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1.
Life Sci ; 258: 118242, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32784056

RESUMO

AIMS: As the spermatogenesis process is targeted by cisplatin (Cis) that changes testicular morphology, alters sperm quality, and hence causes male infertility. This study investigated the possible therapeutic effects of l-carnitine (LC) on Cis impaired spermatogenesis's establishment during the prepubertal phase. MATERIALS AND METHODS: Ninety-six prepubertal Sprague Dawley male rats were divided into four groups. CONTROL GROUP: rats were injected with 0.9% saline solution intraperitoneally (i.p.). LC group: animals were injected for eight weeks, with 250 mg/kg/wk. LC (i.p.). Cis group: animals were injected with a single dose of 5 mg/kg Cis (i.p.). LC + Cis group: animals were pre-injected with LC 250 mg/kg 2 h before Cis injection. The rats were sacrificed at 37, 60, and 90 days old, and their testes were taken for biochemical, molecular, and histopathological studies. The motility, viability, morphology, and DNA fragmentation of sperm in adult rats were also measured. KEY FINDINGS: Group treated with LC and Cis showed an increase in antioxidant and hormonal activity compared to the Cis treated group in the pre and post-pubertal period. Moreover, there was an increase in sperm survival, motility, and DNA integrity. Furthermore, LC showed an increase in the anti-apoptotic and chromatin remodeling genes and a decrease in the pro-inflammatory genes. SIGNIFICANCE: LC could enhance the spermatogenesis process after exposure to Cis during the prepubertal phase by restoring the balance between reactive oxygen species and antioxidant activity, improving hormonal activity, sperm quality and DNA integrity, promoting protamination and blood-testis barrier integrity, and maintaining the testicular architecture.


Assuntos
Carnitina/farmacologia , Cisplatino/toxicidade , Infertilidade Masculina/prevenção & controle , Infertilidade Masculina/fisiopatologia , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Animais , Antineoplásicos/toxicidade , Carnitina/uso terapêutico , Infertilidade Masculina/induzido quimicamente , Masculino , Ratos , Ratos Sprague-Dawley , Maturidade Sexual/fisiologia , Motilidade Espermática/efeitos dos fármacos , Motilidade Espermática/fisiologia , Espermatogênese/fisiologia
2.
PLoS One ; 15(8): e0237097, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810864

RESUMO

Neurofibromatosis type 1 (NF1) is a genetic disorder that affects a range of tissue systems, however the associated muscle weakness and fatigability can have a profound impact on quality of life. Prior studies using the limb-specific Nf1 knockout mouse (Nf1Prx1-/-) revealed an accumulation of intramyocellular lipid (IMCL) that could be rescued by a diet supplemented with L-carnitine and enriched for medium-chain fatty acids (MCFAs). In this study we used the Nf1Prx1-/- mouse to model a range of dietary interventions designed to reduce IMCL accumulation, and analyze using other modalities including in situ muscle physiology and lipid mass spectrometry. Histological IMCL accumulation was significantly reduced by a range of treatments including L-carnitine and high MCFAs alone. A low-fat diet did not affect IMCL, but did provide improvements to muscle strength. Supplementation yielded rapid improvements in IMCL within 4 weeks, but were lost once treatment was discontinued. In situ muscle measurements were highly variable in Nf1Prx1-/- mice, attributable to the severe phenotype present in this model, with fusion of the hips and an overall small hind limb muscle size. Lipidome analysis enabled segregation of the normal and modified chow diets, and fatty acid data suggested increased muscle lipolysis with the intervention. Acylcarnitines were also affected, suggestive of a mitochondrial fatty acid oxidation disorder. These data support the theory that NF1 is a lipid storage disease that can be treated by dietary intervention, and encourages future human trials.


Assuntos
Metabolismo dos Lipídeos , Força Muscular , Músculo Esquelético/metabolismo , Neurofibromatose 1/dietoterapia , Animais , Carnitina/administração & dosagem , Carnitina/uso terapêutico , Suplementos Nutricionais , Ácidos Graxos/administração & dosagem , Ácidos Graxos/uso terapêutico , Feminino , Camundongos , Músculo Esquelético/fisiopatologia , Neurofibromatose 1/genética , Neurofibromina 1/genética
3.
Medicine (Baltimore) ; 99(28): e21061, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664122

RESUMO

Sarcopenia has a negative impact on the prognosis of patients with liver cirrhosis (LC). We investigated the significance of skeletal muscle volume and its changes in LC patients taking levocarnitine (L-carnitine).We retrospectively analyzed 51 LC patients taking L-carnitine from December 2012 to March 2019. Skeletal mass index was calculated as the left-right sum of the major × minor axis of psoas muscle at the third lumbar vertebra, divided by height squared (psoas muscle index [PMI]). Patients were classified into 2 groups (low and normal PMI) depending on PMI < 6.0 and < 3.4 cm/m for men and women, respectively. Changes in PMI per month during L-carnitine administration (ΔPMI/m) were calculated, and we classified the patients into 2 groups (severe and mild muscle atrophy) depending on ΔPMI/m below the lower quartile. We assessed overall survival (OS).At the start of L-carnitine administration, there were no significant differences in OS between groups with low and normal PMI. Multivariate analysis showed that ΔPMI/m (hazard ratio [HR], 0.007; P = .005) and L-carnitine administration period (HR, 0.956; P = .021) were significantly associated with OS. Patients with severe muscle atrophy had a significantly lower OS than those with mild muscle atrophy. There was the positive correlation relationship between ΔPMI/m and L-carnitine administration period.Among LC patients taking L-carnitine, progressive muscle volume loss was a predictor of poor prognosis. L-carnitine administration for longer may be able to prevent muscle volume loss and lead to a better prognosis in LC patients.


Assuntos
Carnitina/uso terapêutico , Cirrose Hepática/epidemiologia , Sarcopenia/tratamento farmacológico , Sarcopenia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Amônia/sangue , Feminino , Humanos , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Músculos Psoas , Estudos Retrospectivos , Sarcopenia/fisiopatologia , Índice de Gravidade de Doença , Fatores Sexuais
4.
J Pediatr Hematol Oncol ; 42(6): 386-390, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32555029

RESUMO

INTRODUCTION: Heart failure, fatal arrhythmias, and cardiac dilatation because of anemia are common causes of ß-thalassemia major-related deaths. The aim of this study was to determine the effect of L-carnitine on echocardiographic changes in ß-thalassemia major and intermedia patients in Besat Hospital in Sanandaj, Iran. METHODS: In a randomized clinical trial, 60 ß-thalassemia patients who were eligible for L-carnitine administration were randomly divided into 2 placebo and study drug groups. The duration of the study was 6 months. Using echocardiography and blood tests, cardiac parameters including left ventricular dilatation, left ventricular hypertrophy, and a number of cardiac blood indices were examined before and after the intervention. The data were analyzed using SPSS V.23 software, χ, and covariance statistical tests. RESULTS: There was no significant difference between the 2 groups in terms of age and sex. Patients treated with L-carnitine have a reduced rate of left ventricular dilatation, left ventricular hypertrophy, and systolic blood pressure compared with controls (P<0.05). Cardiac output increased from 43.5 to 56.5 (P=0.002). CONCLUSIONS: The results of this study showed that the drug has a positive effect on the improvement of cardiac indices in ß-thalassemia patients. Therefore, we suggest that further studies with more samples and other diagnostic modalities of the drug's effect be investigated.


Assuntos
Arritmias Cardíacas/prevenção & controle , Carnitina/uso terapêutico , Ecocardiografia/métodos , Talassemia beta/tratamento farmacológico , Adolescente , Adulto , Arritmias Cardíacas/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Adulto Jovem , Talassemia beta/classificação , Talassemia beta/patologia
5.
Saudi Med J ; 41(6): 590-596, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32518924

RESUMO

OBJECTIVES: To describe the clinical and molecular characteristics of patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency.   Methods: A retrospective observational cross-sectional analysis was conducted on all patients with VLCAD deficiency at  (Genetic/Metabolic Section), Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia from 2000 to 2019. Demographic, clinical, and laboratory data were abstracted from the electronic hospital records using a case report form. Results: A total of 14 children were analyzed. Six presented with hypoglycemia, 4 with cardiomyopathy, and 10 had rhabdomyolysis. Five patients had early onset severe phenotype, while 9 had mild form. The molecular study revealed homozygous mutations in ACADVL in all 14 patients. Three variants were not reported before. All patients were treated with medium-chain triglyceride and carnitine. Ten patients are alive and have normal development, while 4 died. Conclusion: Most of the patients in this cohort presented in the neonatal period either by newborn screening or clinically with hypoglycemia, cardiomyopathy, and rhabdomyolysis. The new molecular variants detected in this study broaden the genetic spectrum of VLCAD deficiency in Saudi Arabia.


Assuntos
Acil-CoA Desidrogenase de Cadeia Longa/deficiência , Síndrome Congênita de Insuficiência da Medula Óssea , Erros Inatos do Metabolismo Lipídico , Doenças Mitocondriais , Doenças Musculares , Acil-CoA Desidrogenase de Cadeia Longa/genética , Cardiomiopatias/etiologia , Carnitina/uso terapêutico , Estudos de Coortes , Síndrome Congênita de Insuficiência da Medula Óssea/diagnóstico , Síndrome Congênita de Insuficiência da Medula Óssea/tratamento farmacológico , Síndrome Congênita de Insuficiência da Medula Óssea/genética , Estudos Transversais , Homozigoto , Humanos , Hipoglicemia/etiologia , Recém-Nascido , Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/tratamento farmacológico , Erros Inatos do Metabolismo Lipídico/genética , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/genética , Doenças Musculares/diagnóstico , Doenças Musculares/tratamento farmacológico , Doenças Musculares/genética , Mutação , Triagem Neonatal , Rabdomiólise/etiologia , Arábia Saudita , Triglicerídeos/uso terapêutico
6.
Nat Rev Nephrol ; 16(8): 471-482, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269302

RESUMO

Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations.


Assuntos
Terapia de Substituição Renal Contínua/métodos , Hiperamonemia/terapia , Diálise Peritoneal/métodos , Distúrbios Congênitos do Ciclo da Ureia/terapia , Arginina/uso terapêutico , Carnitina/uso terapêutico , Criança , Pré-Escolar , Técnica Delfos , Dieta com Restrição de Proteínas , Humanos , Terapia de Substituição Renal Híbrida , Hiperamonemia/metabolismo , Lactente , Recém-Nascido , Nutrição Parenteral/métodos , Fenilacetatos/uso terapêutico , Fenilbutiratos/uso terapêutico , Guias de Prática Clínica como Assunto , Diálise Renal/métodos , Benzoato de Sódio/uso terapêutico , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Complexo Vitamínico B/uso terapêutico
7.
Clin Chim Acta ; 505: 92-97, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32070725

RESUMO

INTRODUCTION: Carnitine is essential for long-chain fatty acid oxidation in muscle and heart. Tissue stores are regulated by organic cation/Cn transporter plasmalemmal Octn2. We previously demonstrated low carnitine in quadriceps/gluteus and heart of adult mdx mice. METHODS: We studied protein and mRNA expression of Octn2, mitochondrial Octn1 and peroxisomal Octn3 in adult male C57BL/10ScSn-DMD mdx/J quadriceps, heart, and diaphragm compared to C57BL/10SnJ mice. RESULTS: We demonstrated reduction in mOctn2 expression on Western blot and similar expression of mOctn1 and mOctn3 in mdx quadriceps, heart and diaphragm. There was a significant upregulation of mOctn1 and mOctn2 mRNA by qRT-PCR in mdx quadriceps and of mOctn2 and mOctn3 mRNA in mdx heart. We showed upregulation of mdx mOctn1 and mOctn3 mRNA but no increase in protein expression. DISCUSSION: Dystrophin deficiency likely disrupts Octn2 expression decreasing muscle carnitine uptake thus contributing to membranotoxic long-chain acyl-CoAs with sarcolemmal and organellar membrane oxidative injury providing a treatment rationale for early L-carnitine in DMD.


Assuntos
Carnitina/química , Carnitina/uso terapêutico , Músculo Esquelético/química , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/genética , Miocárdio/química , Proteínas de Transporte de Cátions Orgânicos/biossíntese , Proteínas de Transporte de Cátions Orgânicos/genética , Membro 5 da Família 22 de Carreadores de Soluto/biossíntese , Membro 5 da Família 22 de Carreadores de Soluto/genética , Simportadores/biossíntese , Simportadores/genética , Animais , Carnitina/metabolismo , Diafragma/metabolismo , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética
8.
Chin J Integr Med ; 26(2): 146-151, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31997237

RESUMO

OBJECTIVE: To evaluate the clinical effectiveness and safety of the Chinese medicine (CM) Qixiong Zhongzi Decoction (, QZD) in the treatment of patients with idiopathic asthenozoospermia. METHODS: A total number of 66 patients with idiopathic asthenozoospermia were included and randomly divided into treatment and control groups by SAS-generated code from January 2015 to August 2016, 33 patients in each group. Patients in the treatment group were administered with 150 mL of QZD twice a day, whereas those in the control group were given 1 g of levocarnitine oral liquid twice a day. The two groups received the indicated medication for 12 weeks and were then followed up for 4 weeks. The primary outcome was sperm motility, and the secondary therapeutic indices were sperm volume, density, pregnancy probability, and CM syndrome score. The comparison between groups was carried out at 4, 8 and 12 weeks, respectively. The safety was determined before and after treatment. RESULTS: (1) Drop-off: 5 cases (7.58%) were lost after treatment (2 from the treatment group and 3 from the control group). (2) Primary outcomes: after 8- and 12-week treatment, the progressive sperms in the two groups were significantly higher than the baseline (all P<0.05); however, the treatment group showed greater improvement compared with the control group at 12-week treatment (22.7% ± 9.0% vs. 14.1% ±8.8%, P<0.05). The increasement of non-progressive grade sperms at both groups was observed at 8- and 12-week treatment with statistical difference (all P<0.05), however, the treatment group showed remarkable improvement compared with the control group at 12-week treatment (38.7% ±14.1% vs. 26.2% ±15.4%, P<0.05). (3) Secondary outcomes: no significant statistical differences were found in semen volume and density (4, 8, and 12-week treatment) and pregnancy probability of patients' wives (12-week treatment) between two groups (all P>0.05), however, the CM syndrome score of the treatment group significantly declined compared with baseline level at each time points (all P<0.05). (4) Safety: no obvious side reactions were found during the treatment in both groups. CONCLUSION: QZD could improve the progressive and non-progressive grade sperm in the treatment of idiopathic asthenozoospermia. It is safe with no obvious side effects.


Assuntos
Astenozoospermia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Adulto , Carnitina/uso terapêutico , Humanos , Masculino , Medicina Tradicional Chinesa , Análise do Sêmen , Motilidade Espermática/efeitos dos fármacos , Resultado do Tratamento
9.
Biol Trace Elem Res ; 193(2): 334-341, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30977089

RESUMO

The primary aim of our study was to determine the influence of taking chromium plus carnitine on insulin resistance, with a secondary objective of evaluating the influences on lipid profiles and weight loss in overweight subjects with polycystic ovary syndrome (PCOS). In a 12-week randomized, double-blind, placebo-controlled clinical trial, 54 overweight women were randomly assigned to receive either supplements (200 µg/day chromium picolinate plus 1000 mg/day carnitine) or placebo (27/each group). Chromium and carnitine co-supplementation decreased weight (- 3.6 ± 1.8 vs. - 1.0 ± 0.7 kg, P < 0.001), BMI (- 1.3 ± 0.7 vs. - 0.3 ± 0.3 kg/m2, P < 0.001), fasting plasma glucose (FPG) (- 5.1 ± 6.0 vs. - 1.1 ± 4.9 mg/dL, P = 0.01), insulin (- 2.0 ± 1.4 vs. - 0.2 ± 1.2 µIU/mL, P < 0.001), insulin resistance (- 0.5 ± 0.4 vs. - 0.04 ± 0.3, P < 0.001), triglycerides (- 18.0 ± 25.2 vs. + 5.5 ± 14.4 mg/dL, P < 0.001), total (- 17.0 ± 20.3 vs. + 3.6 ± 12.0 mg/dL, P < 0.001), and LDL cholesterol (- 13.3 ± 19.2 vs. + 1.4 ± 13.3 mg/dL, P = 0.002), and elevated insulin sensitivity (+ 0.007 ± 0.005 vs. + 0.002 ± 0.005, P < 0.001). In addition, co-supplementation upregulated peroxisome proliferator-activated receptor gamma (P = 0.02) and low-density lipoprotein receptor expression (P = 0.02). Overall, chromium and carnitine co-supplementation for 12 weeks to overweight women with PCOS had beneficial effects on body weight, glycemic control, lipid profiles except HDL cholesterol levels, and gene expression of PPAR-γ and LDLR. Clinical trial registration number: http://www.irct.ir: IRCT20170513033941N38.


Assuntos
Peso Corporal/efeitos dos fármacos , Carnitina/uso terapêutico , Cromo/uso terapêutico , Metaboloma/efeitos dos fármacos , Obesidade/prevenção & controle , Sobrepeso/prevenção & controle , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Carnitina/administração & dosagem , Cromo/administração & dosagem , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Metabolômica , Obesidade/metabolismo , Sobrepeso/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Adulto Jovem
10.
Phytother Res ; 34(4): 859-866, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31849123

RESUMO

Pemphigus vulgaris (PV) is a chronic autoimmune disorder with potentially fatal outcomes. The aim of this study was to investigate the effect of l-carnitine (LC) on secreted frizzled-related protein-5 (SFRP5), omentin, visfatin, and glycemic indices in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 52 patients with PV were divided randomly into two groups to receive 2 g of LC or a placebo for 8 weeks. Serum levels of SFRP5, omentin, visfatin, and also glycemic indices were evaluated at the baseline and end of the study. LC supplementation significantly decreased the serum level of visfatin (95% CI [-14.718, -0.877], p = .05) and increased the serum levels of SFRP5 (95%CI [1.637, 11.380], p < .006) and omentin (95% CI [9.014, 65.286], p < .01). However, LC supplementation had no significant effects on the serum levels of glycemic factors such as insulin (95% CI [-1.125, 3.056], p = .426), fasting blood sugar (95% CI [-4.743, 3.642], p = .894), homeostatic model assessment of insulin resistance (95% CI [-0.305, 0.528], p = .729), and quantitative insulin-sensitivity check index (95% CI [-0.016, -0.010], p = .81). LC supplementation decreased visfatin serum level and increased omentin-1 and SFRP5 serum levels in patients with PV. However, it has no significant effect on the serum levels of insulin and glycemic indices.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Glicemia/efeitos dos fármacos , Carnitina/farmacologia , Citocinas/sangue , Lectinas/sangue , Nicotinamida Fosforribosiltransferase/sangue , Pênfigo/tratamento farmacológico , Adulto , Idoso , Glicemia/metabolismo , Carnitina/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Proteínas Ligadas por GPI/sangue , Indicadores Básicos de Saúde , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Pênfigo/sangue , Pênfigo/metabolismo , Placebos
11.
Ren Fail ; 41(1): 976-986, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31797710

RESUMO

Objective: The present study assesses whether phosphodiesterase type 5 (PDE-5) inhibitor or carnitine exert nephroprotective effects against clinical contrast-induced nephropathy (CIN).Materials and Methods: The present study consisted of three groups of CKD patients. The first group was control group, who were treated with N-acetyl-L-cysteine 1 day before and on the day of radiocontrast administration. The second one was carnitine group, where the patients were infused with carnitine over 10 min 2 h prior to the radiocontrast administration and 24 h post CT. The third one was PDE-5 inhibitor group, where patients were given tadalafil 2 h prior to the administration of the radiocontrast and in the subsequent day. Urine and blood samples were collected before and at the following time sequence: 2, 6, 12, 24, 48, and 120 h after the contrast administration, for creatinine and NGAL determination.Results: Pretreated with N-acetyl-L-cysteine prior to administration of contrast media (CM) to CKD patients caused a significant increase in urinary but not of plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr). In contrast, pretreatment with carnitine prevented the increase in urinary NGAL and reduced SCr below basal levels. Similarly, tadalafil administration diminished the elevation of CM-induced urinary NGAL.Conclusions: These results indicate that carnitine and PDE-5 inhibitors may comprise potential therapeutic maneuvers for CIN.


Assuntos
Carnitina/uso terapêutico , Nefropatias/induzido quimicamente , Inibidores da Fosfodiesterase 5/uso terapêutico , Insuficiência Renal Crônica/complicações , Tadalafila/uso terapêutico , Idoso , Estudos Cross-Over , Feminino , Haptoglobinas/genética , Humanos , Nefropatias/genética , Nefropatias/prevenção & controle , Masculino , Estudos Prospectivos
13.
Artigo em Russo | MEDLINE | ID: mdl-31626181

RESUMO

Acetyl-L-carnitine (ALA) is a biologically active form of L-carnitine, which is a readily available substrate for triggering energy-dependent metabolic processes in the mitochondria. The mechanism of the protective effect of ALA on brain tissue is a significant reduction in the amount of oxygen consumed for energy supply of the needs of the nervous system. ALA also has antioxidant and antiapoptotic activity. In addition, ALK plays a neuromodulating effect on both synaptic morphology and synaptic transmission. The similarity in structure with acetylcholine allows to have a cholinomimetic effect, as well as to show neuroprotective and neurotrophic properties. ALK has an antidepressant and analgesic effect in painful neuropathies. Therefore, ALA is a promising drug for the treatment of polyneuropathy of various origins. Compared with antidepressants efficacy and a minimum of side effects open up wide possibilities of using ALA in the treatment of depression with a low risk of developing NLR.


Assuntos
Acetilcarnitina , Carnitina , Depressão , Polineuropatias , Acetilcarnitina/uso terapêutico , Carnitina/uso terapêutico , Depressão/tratamento farmacológico , Humanos , Neurologia/tendências , Psiquiatria/tendências
14.
Urologiia ; (4): 62-68, 2019 Sep.
Artigo em Russo | MEDLINE | ID: mdl-31535807

RESUMO

INTRODUCTION: Oxidative stress of sperm is a common pathologic condition, which can be detected in 30-80% infertile men. It is established that dietary consumption of antioxidants and microelements contributes to an increase of conception probability in subfertile couples, and also reduces the risk of reproductive losses. Drug complexes influencing various factors of spermatogenesis disturbance (oligo-, astheno-, teratozoospermia), oxidative stress and the level of sperm DNA fragmentation are of greatest and reasonable interest. AIM: To study the effects of complex acetyl-l-carnitine, l-carnitine fumarate and alpha-lipoic acid (SpermActin Forte) on oxidative stress, ejaculate quality and sperm DNA fragmentation in men with infertility. MATERIALS AND METHODS: A total of 80 infertile men aged 25-40 years with increased level of sperm DNA fragmentation and oxidative stress were included in open-label, prospective, randomized study. In Group A (n=20) patients received a placebo for 180 days, and in Group B patients were prescribed to SpermActin Forte, 1 sachet of 10 g once a day. The criteria for the efficiency of therapy included sperm analysis, the level of sperm DNA fragmentation, the level of sperm oxidative stress, as well as information about achievement of pregnancy, obtained by interviewing all participants. RESULTS: In patients taking antioxidant complex SpermActin Forte there were significant positive changes in the main parameters of sperm analysis, including sperm mobility and morphology starting from the third month of therapy. The level of free oxygen radicals (as indicator of oxidative stress) in Group B also significantly decreased (by 86%). A more profound decrease in DNA fragmentation was seen in Group B compared to Group A (21.5% vs. 3.6%). Pregnancy was achieved in 1 and 13 cases in Group A and B, respectively. CONCLUSION: The use of the SpermActin Forte antioxidant complex allowed to improve sperm analysis in most patients, and these changes were significant starting from the third month of therapy. Stimulation of spermatogenesis using the antioxidant complex SpermActin Forte is an effective and safe method of treating male infertility.


Assuntos
Carnitina/uso terapêutico , Infertilidade Masculina/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Acetilcarnitina , Adulto , Método Duplo-Cego , Feminino , Fumaratos , Humanos , Masculino , Estresse Oxidativo , Gravidez , Estudos Prospectivos , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides
15.
Molecules ; 24(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547545

RESUMO

The advantages of peritoneal dialysis (PD) over hemodialysis (HD) are well-documented. Notwithstanding, only a small proportion of patients with end-stage renal disease (ESRD) are managed with PD. This may be related to the high glucose load that PD solutions in current use have on the patient. The effects of such excess glucose include the relatively early limitation of the ultrafiltration capacity of the peritoneal membrane, and the metabolic effects associated with hyperglycemia, e.g., decreased insulin sensitivity. This article describes the advantages that may be realized by the glucose-sparing effects of substituting part of the glucose load with other osmotically active metabolites, particularly L-carnitine. The latter is anticipated to have metabolic advantages of its own, especially as in PD patients, high plasma concentrations can be achieved in the absence of renal clearance. Besides its better biocompatibility, L-carnitine demonstrates anti-anemia action due to its effects on erythropoiesis, and positive effects on the longevity and deformability of erythrocytes. Observations from our trials on the use of carnitine-enriched PD solutions have demonstrated the effectiveness of L-carnitine as an efficient osmolyte in PD, and its favorable effect on the insulin sensitivity of the patients. The significance of these findings for future developments in the use of PD in the management of patients with ESRD is discussed.


Assuntos
Carnitina/uso terapêutico , Falência Renal Crônica/terapia , Diálise Peritoneal/métodos , Eritrócitos/efeitos dos fármacos , Glucose/uso terapêutico , Humanos , Osmose/efeitos dos fármacos , Ultrafiltração/métodos
16.
Nutr Metab Cardiovasc Dis ; 29(11): 1151-1167, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31561944

RESUMO

BACKGROUND AND AIM: l-carnitine has an important role in fatty acid metabolism and could therefore act as an adjuvant agent in the improvement of dyslipidemia. The purpose of present systematic review and meta-analysis was to critically assess the efficacy of l-carnitine supplementation on lipid profiles. METHODS AND RESULTS: We performed a systematic search of all available randomized controlled trials (RCTs) in the following databases: Scopus, PubMed, ISI Web of Science, The Cochrane Library. Mean difference (MD) of any effect was calculated using a random-effects model. In total, there were 55 eligible RCTs included with 58 arms, and meta-analysis revealed that l-carnitine supplementation significantly reduced total cholesterol (TC) (56 arms-MD: -8.53 mg/dl, 95% CI: -13.46, -3.6, I2: 93%), low-density lipoprotein-cholesterol (LDL-C) (47 arms-MD: -5.48 mg/dl, 95% CI: -8.49, -2.47, I2: 94.5) and triglyceride (TG) (56 arms-MD: -9.44 mg/dl, 95% CI: -16.02, -2.87, I2: 91.8). It also increased high density lipoprotein-cholesterol (HDL-C) (51 arms-MD:1.64 mg/dl, 95% CI:0.54, 2.75, I2: 92.2). l-carnitine supplementation reduced TC in non-linear fashion based on dosage (r = 21.11). Meta-regression analysis indicated a linear relationship between dose of l-carnitine and absolute change in TC (p = 0.029) and LDL-C (p = 0.013). Subgroup analyses showed that l-carnitine supplementation did not change TC, LDL-C and TG in patients under hemodialysis treatment. Intravenous l-carnitine and lower doses (>2 g/day) had no effect on TC, LDL-C and triglycerides. CONCLUSION: l-carnitine supplementation at doses above 2 g/d has favorable effects on patients' lipid profiles, but is modulated on participant health and route of administration.


Assuntos
Carnitina/uso terapêutico , Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Carnitina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Hipolipemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
17.
Int J Gynaecol Obstet ; 147(1): 59-64, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31273783

RESUMO

OBJECTIVE: To compare clinical and metabolic profiles between N-acetylcysteine and l-carnitine among women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). METHODS: A randomized trial at Zagazig University between January 2017 and March 2018. Women with CC-resistant PCOS were allocated randomly to receive CC plus N-acetylcysteine or CC plus l-carnitine. The primary outcome was clinical pregnancy rate; secondary outcomes were ovulation rate and metabolic changes. RESULTS: Overall, 162 women completed the study (N-acetylcysteine group, n=82; l-carnitine group, n=80). After 3 months, there was no difference in pregnancy (P=0.15), ovulation (P=0.21), or spontaneous abortion (P=0.11) rates between the two groups. There was no significant decrease in BMI in either group (both P>0.05). There were improvements in menstrual pattern, follicle-stimulating hormone, luteinizing hormone, free testosterone, and insulin resistance markers in both groups (all P<0.05). An improvement in lipid profile was observed only in the l-carnitine group (P<0.001). N-Acetylcysteine treatment led to significantly greater improvement in free testosterone and insulin resistance parameters as compared with l-carnitine (all P<0.05). CONCLUSIONS: Both N-acetylcysteine and l-carnitine were equally effective in improving pregnancy and ovulation rates among women with CC-resistant PCOS. However, N-acetylcysteine was superior in ameliorating insulin resistance and only l-carnitine improved lipid profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03164421.


Assuntos
Acetilcisteína/uso terapêutico , Carnitina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Clomifeno/uso terapêutico , Método Duplo-Cego , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/etiologia , Resistência à Insulina , Ovulação/efeitos dos fármacos , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez , Adulto Jovem
18.
Reprod Fertil Dev ; 31(2): 282-293, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31039949

RESUMO

Polycystic ovary syndrome (PCOS) is related to low levels of serum l-carnitine, which has antioxidant, anti-inflammatory and antiapoptotic properties. The aim of this study was to investigate the effect of l-carnitine on folliculogenesis in mice following induction of PCOS. PCOS was induced by daily injections of testosterone enanthate (1mg per 100g, s.c., for 35 days). NMRI mice (21 days old) were divided into four groups (n=6 per group): Control, Control+l-carnitine, PCOS and PCOS+l-carnitine. Mice were treated with 500mgkg-1, i.p., l-carnitine every second day for 28 days. Ovaries were studied stereologically and serum concentrations of FSH, LH, testosterone, interleukin (IL)-6 and tumour necrosis factor (TNF)-α were determined using ELISA kits. Serum concentrations of malondialdehyde (MDA) and the ferric ion reducing antioxidant power (FRAP) were also analysed. Apoptosis of follicles was evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL). CD31 was assessed immunohistochemically. Data were analysed using one-way analysis of variance (ANOVA) and Tukey's test, differences considered significant at P<0.05.The total volume of the ovary, cortex volume, oocyte volume, zona pellucida thickness and the number of antral follicles increased significantly, whereas the number of primary and preantral follicles decreased significantly, in the PCOS+l-carnitine versus PCOS group. In the PCOS+l-carnitine group, serum concentrations of FSH and FRAP increased significantly, whereas there were significant decreases in serum concentrations of testosterone, LH, MDA, IL-6 and TNF-α, as well as in the percentage of TUNEL-positive apoptotic cells, compared with the PCOS group. l-Carnitine improves folliculogenesis and is therefore suggested as a therapeutic supplement in the treatment of PCOS.


Assuntos
Apoptose/efeitos dos fármacos , Carnitina/farmacologia , Inflamação/tratamento farmacológico , Folículo Ovariano/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Animais , Apoptose/fisiologia , Carnitina/uso terapêutico , Modelos Animais de Doenças , Feminino , Hormônio Foliculoestimulante/sangue , Inflamação/metabolismo , Interleucina-6/sangue , Hormônio Luteinizante/sangue , Malondialdeído/sangue , Camundongos , Folículo Ovariano/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Estresse Oxidativo/fisiologia , Síndrome do Ovário Policístico/metabolismo , Testosterona/sangue , Fator de Necrose Tumoral alfa/sangue
19.
Arch Biochem Biophys ; 668: 16-22, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047871

RESUMO

3-hydroxy-3-methylglutaric aciduria (HMGA) is an inherited disorder of the leucine catabolic pathway in which occurs a deficiency of the 3-hydroxy-3-methylglutaryl-CoA lyase enzyme. Therefore, the organic acids 3-hydroxy-3-methylglutaric (HMG) and 3-methylglutaric (MGA), mainly, accumulate in tissues of affected patients. Lately, much attention has been focused on free radicals as mediators of tissue damage in human diseases, causing lipid peroxidation, protein oxidation and DNA damage. The treatment of this disease is based in a restricted protein ingest and supplementation with l-carnitine (LC), an antioxidant and detoxifying agent. In the present work, we investigated the in vitro oxidative damage to DNA induced by the accumulation of organic acids and oxidative stress parameters in vivo of patients with 3-HMG, as well as the effect of the recommended therapy. The in vitro DNA damage was analyzed by the alkaline comet assay in leukocytes incubated with HMG and MGA (1 mM, 2.5 mM and 5 mM) and co-incubated with LC (90 µM and 150 µM). The in vivo urinary 15-F2t-isoprostane levels and urinary oxidized guanine species were measured by ELISA kits in patient's urine before and after the treatment with LC. HMG and MGA induced a DNA damage index (DI) significantly higher than that of the control group. The DI was significantly reduced in the presence of LC. It was also verified a significant increase of oxidized guanine species and urinary isoprostane levels, biomarker of oxidative DNA damage and lipid peroxidation respectively, in patients before treatment. After the treatment and supplementation with LC, patients presented significantly lower levels of those biomarkers. Analyzing the data together, we can conclude that HMGA patients present oxidative lipid and DNA damage, which is induced by HMG and MGA, and the antioxidant therapy with LC can prevent that kind of injuries.


Assuntos
Acetil-CoA C-Acetiltransferase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Carnitina/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Meglutol/análogos & derivados , Meglutol/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/urina , Acetil-CoA C-Acetiltransferase/metabolismo , Acetil-CoA C-Acetiltransferase/urina , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/urina , Criança , Pré-Escolar , Dinoprosta/análogos & derivados , Dinoprosta/urina , Guanina/análogos & derivados , Guanina/urina , Guanosina/análogos & derivados , Guanosina/urina , Humanos , Lactente , Peroxidação de Lipídeos/efeitos dos fármacos
20.
Ter Arkh ; 91(1): 114-128, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090382

RESUMO

The review presents the results of a number of experimental and clinical studies proving the prospects of using L-carnitine in the clinic of internal diseases. Due to the antioxidant and antihypoxant properties, the additional use of L-carnitine in addition to the main etiopathogenetic therapy is prescribed by cardiologists, nephrologists, neurologists, gerontologists. Experimental studies we conducted earlier showed no effect of L-carnitine on the activity of the P450 CYP 3A4 system, which reduces the likelihood of drug-drug interaction at the level of metabolism of drugs metabolized by P450 3A4. When using L-carnitine as part of complex pharmacotherapy, the drug has an increased safety profile in comorbid patients taking L-carnitine. Keywords: L-carnitine, P450 CYP 3А4, chronic heart failure, myocardial infarction, chronic renal failure, inter-drug interaction, antioxidant, antihypoxant.


Assuntos
Antioxidantes/farmacologia , Carnitina/farmacologia , Citocromo P-450 CYP3A/metabolismo , Cardiopatias/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Coração/efeitos dos fármacos , Falência Renal Crônica/metabolismo , Infarto do Miocárdio/complicações , Antioxidantes/metabolismo , Carnitina/metabolismo , Carnitina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Humanos , Medicina Interna , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo
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