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1.
Eur J Clin Pharmacol ; 78(2): 191-196, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34668986

RESUMEN

PURPOSE: Dysmenorrhea is a common, recurring, painful condition with a global prevalence of 71%. The treatment regime for dysmenorrhea includes hormonal therapies and NSAID, both of which are associated with side effects. A dose of 10 mg melatonin daily has previously been shown to reduce the level of pelvic pain in women with endometriosis. We chose to investigate how this regime, administered during the week of menstruation, would affect women with dysmenorrhea but without any signs of endometriosis, as adjuvant analgesic treatment. METHODS: Forty participants with severe dysmenorrhea were randomized to either melatonin or placebo, 20 in each group. Our primary outcome was pain measured with numeric rating scale (NRS); a difference of at least 1.3 units between the groups was considered clinically significant. Secondary outcomes were use of analgesics, as well as absenteeism and amount of bleeding. Mixed model was used for statistical analysis. RESULTS: Eighteen participants completed the study in the placebo group and 19 in the melatonin group. Mean NRS in the placebo group was 2.45 and 3.18 in the melatonin group, which proved to be statistically, although not clinically significant. CONCLUSION: This randomized, double-blinded, placebo-controlled trial could not show that 10 mg of melatonin given orally at bedtime during the menstrual week had better analgesic effect on dysmenorrhea as compared with placebo. However, no adverse effects were observed. CLINICAL TRIALS: NCT03782740 registered on 17 December 2018.


Asunto(s)
Depresores del Sistema Nervioso Central/uso terapéutico , Dismenorrea/tratamiento farmacológico , Melatonina/uso terapéutico , Absentismo , Adulto , Analgésicos/administración & dosificación , Depresores del Sistema Nervioso Central/administración & dosificación , Depresores del Sistema Nervioso Central/efectos adversos , Femenino , Hemorragia/patología , Humanos , Melatonina/administración & dosificación , Melatonina/efectos adversos , Adulto Joven
2.
Life Sci ; 266: 118913, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33333050

RESUMEN

AIM: Cyclophosphamide (CYP) chemotherapy induces bladder toxicity and hemorrhagic cystitis in cancer patients constituting a current clinical concern. Oxidative inflammatory cascades have been implicated as the mechanism contributing to CYP bladder urotoxicity. We thus assayed to explore whether zinc (Zn) supplementation could mitigate CYP-induced urotoxicity and evaluate the possible underlying mechanism in rats. MAIN METHOD: Rats were orally administered Zn (100 mg/kg b.w./day) for 10 days against urotoxicity induced by single injection of CYP (150 mg/kg b.w., ip) on day 7. KEY FINDINGS: CYP significantly depressed bladder activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) levels, whereas malondialdehyde level was increased prominently. In addition, CYP induced marked increases in the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by histological alterations. CYP prominently increased bladder inducible nitric oxide synthase (iNOS) activity, nuclear factor-kappa B (NF-ĸB) and expression of caspase-3 protein. Zinc supplementation considerably abrogated the bladder urotoxicity by restoring redox balance, proinflammatory and apoptotic cascades and alleviated histopathological changes. SIGNIFICANCE: This is the first to reveal zinc potential to prevent CYP-induced urotoxic hemorrhagic cystitis via restoring redox balance and enhancing anti-inflammatory and antiapoptotic mechanisms in rat bladder.


Asunto(s)
Ciclofosfamida/toxicidad , Cistitis/prevención & control , Suplementos Dietéticos , Regulación de la Expresión Génica/efectos de los fármacos , Hemorragia/prevención & control , Zinc/farmacología , Animales , Antineoplásicos Alquilantes/toxicidad , Caspasa 3/química , Caspasa 3/genética , Caspasa 3/metabolismo , Cistitis/inducido químicamente , Cistitis/metabolismo , Cistitis/patología , Hemorragia/inducido químicamente , Hemorragia/metabolismo , Hemorragia/patología , Masculino , FN-kappa B/antagonistas & inhibidores , FN-kappa B/genética , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Ratas Wistar
3.
Methods Mol Biol ; 2225: 241-255, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33108667

RESUMEN

Systemic lupus erythematosus (SLE) is a multifactorial and heterogeneous autoimmune disease involving multiple organ systems and tissues. Lupus nephritis occurs in approximately 60% of patients with SLE and is the leading cause of morbidity. Diffuse alveolar hemorrhage (DAH) is a rare but very serious complication of SLE with a greater than 50% associated mortality. The etiology of SLE is unclear but has proposed genetic, hormonal, and environmental aspects. Pristane is a saturated terpenoid alkane and has become the most popular laboratory model for inducing lupus in mice. The pristane model of SLE has the capacity to reproduce many components of the human presentation of the disease. Previous studies have demonstrated that virus-derived immune-modulating proteins have the potential to control inflammatory and autoimmune disorders. Serp-1, a 55 kDa secreted and highly glycosylated immune modulator derived from myxoma virus (MYXV), has potent immunomodulatory activity in models of vasculitis, viral sepsis, collagen-induced arthritis, and transplant rejection. This chapter describes the mouse preclinical pristane lupus model as a method to examine virus-derived protein efficacy for treating autoimmune diseases and specifically lupus nephritis and DAH.


Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Hemorragia/prevención & control , Factores Inmunológicos/farmacología , Nefritis Lúpica/tratamiento farmacológico , Myxoma virus/química , Proteinuria/tratamiento farmacológico , Proteínas Virales/farmacología , Animales , Autoanticuerpos/biosíntesis , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Femenino , Hemorragia/inmunología , Hemorragia/patología , Humanos , Factores Inmunológicos/inmunología , Inyecciones Intraperitoneales , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Pulmón/patología , Nefritis Lúpica/inducido químicamente , Nefritis Lúpica/inmunología , Nefritis Lúpica/patología , Ratones , Ratones Endogámicos BALB C , Proteinuria/inducido químicamente , Proteinuria/inmunología , Proteinuria/patología , Terpenos/administración & dosificación , Resultado del Tratamiento , Proteínas Virales/inmunología
4.
Toxicol Lett ; 335: 91-97, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33157172

RESUMEN

Nemopilema nomurai venom (NnV) is severely toxic to many organisms. However, the mechanism of its poisoning has not been properly understood yet. The present work demonstrates that zebrafish (Danio rerio) is an alternative vertebrate model for studying NnV jellyfish venom for the first time. In this model, NnV appears to cause severe hemorrhage and inflammation in cardiopulmonary regions of zebrafish. NnV also altered the swimming behavior of zebrafish accompanied by a significant downregulation of acetylcholinesterase (AChE) activity in brain tissues. Histopathological changes observed for various organs of D. rerio caused by NnV corresponded to an increase in lactate dehydrogenase (LDH) activity in tissues. NnV also significantly altered glutathione S-transferase (GST) activity in cardiopulmonary and brain tissues of D. rerio. SDS-PAGE revealed many protein bands of NnV of various sizes after silver staining. Taken together, these results indicate that Danio rerio can be a useful alternative animal model for jellyfish venom toxicology studies. Findings of the present study also suggest that Danio rerio could be used to develop an effective treatment strategy and discover the mechanism of action of jellyfish venom envenomation.


Asunto(s)
Venenos de Cnidarios/toxicidad , Modelos Animales de Enfermedad , Hemorragia/inducido químicamente , Síndromes de Neurotoxicidad/etiología , Escifozoos/química , Pez Cebra , Animales , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Venenos de Cnidarios/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Corazón/efectos de los fármacos , Hemorragia/metabolismo , Hemorragia/patología , Miocardio/patología , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Tamaño de los Órganos/efectos de los fármacos , Especificidad de Órganos , Sistema Respiratorio/efectos de los fármacos , Sistema Respiratorio/patología
5.
Ulus Travma Acil Cerrahi Derg ; 26(6): 853-858, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33107963

RESUMEN

BACKGROUND: Algan Hemostatic Agent (AHA) is a multi-herbal extract containing a standardized amount of Achillea millefolium, Juglans regia, Lycopodium clavatum, Rubus caesius or Rubis fruciosus, Viscum album, and Vitis vinifera, each of which is effective in hemostasis. In this study, we aimed to investigate the effects of AHA on bleeding time in a rat tail hemorrhage model. METHODS: Forty-eight Sprague Dawley rats (5-7 weeks old, 180-210 g) were randomly and equally allocated to six groups as follows: heparin plus saline (heparinized control), heparin plus AHA-soaked sponge, heparin plus liquid form of AHA, saline (non-heparinized control), AHA-soaked sponge and liquid form of AHA. Heparin (640 IU/kg) was administered intraperitoneally three times a day for three days in heparinized groups. For the bleeding model, the tail of rats was transected. According to the study group, either saline- or AHA-soaked sponge or liquid form of AHA was applied over the hemorrhage area. In AHA- or saline-soaked sponge groups, once the bleeding time had started, it was checked every 10 seconds. If the bleeding did not stop after 40 seconds, it was accepted as a failure. In liquid AHA group, the duration of bleeding was measured using a chronometer and defined as the time (seconds) from wounding until the bleeding stopped. RESULTS: Bleeding time in the heparinized and non-heparinized control groups was over 40 seconds. After applying the sponge form of AHA on the wound area, bleeding time was significantly shortened to less than 20 seconds in both heparinized and non-heparinized rats (p<0.001 for both). The liquid form of AHA stopped bleeding in 5.0±1.2 seconds and 8.0±1.3 seconds in heparinized and non-heparinized groups, respectively. CONCLUSION: AHA is a highly effective topical hemostatic agent in a rat tail hemorrhage model, thus may provide for a unique clinically effective option for control of bleeding during surgical operations or other emergencies.


Asunto(s)
Tiempo de Sangría , Hemostáticos/farmacología , Preparaciones de Plantas/farmacología , Cola (estructura animal) , Animales , Modelos Animales de Enfermedad , Hemorragia/patología , Hemostasis/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Cola (estructura animal)/irrigación sanguínea , Cola (estructura animal)/efectos de los fármacos
6.
Mol Imaging ; 19: 1536012120934965, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32609570

RESUMEN

BACKGROUND: Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that causes an increase in tumor perfusion, a phenomenon termed the super-enhanced permeability and retention effect. Currently, in vivo treatment efficacy of NIR-PIT is observable days after treatment, but monitoring would be improved by more acute detection of intratumor change. Fluorescence imaging may detect increased tumor perfusion immediately after treatment. METHODS: In the first experiment, athymic nude mouse models bearing unilateral subcutaneous flank tumors were treated with either NIR-PIT or laser therapy only. In the second experiment, mice bearing bilateral flank tumors were treated with NIR-PIT only on the left-sided tumor. In both groups, immediately after treatment, indocyanine green was injected at different doses intravenously, and mice were monitored with the Shimadzu LIGHTVISION fluorescence imaging system for 1 hour. RESULTS: Tumor-to-background ratio of fluorescence intensity increased over the 60 minutes of monitoring in treated mice but did not vary significantly in control mice. Tumor-to-background ratio was highest in the 1 mg kg-1 and 0.3 mg kg-1 doses. In mice with bilateral tumors, tumor-to-untreated tumor ratio increased similarly. CONCLUSIONS: Acute changes in tumor perfusion after NIR-PIT can be detected by real-time fluorescence imaging.


Asunto(s)
Sistemas de Computación , Inmunoterapia , Verde de Indocianina/química , Rayos Infrarrojos , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Imagen Óptica , Fototerapia , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Hemorragia/patología , Humanos , Ratones Desnudos , Necrosis
7.
Am J Forensic Med Pathol ; 41(1): 1-4, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31977349

RESUMEN

The popularity of e-cigarettes (vaping) has been on the rise in recent years, but the adverse effects of vaping have been greatly unknown. In 2019, the use of vaping products has been linked to an outbreak of severe lung disease, some cases of which have progressed to death. One death attributed to vaping is presented with emphasis on the gross and histopathological findings from the autopsy. These findings were correlated with the patient's clinical course and medicolegal investigation to determine the cause of death. To our knowledge, this is the first confirmed death in the United States that was directly attributed to the use of vaping.


Asunto(s)
Lesión Pulmonar Aguda/patología , Sistemas Electrónicos de Liberación de Nicotina , Pulmón/patología , Síndrome de Dificultad Respiratoria/patología , Vapeo/efectos adversos , Lesión Pulmonar Aguda/etiología , Adulto , Cannabinoides , Proliferación Celular , Neumonía en Organización Criptogénica/diagnóstico , Femenino , Fibroblastos/patología , Patologia Forense , Hemorragia/patología , Humanos , Hipertensión , Hipertrofia Ventricular Izquierda/patología , Macrófagos/patología , Miocardio/patología , Obesidad Mórbida , Tamaño de los Órganos , Aceites de Plantas , Alveolos Pulmonares/patología , Síndrome de Dificultad Respiratoria/etiología , Estados Unidos , Remodelación Vascular
8.
Sci Adv ; 5(10): eaax4895, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31681846

RESUMEN

Targeting hypoxia-sensitive pathways in immune cells is of interest in treating diseases. Here, we demonstrate that physiologic hypoxia (1% O2), as encountered in bone marrow and spleen, accelerates human M2 macrophage efferocytosis of apoptotic-neutrophils and senescent erythrocytes via lipolysis-dependent biosynthesis of specialized pro-resolving mediators (SPMs), i.e. resolvins, protectins, maresins and lipoxin. SPM-production was enhanced via hypoxia in M2 macrophages interacting with neutrophils and erythrocytes enabling structural elucidation of a novel eicosapentaenoic acid (EPA)-derived resolvin, resolvin E4 (RvE4) that stimulates efferocytosis of senescent erythrocytes and more potently than aspirin in mouse hemorrhagic exudates. In hypoxia, glycolysis inhibition enhanced neutrophil RvE4-SPM biosynthesis. Human macrophage-erythrocyte co-incubations in physiologic hypoxia produced RvE4-SPM from erythrocyte stores of omega-3 fatty acids. These results indicate that hypoxic environments, including bone marrow and spleen as well as sites of inflammation, activate SPM-biosynthetic circuits that in turn stimulate resolution and clearance of senescent erythrocytes and apoptotic neutrophils.


Asunto(s)
Hipoxia/metabolismo , Metaboloma , Apoptosis , Comunicación Celular , Hipoxia de la Célula , Membrana Eritrocítica/metabolismo , Eritrocitos/metabolismo , Glucólisis , Hemorragia/patología , Humanos , Mediadores de Inflamación/metabolismo , Leucocitos/metabolismo , Macrófagos/metabolismo , Masculino , Neutrófilos
9.
Forensic Sci Int ; 300: e24-e30, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31023496

RESUMEN

Realgar (arsenic sulfide) is widely used in combination with other herbs as Chinese patent medicine to treat a variety of diseases in China. As a mineral arsenic, its mild toxicity was also well known. Longtime over-dose usage or wrongly oral intake of realgar can cause chronic arsenic poisoning and/or death, but acute fatal arsenic poisoning resulted from short-term dermal use of realgar-containing medicine was very rare. Here, we present the case of a 35-year-old Chinese man, who was diagnosed with severe psoriasis and died of fatal acute arsenic poisoning after he applied a local folk prescription ointment containing mainly the realgar to the affected skin for about 4 days. The autopsy showed multiple punctate hemorrhages over the limbs, pleural effusion, edematous lungs with consolidation, mild myocardial hypertrophy and normal-looking kidneys. The histopathological examination of renal tissue showed severe degeneration, necrosis and desquamation of renal tubular epithelial cells, presence of protein cast and a widened edematous interstitium with interstitial fibrosis. The presence of arsenic in large amount in the ointment (about 6%), in blood (1.76 µg/mL), and in skin (4.71 µg/g), were confirmed analytically. We also provide the clinical records of the deceased and briefly reviewed 7 similar cases in literature (6 in Chinese and 1 in English) in the past 30 years in China.


Asunto(s)
Intoxicación por Arsénico/etiología , Medicina Tradicional China/efectos adversos , Sulfuros/envenenamiento , Administración Tópica , Adulto , Intoxicación por Arsénico/patología , Arsenicales/administración & dosificación , Arsenicales/análisis , China , Hemorragia/patología , Humanos , Riñón/patología , Pulmón/patología , Masculino , Pomadas , Derrame Pleural/patología , Piel/química , Sulfuros/administración & dosificación , Sulfuros/análisis
10.
Cancer Med ; 8(3): 1044-1053, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30767432

RESUMEN

BACKGROUND: Rivaroxaban could be an attractive alternative to low molecular weight heparin for the treatment of cancer-associated venous thromboembolism (VTE) but the safety and effectiveness remain unclear. We examined risk of recurrent VTE and major bleeding associated with rivaroxaban treatment of cancer-associated VTE. METHODS: Through linkage of nationwide Danish registries, we identified all adults with cancer-associated VTE initiating treatment with rivaroxaban, 2012-2017. We estimated rates and absolute risk of the primary outcome of recurrent VTE and major bleeding; all-cause mortality was studied as a secondary outcome. RESULTS: We identified 8901 patients with cancer-associated VTE of whom 476 (5.3%) redeemed a prescription for rivaroxaban within 30 days of VTE diagnosis (mean age 71.5 years, 41% females, 57% with pulmonary embolism). Median time from cancer diagnosis to rivaroxaban prescription was 31 days (interquartile range 12-73 days). Most frequent cancers were gastrointestinal (26.1%), genitourinary (23.3%), and hematological cancer (12.6%). Few had distant metastases (7.1%). At 6 months, recurrent VTE occurred in 6.1% (15.1 events per 100 person-years) with the highest absolute risks for genitourinary cancer (8.1%), gastrointestinal cancer (7.3%), and breast cancer (6.5%). Major bleeding occurred in 1.9% (5.3 events per 100 person-years), in particular, in genitourinary cancer (4.5%) and lung cancer (4.2%). Eighty deaths (17.8%) occurred during follow up. CONCLUSION: In this clinical practice setting, rivaroxaban was rarely used for cancer-associated VTE. However, among those who received rivaroxaban, the treatment appeared safe and effective with rates comparable to previous studies of selected populations.


Asunto(s)
Inhibidores del Factor Xa/uso terapéutico , Neoplasias/sangre , Rivaroxabán/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Anciano , Estudios de Cohortes , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/etiología , Hemorragia/patología , Humanos , Masculino , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Neoplasias/patología , Factores de Riesgo , Rivaroxabán/efectos adversos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/patología
11.
J Forensic Sci ; 64(3): 786-790, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30312472

RESUMEN

Yellow phosphorous (YP) is the toxic form of elemental phosphorous and the chief constituent of firecrackers and rodenticides. In India, the rodenticide paste is frequently used for the suicidal purpose. This study is an autopsy-based observational study which describes the histopathological features of heart, lungs, liver, and kidney of fatal cases of YP poisoning. The most common autopsy features in the viscera were congestion and petechial hemorrhage. The liver histopathology findings were microvesicular steatosis (68%), hepatic necrosis (62%), macrovesicular steatosis (50%), inflammatory cells (46%), sinusoidal congestion (40%), cholestasis (32%), and toxic hepatitis (18%). Hepatic necrosis ranged from being focal to centrizonal in distribution. Congestion was the most common feature observed in the lungs and the kidney. This is the largest autopsy-based study on YP poisoning till date. The histopathological features of liver were consistent with YP poisoning whereas the findings of heart, lungs, and kidney were nonspecific in nature.


Asunto(s)
Fósforo/envenenamiento , Rodenticidas/envenenamiento , Adulto , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Edema/patología , Hígado Graso/patología , Femenino , Patologia Forense , Hemorragia/patología , Humanos , India , Riñón/patología , Hígado/patología , Pulmón/patología , Masculino , Persona de Mediana Edad , Miocardio/patología , Necrosis , Estudios Prospectivos , Púrpura/patología , Vacuolas/patología , Adulto Joven
12.
BJU Int ; 123(4): 585-594, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30113758

RESUMEN

INTRODUCTION: Haemorrhage is a frequent complication of radiation cystitis leading to emergency presentations in patients with prior pelvic radiation therapy. Standard initial patient management strategies involve resuscitation, bladder washout with clot evacuation and continuous bladder irrigation. Beyond this, definitive surgical treatment is associated with significant morbidity and mortality. Alternative less invasive management options for non-emergent haemorrhagic cystitis include systemic medical therapies, hyperbaric oxygen (HBO), intravesical therapies and laser ablation. However, evidence to support and compare treatment for haemorrhagic radiation cystitis is limited. METHODS: Herein, a literature search pertaining to the current management of haemorrhagic cystitis was conducted. RESULTS: In total, 23 studies were included in this review with 2 studies reviewing systemic therapy, 7 studies evaluating HBO therapy, 10 studies investigating a variety of intravesical therapies and the remaining 4 were relating to ablative therapies. Across these studies, the patient groups were heterogenous with small numbers and variable follow up periods. CONCLUSION: With evaluation of existing literature, this narrative review also provides a stepwise clinical algorithm to aid the urologist in treating patients presenting with complications associated with radiation cystitis.


Asunto(s)
Cistitis/terapia , Hemorragia/patología , Oxigenoterapia Hiperbárica , Terapia por Láser , Traumatismos por Radiación/terapia , Irrigación Terapéutica , Vejiga Urinaria/efectos de la radiación , Cistitis/etiología , Cistitis/patología , Hemorragia/etiología , Humanos , Traumatismos por Radiación/patología , Vejiga Urinaria/patología
13.
Int J Mol Med ; 43(1): 575-582, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30387814

RESUMEN

Aberrant activation of platelets has a critical role in thrombotic vascular events, including atherosclerosis, arterial thrombosis and myocardial infarction. The process of platelet activation is associated with multiple intracellular signaling pathways, including the phosphoinositide 3­kinase/AKT serine/threonine kinase (Akt) pathway. The well­known medicinal herb Rhizoma Ligusticum Wallichii (RLW) has long been used in China to clinically treat various cardiovascular disorders. As the most pharmacologically active component of RLW, ligustrazine has been demonstrated to possess a potent antiplatelet activity. However, the precise mechanisms mediating the bioactivities of ligustrazine have not been thoroughly elucidated. The present study evaluated the effects of ligustrazine hydrochloride (LH; the clinical­grade form of ligustrazine) on platelet activation and investigated the underlying molecular mechanisms. In vitro and ex vivo platelet activation models were used, established by stimulating rat platelet­rich plasma either with the platelet activator adenosine diphosphate (ADP) or with the specific Akt pathway activator insulin­like growth factor­1 (IGF­1). The results demonstrated that treatment with LH significantly and dose­dependently inhibited ADP­induced platelet aggregation, in addition to thromboxane A2 (TXA2) secretion and intracellular Ca2+ mobilization in platelets, in vitro and ex vivo. In addition, LH markedly suppressed ADP­induced Akt phosphorylation in vitro and ex vivo. Furthermore, LH markedly inhibited IGF­1­induced Akt phosphorylation, platelet aggregation, TXA2 formation and Ca2+ mobilization in vitro. Finally, LH was able to reverse adrenaline­induced shortening of bleeding time. Taken together, these results suggested that ligustrazine possesses a broad range of antiplatelet activities without apparent hemorrhagic side-effects, and suppression of Akt signaling may be one of the mechanisms by which ligustrazine exerts its antiplatelet activities.


Asunto(s)
Activación Plaquetaria/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirazinas/farmacología , Transducción de Señal , Animales , Calcio/metabolismo , Hemorragia/patología , Factor I del Crecimiento Similar a la Insulina/farmacología , Masculino , Fosforilación/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Pirazinas/química , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Tromboxano A2/metabolismo
14.
Platelets ; 30(7): 886-892, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30346851

RESUMEN

High-dose dexamethasone (HD-DXM) is debated as a second-line therapy for chronic Immune thrombocytopenia (ITP) in children. The aim of this study is to evaluate the efficacy and safety of HD-DXM as an emergency therapy in uncontrolled bleeding in children with chronic ITP and to assess its immunological effect on dendritic cells (DCs) percentage and their co-stimulatory markers CD86 and CD83. Totally, 20 children previously diagnosed as chronic ITP were enrolled in this study and all admitted to hospital with uncontrolled bleeding. Patients received HD-DXM as a single daily dose for 4 days. Blood samples were withdrawn from patients just prior to HD-DXM therapy and on day 5 to evaluate the platelet count and for flowcytometric analysis of DCs. Daily assessment of bleeding severity was performed. The platelet counts significantly increased in patients after 5 days of initiation of therapy compared with platelet count before therapy (p-value = 0. 0002). Control of bleeding observed in (90%), complete response (CR) documented in (50%), response (R) documented in (40%), and no response (NR) documented in (10%) of patients. The time to respond was raging from 1 to 3 days and minor complication recorded in two patients. Both plasmacytoid DCs and myeloid DCs percentage and their expression of co-stimulatory markers, CD86 and CD83 decreased significantly after HD-DXM therapy. Conclusion: short course of HD-DXM as a rescue therapy seems to be an effective alternative emergency treatment for uncontrolled bleeding in chronic ITP children especially in nations with limited resources.


Asunto(s)
Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Hemorragia/tratamiento farmacológico , Hemorragia/etiología , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adolescente , Antiinflamatorios/farmacología , Niño , Preescolar , Dexametasona/farmacología , Femenino , Hemorragia/patología , Humanos , Masculino , Púrpura Trombocitopénica Idiopática/patología , Resultado del Tratamiento
15.
Biosci Rep ; 38(6)2018 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-30341244

RESUMEN

OBJECTIVE: To compare the efficacy and safety of rivaroxaban, apixaban and enoxaparin for thromboprophylaxis after arthroplastic surgery. METHODS: We conducted a meta-analysis containing a wide range of randomized controlled trials about efficiency and safety of rivaroxaban, apixaban and enoxaparin for thromboprophylaxis after arthroplastic surgery in the recent decade from January 2006 to June 2018. The present study separately analyzed the following key components: the different efficiency and safety for rivaroxaban and enoxaparin; apixaban and enoxaparin; and enoxaparin and other new developed anticoagulants. RESULTS: Sixteen studies containing 58885 patients were included. In results of efficacy outcomes, total events occurred in 4.89% patients of rivaroxaban group and 9.55% patients of the control group; however, no significant difference was observed in apixaban groups of their efficacy outcomes. Primary events didn't show significant difference when comparing apixaban with the control or comparing enoxaparin with the control. In analysis of safety outcomes, bleeding events occurred in 3.41% patients of rivaroxaban group compared with 2.84% patients of the control groups; bleeding events in apixaban groups were 4.09% compared with the control groups 4.64%. Bleeding events occurred in 3.51% patients of enoxaparin group, slightly lower than 5.82% of the control group. CONCLUSION: Direct oral anticoagulant, rivaroxaban might have better efficacy outcomes in thromboprophylaxis after arthroplastic surgery; however, apixaban showed no significantly different efficacy outcomes compared with enoxaparin, and enoxaparin may have equal or even better safety outcomes compared with direct oral anticoagulants.


Asunto(s)
Anticoagulantes/uso terapéutico , Artroplastia/efectos adversos , Hemorragia/prevención & control , Tromboembolia Venosa/prevención & control , Enoxaparina/uso terapéutico , Femenino , Hemorragia/etiología , Hemorragia/patología , Humanos , Masculino , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Rivaroxabán/uso terapéutico , Tromboembolia Venosa/etiología
17.
J Pediatr Hematol Oncol ; 40(8): 609-615, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29734214

RESUMEN

In this study, we investigated the effects of pomegranate on alleviating cyclophosphamide-induced hemorrhagic cystitis (HC). Initially, 16 Sprague-Dawley rats were allocated into 4 groups: group 1 (control), group 2 (CP) in which HC was induced by cyclophosphamide; group 3 (CP+M), HC-induced rats that received Mesna regimen, and group 4 (CP+P), which compromised rats that had been on a 14-day diet of pomegranate juice before HC induction. Cystometry was performed a few hours before euthanasia; after euthanasia, aortic blood samples and bladder tissue samples were obtained to perform TUNEL assay, and histopathologic and biochemical assessments. Urodynamic findings revealed that mean detrusor pressure in CP+P was significantly lower compared with that in CP and CP+M (P<0.05). Histopathologically, urothelium destruction and inflammation were lower in CP+P and CP+M compared with that in CP. Collagen destruction was less prominent in CP+P compared with that in CP and CP+M. Tissue and plasma levels of malondialdehyde were significantly lower in CP+P versus CP (P<0.05). Catalase activity and total protein thiol group levels in plasma and bladder tissue were higher in CP+P versus CP (P<0.05). The TUNEL positivity in CP+P was significantly weaker than that in CP, indicating less DNA fragmentation and apoptosis. Pomegranate's characteristics could significantly affect the inflammatory and destructive process of hemorrhagic cystitis.


Asunto(s)
Ciclofosfamida/efectos adversos , Cistitis , Hemorragia , Lythraceae/química , Mesna/farmacología , Extractos Vegetales/farmacología , Urotelio , Animales , Ciclofosfamida/farmacología , Cistitis/inducido químicamente , Cistitis/tratamiento farmacológico , Cistitis/metabolismo , Cistitis/patología , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Hemorragia/metabolismo , Hemorragia/patología , Masculino , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Urodinámica/efectos de los fármacos , Urotelio/metabolismo , Urotelio/patología
18.
Support Care Cancer ; 26(9): 3135-3141, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29594490

RESUMEN

OBJECTIVE: To identify the frequency and characteristics of bleeding complications during acute inpatient rehabilitation of hematologic malignancy patients with severe thrombocytopenia. DESIGN: Retrospective descriptive analysis. SETTING: Comprehensive cancer center acute inpatient rehabilitation unit. PARTICIPANTS: Consecutive hematologic malignancy patients with a platelet count of less than or equal to 20,000/microliter (µL) on the day of acute inpatient rehabilitation admission from 1/1/2005 through 8/31/2016. INTERVENTIONS: Medical records were retrospectively analyzed for demographic, laboratory, and medical data. Patients were rehabilitated using the institutional exercise guidelines for thrombocytopenic patients. MAIN OUTCOME MEASURES: Bleeding events noted in the medical record. RESULTS: Out of 135 acute inpatient rehabilitation admissions, 133 unique patients were analyzed with a total of 851 inpatient rehabilitation days. The mean platelet count was 14,000/µL on the day of admission and 22,000/µL over the course of the rehabilitation admission. There were 252 days of inpatient rehabilitation where patients had less than 10,000/µL platelets. A total of 97 bleeding events were documented in 77/135 (57%) admissions. Of the 97 bleeding events, 72 (74%), 14 (14%), and 11 (11%) were considered to be of low, medium, and high severity, respectively. There were 4/97 (4%) bleeding events that were highly likely attributable to physical activity but only 1/4 was considered high severity. Bleeding rates were .09, .08, .17, and .37 for > 20,000, 15-20,000, 10-15,000, and < 10,000/µL mean platelet counts respectively (p = .003). Forty-four percent of patients were transferred back to the primary acute care service with infection being the most common reason for transfer. CONCLUSIONS: This study is the first to examine exercise-related bleeding complications during acute inpatient rehabilitation in severely thrombocytopenic hematologic cancer patients. Bleeding rates increased with lower platelet counts. However, using the exercise guidelines for severely thrombocytopenic patients, the risk of severe exercise-related bleeding events was low.


Asunto(s)
Neoplasias Hematológicas/complicaciones , Hemorragia/etiología , Trombocitopenia/complicaciones , Femenino , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/rehabilitación , Hemorragia/patología , Hospitalización , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombocitopenia/patología
19.
Artif Cells Nanomed Biotechnol ; 46(8): 1562-1571, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28925715

RESUMEN

Schizonepetae Herba Carbonisata (SHC) has been used in traditional Chinese medicine (TCM) to treat haemorrhagic diseases for more than 1000 years. However, little information is available on its haemostatic components and mechanism. In this study, we developed novel water-soluble carbon dots (CDs) in aqueous extracts of SHC for the first time and a modified pyrolysis method was used to prepare the SHC using Schizonepetae Herba (SH) as the sole precursor. The SHC-CDs were characterized using transmission electron microscopy (TEM), high-resolution TEM (HRTEM), Fourier transform infrared (FT-IR), ultraviolet-visible (UV-Vis) and fluorescence spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and high-performance liquid chromatography (HPLC). Furthermore, the CDs with a quantum yield (QY) around 2.26% exhibited no toxicity within approximately 0.84 mg/mL in the CCK-8 assay. More interestingly, tail haemorrhaging and liver haemorrhaging experiments showed that CDs-treated mice had significantly shorter bleeding time than did normal saline (NS)-treated control group. Coagulation assays suggested that SHC-CDs could stimulate the extrinsic blood coagulation system and activate the fibrinogen system. These results suggested that SHC-CDs possess a remarkable haemostatic property, which provides evidence to support the further investigation of the considerable potential and effective material basis of TCM.


Asunto(s)
Medicamentos Herbarios Chinos/química , Hemorragia/tratamiento farmacológico , Nanoestructuras , Animales , Tiempo de Sangría , Hemorragia/metabolismo , Hemorragia/patología , Hemostáticos/química , Hemostáticos/farmacología , Masculino , Ratones , Nanoestructuras/química , Nanoestructuras/uso terapéutico
20.
Anim Sci J ; 88(11): 1860-1869, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28677164

RESUMEN

In order to investigate the effect of dietary soybean phospholipid supplement on hepatic and serum indexes relevant to fatty liver hemorrhagic syndrome (FLHS) in layers, 135 300-day-old Hyline Brown layers were randomly divided into three groups (control, pathology and prevention), and each group had 45 layers with three replicates. Birds in the three groups were respectively fed the control diet, high-energy low-protein diet and high-energy high-protein diet affixed with 3% soybean phospholipid instead of maize. Results showed in the 30th day, birds' livers in the pathology group became yellowish, enlarged in size and had hemorrhagic spots, while the prevention and control groups' layers did not have such pathological changes. Contents of triglyceride, total cholesterol, low-density lipoprotein - cholesterol, non-esterified fatty acid and malondialdehyde in serum or liver homogenate in prevention and control groups were remarkably lower than those in the pathology group (P < 0.05 or P < 0.01), as with the activities of glutamic oxalacetic transaminase and glutamic-pyruvic transaminase (P < 0.01); high-density lipoprotein - cholesterol value was strikingly higher than that of the pathology group (P < 0.01). It is suggested dietary soybean phospholipids supplement may effectively improve hepatic and blood indexes relevant to FLHS, which provides a new point for preventing FLHS occurrence rate in laying flocks and treating human non-alcohol fatty liver disease.


Asunto(s)
Dieta/veterinaria , Suplementos Dietéticos , Hígado Graso/prevención & control , Hígado Graso/veterinaria , Glycine max , Hemorragia/prevención & control , Hemorragia/veterinaria , Hígado/metabolismo , Fosfolípidos/administración & dosificación , Enfermedades de las Aves de Corral/metabolismo , Enfermedades de las Aves de Corral/prevención & control , Animales , Pollos , Hígado Graso/metabolismo , Hígado Graso/patología , Femenino , Hemorragia/metabolismo , Hemorragia/patología , Hipercolesterolemia/sangre , Hipercolesterolemia/metabolismo , Hígado/patología , Malondialdehído/sangre , Malondialdehído/metabolismo , Enfermedades de las Aves de Corral/patología , Síndrome , Triglicéridos/sangre , Triglicéridos/metabolismo
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