent, such knowledge is acutely needed to understand how these creatures may respond to their changing world.


Assuntos
Voo Animal , Vento , Animais , Aves , Comportamento Animal , Movimento (Física)
3.
Anim Sci J ; 93(1): e13796, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36502272

RESUMO

The authors investigated the relationship between frame rates and subpopulation structure of bovine sperm divided by their motility analyzed by a computer-assisted sperm analysis (CASA). Kinematic parameters of bovine sperm incubated in Brackett & Oliphant medium with and without calcium ionophore for 0, 1, 5, 10, 15, 20, 25, and 30 min were evaluated by a CASA at 150 frames per second (fps) and analyzed structure of sperm motility subpopulation by cluster analysis. Then, we converted CASA data at 150 fps to 75, 50, and 30 fps and evaluated the structures of sperm motility subpopulation at different fps in each sperm by a discriminant analysis. As the results, the structure of sperm motility subpopulation was affected by frame rate. Sperm were divided into six clusters at 150, 75, and 50 fps; on the other hand, there were five clusters at 30 fps. Straight-line velocity was similar at all frame rates. However, as the frame rate became higher, curvilinear velocity and beat cross frequency of sperm head increased significantly, whereas lateral sperm head displacement decreased significantly. In conclusion, higher frame rate at 150 fps is recommended to capture the trajectory of sperm accurately by CASA in the present study.


Assuntos
Sêmen , Motilidade dos Espermatozoides , Masculino , Bovinos , Animais , Análise do Sêmen/veterinária , Espermatozoides , Computadores
4.
Cell Rep ; 41(4): 111548, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36288708

RESUMO

Translation of 5' terminal oligopyrimidine (TOP) mRNAs encoding the protein synthesis machinery is strictly regulated by an amino-acid-sensing mTOR pathway. However, its regulatory mechanism remains elusive. Here, we demonstrate that TOP mRNA translation positively correlates with its poly(A) tail length under mTOR active/amino-acid-rich conditions, suggesting that TOP mRNAs are post-transcriptionally controlled by poly(A) tail-length regulation. Consistent with this, the tail length of TOP mRNAs dynamically fluctuates in response to amino acid availability. The poly(A) tail shortens under mTOR active/amino-acid-rich conditions, whereas the long-tailed TOP mRNAs accumulate under mTOR inactive/amino-acid-starved (AAS) conditions. An RNA-binding protein, LARP1, is indispensable for the process. LARP1 interacts with non-canonical poly(A) polymerases and induces post-transcriptional polyadenylation of the target. Our findings illustrate that LARP1 contributes to the selective accumulation of TOP mRNAs with long poly(A) tails under AAS, resulting in accelerated ribosomal loading onto TOP mRNAs for the resumption of translation after AAS.


Assuntos
Autoantígenos , Ribonucleoproteínas , RNA Mensageiro/metabolismo , Ribonucleoproteínas/metabolismo , Autoantígenos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ribossomos/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Polinucleotídeo Adenililtransferase/genética , Aminoácidos/metabolismo , Biossíntese de Proteínas
5.
J Exp Biol ; 225(9)2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35441228

RESUMO

Diving bradycardia is a reduction in the heart rate mediated by the parasympathetic system during diving. Although diving bradycardia is pronounced in aquatic mammals and birds, the existence of this response in aquatic reptiles, including sea turtles, remains under debate. Using the parasympathetic blocker atropine, we evaluated the involvement of the parasympathetic nervous system in heart rate reduction of loggerhead sea turtles (Caretta caretta) during voluntary diving in tanks. The heart rate of the control group dropped by 40-60% from the pre-dive value at the onset of diving; however, administration of atropine significantly inhibited heart rate reduction (P<0.001). Our results indicate that, similar to mammals and birds, the heart rate reduction in sea turtles while diving is primarily mediated by the parasympathetic nervous system. In conclusion, we suggest that diving bradycardia exists not only in aquatic mammals and birds but also in aquatic reptiles.


Assuntos
Tartarugas , Animais , Atropina/farmacologia , Bradicardia , Frequência Cardíaca/fisiologia , Mamíferos , Tartarugas/fisiologia
6.
Front Physiol ; 13: 811947, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250617

RESUMO

Heart rate measurement is an essential method for evaluating the physiological status of air-breathing diving animals. However, owing to technical difficulties, many marine animals require an invasive approach to record an electrocardiogram (ECG) in water, limiting the application of this approach in a wide range of marine animals. Recently, a non-invasive system was reported to measure the ECG of hard-shelled sea turtles by pasting the electrodes on the dorsal side of the shell, although the ECG obtained from the moving turtle contains noise produced by muscle contraction. Here, we report that clear ECGs can be obtained by placing the electrodes on the ventral side rather than the dorsal side in loggerhead sea turtles. Using our method, clearer ECG signals were obtained with less electrical noise, even when turtles are swimming. According to the anatomical features, the electrode position on the ventral side is closer to the heart than the dorsal side, minimizing the effects of noise generated by the skeletal muscle. This new biologging technique will elucidate the functioning of the circulatory system of sea turtles during swimming and their adaptabilities to marine environments. This article is part of the theme issue "Methods and Applications in Physio-logging."

7.
Biol Open ; 11(3)2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35225332

RESUMO

Heart rates of air-breathing diving animals can change on a short time scale due to the diving response during submergence. Heart rate is used frequently as a proxy for indirectly estimating metabolic rates on a fine time scale. However, most studies to date have been conducted on endothermic diving animals, and the relationships between metabolic rates and heart rates in ectothermic diving animals have not been well studied. Sea turtles are unique model organisms of diving ectotherms because they spend most of their life in the ocean and perform deep and/or long dives. In this study, we examined the relationship between heart rates and metabolic rates in captive loggerhead turtles, Caretta caretta, to estimate oxygen consumption rates during each dive based on heart rates. The oxygen consumption rates (V̇O2: mlO2 min-1 kg-1) and average heart rates (fH: beats min-1) were measured simultaneously in indoor tanks at water temperatures of 15-25°C. Our results showed that oxygen consumption rate was affected by heart rate and water temperature in loggerhead turtles. Based on the collected data, we formulated the model equation as V̇O2=0.0124fH+0.0047Tw - 0.0791. The equation can be used for estimating fine-scaled field metabolic rates in free-ranging loggerhead turtles. The results of this study will contribute to future comparative studies of the physiological states of ectothermic diving animals.


Assuntos
Mergulho , Tartarugas , Animais , Mergulho/fisiologia , Frequência Cardíaca/fisiologia , Consumo de Oxigênio/fisiologia , Temperatura , Tartarugas/fisiologia
8.
PLoS One ; 16(7): e0254454, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270571

RESUMO

The study of seabird behaviour has largely relied on animal-borne tags to gather information, requiring interpretation to estimate at-sea behaviours. Details of shallow-diving birds' foraging are less known than deep-diving species due to difficulty in identifying shallow dives from biologging devices. Development of smaller video loggers allow a direct view of these birds' behaviours, at the cost of short battery capacity. However, recordings from video loggers combined with relatively low power usage accelerometers give a means to develop a reliable foraging detection method. Combined video and acceleration loggers were attached to streaked shearwaters in Funakoshi-Ohshima Island (39°24'N,141°59'E) during the breeding season in 2018. Video recordings were classified into behavioural categories (rest, transit, and foraging) and a detection method was generated from the acceleration signals. Two foraging behaviours, surface seizing and foraging dives, are reported with video recordings. Surface seizing was comprised of successive take-offs and landings (mean duration 0.6 and 1.5s, respectively), while foraging dives were shallow subsurface dives (3.2s mean duration) from the air and water surface. Birds were observed foraging close to marine predators, including dolphins and large fish. Results of the behaviour detection method were validated against video recordings, with mean true and false positive rates of 90% and 0%, 79% and 5%, and 66% and <1%, for flight, surface seizing, and foraging dives, respectively. The detection method was applied to longer duration acceleration and GPS datasets collected during the 2018 and 2019 breeding seasons. Foraging trips lasted between 1 - 8 days, with birds performing on average 16 surface seizing events and 43 foraging dives per day, comprising <1% of daily activity, while transit and rest took up 55 and 40%, respectively. This foraging detection method can address the difficulties of recording shallow-diving foraging behaviour and provides a means to measure activity budgets across shallow diving seabird species.


Assuntos
Aves , Comportamento Alimentar , Animais , Estações do Ano
9.
Philos Trans R Soc Lond B Biol Sci ; 376(1830): 20200222, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34121465

RESUMO

To measure the heart rate of unrestrained sea turtles, it has been believed that a probe must be inserted inside the body owing to the presence of the shell. However, inserting the probe is invasive and difficult to apply to animals in the field. Here, we have developed a non-invasive heart rate measurement method for some species of sea turtles. In our approach, an electrocardiogram (ECG) was performed using an animal-borne ECG recorder and two electrodes-which were electrically insulated from seawater-pasted on the carapace. Based on the measured ECG, the heartbeat signals were identified with an algorithm using a band-pass filter. We implemented this algorithm in a user-friendly program package, ECGtoHR. In experiments conducted in a water tank and in a lagoon, we successfully measured the heart rate of loggerhead, olive ridley and black turtles, but not green and hawksbill turtles. The average heart rate of turtles when resting underwater was 6.2 ± 1.9 beats min-1 and that when moving at the surface was 14.0 ± 2.4 beats min-1. Our approach is particularly suitable for endangered species such as sea turtles, and has the potential to be extended to a variety of other free-ranging species. This article is part of the theme issue 'Measuring physiology in free-living animals (Part I)'.


Assuntos
Organismos Aquáticos/fisiologia , Frequência Cardíaca/fisiologia , Fisiologia/instrumentação , Tartarugas/fisiologia , Exoesqueleto , Animais , Água do Mar
10.
Philos Trans R Soc Lond B Biol Sci ; 376(1831): 20200225, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34176321

RESUMO

Heart rate monitoring in free-ranging cetaceans to understand their behavioural ecology and diving physiology is challenging. Here, we developed a simple, non-invasive method to monitor the heart rate of cetaceans in the field using an electrocardiogram-measuring device and a single suction cup equipped with an electrode. The unipolar suction cup was placed on the left lateral body surface behind the pectoral fin of Risso's dolphins (Grampus griseus) and a false killer whale (Pseudorca crassidens) in captivity; their heart rate was successfully monitored. We observed large heart rate oscillations corresponding to respiration in the motionless whales during surfacing (a false killer whale, mean 47 bpm, range 20-75 bpm; Risso's dolphins, mean ± s.d. 61 ± 15 bpm, range 28-120 bpm, n = 4 individuals), which was consistent with the sinus arrhythmia pattern (eupneic tachycardia and apneic bradycardia) observed in other cetaceans. Immediately after respiration, the heart rate rapidly increased to approximately twice that observed prior to the breath. Heart rate then gradually decreased at around 20-50 s and remained relatively constant until the next breath. Furthermore, we successfully monitored the heart rate of a free-swimming Risso's dolphin. The all-in-one suction cup device is feasible for field use without restraining animals and is helpful in further understanding the diving physiology of free-ranging cetaceans. This article is part of the theme issue 'Measuring physiology in free-living animals (Part II)'.


Assuntos
Golfinhos/fisiologia , Testes de Função Cardíaca/veterinária , Frequência Cardíaca , Fisiologia/instrumentação , Animais , Feminino , Testes de Função Cardíaca/instrumentação , Masculino
12.
Yakugaku Zasshi ; 139(4): 519-523, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30930380

RESUMO

Recently, we considered the term 'integrated community care system' and aimed to play a role in the process by joining various healthcare occupations as part of this new integrated system. Given our company's ties with people involved in a range of occupations, we are poised to play a liaison role. We called a "face-to-face meeting" with local healthcare practitioners to begin exploring this cooperation. We believe that as meetings such as these become more widespread across the Kinki Region, they can serve as part of an integrated community care system. Through the formation of a number of alliances by this means, we hope to facilitate the transition to an integrated community care system. The meetings will provide opportunities for a range of healthcare and long-term care professionals, such as physicians, pharmacists, care managers, social workers, and home-visit nurses, to engage in discussions centered on the interests and needs of patients. Another important topic is whether we can derive from these conversations efforts that would assist in the development of "health support pharmacies". In that regard, we have set up some support tools for pharmacies that have held health fairs for local inhabitants. We consider these meetings beneficial in finding a solution to the situation of "polypharmacy"-a recent medical problem. We hope that our meetings will create an opportunity to work cooperatively toward a vision for the future of healthcare and long-term care within a community, through communicating and sharing our proposals for pharmacists based on these experiences.


Assuntos
Serviços de Saúde Comunitária , Prestação Integrada de Cuidados de Saúde , Indústria Farmacêutica , Colaboração Intersetorial , Serviços de Saúde Comunitária/tendências , Humanos , Comunicação Interdisciplinar , Japão , Equipe de Assistência ao Paciente , Farmacêuticos , Papel Profissional
13.
Endocr J ; 66(4): 295-300, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30814440

RESUMO

Therapeutic blocking antibodies against programmed death 1 (PD1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) are applied for advanced cancer therapy, but induce a wide range of immune-related adverse events. In our recent case of a 52-year-old female doctor suffering from breast cancer having metastasized to the lung and liver, it was decided to use nivolumab to prevent the disease progressing after excisional surgeries and multiple chemotherapies. One month after completing the nivolumab course, fatigue, hypoglycemia and hypotension developed and isolated ACTH deficiency (IAD) was diagnosed. A further month later, under steroid supplementation, hyperglycemia emerged alongside thirst and polydipsia, prompting a diagnosis of fulminant type 1 diabetes (FT1D). Her susceptibility to type 1 diabetes was examined by HLA haplotype and CTLA4 gene polymorphism analyses. Polymorphisms CT60G>A and +49G>A in CTLA4 both generated a GG genotype. Our patient manifested one of the rarest combinations of autoimmune disease induced by nivolumab. Whereas the HLA haplotype was unsusceptible to autoimmune type 1 diabetes, polymorphisms of CTLA4, the antibody of which frequently causes hypophysitis, were susceptible to FT1D. Peripheral modulation of activated T cells, mainly by PD-1 antibodies, induced FT1D associated with IAD in patients with CTLA4 polymorphism. This case reveals hints of the T-cell etiology in T1D and evidence of CTLA4 involvement in IAD.


Assuntos
Hormônio Adrenocorticotrópico/deficiência , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Diabetes Mellitus Tipo 1/etiologia , Doenças do Sistema Endócrino/induzido quimicamente , Doenças Genéticas Inatas/induzido quimicamente , Hipoglicemia/induzido quimicamente , Nivolumabe/efeitos adversos , Antígeno CTLA-4/genética , Doenças do Sistema Endócrino/complicações , Feminino , Doenças Genéticas Inatas/complicações , Humanos , Hipoglicemia/complicações , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
14.
Diabetes Obes Metab ; 21(2): 388-392, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30146790

RESUMO

AIM: To elucidate the mechanisms involved in the sequential use of SGLT2 and DPP4 inhibitors (SGLT2i and DPP-4i). METHODS: Twenty-six type-2 diabetes mellitus patients were recruited into a stepped regimen of 100 mg of canagliflozin daily from day 1, supplemented with 20 mg of teneligliptin daily from day 4. Glucose (Glu), insulin and glucagon were measured at fasting and after ingesting a mixed meal on days 1, 4 and 6. RESULTS: Canagliflozin decreased fasting plasma glucose to an extent inversely proportional to the change in the glucagon-to-insulin (G/I) ratio. This correlation at fasting was maintained when adding teneligliptin, while the change in the area under the curve of Glu (GluAUC) correlated closely with that in the G/I ratio at fasting and 60 min with canagliflozin. Moreover, these correlations persisted at 60 and 120 min postprandially, but not at fasting on day 6 when teneligliptin was added. CONCLUSION: The result suggested that the dominant mechanism responsible for the glucose metabolism reflected in the G/I ratio was attributable to SGLT2i and that its active mechanism persisted, despite adding a DPP-4i.


Assuntos
Canagliflozina/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Pirazóis/administração & dosagem , Tiazolidinas/administração & dosagem , Adulto , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Feminino , Glucagon/metabolismo , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem
15.
J Vet Med Sci ; 79(8): 1359-1365, 2017 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-28626150

RESUMO

In the present study, bull sperm in the first and second ejaculates were divided into subpopulations based on their motility characteristics using a cluster analysis of data from computer-assisted sperm motility analysis (CASA). Semen samples were collected from 4 Japanese black bulls. Data from 9,228 motile sperm were classified into 4 clusters; 1) very rapid and progressively motile sperm, 2) rapid and circularly motile sperm with widely moving heads, 3) moderately motile sperm with heads moving frequently in a short length, and 4) poorly motile sperm. The percentage of cluster 1 varied between bulls. The first ejaculates had a higher proportion of cluster 2 and lower proportion of cluster 3 than the second ejaculates.


Assuntos
Bovinos/fisiologia , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/classificação , Espermatozoides/fisiologia , Animais , Análise por Conglomerados , Ejaculação/fisiologia , Masculino , Análise do Sêmen/veterinária
16.
Lipids Health Dis ; 16(1): 122, 2017 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-28646901

RESUMO

BACKGROUND: Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. METHODS: In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited. We investigated the difference in cholesterol lowering effect between ezetimibe (10 mg) add-on statin (EAT) group and double-dose statin (DST) group. Changes of parameters related to atherosclerotic event risks were assessed. RESULTS: The reduction of LDL-C was larger in the EAT group (28.3%) than in the DST group (9.2%) at 52 weeks as well as the primary endpoint of 12 weeks. EAT achieved significant lower levels of TC and apo B, respectively. Both treatments attained significant reduction in sd-LDL-C or hsCRP on this long-term basis. Notably, sd-LDL-C in EAT reduced as low as 36.1 ± 14.9 mg/dl to reach near the threshold (35.0 mg/dl) for atherosclerosis with significantly higher achievement rate (55.6%) than DST treatment. Simultaneously, hsCRP reduction by EAT attained as low value as 0.52 ± 0.43 mg/l. CONCLUSIONS: In the present 52-week long-term period, ezetimibe add-on therapy showed a robust advantage in lowering LDL-C and in attaining target LDL-C values compared with the doubling of statin dose. Moreover, it's meaningful that sd-LDL, powerfully atherogenic lipoprotein, exhibited prominent decrease consistently prominently by ezetimibe add-on therapy. DM patients with hypercholesterolemia are at high risk for CAD, and adding ezetimibe onto usual-dose statin treatment in Japan has been suggested as the first-line therapy for those DM patients who failed to attain the target LDL-C value (UMIN000002593).


Assuntos
Anticolesterolemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ezetimiba/uso terapêutico , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Estudos Prospectivos
17.
J Pharmacol Sci ; 129(3): 200-4, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26603529

RESUMO

This study aimed to elucidate the protective potential of angiostatin in inflamed endothelial cells in culture. We assessed the effect of angiostatin on the expression of ICAM-1 and eNOS. Angiostatin prevented IL-1ß-induced down-regulation of eNOS expression, but produced no significant changes on IL-1ß-induced up-regulation of ICAM-1. We then explored the effect of angiostatin on IL-1ß-mediated inflammatory signaling and found that angiostatin inhibited IL-1ß-mediated nuclear translocation of NF-κB. Thus, our results suggest that angiostatin prevents IL-1ß-induced down-regulation of eNOS expression via inhibition of the NF-κB cascade; this may be the anti-inflammatory mechanism of angiostatin.


Assuntos
Angiostatinas/farmacologia , Regulação para Baixo/efeitos dos fármacos , Interleucina-1beta/efeitos adversos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Células Cultivadas , Depressão Química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Transdução de Sinais
18.
PLoS One ; 10(9): e0138332, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26398887

RESUMO

BACKGROUND: There exists a subpopulation of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C, representing a major risk of CVD. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks. METHODS: Lipid changes were assessed in a randomized, multicenter, 12-week, open-label study comparing a high-potency statin (10mg of atorvastatin or 1mg of pitavastatin) plus ezetimibe (EAT: n = 53) with a double dose of statin (20mg of atorvastatin or 2mg of pitavastatin) (DST: n = 56) in DM subjects who had failed to achieve the optimal LDL-C targets. Lipid variables were compared with a primary focus on LDL-C and with secondary focuses on the percentage of patients who reached the LDL-C targets and changes in the levels of RLP-C (remnant like particle cholesterol) and sd-LDL-C, two characteristic atherogenic risks of DM. RESULTS: The reduction of LDL-C (%), the primary endpoint, differed significantly between the two groups (-24.6 in EAT vs. -10.9 in DST). In the analyses of the secondary endpoints, EAT treatment brought about significantly larger reductions in sd-LDL-C (-20.5 vs. -3.7) and RLP-C (-19.7 vs. +5.5). In total, 89.4% of the patients receiving EAT reached the optimized treatment goal compared to 51.0% of the patients receiving DST. The changes in TC (-16.3 vs. -6.3) and non-HDL-C (-20.7 vs. -8.3) differed significantly between the two groups. CONCLUSION: Ezetimibe added to high-potency statin (10 mg of atorvastatin or 1 mg of pitavastatin) was more effective than the intensified-dose statin (20 mg of atorvastatin or 2 mg of pitavastatin) treatment not only in helping T2DM patients attain more LDL-C reduction, but also in improving their atherogenic lipid profiles, including their levels of sd-LDL-C and RLP-C. We thus recommend the addition of ezetimibe to high-potency statin as a first line strategy for T2DM patients with insufficient statin response. TRIAL REGISTRATION: The UMIN Clinical Trials Registry UMIN000002593.


Assuntos
Anticolesterolemiantes/farmacologia , LDL-Colesterol/antagonistas & inibidores , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ezetimiba/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Chem Senses ; 40(9): 641-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26377346

RESUMO

Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mate choice is more crucial than males' for successful reproduction because of the high cost of producing gametes and limited chances to mate. However, the mechanism of female inbreeding avoidance is still unclear. To elucidate the mechanism underlying inbreeding avoidance by females, we conducted Y-maze behavioral assays using BALB/c and C57BL/6 female mice. In both strains, the avoidance of male urine from the same strain was lower in the low estrogen phase than in the high estrogen phase. The estrous cycle-dependent avoidance was completely prevented by vomeronasal organ (VNO) removal. To assess the regulation of the vomeronasal system by estrogen, the neural excitability was evaluated by immunohistochemistry of the immediate early gene products. Although estrogen did not affect neural excitability in the VNO, estrogen enhanced the neural excitability of the mitral cell layer in the AOB induced by urine from the cognate males. These results suggest that female mice avoid odor from genetically similar males in an estrogen-dependent manner via the vomeronasal system and the excitability of the mitral cells in the AOB is presumed to be regulated by estrogen.


Assuntos
Odorantes , Órgão Vomeronasal/metabolismo , Animais , Comportamento Animal/fisiologia , Estradiol/administração & dosagem , Feminino , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Bulbo Olfatório/metabolismo , Feromônios/urina , Proteínas Proto-Oncogênicas c-fos/metabolismo
20.
PLoS One ; 10(3): e0118761, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25807552

RESUMO

We tagged 82 lactating northern fur seals (Callorhinus ursinus) with tri-axial accelerometers and magnetometers on two eastern Bering Sea islands (Bogoslof and St. Paul) with contrasting population trajectories. Using depth data, accelerometer data and spectral analysis we classified time spent diving (30%), resting (~7%), shaking and grooming their pelage (9%), swimming in the prone position (~10%) and two types of previously undocumented rolling behavior (29%), with the remaining time (~15%) unspecified. The reason for the extensive rolling behavior is not known. We ground-truthed the accelerometry signals for shaking and grooming and rolling behaviors--and identified the acceleration signal for porpoising--by filming tagged northern fur seals in captivity. Speeds from GPS interpolated data indicated that animals traveled fastest while in the prone position, suggesting that this behavior is indicative of destination-based swimming. Very little difference was found in the percentages of time spent in the categorical behaviors with respect to breeding islands (Bogoslof or St. Paul Island), forager type (cathemeral or nocturnal), and the region where the animals foraged (primarily on-shelf <200 m, or off-shelf > 200 m). The lack of significant differences between islands, regions and forager type may indicate that behaviors summarized over a trip are somewhat hardwired even though foraging trip length and when and where animals dive are known to vary with island, forager type and region.


Assuntos
Comportamento Animal/fisiologia , Otárias/fisiologia , Lactação/fisiologia , Atividade Motora/fisiologia , Natação/fisiologia , Acelerometria , Animais , Ecossistema , Feminino , Ilhas
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