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1.
Neurosciences (Riyadh) ; 27(4): 263-269, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36252976

RESUMO

OBJECTIVES: To establish the normal Creatine phosphokinase (CPK) range in newborns of all 3 modes of delivery and prove that high CPK level in neonates is not specific a indicator for muscular pathology. METHODS: This is a prospective cohort study that is conducted in King Abdulaziz Medical City and King Abdullah Specialized Children Hospital in Riyadh and included 504 term neonates who were born between March 2021 and August 2021. Two hundred and fifty three were males and 251 were females. Data and consents were managed and collected using 2 coordinators. RESULTS: Duration of the second stage of labor, age on the first CPK test and fetal gestational age were significantly correlated with CPK values (r=0.197, r=-0.234, r=0.274, respectively). The normal ranges for each delivery type were 334 U/L-2667U/L in normal spontaneous vaginal delivery, 265U/L-1182U/L in elective cesarean section, and 223U/L-3082 U/L in emergency cesarean section. CONCLUSION: The CPK was elevated in all neonates in all 3 modes of deliveries. An elevated levels of CPK in neonates is not a specific indicator for any congenital muscular pathology.


Assuntos
Cesárea , Creatina Quinase , Doenças Musculares , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Creatina Quinase/sangue , Idade Gestacional , Músculos , Estudos Prospectivos , Doenças Musculares/congênito
2.
Int Clin Psychopharmacol ; 37(6): 255-262, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35779068

RESUMO

The aim of the study was to evaluate the reference range of amisulpride for Chinese patients with schizophrenia and to assess its possible influencing factors based on therapeutic drug monitoring information. The relative adverse reactions of patients induced by amisulpride were also systematically investigated. A total of 425 patients with schizophrenia were assessed, including Positive and Negative Syndrome Scales, Treatment Emergent Symptom Scale, blood routine examination, hepatorenal function, lipids, hormones, as well as myocardial enzymes at baseline, and following treatment with amisulpride for 8 weeks. The steady-state plasma concentration of amisulpride was assayed using two-dimensional liquid chromatography. At the same dose, the amisulpride plasma concentration of patients combined with clozapine was higher than that without clozapine. The therapeutic reference range of amisulpride can be defined as 230.3-527.1 ng/ml for Chinese patients with schizophrenia. The potential side effects appear to be associated with significantly increased levels of LDH, CK, creatine kinase isoenzyme (CK-MB), TC and decreased level of E 2 , relative to the amisulpride plasma concentration. These findings could provide individualized medication and reduce the adverse effects of amisulpride for Chinese patients with schizophrenia.


Assuntos
Amissulprida , Antipsicóticos , Clozapina , Esquizofrenia , Amissulprida/efeitos adversos , Amissulprida/farmacocinética , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Clozapina/farmacocinética , Creatina Quinase/sangue , Monitoramento de Medicamentos , Hormônios/sangue , Humanos , Isoenzimas/sangue , Lipídeos/sangue , Esquizofrenia/tratamento farmacológico
3.
J Strength Cond Res ; 36(6): 1648-1654, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35622110

RESUMO

ABSTRACT: Botelho, R, Abad, CCC, Spadari, RC, Winckler, C, Garcia, MC, and Guerra, RLF. Psychophysiological stress markers during preseason among elite female soccer players. J Strength Cond Res 36(6): 1648-1654, 2022-This study aimed to investigate changes and correlations between mood states and various physiological stress markers after a 7-week preseason period among elite female soccer players. Twenty-four elite female soccer players participated in this study (26.4 ± 3.7 years). Their internal training load, mood states, day and evening salivary testosterone and cortisol concentrations, blood creatine kinase concentration (CK), and heart rate variability (HRV) were assessed during the first week of preseason (PRE), and again 7 weeks after a systematic training period (END). After the preseason, there were significant increases in subject negative mood scales (p ≤ 0.03; Effect Size [ES] > 0.60), total mood scores (p = 0.01; QI = 100/0/0; ES = 1.32), day and evening testosterone and cortisol concentrations (p ≤ 0.03; ES > 0.54), and CK concentrations (p = 0.01; QI = 100/0/0; ES = 1.54). Correlations were found between cortisol and tension (r = 0.53 and 0.60; p ≤ 0.02), cortisol and confusion (r = 0.75; p = 0.01), and cortisol and the LF/HF index of HRV (r = -0.52; p = 0.04). Mood states (except vigor), salivary testosterone, and cortisol concentrations, as well as CK, showed significant changes after a 7-week systematic training system. The cortisol was the factor most highly related to various mood states (including tension and confusion), and with the HRV indices. Coaches and researchers can use these data to design, monitor, and control soccer training programs, in particular throughout the preseason period.


Assuntos
Atletas , Hidrocortisona , Futebol , Estresse Fisiológico , Estresse Psicológico , Adulto , Atletas/psicologia , Biomarcadores/análise , Biomarcadores/sangue , Creatina Quinase/sangue , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hidrocortisona/análise , Estresse Ocupacional/fisiopatologia , Estresse Ocupacional/psicologia , Psicofisiologia , Saliva/química , Futebol/fisiologia , Futebol/psicologia , Estresse Fisiológico/fisiologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Testosterona/análise , Adulto Jovem
4.
Biomed Pharmacother ; 148: 112757, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35231696

RESUMO

BACKGROUND: Muscle pain and muscle weakness, common symptoms among statin-treated patients, may worsen with COVID-19 infection. AIMS: The aim of the paper was to find out if concomitant COVID-19 infections increase the frequency of specific side effects of statins such as muscle pain and muscle weakness. METHOD: A total of 66 patients diagnosed with COVID-19 without comorbidities participated in the study. The patients were divided into two groups: statin-users who had not experienced adverse effects of statins in the past (statin group (SG)) and patients who had not used any drugs in the past six months (control group (CG)). The severity of muscle pain and creatinine kinase (CK) activity was evaluated in each patient, and muscle weakness was confirmed by a dynamometer test (grip strength on both hands). RESULTS: In SG, muscle pain was more common and it was characterized by a high level of intensity. Muscle weakness occurred more frequently in the SG and it was more frequent compared to CG. The CK parameter was observed to be higher in the SG compared to the CG and was often associated with the severity of muscle pain in the range of moderate to severe. CONCLUSIONS: Our study indicates that COVID-19 is associated with the higher risk of occurrence of typical statin-related side effects, especially with more advanced age, which should be considered in future trials and treatments.


Assuntos
COVID-19/epidemiologia , COVID-19/fisiopatologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Debilidade Muscular/induzido quimicamente , Mialgia/induzido quimicamente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Creatina Quinase/sangue , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Estudos Retrospectivos , SARS-CoV-2
5.
Biomed Pharmacother ; 148: 112775, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35240528

RESUMO

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.


Assuntos
Infarto do Miocárdio/patologia , Extratos Vegetais/farmacologia , Rheum , Animais , Creatina Quinase/sangue , Relação Dose-Resposta a Droga , Isoproterenol/farmacologia , L-Lactato Desidrogenase/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/efeitos dos fármacos
6.
Lasers Med Sci ; 37(4): 2135-2144, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35246766

RESUMO

Photobiomodulation therapy (PBM) is often used to treat musculoskeletal disorders such as chronic non-specific low back pain (NSCLBP) as it can have positive effects on biomarkers-creatine kinase (CK) and serum cortisol levels-related to stress caused by physical exercise, such as deep water running (DWR) or by pain. The aim of this study was to evaluate the effects of the combination of PBM and aquatic exercise (DWR) on the intensity of pain, disability, 6-min walk test adapted (6WTA), and on cortisol and creatine kinase (CK) levels in a population with NSCLBP. The participants were allocated into three groups: TGPBM (Photobiomodulation and Training Group), TGPLA (Placebo Photobiomodulation and Training Group), and the GPBM (Photobiomodulation Group). Information regarding anthropometric data, blood pressure, and heart rate were collected, and the questionnaires were applied: IPAQ-Short Form, Oswestry Disability Index, and the Visual Analog Scale for Pain. The submaximal exercise test (6WTA) was performed. Blood was collected for analysis of cortisol and CK levels. The training sessions were performed twice a week, for 4 weeks. In the intragroup comparisons, there were statistically significant changes in the TGPBM and GPBM groups in the outcomes pain intensity, disability (reductions in both groups), and in cortisol (increased in the TGPBM and reduced in the GPBM); in the TGPLA group, there was a statistically significant reduction only in the outcome of pain intensity. In the intergroup comparison, in the comparison between TGPBM and TGPLA, there was a statistically significant difference in the level of cortisol, as well as in the comparison between TGPBM and GPBM, in which there was a statistically significant difference for this same outcome (cortisol) and for the 6WTA outcome. The effects of the combination of PBM and aquatic exercise have positive effects on reducing pain intensity, disability, and cortisol levels, but its effects on other variables (6WTA and CK) are too small to be considered significant. Trial registration number: NCT03465228-April 3, 2019; retrospectively registered (ClinicalTrials.gov).


Assuntos
Dor Crônica , Terapia por Exercício , Dor Lombar , Terapia com Luz de Baixa Intensidade , Corrida , Dor Crônica/radioterapia , Dor Crônica/terapia , Creatina Quinase/sangue , Humanos , Hidrocortisona/sangue , Dor Lombar/radioterapia , Resultado do Tratamento , Água
8.
J Therm Biol ; 104: 103187, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35180966

RESUMO

Plyometric training has been used in several sports and fitness programs to improve jumping ability and explosive strength, both in individual and team sports. Eccentric muscle actions, such as those performed during plyometric jumps, induce muscle damage and consequently a rise in skin temperature (Tsk). Thus, the purpose of this study is to assess the response of infrared thermography measurement as an indirect marker of muscle damage after a protocol of plyometric jumps in physically active subjects. Therefore, for the aim of this study ten male subjects with no previous experience in plyometric training participated in the research (age 22.5 ± 3.3 years, weight 71.7 ± 11.0 kg, height 171.1 ± 5.3 cm, and fat mass 15.5 ± 4.7%). To assess the muscle damage, countermovement jump (CMJ), creatine kinase (CK), delayed-onset muscle soreness (DOMS) and infrared thermography (IRT) were measured at 24, 48, and 72 h after plyometric exercise. The acute exercise protocol of plyometric jumps induced muscle damage, as shown by the CK and DOMS (24 and 48 h, p < 0.05) but no statistical difference was shown between the moments analyzed in Tsk (warm zone). Nevertheless, when comparing baseline to 48h, a moderate effect was found in the Tsk (warm zone) for anterior right thigh (ES = 1.1) and posterior left thigh (ES = 0.9) and large effect was found for anterior left thigh (ES = 1.4) and posterior right thigh (ES = 1.3). A moderate effect in the Tsk (warm zone) was found for posterior right and left thigh (ES = 0.9 and ES = 1.1, respectively) when comparing baseline to 72h of IRT. These results suggest that a plyometric jumping session alters CK and DOMS, as well as the thigh's skin temperature in an evident way, bringing up a possible relation with markers of muscle damage.


Assuntos
Músculo Esquelético/fisiopatologia , Exercício Pliométrico , Temperatura Cutânea/fisiologia , Termografia , Adulto , Biomarcadores/análise , Creatina Quinase/sangue , Humanos , Raios Infravermelhos , Extremidade Inferior/fisiologia , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/lesões , Mialgia/etiologia , Mialgia/fisiopatologia , Adulto Jovem
9.
J Appl Physiol (1985) ; 132(4): 966-973, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35175101

RESUMO

This study aimed to clarify 1) the influence of genetic polymorphisms in the cytochrome P450 aromatase gene (CYP19A1) on circulating estradiol levels in men and 2) whether estrogen-related genetic polymorphisms, such as the CYP19A1 rs936306 and estrogen receptor-α (ESR1) rs2234693 polymorphisms, predict exercise-induced serum creatine kinase (CK) activity, which is an index of skeletal muscle membrane disruption. Serum estradiol levels were examined in young men (n = 167). In a different cohort, serum CK activity was analyzed in a 2-day ultramarathon race: baseline, after the first day, and after the second day (114 males and 25 females). Genetic polymorphisms in CYP19A1 rs936306 C/T and ESR1 rs2234693 T/C were analyzed using the TaqMan SNP Genotyping Assay. Male subjects with the TT genotype of the CYP19A1 polymorphism exhibited significantly higher serum estradiol levels than the C allele carriers. Male runners had significantly higher postrace serum CK activity than female runners. The change in the CK activity during the ultramarathon race was significantly lower in male subjects with the CYP19A1 TT genotype than in those with the CC + CT genotypes and was correlated with the number of C alleles in ESR1 rs2234693 in male subjects. Furthermore, the genotype scores of these two polymorphisms were significantly correlated with changes in serum CK activity during race (r = -0.279, P = 0.003). The results of this study suggest that genetic polymorphisms in CYP19A1 rs936306 influence serum estradiol levels in men, and genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity in men.NEW & NOTEWORTHY Men with the TT genotype of the CYP19A1 polymorphism exhibited higher circulating estradiol levels than the TC + CC genotype. The TT genotype in the CYP19A1 polymorphism and the C allele of the ESR1 polymorphism, an allele increasing ESR1 expression, were associated with low serum CK activity after the ultramarathon. A combination of these polymorphisms was correlated with changes in the serum CK activity. Therefore, estrogen-related genetic polymorphisms partially predict exercise-induced muscle damage, that is, skeletal muscle membrane disruption.


Assuntos
Aromatase , Creatina Quinase , Receptor alfa de Estrogênio , Corrida , Aromatase/genética , Estudos de Coortes , Creatina Quinase/sangue , Receptor alfa de Estrogênio/genética , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
10.
Toxicology ; 468: 153113, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35101590

RESUMO

5-Fluorouracil (5-FU) was a key chemotherapeutic agent in the treatment of different solid tumors. However, cardiotoxicity was included among the therapeutic strategies of 5-FU. The molecular mechanism of cardiotoxicity induced by 5-FU remains unclear. The aim of the study was to investigate whether ferroptosis was involved in 5-FU-induced cardiotoxicity in vivo and in vitro. The in vivo cardiotoxicity model was induced by intraperitoneal injection of 5-FU at the dose of 15, 30, 60 mg/kg for 7 days. Body weight, general condition and plasma enzyme activities of the mice were observed to evaluate heart function. In addition, HE staining, MASSON staining and TEM technology was used. Western-blot analysis were performed to evaluate the protein level of iron transport, iron storage and reactive oxygen species (ROS) of ferroptosis. In H9c2 cardiomyocyte cells, cell viability, generation of ROS, mitochondrial activity and cellular Fe2+ levels were measured. The in vivo results showed that 5-FU significantly impaired cardiac function and structure. The serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels were significantly increased in 5-FU group. HE and MASSON staining showed that 5-FU caused structural injuries. In addition, 5-FU increased the level of ferroptosis markers involving malonaldehyde (MDA) and Fe2+ content. Ferrostatin-1 (Fer-1) was an aromatic amine that specifically binds with lipid ROS and protects cells against lipid peroxidation. Furthermore, 5-FU markedly induced ferroptosis in H9c2 cardiomyocyte cells, which mainly embodied as declined cell vitality, accumulated iron, elevated lipid peroxides. Conversely, inhibition of ferroptosis by Fer-1 completely abolished 5-FU-induced effects. Both in vivo and in vitro experiments indicated that 5-FU increased the expression of ferroptosis, mainly by reducing the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1), but enhancing the expression of transferrin receptor 1 (TfR1). In conclusion, the present study suggested that ROS and iron homeostasis dependent ferroptosis played a vital role in 5-FU induced cardiotoxicity.


Assuntos
Ferroptose/fisiologia , Ferro/metabolismo , Miocárdio/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Western Blotting , Peso Corporal/efeitos dos fármacos , Corantes , Creatina Quinase/sangue , Ecocardiografia , Amarelo de Eosina-(YS) , Corantes Fluorescentes , Fluoruracila/farmacologia , Coração/anatomia & histologia , Coração/efeitos dos fármacos , Coração/fisiologia , Hematoxilina , Homeostase , L-Lactato Desidrogenase/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Mitocôndrias/fisiologia , Miocárdio/ultraestrutura , Tamanho do Órgão/efeitos dos fármacos , Plasma/química , Nitrato de Prata
11.
Toxicol Ind Health ; 38(1): 11-18, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35100895

RESUMO

Musculoskeletal disorders (MSDs) are considered a growing problem among healthcare personnel, especially service workers. The emergency room (ER) service workers are highly exposed to work-related risk factors which predispose them to MSDs. A cross-sectional study was performed on 78 ER workers. Full medical and occupational histories were taken. The Standardized Nordic Questionnaire (SNQ) was used for the assessment of musculoskeletal symptoms. Clinical examination was done with special emphasis on the locomotors system, and serum levels of muscle enzymes, including creatine kinase (CK) and creatine kinase isoenzyme (CK-MM), were measured. The study aims to detect the prevalence of occupational musculoskeletal disorders (MSDs) among ER workers at University hospitals, and assessment of CK-MM as a biomarker used in the early detection of MSDs. We found that 71.8% of the participants were complaining of musculoskeletal disorder in the last 7 days before the study, while only 34.6% were complaining of musculoskeletal disorder in the last 12 months before the study. The knee joint was the most commonly affected site in the past 7 days, by 39.7%. On the other hand, the highest prevalent disorder in the last 12 months was for the ankle joint (17.9%) with significantly high levels of serum CK-MM. In conclusion, musculoskeletal injuries are a common complaint among healthcare occupations, especially among ER service workers that need regular health education and ergonomic training programs. Monitoring of serum CK-MM level with cut-off value 90 ng\ml could be used as a novel approach for the early detection of work-related musculoskeletal disorders.


Assuntos
Creatina Quinase/sangue , Serviço Hospitalar de Emergência , Pessoal de Saúde , Doenças Musculoesqueléticas/sangue , Doenças Profissionais/sangue , Adulto , Biomarcadores/sangue , Estudos Transversais , Egito/epidemiologia , Feminino , Humanos , Masculino , Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/epidemiologia , Prevalência , Inquéritos e Questionários
12.
PLoS One ; 17(2): e0263772, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35139123

RESUMO

The 24 h responses to professional female netball-specific training were examined. British Superleague players (n = 14) undertook a 90-min on-court training session incorporating key movement, technical, and scenario-specific match-play drills. Perceptual (mood, fatigue, soreness), neuromuscular (countermovement jump peak power output [PPO], PPO relative to mass [PPOrel], jump height [JH]), endocrine (salivary cortisol [C], testosterone [T] concentrations) and biochemical (creatine kinase concentrations [CK]) markers were assessed at baseline (immediately before; Pre), and immediately, two and 24 hours after (+0h, +2h, +24h) training. Session (sRPE) and differential (dRPE) ratings of perceived exertion were recorded at +0h. Identification of clear between time-point differences were based on the 95% confidence interval (CI) for mean differences relative to baseline values not overlapping. At +0h, C (raw unit mean difference from baseline; 95% CI: 0.16; 0.06 to 0.25 µg·dl-1), T (32; 20 to 45 pg⋅ml-1), CK (39; 28 to 50 u·L-1), PPOrel (2.4; 0.9 to 3.9 W·kg-1) and PPO (169; 52 to 286 W) increased. At +2h, fatigue (15; 7 to 24 AU), CK (49; 38 to 60 u·L-1), and soreness (14; 3 to 25 AU) increased, while T (-24; -37 to -11 pg⋅ml-1) and mood (-20; -27 to -12 AU) reduced. At +24h, CK increased (25; 13 to 36 u·L-1) whereas PPOrel (-1.6; -3.2 to -0.1 W·kg-1) and JH (-0.02; -0.03 to -0.08 m) reduced. Responses were variable specific, and recovery of all variables did not occur within 24h. The residual effects of the prior stimulus should be accounted for in the planning of training for professional female netball players.


Assuntos
Afeto/fisiologia , Atletas , Desempenho Atlético/fisiologia , Basquetebol , Condicionamento Físico Humano/fisiologia , Adulto , Atletas/psicologia , Desempenho Atlético/psicologia , Basquetebol/fisiologia , Basquetebol/psicologia , Creatina Quinase/sangue , Fadiga/etiologia , Fadiga/metabolismo , Fadiga/fisiopatologia , Feminino , Hormônios/análise , Hormônios/metabolismo , Humanos , Hidrocortisona/análise , Hidrocortisona/metabolismo , Músculo Esquelético/fisiologia , Mialgia/etiologia , Mialgia/metabolismo , Mialgia/fisiopatologia , Condicionamento Físico Humano/psicologia , Saliva/química , Saliva/metabolismo , Testosterona/análise , Testosterona/metabolismo , Reino Unido , Adulto Jovem
13.
Rinsho Shinkeigaku ; 62(2): 135-139, 2022 Feb 19.
Artigo em Japonês | MEDLINE | ID: mdl-35095048

RESUMO

A 69-year-old man visited our hospital complaining of fatigue in the lower extremities while walking. The patient had a two-year history of congestive heart failure and received a permanent artificial pacemaker implantation for sick sinus syndrome. Physical examination revealed proximal muscle weakness and exaggerated lumbar lordosis. Serum creatine kinase level was 1,455 U/l. The atrophies of the paraspinal muscles at thoracic to lumbar spine levels, rectus abdominis and soleus muscles were detected on computed tomography. Muscle biopsy showed mild to moderate variability in muscle fiber size with regenerating and necrotic muscle fibers. Mononuclear cell infiltration was not found. HLA-ABC expression was minimum. After anti-mitochondrial M2 antibody was detected, administration of oral prednisolone resulted in improvements in muscle strength and serum creatine kinase level. Based on the clinical course, examination and clinical findings, the patient was diagnosed as anti-mitochondrial M2 antibody positive myositis. Anti-mitochondrial M2 positive myositis is not only difficult to diagnose by muscle biopsy, but can also be preceded or complicated by fatal cardiac complications.


Assuntos
Insuficiência Cardíaca , Miosite , Idoso , Creatina Quinase/sangue , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Músculo Esquelético/patologia , Miosite/diagnóstico , Prednisolona
14.
Lancet Gastroenterol Hepatol ; 7(3): 219-229, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35065058

RESUMO

BACKGROUND: Surgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma. METHODS: For this single-arm, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma (stage Ib, II, and IIIb) were enrolled and received two cycles of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by surgical resection. Eligible patients were aged 18 years or older, had confirmed resectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate liver function. Patients were excluded if they had metastatic disease, if the surgery was not expected to be curative, if they had a known additional malignancy requiring active treatment, or if they required systemic steroid treatment or any other immunosuppressive therapy. After resection, patients received an additional eight cycles of cemiplimab 350 mg intravenously every 3 weeks in the adjuvant setting. The primary endpoint was significant tumour necrosis on pathological examination (defined as >70% necrosis of the resected tumour). Secondary endpoints included delay of surgery, the proportion of patients with an overall response, change in CD8+ T-cell density, and adverse events. Tumour necrosis and response were analysed in all patients who received at least one dose of cemiplimab and completed surgical resection; safety and other endpoints were analysed in the intention-to-treat population. Patients underwent pre-treatment biopsies and blood collection throughout treatment. This trial is registered with ClinicalTrials.gov (NCT03916627, Cohort B) and is ongoing. FINDINGS: Between Aug 5, 2019, and Nov 25, 2020, 21 patients were enrolled. All patients received neoadjuvant cemiplimab, and 20 patients underwent successful resection. Of the 20 patients with resected tumours, four (20%) had significant tumour necrosis. Three (15%) of 20 patients had a partial response, and all other patients maintained stable disease. 20 (95%) patients had a treatment-emergent adverse event of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were increased aspartate aminotransferase (in four patients), increased blood creatine phosphokinase (in three), constipation (in three), and fatigue (in three). Seven patients had grade 3 adverse events, including increased blood creatine phosphokinase (in two patients) and hypoalbuminaemia (in one). No grade 4 or 5 events were observed. One patient developed pneumonitis, which led to a delay in surgery by 2 weeks. INTERPRETATION: This report is, to our knowledge, the largest clinical trial of a neoadjuvant anti-PD-1 monotherapy reported to date in hepatocellular carcinoma. The observed pathological responses to cemiplimab in this cohort support the design of larger trials to identify the optimal treatment duration and definitively establish the clinical benefit of preoperative PD-1 blockade in patients with hepatocellular carcinoma. FUNDING: Regeneron Pharmaceuticals.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Aspartato Aminotransferases/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Creatina Quinase/sangue , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante
15.
J Clin Lab Anal ; 36(3): e24216, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35076953

RESUMO

BACKGROUND: Coronavirus disease 2019, COVID-19, has reached all the corners of the world and was declared by the WHO as a global pandemic and public health emergency of international concern on the January 31, 2020. Allocating quick and specific biomarkers to predict the disease severity upon admission to hospital became a crucial need. This study, therefore, aimed at exploring the relationship between laboratory results in COVID-19 patients admitted to hospital and the final outcome in these patients. METHODS: Retrospective analysis was performed on the medical records of 310 COVID-19-positive patients admitted to Uhod Hospital, the referral hospital in the area of Madinah, Kingdom of Saudi Arabia, between the April 13 and the July 29, 2020. The association of laboratory results with the survival/mortality outcomes was studied. RESULTS: It was demonstrated that lymphopenia, prolonged aPTT, high INR, high D. dimer and high CK are valuable prognostic predictors of the severity of the disease at early stages that can determine the outcome. Based on the results of the multiple logistic regression, the variables that are associated with death outcome are aPTT, HR, RR, ALT and CK level CONCLUSION: It is proposed to perform these tests on admission to hospital for moderate to severe COVID-19 patients to improve the management of those cases and reduce mortality.


Assuntos
COVID-19 , Hospitalização/estatística & dados numéricos , Adulto , Idoso , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/fisiopatologia , Creatina Quinase/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Arábia Saudita
16.
BMC Complement Med Ther ; 22(1): 28, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35090456

RESUMO

BACKGROUND: Acupuncture therapy has been widely used as an alternative therapy to treat multiple diseases, such as sequelae of stroke, pain, facial paralysis and so on. In recent years, few adverse events related to acupuncture treatment have been reported, among which hematoma, bleeding and dizziness are the main manifestations. However, to date, there have been no existing cases reported the association between acupuncture therapy and asymptomatic/pauci-symptomatic hyperCKemia. CASE PRESENTATION: We report a patient who developed hyperCKemia during 5 sessions of acupuncture at different frequencies. After stopping acupuncture treatment for 1 month, follow-up showed a significant downward trend in serum creatine kinase (sCK). However, after that this patient started to get acupuncture treatment again in order to improve the sequelae of stroke. Meantime, the sCK rose again. CONCLUSION: HyperCKemia may associated with acupuncture therapy. All kinds of adverse events of acupuncture should be recorded comprehensively and objectively so as to improve the safety standard system of acupuncture therapy.


Assuntos
Terapia por Acupuntura/efeitos adversos , Creatina Quinase/sangue , Animais , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/terapia
17.
Am J Physiol Cell Physiol ; 322(2): C283-C295, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35020501

RESUMO

Limb-girdle muscular dystrophy R12 (LGMD-R12) is caused by recessive mutations in the Anoctamin-5 gene (ANO5, TMEM16E). Although ANO5 myopathy is not X-chromosome linked, we performed a meta-analysis of the research literature and found that three-quarters of patients with LGMD-R12 are males. Females are less likely to present with moderate to severe skeletal muscle and/or cardiac pathology. Because these sex differences could be explained in several ways, we compared males and females in a mouse model of LGMD-R12. This model recapitulates the sex differences in human LGMD-R12. Only male Ano5-/- mice had elevated serum creatine kinase after exercise and exhibited defective membrane repair after laser injury. In contrast, by these measures, female Ano5-/- mice were indistinguishable from wild type. Despite these differences, both male and female Ano5-/- mice exhibited exercise intolerance. Although exercise intolerance of male mice can be explained by skeletal muscle dysfunction, echocardiography revealed that Ano5-/- female mice had features of cardiomyopathy that may be responsible for their exercise intolerance. These findings heighten concerns that mutations of ANO5 in humans may be linked to cardiac disease.


Assuntos
Anoctaminas/deficiência , Cardiomiopatias/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Miocárdio/metabolismo , Animais , Anoctaminas/genética , Cardiomiopatias/genética , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Creatina Quinase/sangue , Tolerância ao Exercício , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Contração Muscular , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular do Cíngulo dos Membros/fisiopatologia , Miocárdio/patologia , Caracteres Sexuais , Fatores Sexuais
19.
J Pharm Pract ; 35(1): 148-151, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32924753

RESUMO

Daptomycin possesses excellent activity against many multidrug-resistant gram positive organisms. However, a side effect of concern with daptomycin is skeletal muscle injury, which is manifested in the form of elevated creatine phosphokinase (CPK). Management of such CPK elevations has traditionally been discontinuation of the offending agent, with many studies showing a resolution of a normal CPK level within 1 week of discontinuation and no long term adverse effects. Nevertheless, the question remains if daptomycin can be successfully restarted in such patients. Here, we present a case of a "daptomycin holiday" in which daptomycin was withheld upon CPK elevation and successfully reintroduced to the patient's regimen again after several days without further elevation of the CPK. The patient had a peak CPK of 2,557 U/L, and had no associated symptoms. A hypothesis for this holiday could be the adaptability of the skeletal muscle myocytes, in which the extra period between doses may allow for additional recovery of the membrane structure to further daptomycin exposure. Giving an asymptomatic patient with elevated CPK level, a short daptomycin holiday to allow for the CPK level to trend downward before resuming daptomycin therapy could be a potential strategy in patients for whom continuing daptomycin is still preferred.


Assuntos
Creatina Quinase/sangue , Daptomicina , Antibacterianos/administração & dosagem , Daptomicina/administração & dosagem , Humanos , Estudos Retrospectivos
20.
Eur J Appl Physiol ; 122(1): 255-266, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34674024

RESUMO

PURPOSE: Unaccustomed eccentric contractions generally result in a long-lasting contractile impairment, referred to as prolonged low-frequency force depression (PLFFD), and delayed-onset muscle soreness (DOMS). We here used repeated drop jumps (DJs) as an eccentric contraction model and studied the effects of increasing the time between DJs from 20 s to 5 min. We hypothesized that both PLFFD and DOMS would be less marked at the longer DJ interval due to the longer time to restore structural elements between DJs. METHODS: Young men (n = 12) randomly performed 50 DJs with either 20-s (DJ-20 s) or 5-min (DJ-5 min) rest between DJs. Voluntary, 20 Hz and 100 Hz electrically stimulated isometric knee extension torques and muscle soreness were monitored before and for 7 days after DJs; serum CK activity was measured to assess muscle fibre protein leakage. In additional experiments, changes in mRNA levels were assessed in muscle biopsies collected before and 1 h after exercise. RESULTS: A marked PLFFD was observed with both protocols and the extent of 20 Hz torque depression was smaller immediately and 1 day after DJ-5 min than after DJ-20 s (p < 0.05), whereas the MVC and 100 Hz torques were similarly decreased with the two protocols. Markedly larger differences between the two protocols were observed for the muscle soreness score, which 1-4 days after exercise was about two times larger with DJ-20 s than with DJ-5 min (p < 0.01). CONCLUSIONS: The larger protective effect of the longer DJ interval against DOMS than against PLFFD indicates that their underlying mechanisms involve different structural elements.


Assuntos
Joelho/fisiologia , Contração Muscular/fisiologia , Mialgia/prevenção & controle , Descanso , Adulto , Biomarcadores/sangue , Biópsia por Agulha , Creatina Quinase/sangue , Estimulação Elétrica , Humanos , Masculino , Medição da Dor , Fatores de Tempo , Torque , Adulto Jovem
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