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1.
Nutrients ; 13(3)2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33802720

RESUMEN

Oral iron supplementation constitutes the first line treatment for iron deficiency anemia (IDA), with daily doses between 80 mg and 200 mg of elemental iron. Ferrous salts, such as ferrous sulphate (FeSO4), while efficacious, frequently give rise to gastrointestinal side effects. In the present paper we attempted to directly compare the efficacy of an alternative to the FeSO4 formulation, which presents a better tolerability profile, iron protein succinylate (Ferplex®). In a diet-induced anemia model, rats were treated by oral gavage with vehicle, FeSO4, or Ferplex® at a human-dose equivalent of 80 mg and 200 mg of elemental iron. We evaluated the change in anemia-related hematological and biochemical parameters, conducting a histological examination of the intestine at sacrifice. Results indicate that both types of iron supplementation are equally effective in the treatment of IDA, restoring hemoglobin, hematocrit, erythrocytes, free iron and transferrin levels in 15 days, with no statistical differences between treated groups and control. The impact of anemia on body weight was also attenuated following treatment with both iron supplements. Thrombocyte and reticulocyte levels, altered by the anemic condition, returned to homeostasis after 15 days of either FeSO4 or Ferplex® treatment. Importantly, the lower and higher doses of iron were equally effective, thus supporting the current school of thought which states that lower therapeutic doses are sufficient for management of IDA. In addition, the study shows for the first time that oral treatment with Ferplex® does not increase serum hepcidin. Finally, Ferplex® induced minimal iron depositions in the intestinal tissue compared to FeSO4.


Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Compuestos Ferrosos/uso terapéutico , Metaloproteínas/uso terapéutico , Succinatos/uso terapéutico , Animales , Recuento de Eritrocitos , Índices de Eritrocitos , Compuestos Ferrosos/administración & dosificación , Hemoglobinas/análisis , Masculino , Metaloproteínas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Succinatos/administración & dosificación
2.
Can J Physiol Pharmacol ; 99(1): 72-79, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32910863

RESUMEN

Examination of the patterns of free-radical processes (FRP) and changes of the early screening markers to predict the course of hemorrhagic stroke (HS) and applied pathophysiologically based therapy can be of great practical importance. This study aimed to determine early changes in the parameters of oxidative stress and routine biochemistry blood tests in patients with HS and to assess their relationship with clinical outcome. The effects of early applied cytoflavin were also investigated. The prospective study included 151 patients with HS. Forty-eight percent of patients in the standard conservative therapy were given cytoflavin antioxidant energy therapy from the first day of hospitalization. The neurological status, neuroimaging, biochemical blood tests and FRP were assessed on days 1, 5, 10, and 20 of hospitalization. In patients with HS, an imbalance of all stages of FRP was detected proportionately to the severity of HS. The malondialdehyde concentration above 5.3 µmol/L, the number of leukocytes above 15 800, glucose above 11.9 mmol/L, lactate dehydrogenase above 574 IU/L, and lactate above 2.5 mmol/L, detected on the first day, predetermined a high risk of death. Additional cytoflavin treatment allowed stabilizing the clinical laboratory picture of HS, improved the treatment results, and reduced hospital mortality rate.


Asunto(s)
Antioxidantes/administración & dosificación , Mononucleótido de Flavina/administración & dosificación , Accidente Cerebrovascular Hemorrágico/mortalidad , Inosina Difosfato/administración & dosificación , Niacinamida/administración & dosificación , Succinatos/administración & dosificación , Anciano , Animales , Biomarcadores/sangre , Glucemia , Encéfalo/diagnóstico por imagen , Combinación de Medicamentos , Femenino , Accidente Cerebrovascular Hemorrágico/sangre , Accidente Cerebrovascular Hemorrágico/diagnóstico , Accidente Cerebrovascular Hemorrágico/tratamiento farmacológico , Mortalidad Hospitalaria , Humanos , L-Lactato Deshidrogenasa/sangre , Ácido Láctico/sangre , Imagen por Resonancia Magnética , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Pronóstico , Estudios Prospectivos , Medición de Riesgo/métodos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
3.
Clin Cardiol ; 42(10): 899-907, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31339594

RESUMEN

BACKGROUND: Vasospastic angina (VSA) is characterized by coronary spasm, which can be aggravated by vasoactive substances such as serotonin. Hypothesis Sarpogrelate, a selective serotonin receptor antagonist, and high-dose statin have some effects on the reduction of coronary spasm in patients with VSA. METHODS: We recruited 100 patients with angiographically confirmed VSA, and randomly assigned them into four groups: sarpogrelate with high-dose statin (Group A, n = 25), sarpogrelate with low-dose or no statin (Group B, n = 25), placebo with high-dose statin (Group C, n = 25), and placebo with low-dose or no statin (Group D, n = 25). The primary endpoint was the remission of coronary spasm on 1-year follow-up provocation test. RESULTS: The most common site of coronary spasm was left anterior descending artery (42%). Most patients (96%) took calcium channel blockers, and 46% were treated with vasodilators. Overall, 40% of patients reported no chest pain at 1 year, and 23% showed complete remission of coronary spasm on 1-year follow-up provocation test. No difference was observed in symptomatic and angiographically complete remission rate between the sarpogrelate and the placebo group. Although the apolipoprotein B level at the 1-year follow-up was significantly lower in the high-dose statin group, symptomatic and angiographic outcomes were not different according to statin intensity. Distal thrombolysis in myocardial infarction (TIMI) flow on initial provocation test was independently associated with angiographically complete remission. CONCLUSIONS: Sarpogrelate or high-dose statin did not significantly improve the angiographic remission rate in patients with VSA. Distal TIMI flow on initial provocation test could predict the complete remission of coronary spasm at follow-up.


Asunto(s)
Angina de Pecho/tratamiento farmacológico , Vasoespasmo Coronario/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Succinatos/administración & dosificación , Adulto , Anciano , Angina de Pecho/diagnóstico , Angina de Pecho/etiología , Angiografía Coronaria , Vasoespasmo Coronario/complicaciones , Vasoespasmo Coronario/diagnóstico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Inducción de Remisión/métodos , Antagonistas de la Serotonina/administración & dosificación , Resultado del Tratamiento , Adulto Joven
4.
Nutrients ; 11(3)2019 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-30818782

RESUMEN

BACKGROUND: The intense efforts made during 3-week stage races may reduce iron metabolism and hematological parameters. These efforts may increase the levels of circulating muscle damage markers and some hormones. All of these physiological changes may have negative consequences not only for the performance of athletes but also for their health. The main aim of this study was to evaluate the effects of supplementation with 80 mg/day of iron on haematological parameters, serum cortisol and biochemical muscle indicators on elite male cyclists during the 3-week stage race the Vuelta a España. Our secondary aim was to examine whether the hematological profile is associated with muscular damage parameters and cortisol. METHODS: Eighteen elite male cyclists from two teams were randomly assigned to one of two groups: (1) control group (CG, n = 9; age: 26.1 ± 4.6 years; maximum oxygen uptake per kg: 78.0 ± 5.4 mL/kg/min) or (2) group treated with 80 mg/day iron (800 mg of iron protein succinylate, ITG, n = 9; age: 25.7 ± 6.4 years; maximum oxygen uptake per kg: 77.6 ± 6.5 mL/kg/min). The cyclists were subjected to blood tests one week before the start of the race (T1) and after 4 weeks of treatment, coinciding with the end of the competition (T2). Iron metabolism parameters, muscle damage indicators and serum cortisol were assessed. Repeated-measures ANOVA with group as a factor (GC and ITG) were used to examine the differences between groups throughout the study (time × group) after iron supplementation treatment. RESULTS: Significant differences were observed between groups throughout the study in the group-by-time interaction and changes in serum iron (GC: -8.93 ± 10.35% vs. ITG: 0.60 ± 8.64%; p = 0.018), ferritin (GC: -13.88 ± 23.53% vs. ITG: 91.08 ± 118.30%; p = 0.004), haemoglobin (GC: 10.00 ± 3.32% vs. ITG: 13.04 ± 5.64%; p < 0.001), haematocrit (GC: -1.17 ± 3.78% vs. ITG: 7.32 ± 3.92%; p < 0.001) and cortisol (GC: 24.74 ± 25.84% vs. ITG: ⁻13.54 ± 13.61%; p = 0.005). However, no significant group-by-time interaction was observed for the circulating muscle biomarkers. Additionally, significant negative correlations of serum iron, haemoglobin and haematocrit with muscle circulating biomarkers and cortisol (p < 0.05) were observed. CONCLUSIONS: Oral iron supplementation with 80 mg/day iron (800 mg of iron protein succinylate) effectively prevented a decline in haematological parameters (serum iron, ferritin, haemoglobin and haematocrit) and maintained optimal levels of recovery in elite cyclists during the Vuelta a España. Moreover, the hematological values were shown to have relationship with muscular recovery parameters.


Asunto(s)
Ciclismo , Hidrocortisona/sangre , Hierro/metabolismo , Metaloproteínas/administración & dosificación , Músculo Esquelético/lesiones , Succinatos/administración & dosificación , Adulto , Biomarcadores , Suplementos Dietéticos , Humanos , Masculino , Consumo de Oxígeno , Adulto Joven
5.
Khirurgiia (Mosk) ; (11): 44-48, 2018.
Artículo en Ruso | MEDLINE | ID: mdl-30531753

RESUMEN

The aim of the study was to evaluate the impact of various variants of multimodal anesthesia on the cognitive functions of elderly patients after surgical interventions on pelvic organs, the development of preventive measures for POCD. MATERIAL AND METHODS: A study was conducted in 76 elderly patients aged 62 to 84 years with an increased risk of developing POCD. Of these, 46 women and 30 men. Patients were divided into two groups, depending on the type of anesthesia. The 1st group consisted of 37 patients who had low-flow anesthesia with sevoflurane combined with epidural analgesia. 2nd - 39 patients who had anticipated multimodal analgesia on the basis of systemic administration of lidocaine, sulphate magnesia, verapamil. In each group, patients are divided into subgroups - the main (O) and control (K). In the main subgroups anesthetics were supplemented with 20 ml. Cytoflavin, administered 20-25 minutes before the end of surgery and on the 1-3 days of the perioperative period. Cognitive functions were assessed by standardized scales: Mini Mental State Examination (MMSE), Montreal Cognitive Evaluation Scale (MoCA), Frontal Assessment Batteries (FAB). The level of anxiety and depression was determined by the hospital scale of anxiety and depression (HADS). RESULTS: At oncological patients of advanced age in 52.5% of cases there is a moderate degree of cognitive impairment. In the perioperative period, in the study groups, when using different variants of multimodal anesthesia, there is an equivalent transient decrease in cognitive functions by 12.5 and 12.8%. The use of cytoflavin can reduce the manifestation of POCD from 1-day perioperative period, improve the cognitive status of patients. CONCLUSION: In cancer patients of advanced age, cognitive impairment is observed, aggravated after surgical treatment, regardless of the variant of multimodal anesthesia. Protection by Cytoflavin allows to restore the cognitive functions of elderly cancer patients, reduce the manifestations of POCD.


Asunto(s)
Anestesia/efectos adversos , Anestésicos/efectos adversos , Disfunción Cognitiva/prevención & control , Mononucleótido de Flavina/administración & dosificación , Inosina Difosfato/administración & dosificación , Fármacos Neuroprotectores/administración & dosificación , Niacinamida/administración & dosificación , Neoplasias Pélvicas/cirugía , Succinatos/administración & dosificación , Anciano , Anciano de 80 o más Años , Anestesia/métodos , Anestesia Epidural/efectos adversos , Anestesia General/efectos adversos , Anestésicos/administración & dosificación , Cognición/efectos de los fármacos , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Combinación de Medicamentos , Femenino , Mononucleótido de Flavina/farmacología , Humanos , Inosina Difosfato/farmacología , Masculino , Persona de Mediana Edad , Fármacos Neuroprotectores/farmacología , Pruebas Neuropsicológicas , Niacinamida/farmacología , Succinatos/farmacología , Procedimientos Quirúrgicos Operativos/efectos adversos
6.
Georgian Med News ; (283): 89-96, 2018 Oct.
Artículo en Ruso | MEDLINE | ID: mdl-30516501

RESUMEN

The aim of the study was to assess the impact of cytoflavin and bioflavin therapy on the dynamics of clinical and psychophysiological status of patients with Osteochondrosis. 150 patients with osteochondrosis of a backbone were investigated. The patients were divided into two groups using method of randomization: the main group - 75 patients - and control group -75 patients. All patients received a standard treatment (non-steroidal anti-inflammatory drugs, myorelaxants, chondroprotectors, as well as physiotherapy). The main group in addition to standard treatment received biofeedback therapy and cytoflavin. The results showed that cytoflavin and biofeedback therapy significantly enhanced the positive effect of standard treatment and significantly increased the quality of life of patients. It is recommended to treat elderly patients with neurological complications of spinal osteochondrosis with Cytoflavin in combination with biofeedback therapy Before prescribing biofeedback therapy and Cytoflavin it is necessary to take into account a number of positive and negative predictors of their effectiveness in reducing severity of pain syndrome.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Biorretroalimentación Psicológica , Mononucleótido de Flavina/uso terapéutico , Inosina Difosfato/uso terapéutico , Enfermedades del Sistema Nervioso/terapia , Niacinamida/uso terapéutico , Modalidades de Fisioterapia , Osteocondrosis de la Columna Vertebral/terapia , Succinatos/uso terapéutico , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Terapia Combinada , Combinación de Medicamentos , Mononucleótido de Flavina/administración & dosificación , Humanos , Inosina Difosfato/administración & dosificación , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/psicología , Niacinamida/administración & dosificación , Estudios Retrospectivos , Osteocondrosis de la Columna Vertebral/tratamiento farmacológico , Osteocondrosis de la Columna Vertebral/psicología , Succinatos/administración & dosificación , Encuestas y Cuestionarios , Resultado del Tratamiento
7.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1081-1082: 8-14, 2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29494984

RESUMEN

Chicoric acid (CA) is an active derivative of caffeic acid, which is naturally present in many medicinal plants and vegetables. In the present study, the metabolic profile of CA was determined in rat plasma, urine and feces and was subsequently used to propose the metabolic pathways of CA. CA (100 mg/kg) was orally administered to rats by gastric intubation. Then, the plasma, urine and feces samples were collected and treated with methanol and acetonitrile (1:1, V/V) to precipitate the proteins. The pretreated samples were separated by ultra performance liquid chromatography (UPLC) equipped with an HSS T3 column (2.1 mm × 100 mm I.D., 1.7 µm) and with quadrupole time-of-flight mass spectrometry (Q-TOF-MS) as the detection method. A total of nineteen metabolites were detected and identified based on the characteristics of their deprotonated ions in the plasma, urine and feces samples. The results revealed that the metabolism of CA followed a number of known in-vivo mammalian biotransformation pathways including hydrolysis, reduction, methylation, sulfation, glucuronidation, acetylation, isomerization and deoxygenation.


Asunto(s)
Ácidos Cafeicos/análisis , Ácidos Cafeicos/metabolismo , Cromatografía Liquida/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Succinatos/análisis , Succinatos/metabolismo , Administración Oral , Animales , Ácidos Cafeicos/administración & dosificación , Heces/química , Límite de Detección , Modelos Lineales , Masculino , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Succinatos/administración & dosificación
8.
Khirurgiia (Mosk) ; (5): 52-58, 2016.
Artículo en Ruso | MEDLINE | ID: mdl-27271720

RESUMEN

AIM: The purpose of the research was to study the effectiveness of enteral insufficiency correction at an acute peritonitis by applying minimally invasive techniques, electrical stimulation and rehabilitation of the bowel and abdominal intestine using Remaxol drug. MATERIAL AND METHODS: The analysis of the results of clinical and laboratory examination and treatment of 110 patients with acute diffuse peritonitis. In the comparison group (62 patients) in the early postoperative period applied standardized treatment, including software reorganization of the abdominal cavity, in the study group (48 patients) -- a comprehensive treatment that includes software laparoscopic sanation abdominal electrical stimulation of the duodenum, and intra-abdominal (single dose, 200 ml), and intracolonic (200 ml, 2 times daily) administration Remaxol. It was noted a significant improvement in treatment outcomes, including reduced mortality by 2.3 times, the shortening of hospital stay by 1.3 times. RESULTS: The major component of the positive effect of the developed scheme of therapy is its ability to promptly arrest the effects of enteral insufficiency, maintain the functional status of the liver. The relatively rapid recovery of motor and intestinal barrier function leads to a lowering of enteral insufficiency syndrome, which along with increased liver detoxification ability underlies the significant reduction of endogenous intoxication in three days. An important contribution to the effectiveness of the treatment makes intra and intracolonic administration Remaxol. The drug, possessing antioxidant, antihypoxic, hepatoprotective effects, contributes to the relatively rapid improvement of the barrier function of the peritoneum and intestines, detoxification ability of the liver recovery that significantly contributes to the relief of endogenous intoxication.


Asunto(s)
Cavidad Abdominal/cirugía , Terapia por Estimulación Eléctrica/métodos , Motilidad Gastrointestinal , Lavado Peritoneal/métodos , Peritonitis , Succinatos/administración & dosificación , Adulto , Colon/efectos de los fármacos , Colon/patología , Colon/fisiopatología , Femenino , Humanos , Laparoscopía/métodos , Hígado/efectos de los fármacos , Hígado/fisiopatología , Masculino , Persona de Mediana Edad , Peritonitis/diagnóstico , Peritonitis/etiología , Peritonitis/terapia , Sustancias Protectoras/administración & dosificación , Estudios Retrospectivos , Federación de Rusia , Resultado del Tratamiento
9.
Antiviral Res ; 131: 9-18, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27079946

RESUMEN

Porcine reproductive and respiratory syndrome virus (PRRSV), a common viral pathogen, causes huge annual economic losses to the swine industry worldwide. After triggering by specific ligands, the Toll-like receptor 7 (TLR7), a type of pattern-recognition receptor (PRR), induces antiviral cytokines production. Previously, we synthesized an adenine analog, designated SZU101, a TLR7-specific ligand. In this study, we assessed the inhibitory effect of SZU101 on PRRSV infection in vitro. SZU101 significantly suppressed PRRSV infection in primary porcine alveolar macrophages (PAMs) in a dose-dependent manner. Moreover, SZU101-induced inhibition involved NF-κB pathway activation in PAMs to initiate expression of TLR7-mediated cytokines and induce expression of downstream signaling IFN-stimulated genes (ISGs). Chloroquine, a TLR7 inhibitor, and BAY 11-7082, an NF-κB inhibitor, reversed both the SZU101-induced antiviral effect and induction of cytokine genes and ISGs expression. Therefore, SZU101 antiviral effects depend at least in part on TLR7-NF-κB signaling pathway. Additionally, administration of SZU101 enhanced the humoral and cell-mediated immune responses against PRRSV antigens in mice. Given these results, SZU101 holds promise as an antiviral agent and a vaccine adjuvant to prevent PRRSV infection in pigs.


Asunto(s)
Adenina/análogos & derivados , Antivirales/farmacología , Macrófagos Alveolares/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/efectos de los fármacos , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Succinatos/farmacología , Receptor Toll-Like 7/metabolismo , Adenina/administración & dosificación , Adenina/síntesis química , Adenina/inmunología , Adenina/farmacología , Amebicidas/farmacología , Animales , Cloroquina/farmacología , Citocinas/biosíntesis , Citocinas/efectos de los fármacos , Citocinas/genética , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno , Inmunidad Celular , Inmunidad Humoral , Macrófagos Alveolares/efectos de los fármacos , FN-kappa B/metabolismo , Nitrilos/farmacología , Transducción de Señal/efectos de los fármacos , Succinatos/administración & dosificación , Succinatos/síntesis química , Succinatos/inmunología , Sulfonas/farmacología , Porcinos , Receptor Toll-Like 7/química , Receptor Toll-Like 7/inmunología
10.
Theranostics ; 6(3): 302-17, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26909107

RESUMEN

To significantly promote tumor uptake and penetration of therapeutics, a nanovehicle system comprising poly(lactic-co-glycolic acid) (PLGA) as the hydrophobic cores coated with pH-responsive N-acetyl histidine modified D-α-tocopheryl polyethylene glycol succinate (NAcHis-TPGS) is developed in this work. The nanocarriers with switchable surface charges in response to tumor extracellular acidity (pHe) were capable of selectively co-delivering indocyanine green (ICG), a photothermal agent, and doxorubicin (DOX), a chemotherapy drug, to tumor sites. The in vitro cellular uptake of ICG/DOX-loaded nanoparticles by cancer cells and macrophages was significantly promoted in weak acidic environments due to the increased protonation of the NAcHis moieties. The results of in vivo and ex vivo biodistribution studies demonstrated that upon intravenous injection the theranostic nanoparticles were substantially accumulated in TRAMP-C1 solid tumor of tumor-bearing mice. Immunohistochemical examination of tumor sections confirmed the active permeation of the nanoparticles into deep tumor hypoxia due to their small size, pHe-induced near neutral surface, and the additional hitchhiking transport via tumor-associated macrophages. The prominent imaging-guided photothermal therapy of ICG/DOX-loaded nanoparticles after tumor accumulation induced extensive tumor tissue/vessel ablation, which further promoted their extravasation and DOX tumor permeation, thus effectively suppressing tumor growth.


Asunto(s)
Antineoplásicos/farmacocinética , Terapia Combinada/métodos , Portadores de Fármacos , Fármacos Fotosensibilizantes/farmacocinética , Polietilenglicoles/administración & dosificación , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Succinatos/administración & dosificación , Administración Intravenosa , Animales , Modelos Animales de Enfermedad , Doxorrubicina/farmacocinética , Quimioterapia/métodos , Hipertermia Inducida/métodos , Verde de Indocianina/farmacocinética , Masculino , Ratones Endogámicos C57BL , Nanopartículas/administración & dosificación , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Distribución Tisular
11.
Am J Chin Med ; 42(3): 679-92, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24871659

RESUMEN

Cichoric acid extract (CAE) from Echinacea purpurea L. was used to investigate the anti-arthritic effect by using collagen-induced arthritis (CIA) rat model. The hind paw swelling volume and the body weight were measured and recorded. All the drug solutions were administered orally to rats for a total of 28 days. On day 28, the rats were anaesthetized and decapitated. The thymus and spleen were weighed for the determination of the organ index. The concentration of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1ß) and prostaglandin E2 (PGE-2) in the serum was measured using commercially available ELISA kits. Total and phosphor-NF-κB and Cox-2 protein expression in synovial tissues were determined by histological slides quantification and western blot analysis. Our data showed that administration of all doses of CAE (8, 16, and 32 mg/kg) significantly decreased the paw swelling, restored body weight gain and decreased the organ index of the thymus and spleen compared with that of the CIA group. CAE (8, 16, and 32 mg/kg) treatment significantly reduced the levels of TNFα, IL-1ß and PGE-2 in serum compared with the CIA group. Histopathological analysis demonstrated that CAE has obvious anti-arthritic activity. In addition, CAE (32 mg/kg) significantly decreased the levels of nuclear factor-κB (NF-κB), TNFα and cyclooxygenase 2 (Cox-2) in synovium tissues of the ankle joint compared with the CIA group. Furthermore, CAE administration significantly decreased the protein expression of phosphor-NF-κB and Cox-2 in synovium tissues of the knee joint compared with the CIA group. The results suggest that the anti-inflammatory activity of CAE may account for its anti-arthritic effect, and CAE could be a potential therapeutic drug for the treatment of rheumatoid arthritis (RA).


Asunto(s)
Antiinflamatorios , Artritis Experimental/tratamiento farmacológico , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/uso terapéutico , Echinacea/química , Fitoterapia , Succinatos/farmacología , Succinatos/uso terapéutico , Administración Oral , Animales , Artritis Experimental/metabolismo , Ácidos Cafeicos/administración & dosificación , Ácidos Cafeicos/aislamiento & purificación , Ciclooxigenasa 2/metabolismo , Dinoprostona/sangre , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Interleucina-1beta/sangre , Articulación de la Rodilla/metabolismo , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Soluciones , Succinatos/administración & dosificación , Succinatos/aislamiento & purificación , Membrana Sinovial/metabolismo , Factor de Necrosis Tumoral alfa/sangre
12.
Pharm Biol ; 52(7): 883-9, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24517279

RESUMEN

CONTEXT: Available artemisinin-combination therapies (ACTs) are expensive. Various traditional herbal remedies for malaria involve plants, proven scientifically to have antiplasmodial effects, e.g., Azadirachta indica A. Juss. (Meliaceae). OBJECTIVE: Combination of an artemisinin-based compound and a medicinal herb extract will provide an indigenous alternative/herb-based ACT. MATERIALS AND METHODS: The in vivo schizontocidal activity of the crude aqueous extract of 100, 500, and 1000 mg/kg of A. indica fresh leaves (NCE) and 6, 15, and 20 mg/kg of artesunic acid were determined, alone and in combination, while keeping the dose of artesunic acid constant at 15 mg/kg, using the Peter's 4-day suppressive test and Swiss albino mice. The ED50 was calculated from the dose-response relationships. Percentage survival and cure were also determined. RESULTS: The average yield of two extractions of NCE was 8.33 ± 1.67%. Combination of 1000 mg/kg of NCE and 15 mg/kg of artesunic acid, produced a significant reduction of parasitemia (96.87%), compared to 20 mg/kg of artesunic acid alone (68.14%). The combination had an ED50 of 0.58 mg/kg while that of artesunic acid alone was 8.814 mg/kg. The combinations of NCE with artesunic acid produced a cure, although the artesunic acid did not produce a cure in 30 d. DISCUSSION: NCE increased the activity of artesunic acid in terms of reduction in parasitemia, and increased survival time and cure rate. CONCLUSION: The combination of an artemisinin and aqueous extract of neem leaf is possible, providing a potentiated reduction of parasitemia, and increased cure rate.


Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Azadirachta/química , Malaria/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Plasmodium berghei/efectos de los fármacos , Succinatos/uso terapéutico , Animales , Antimaláricos/farmacología , Artemisininas/administración & dosificación , Artemisininas/farmacología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Malaria/parasitología , Ratones , Parasitemia/tratamiento farmacológico , Parasitemia/parasitología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Esquizontes/efectos de los fármacos , Succinatos/administración & dosificación , Succinatos/farmacología
13.
J Agric Food Chem ; 62(6): 1310-23, 2014 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-24428171

RESUMEN

We investigated the effects of an ethanol extract of C. denticulatum (EECD) in a mouse model of glaucoma established by optic nerve crush (ONC), and found that EECD significantly protected against retinal ganglion cell (RGC) death caused by ONC. Furthermore, EECD effectively protected against N-methyl-d-aspartate-induced damage to the rat retinas. In vitro, EECD attenuated transformed retinal ganglion cell (RGC-5) death and significantly blunted the up-regulation of apoptotic proteins and mRNA level induced by 1-buthionine-(S,R)-sulfoximine combined with glutamate, reduced reactive oxygen species production by radical species, and inhibited lipid peroxidation. The major EECD components were found to be chicoric acid and 3,5-dicaffeoylquinic acid (3,5-DCQA) that have shown beneficial effects on retinal degeneration both in vitro and in vivo studies. Thus, EECD could be used as a natural neuroprotective agent for glaucoma, and chicoric acid and 3,5-DCQA as mark compounds for the development of functional food.


Asunto(s)
Asteraceae/química , Ácidos Cumáricos/administración & dosificación , Ácidos Cumáricos/análisis , Estrés Oxidativo , Enfermedades de la Retina/prevención & control , Animales , Apoptosis/efectos de los fármacos , Ácidos Cafeicos/administración & dosificación , Ácidos Cafeicos/análisis , Ácido Clorogénico/administración & dosificación , Ácido Clorogénico/análogos & derivados , Ácido Clorogénico/análisis , Modelos Animales de Enfermedad , Glaucoma/etiología , Glaucoma/prevención & control , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , N-Metilaspartato/administración & dosificación , Compresión Nerviosa , Fármacos Neuroprotectores , Nervio Óptico , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-Dawley , Enfermedades de la Retina/etiología , Succinatos/administración & dosificación , Succinatos/análisis
14.
Oncotarget ; 4(4): 502-30, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23594434

RESUMEN

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Aprepitant , Artemisininas/administración & dosificación , Auranofina/administración & dosificación , Captopril/administración & dosificación , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Disulfiram/administración & dosificación , Gluconatos/administración & dosificación , Humanos , Cetoconazol/administración & dosificación , Morfolinas/administración & dosificación , Nelfinavir/administración & dosificación , Sertralina/administración & dosificación , Succinatos/administración & dosificación , Temozolomida
15.
Ter Arkh ; 85(11): 58-61, 2013.
Artículo en Ruso | MEDLINE | ID: mdl-24432601

RESUMEN

AIM: To evaluate the efficiency of using remaxol in the combination treatment of patients with leptospirosis. SUBJECTS AND METHODS: Thirty patients (29 men and 1 woman) with leptospirosis were treated with remaxol. The icteric and anicteric forms of the disease were diagnosed in 28 and 2 patients, respectively. Moderate, severe, and very severe leptospirosis were observed in 3, 24, and 3 cases, respectively. Remaxol was injected intravenously as a ready-to-use infusion solution 400 ml/day; the treatment duration was 3 to 9 days at the height of the disease. RESULTS: Clinical improvement and normalization of laboratory parameters were achieved in the course of the disease. There were no deaths. During early convalescence at 4-5 weeks of the disease, the patients taking remaxol at the height of the disease were substantially more rarely recorded to have general weakness, fever, anorexia, myalgia, leukocytosis, increased erythrocyte sedimentation rate, and hyperbilirubinemia than those untreated with this drug. CONCLUSION: The performed study established the clinical efficacy of remaxol when used in the combination treatment of patients with leptospirosis.


Asunto(s)
Antibacterianos/uso terapéutico , Leptospirosis/tratamiento farmacológico , Succinatos/administración & dosificación , Adulto , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
16.
Klin Med (Mosk) ; 90(7): 56-8, 2012.
Artículo en Ruso | MEDLINE | ID: mdl-23019978

RESUMEN

Sports nutrition for 35 athletes was supplemented by the metabolic preparation cytoflavin 1 month before a pre-competition training camp. Their physical status was estimated using a specialized Omega-C hardware-software complex. It was shown that cytoflavin promotes physical fitness of the athletes by improving energy supply, psychoemotional conditions, and competition form. It is recommended to use cytoflavin for the training of athletes in the pre-competition period.


Asunto(s)
Rendimiento Atlético/fisiología , Suplementos Dietéticos , Mononucleótido de Flavina/farmacología , Inosina Difosfato/farmacología , Niacinamida/farmacología , Aptitud Física/fisiología , Succinatos/farmacología , Adulto , Combinación de Medicamentos , Mononucleótido de Flavina/administración & dosificación , Humanos , Inosina Difosfato/administración & dosificación , Niacinamida/administración & dosificación , Succinatos/administración & dosificación
17.
Eksp Klin Farmakol ; 75(8): 39-43, 2012.
Artículo en Ruso | MEDLINE | ID: mdl-23012995

RESUMEN

The functional activity of mitochondria of the muscular coat of small intestine (MCSI) has been studied in the normal state and under experimental widespread purulent peritonitis (WPP) conditions. The experiments have been carried out on a group of 55 male rabbits of chinchilla breed. It is established that, as a result of the WPP development, the functional activity of mitochondria in MCSI considerably decreases. The comparative analysis of the efficiency of metabolic drugs cytoflavin and neoton showed advantage of the citoflavin preparation, the administration of which allowed the indices of mitochondria in intact animals to be exceeded on the fifth day of postoperative period. The research results show expediency of a complex treatment of WPP using cytoflavin preparation for the normalization of biological oxidation processes and elimination of enteric insufficiency.


Asunto(s)
Mononucleótido de Flavina/uso terapéutico , Inosina Difosfato/uso terapéutico , Intestino Delgado/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Niacinamida/uso terapéutico , Fosforilación Oxidativa/efectos de los fármacos , Peritonitis/tratamiento farmacológico , Fosfocreatina/uso terapéutico , Succinatos/uso terapéutico , Animales , Bacillus , Combinación de Medicamentos , Escherichia coli , Mononucleótido de Flavina/administración & dosificación , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Inosina Difosfato/administración & dosificación , Intestino Delgado/metabolismo , Intestino Delgado/patología , Masculino , Mitocondrias/metabolismo , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Músculo Liso/patología , Niacinamida/administración & dosificación , Peritonitis/metabolismo , Peritonitis/patología , Fosfocreatina/administración & dosificación , Conejos , Succinatos/administración & dosificación , Supuración
18.
Artículo en Ruso | MEDLINE | ID: mdl-22908466

RESUMEN

This article reports the results of applying basic pharmacotherapy (enalapril, cytoflavin) and its combination with physical factors (transcranial electrostimulation, combined application oftranscranial electrostimulation and low-frequency magnetic therapy) in the complex treatment of patients with stage I-II dyscirculatory encephalopathy. The study has demonstrated that the combined treatment with cytoflavin, enalapril, transcranial electrostimulation and low-frequency magnetic therapy produced the most pronounced therapeutic effect (82.5%), as confirmed by positive dynamics of clinical and functional parameters.


Asunto(s)
Circulación Cerebrovascular/fisiología , Trastornos Cerebrovasculares/terapia , Terapia por Estimulación Eléctrica/métodos , Estimulación Magnética Transcraneal/métodos , Adulto , Anciano , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/tratamiento farmacológico , Trastornos Cerebrovasculares/fisiopatología , Terapia Combinada , Combinación de Medicamentos , Enalapril/administración & dosificación , Enalapril/uso terapéutico , Femenino , Mononucleótido de Flavina/administración & dosificación , Mononucleótido de Flavina/uso terapéutico , Humanos , Inosina Difosfato/administración & dosificación , Inosina Difosfato/uso terapéutico , Masculino , Persona de Mediana Edad , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/uso terapéutico , Niacinamida/administración & dosificación , Niacinamida/uso terapéutico , Índice de Severidad de la Enfermedad , Succinatos/administración & dosificación , Succinatos/uso terapéutico , Resultado del Tratamiento
19.
Urologiia ; (5): 64-6, 68, 2012.
Artículo en Ruso | MEDLINE | ID: mdl-23342619

RESUMEN

The problem of chronic prostatitis (CP) and erectile dysfunction (ED) involves not only their high prevalence, but also the insufficient effectiveness of their treatments. In this regard, there is need for administration the pathogenetic drugs with antihypoxic, antioxidant and neuroprotective effects and improving blood flow to the genitals. The study included 60 men with CP associated with ED, aged 22 to 60 years. Patients were randomized into 2 groups of 30 people. Patients of comparison group received baseline therapy (alpha1-adrenoblockers, non-specific anti-inflammatory drugs, digital prostate massage and vacuum phallostimulation). Antibiotics were applied on the basis of their potential effectiveness in chronic abacterial prostatitis. In addition to the above treatment, patients of main group received step-down therapy with cytoflavin (in infusion, then oral administration). Positive dynamics was noted in both groups of patients; however, according to the indicators of the severity of pain and dysuria, as well as quality of life, positive dynamics in the main group of patients was more significant. Similarly, the dynamics of objective criteria for inflammation in the prostate gland was more pronounced when using cytoflavin. After treatment, the rigid phase of erection during vacuum fallotest occurred within 2-3 min from the beginning of the procedure in 16 (53.3%) patients of main group and only in 9 (30%) patients of comparison group. During follow-up examination at 6 months after treatment, stable remission was found in 75% of patients of main group. Thus, the inclusion of cytoflavin in the scheme of complex treatment of patients with abacterial CP associated with ED is pathogenetically justified, makes it more efficient and provides good DFS.


Asunto(s)
Disfunción Eréctil/terapia , Mononucleótido de Flavina/administración & dosificación , Inosina Difosfato/administración & dosificación , Niacinamida/administración & dosificación , Prostatitis/terapia , Succinatos/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Adulto , Antiinflamatorios/administración & dosificación , Enfermedad Crónica , Combinación de Medicamentos , Disfunción Eréctil/complicaciones , Disfunción Eréctil/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Modalidades de Fisioterapia , Prostatitis/complicaciones , Prostatitis/fisiopatología
20.
Eksp Klin Farmakol ; 74(8): 13-6, 2011.
Artículo en Ruso | MEDLINE | ID: mdl-22232908

RESUMEN

Experiment carried out on laboratory animals (rats) were aimed at comparative evaluation of the effect of several neuroprotective drugs under the conditions of model brain ischemia-reperfusion. The experimental methods included staining of brain tissue sections by hematoxiline-eosine, Nissl staining, and expression of NOS1, NOS3, TRAIL by imunnohistological means. The intensity of damage in various parts of brain and the nature of apoptosis without neuroprotection and with popular neuroprotectors (cytoflavin, actovegin, mexidol) and a test drug at the stage ofpreclinical trial (AKF-90-7) were evaluated. Characteristic cytotoxic (coagulative pycnomorphic and colliquative necrosis of neurons) and vascular (hemostasia, erythropedesis) changes were revealed. The neuroprotective effectof drugs decreases in the following order: AKF-90-7 > cytoflavin > actovegin > mexidol.


Asunto(s)
Encéfalo/efectos de los fármacos , Glicina/análogos & derivados , Hemostasis/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Picolinas/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Animales , Encéfalo/metabolismo , Encéfalo/patología , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Eosina Amarillenta-(YS)/análisis , Mononucleótido de Flavina/administración & dosificación , Mononucleótido de Flavina/uso terapéutico , Glicina/administración & dosificación , Glicina/uso terapéutico , Hematoxilina/análisis , Hemo/administración & dosificación , Hemo/análogos & derivados , Hemo/uso terapéutico , Inmunohistoquímica , Inosina Difosfato/administración & dosificación , Inosina Difosfato/uso terapéutico , Masculino , Necrosis/prevención & control , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/administración & dosificación , Niacinamida/administración & dosificación , Niacinamida/uso terapéutico , Óxido Nítrico Sintasa de Tipo I/análisis , Óxido Nítrico Sintasa de Tipo I/biosíntesis , Óxido Nítrico Sintasa de Tipo III/análisis , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Picolinas/administración & dosificación , Ratas , Ratas Endogámicas , Daño por Reperfusión/sangre , Succinatos/administración & dosificación , Succinatos/uso terapéutico , Ligando Inductor de Apoptosis Relacionado con TNF/análisis , Ligando Inductor de Apoptosis Relacionado con TNF/biosíntesis
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