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1.
Chem Biodivers ; : e202400756, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847466

RESUMO

This study reports chemical composition, phytotoxic and antibiofilm activities of essential oils (EOs) of R. dasycarpa and R. sphaerocarpa from Morocco. EOs were analyzed by GC/MS and their phytotoxicities were evaluated against germination and seedling growth of Lolium multiflorum, Sinapis alba and Raphanus sativus. The antimicrobial and anti-biofilm activities were studied against Gram-negative (Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii) and Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes). Both EOs were abundant in oxygenated monoterpenes (40.01% and 23.57 %, respectively). Carvacrol is the predominant component in R. dasycarpa EO (17.80 %), and it also represents an appreciable amount in R. sphaerocarpa (8.96 %). R. sphaerocarpa showed total inhibition at high doses against all seeds. S. alba seeds were the most sensitive to all EOs. Minimum inhibitory concentration (MIC) values indicated significant inhibition for R. sphaerocarpa, between 24 and 30 µg/mL, with a remarkable antibacterial potential and biofilm formation inhibition. R. sphaerocarpa EO showed significant biofilm inhibition with variable efficacy depending on the strain and concentration, except for S. aureus. R. dasycarpa exhibited activity against all bacterial strains and effect on metabolism with activity also on mature biofilms. Results suggest that Retama EOs could have potential applications in the fields of food and health.

2.
J Endocrinol Invest ; 43(7): 947-958, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31939196

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level, having a role in many biological processes, such as control of cell proliferation, cell cycle, and cell death. Altered miRNA expression has been reported in many neoplasms, including pituitary adenomas (PAs). PURPOSE: In this study, we aimed to evaluate the expression of 20 miRNAs involved in pathways relevant to pituitary pathophysiology, in PAs and normal pituitary tissue and to correlate their expression profile with clinical and pathological features. METHODS: Pituitary tumor samples were obtained during transphenoidal surgery from patients with non-functioning (NFPA, n = 12) and functioning (n = 11, 5 GH-, 3 ACTH-, 3 PRL-omas) PAs. The expression of selected miRNAs in PAs and in normal pituitary was analyzed by RT-qPCR. miRNAs expression was correlated with demographic, clinical, and neuroradiological data and with histopathological features including pituitary hormones immunostaining, Ki-67 proliferation index, and p53 immunohistochemistry evaluation. RESULTS: All evaluated miRNAs except miR-711 were expressed in both normal and tumor pituitary tissue. Seventeen miRNAs were significantly down-regulated in pituitary tumors compared to normal pituitary. miRNAs were differentially expressed in functioning PAs or in NFPAs, as in the latter group miR-149-3p (p = 0.036), miR-130a-3p (p = 0.014), and miR-370-3p (p = 0.026) were significantly under expressed as compared to functioning tumors. Point-biserial correlation analysis demonstrated a negative correlation between miR-26b-5p and Ki-67 (p = 0.031) and between miR-30a-5p and 'atypical' morphological features (p = 0.038) or cavernous sinus invasion (p = 0.049), while 508-5p was inversely correlated with clinical aggressiveness (p = 0.043). CONCLUSIONS: In this study, we found a significant down-regulation of 17 miRNAs in PAs vs normal pituitary, with differential expression profile related to functional status and tumor aggressiveness.


Assuntos
Adenoma/genética , Adenoma/patologia , MicroRNAs/genética , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Adenoma/diagnóstico , Adenoma/terapia , Adulto , Idoso , Proliferação de Células/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Testes de Função Hipofisária , Hipófise/metabolismo , Hipófise/fisiologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/terapia , Prognóstico
3.
Br J Pharmacol ; 167(1): 95-108, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22471974

RESUMO

BACKGROUND AND PURPOSE: Inflammation plays a key role in the development of benign prostatic hyperplasia (BPH). Eicosanoids derived from the COX and 5-lipoxygenase (5-LOX) pathways are elevated in the enlarging prostate. Flavocoxid is a novel flavonoid-based 'dual inhibitor' of the COX and 5-LOX enzymes. This study evaluated the effects of flavocoxid in experimental BPH. EXPERIMENTAL APPROACH: Rats were treated daily with testosterone propionate (3 mg·kg(-1) s.c.) or its vehicle for 14 days to induce BPH. Animals receiving testosterone were randomized to receive vehicle (1 mL·kg(-1) , i.p.) or flavocoxid (20 mg·kg(-1) , i.p.) for 14 days. Histological changes, eicosanoid content and mRNA and protein levels for apoptosis-related proteins and growth factors were assayed in prostate tissue. The effects of flavocoxid were also tested on human prostate carcinoma PC3 cells. KEY RESULTS: Flavocoxid reduced prostate weight and hyperplasia, blunted inducible expression of COX-2 and 5-LOX as well as the increased production of PGE(2) and leukotriene B(4) (LTB(4) ), enhanced pro-apoptotic Bax and caspase-9 and decreased the anti-apoptotic Bcl-2 mRNA. Flavocoxid also reduced EGF and VEGF expression. In PC3 cells, flavocoxid stimulated apoptosis and inhibited growth factor expression. Flavocoxid-mediated induction of apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-FMK, in PC3 cells, suggesting an essential role of caspases in flavocoxid-mediated apoptosis during prostatic growth. CONCLUSION AND IMPLICATIONS: Our results show that a 'dual inhibitor' of the COX and 5-LOX enzymes, such as flavocoxid, might represent a rational approach to reduce BPH through modulation of eicosanoid production and a caspase-induced apoptotic mechanism.


Assuntos
Catequina/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Inibidores de Lipoxigenase/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Araquidonato 5-Lipoxigenase/metabolismo , Caspase 9/metabolismo , Catequina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/metabolismo , Combinação de Medicamentos , Fator de Crescimento Epidérmico/genética , Humanos , Leucotrieno B4/metabolismo , Inibidores de Lipoxigenase/farmacologia , Masculino , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
4.
Int J Androl ; 35(2): 133-44, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21651579

RESUMO

The effects of polydeoxyribonucleotide (PDRN), an agonist of the A2A adenosine receptors which when activated positively influences sperm activity, were tested in an experimental testicular ischaemia/reperfusion injury model. Anaesthetized male Sprague-Dawley rats were subjected to testicular torsion-induced ischaemia, followed by reperfusion (TI/R). Immediately after detorsion, randomized animals, including SHAM, received intraperitoneal injections of: (i) vehicle (1 mL/kg 0.9% NaCl solution); (ii) PDRN (8 mg/kg); (iii) DMPX (3,7-dimethyl-1-propargilxanthine, 0.1 mg/kg); or (iv) PDRN (8 mg/kg) + DMPX (0.1 mg/kg). Animals were euthanized at 1, 7 and 30 days following reperfusion. Vascular endothelial growth factor (VEGF) expression is normally associated with adenosine A2A receptor stimulation. After treatment, VEGF mRNA/protein expression quantified by qPCR and Western blot, vascular endothelial growth factor receptor-1 (VEGFR1) and endothelial nitric oxide synthase (eNOS) mRNA measured by qPCR, VEGF and VEGFR1 assessed using immunohistochemical methods, histological staining and spermatogenic activity were all analysed. Testis ischaemia-reperfusion (TI/R) injury caused increases in VEGF mRNA and protein, VEGFR1 and eNOS mRNA, histological damage and reduced spermatogenic activity. Immunostaining showed a lower expression of VEGF in germinal epithelial cells and a strong expression of VEGFR1 in Leydig cells after TI/R. PDRN administration increased significantly VEGF message/protein, VEGFR1 and eNOS message, decreased histological damage and ameliorated spermatogenic activity. PDRN might be useful in the management of testicular torsion.


Assuntos
Agonistas do Receptor A2 de Adenosina/farmacologia , Polidesoxirribonucleotídeos/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Torção do Cordão Espermático/tratamento farmacológico , Espermatogênese/efeitos dos fármacos , Testículo/irrigação sanguínea , Animais , Imuno-Histoquímica , Células Intersticiais do Testículo/metabolismo , Masculino , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Torção do Cordão Espermático/metabolismo , Torção do Cordão Espermático/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
Eur Rev Med Pharmacol Sci ; 15(4): 458-60, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21608443

RESUMO

Multiple sclerosis is common among women of childbearing age. Neuraxial blocks have been administered to them with reluctance because of the hypothetical risk that local anesthetics might be more histotoxic to neural tissue already compromised by multiple sclerosis. In spite of the lack of uniform guidelines on disorders in pregnancy like multiple sclerosis, and of the published data that sometimes contrast each other, experience gained in recent years has indicated that regional anesthesia is safe even in these patients, but there aren't many published cases. We describe the case of a pregnant woman affected by multiple sclerosis in which we administered spinal anesthesia for a cesarean section, and we analyzed the aspects that literature defines as critical points in this group of patients. The results were favorable with regard to the level, intensity and duration of anesthesia. No neurological exacerbations were recognized during the hospital stay, nor during the follow-up that lasted 12 months.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Esclerose Múltipla/complicações , Doenças do Sistema Nervoso/etiologia , Complicações na Gravidez , Adulto , Feminino , Seguimentos , Humanos , Gravidez
6.
Phytomedicine ; 18(10): 879-86, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-21397481

RESUMO

Genistein aglycone (GEN) has a favorable effect on bone loss. We investigated the effects of GEN alone or in combination with supplemental calcium and vitamin D(3) in an animal model of bone loss to evaluate if there was additional benefit. Ovariectomized (OVX) and SHAM-OVX rats were used. OVX were divided into 12 groups and randomized to receive: GEN at 27, 54, 200, 500 or 1000 mg (human equivalent dose (HED)/day/ip injection alone or with calcium carbonate (Ca) (360 mg/kg/day/gavages) and vitamin D(3) (D(3)) (50 IU/kg/day/gavages) or Ca/D(3) without GEN or untreated for 6 weeks. SHAM-OVX were randomized into 7 groups and treated with: Ca and D(3) alone or in combination with GEN (same doses as OVX), or left untreated. Bone mineral density (BMD), bone-alkaline phosphatase (b-ALP), collagen C-telopeptides (CTX), osteoprotegerin (OPG) and soluble receptor activator of NFκB ligand (sRANKL) were assessed. Femurs were excised and tested for breaking strength and histology. Uterine weight was analyzed to assess GEN's estrogenic effects on the SHAM-OVX. The most effective dose of GEN, independent of Ca/D(3) supplementation, was 54 mg/day. Higher doses yielded no further improvement in bone biomarkers, histology or strength. Only 1000 mg/day HED of genistein produced statistically significant changes in uterine weight of the SHAM-OVX. This study suggests that 54 mg/day of GEN is the threshold dose for efficacy. In addition, supplemental calcium and vitamin D(3), beyond normal dietary intake do not enhance the effects of genistein on improving measures of bone loss. This observation has implications regarding the use of calcium and vitamin D(3) supplementation.


Assuntos
Doenças Ósseas Metabólicas/tratamento farmacológico , Carbonato de Cálcio/farmacologia , Colecalciferol/farmacologia , Genisteína/uso terapêutico , Fosfatase Alcalina/metabolismo , Animais , Densidade Óssea , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/farmacologia , Força Compressiva , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Fêmur/anatomia & histologia , Fêmur/efeitos dos fármacos , Genisteína/administração & dosagem , Osteoprotegerina/efeitos dos fármacos , Ovariectomia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Ligante RANK/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sophora/química , Útero/efeitos dos fármacos
7.
Br J Pharmacol ; 161(5): 1002-11, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20977452

RESUMO

BACKGROUND AND PURPOSE: Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. EXPERIMENTAL APPROACH: Rats were given CER (80 µg·kg⁻¹ for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg⁻¹ i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B4 and prostaglandin (PG)E2 ; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. KEY RESULTS: Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B4 and prostaglandin E2 levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. CONCLUSIONS AND IMPLICATIONS: Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition.


Assuntos
Catequina/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Lipoxigenase/farmacologia , Pancreatite/tratamento farmacológico , Doença Aguda , Animais , Araquidonato 5-Lipoxigenase/efeitos dos fármacos , Araquidonato 5-Lipoxigenase/metabolismo , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Combinação de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Masculino , Pancreatite/fisiopatologia , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-Dawley
8.
Br J Pharmacol ; 160(5): 1185-94, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20590611

RESUMO

BACKGROUND AND PURPOSE: Oestrogen loss at menopause is frequently related to poor wound healing. Genistein has been tested in anti-ageing cosmetic preparations with interesting results on skin health. Here, we investigated the effects of the genistein aglycones, given systemically, in an incisional model of wound healing, compared to systemic oestradiol and raloxifene. EXPERIMENTAL APPROACH: Six months after ovariectomy (OVX), rats were randomly assigned to groups of 12 animals each and treated daily with genistein aglycone (1 and 10 mg kg(-1) s.c.), raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.) or 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.) for 12 weeks. Untreated OVX and sham OVX rats were used as controls. Then, 14 or 7 days before the end of the experiment, an incisional wound healing procedure was performed and skin specimens were collected to evaluate molecular, histological and functional measurements. KEY RESULTS: Seven and fourteen days after wounding, samples from OVX rats showed a decrease in transforming growth factor-beta1, tissue transglutaminase 2 and vascular endothelial growth factor compared to samples from sham OVX rats. Oestradiol, raloxifene and genistein all significantly modified this decrease, but the lowest genistein dose exerted a greater effect than the other treatments. Moreover, the lowest dose of genistein was the most effective in improving skin healing and wound tensile strength. CONCLUSIONS AND IMPLICATIONS: Genistein aglycone might be an alternative therapy for the management of skin wound healing.


Assuntos
Etinilestradiol/administração & dosagem , Genisteína/administração & dosagem , Fitoestrógenos/administração & dosagem , Cloridrato de Raloxifeno/administração & dosagem , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Procedimentos Cirúrgicos Dermatológicos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Proteínas de Ligação ao GTP/metabolismo , Ovariectomia , Proteína 2 Glutamina gama-Glutamiltransferase , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Pele/metabolismo , Pele/patologia , Resistência à Tração/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Transglutaminases/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Curr Med Chem ; 17(27): 3007-18, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20629630

RESUMO

Osteoporosis is characterized by reduced bone mass and structural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk. Bone loss further increases in postmenopausal women when the ovaries stop making estrogens. Women undergoing treatment for osteoporosis require long-term dosing therapeutic regimens, that offer no symptomatic relief, and may cause side effects. To avoid this problem, many therapeutic alternatives have been proposed. Epidemiological data support a robust relationship between soy isoflavones, fracture incidence and bone mineral density in osteoporotic, postmenopausal women. These suggest that a high isoflavone intake, restores the metabolic balance of bone formation and resorption. However, this matter is still controversial and several reports show negative results, probably because different doses and/or isoflavones have been used. Although it is difficult to identify the specific isoflavone most involved in preventing or restoring bone loss, a review of current literature based on new encouraging preclinical and clinical data, indicates that aglycone genistein appears to be the most effective isoflavone in preserving bone health. Genistein aglycone, through a peculiar anti-osteoporotic dual mode of action, can positively regulate bone cell metabolism rebalancing bone turnover towards bone formation. Genistein in fact stimulates osteoblast and inhibits osteoclast function, mainly through the osteoprotegerin-sRANKL system. The positive results achieved by genistein aglycone intake, in terms of efficacy and safety, have stimulated the development of specially formulated medical food products for the clinical management of postmenopausal bone loss.


Assuntos
Genisteína/uso terapêutico , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Fitoestrógenos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Ensaios Clínicos como Assunto , Genisteína/farmacologia , Humanos , Osteoporose/patologia , Fitoestrógenos/farmacologia , Inibidores de Proteínas Quinases/farmacologia
10.
Nutr Metab Cardiovasc Dis ; 20(5): 332-40, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19631515

RESUMO

BACKGROUND AND AIM: Recent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women. We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women. METHODS AND RESULTS: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54mg of genistein aglycone (n=71) or placebo (n=67), daily. Both arms received calcium and vitamin D(3) in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured. Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group. CONCLUSIONS: After 3-years of treatment, genistein aglycone plus calcium, vitamin D(3) and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Genisteína/farmacologia , Homocisteína/sangue , Carbonato de Cálcio/administração & dosagem , Colecalciferol/administração & dosagem , Feminino , Seguimentos , Genisteína/efeitos adversos , Humanos , Resistência à Insulina , Lipídeos/sangue , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Pós-Menopausa , Projetos de Pesquisa , Fatores de Risco
11.
Br J Pharmacol ; 157(8): 1410-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19681869

RESUMO

BACKGROUND AND PURPOSE: The flavonoids, baicalin and catechin, from Scutellaria baicalensis and Acacia catechu, respectively, have been used for various clinical applications. Flavocoxid is a mixed extract containing baicalin and catechin, and acts as a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (LOX) enzymes. The anti-inflammatory activity, measured by protein and gene expression of inflammatory markers, of flavocoxid in rat peritoneal macrophages stimulated with Salmonella enteritidis lipopolysaccharide (LPS) was investigated. EXPERIMENTAL APPROACH: LPS-stimulated (1 microg.mL(-1)) peritoneal rat macrophages were co-incubated with different concentrations of flavocoxid (32-128 microg.mL(-1)) or RPMI medium for different incubation times. Inducible COX-2, 5-LOX, inducible nitric oxide synthase (iNOS) and inhibitory protein kappaB-alpha (IkappaB-alpha) levels were evaluated by Western blot analysis. Nuclear factor kappaB (NF-kappaB) binding activity was investigated by electrophoretic mobility shift assay. Tumour necrosis factor-alpha (TNF-alpha) gene and protein expression were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Finally, malondialdehyde (MDA) and nitrite levels in macrophage supernatants were evaluated. KEY RESULTS: LPS stimulation induced a pro-inflammatory phenotype in rat peritoneal macrophages. Flavocoxid (128 microg.mL(-1)) significantly inhibited COX-2 (LPS = 18 +/- 2.1; flavocoxid = 3.8 +/- 0.9 integrated intensity), 5-LOX (LPS = 20 +/- 3.8; flavocoxid = 3.1 +/- 0.8 integrated intensity) and iNOS expression (LPS = 15 +/- 1.1; flavocoxid = 4.1 +/- 0.4 integrated intensity), but did not modify COX-1 expression. PGE(2) and LTB(4) levels in culture supernatants were consequently decreased. Flavocoxid also prevented the loss of IkappaB-alpha protein (LPS = 1.9 +/- 0.2; flavocoxid = 7.2 +/- 1.6 integrated intensity), blunted increased NF-kappaB binding activity (LPS = 9.2 +/- 2; flavocoxid = 2.4 +/- 0.7 integrated intensity) and the enhanced TNF-alpha mRNA levels (LPS = 8 +/- 0.9; flavocoxid = 1.9 +/- 0.8 n-fold/beta-actin) induced by LPS. Finally, flavocoxid decreased MDA, TNF and nitrite levels from LPS-stimulated macrophages. CONCLUSION AND IMPLICATIONS: Flavocoxid might be useful as a potential anti-inflammatory agent, acting at the level of gene and protein expression.


Assuntos
Catequina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Flavonoides/farmacologia , Lipopolissacarídeos/farmacologia , Inibidores de Lipoxigenase , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Combinação de Medicamentos , Ensaio de Imunoadsorção Enzimática , Proteínas I-kappa B/metabolismo , Macrófagos Peritoneais/metabolismo , Masculino , Inibidor de NF-kappaB alfa , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
13.
Br J Pharmacol ; 156(8): 1287-95, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19302595

RESUMO

BACKGROUND AND PURPOSE: Glucocorticoid-induced osteoporosis (GIO) is the leading cause of secondary osteoporosis. Clinical evidence suggests a role for genistein aglycone in the treatment of post-menopausal osteopenia although proof of efficacy in comparison with currently available treatments is still lacking. To clarify this issue, we investigated the effects of genistein on bone compared with alendronate in experimental GIO. EXPERIMENTAL APPROACH: A total of 28 female Sprague-Dawley rats were used. GIO was induced by daily injections of methylprednisolone (MP; 30 mg x kg(-1) s.c.) for 60 days. Sham GIO animals (Sham-MP) were injected daily with the MP vehicle. At the end of the osteoporosis development period, MP rats were randomized to receive: vehicle (n= 7), genistein aglycone (5 mg x kg(-1) s.c.; n= 7) or alendronate (0.03 mg x kg(-1) s.c.; n= 7). Treatment lasted 60 days. Sham-MP animals were treated with vehicle for an additional 60 days. At the beginning and at the end of treatments, animals were examined for bone mineral density and bone mineral content. Bone-alkaline phosphatase and carboxy-terminal collagen cross links were determined; femurs were removed and tested for breaking strength and histology. KEY RESULTS: Genistein aglycone showed a greater increase in bone mineral density, bone mineral content and in breaking strength than alendronate and significantly increased bone-alkaline phosphatase (bone formation marker), reduced carboxy-terminal collagen cross links (bone resorption marker), compared with alendronate. Both treatments improved bone histology and the histological score. CONCLUSION AND IMPLICATIONS: The results strongly suggest that the genistein aglycone might be an alternative therapy for the management of secondary osteoporosis.


Assuntos
Alendronato/farmacologia , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Fraturas do Fêmur/prevenção & controle , Fêmur/efeitos dos fármacos , Genisteína/farmacologia , Osteoporose/tratamento farmacológico , Alendronato/administração & dosagem , Fosfatase Alcalina/metabolismo , Animais , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Feminino , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/fisiopatologia , Fêmur/metabolismo , Fêmur/patologia , Fêmur/fisiopatologia , Genisteína/administração & dosagem , Injeções Subcutâneas , Metilprednisolona , Osteoporose/induzido quimicamente , Osteoporose/complicações , Osteoporose/fisiopatologia , Peptídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
14.
Food Chem Toxicol ; 46(11): 3528-33, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18834916

RESUMO

Monensin, a well known ionophore antibiotic, may cause severe damage in neuronal cells by altering Na+/K+-ATPase and Ca2+-ATPase. We investigated whether IRFI-042, a synthetic analogue of vitamin E, may block lipid peroxidation in neuronal cells and protect against monensin neurotoxicity in chicks. Monensin toxicity was induced in chicks by once-daily administration (150 mg/kg by oral gavages), for 8 days. Sham animals received a saline solution and were used as controls. All animals were randomized to receive either IRFI-042 (20 mg/kg) or its vehicle. Survival rate, brain lipid peroxidation, mRNA for neuronal and inducible nitric oxide synthases (nNOS and iNOS) and brain histological evaluations, including immunohistochemical expression of nNOS and iNOS were performed. Monensin administration decreased survival rate, induced behavioural changes, increased brain lipid peroxidation, reduced brain nNOS mRNA and immunostaining and enhanced iNOS mRNA and immunostaining in the brain in chicks. IRFI-042 significantly improved the survival rate and counteracted monensin-induced changes in chick brains. Our data suggest that monensin is responsible of neurotoxicity in chicks by inducing oxidative stress/lipid peroxidation and that IRFI-042 might represent a useful pharmacological approach to protect against the neuronal damage induced by this monovalent carboxylic ionophorous polyether antibiotic.


Assuntos
Benzofuranos/farmacologia , Encefalopatias/induzido quimicamente , Encefalopatias/prevenção & controle , Encéfalo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Monensin/antagonistas & inibidores , Animais , Encéfalo/enzimologia , Encéfalo/metabolismo , Encéfalo/patologia , Encefalopatias/mortalidade , Galinhas , Imuno-Histoquímica , Masculino , Monensin/toxicidade , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , RNA/biossíntese , RNA/isolamento & purificação , Distribuição Aleatória , Taxa de Sobrevida
15.
Br J Pharmacol ; 155(6): 896-905, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18695641

RESUMO

BACKGROUND AND PURPOSE: Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis. EXPERIMENTAL APPROACH: Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg(-1) s.c.); alendronate (0.003 and 0.03 mg kg(-1) s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.); 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology. KEY RESULTS: Genistein (10 mg kg(-1)) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels. CONCLUSIONS AND IMPLICATIONS: The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.


Assuntos
Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Estradiol/uso terapêutico , Genisteína/uso terapêutico , Osteoporose/tratamento farmacológico , Cloridrato de Raloxifeno/uso terapêutico , Alendronato/farmacologia , Animais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estradiol/farmacologia , Feminino , Genisteína/farmacologia , Ovariectomia , Fitoestrógenos/farmacologia , Fitoestrógenos/uso terapêutico , Cloridrato de Raloxifeno/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
18.
Pediatr Med Chir ; 12(6): 687-90, 1990.
Artigo em Italiano | MEDLINE | ID: mdl-2093893

RESUMO

The authors report a case of infant visceral Leishmaniosis observed in their Department, that showed unusual clinical finding (absence of fever). They emphasize the current epidemiologic situation and recommend to consider the disease in the diagnosis of long term syndroms occurring without fever and with hepatosplenomegaly.


Assuntos
Leishmaniose Visceral , Antiprotozoários/uso terapêutico , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Prognóstico
19.
Pediatr Med Chir ; 5(1-2): 133-5, 1983.
Artigo em Italiano | MEDLINE | ID: mdl-6138753

RESUMO

The Authors describe the case of a little girl from Buenos Aires that presents, as regards the clinical picture and the course, the features of Kawasaki illness. It is the first case described in Calabria. The Authors come to the hypothesis that Kawasaki illness, could be a benign variant of periarteritis nodosa, caused from an infections noxa (Rickettsie?).


Assuntos
Síndrome de Linfonodos Mucocutâneos , Antibacterianos/uso terapêutico , Aspirina/uso terapêutico , Pré-Escolar , Feminino , Humanos , Doenças do Complexo Imune , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/etiologia , Poliarterite Nodosa/complicações , Prednisolona/uso terapêutico , Infecções por Rickettsia/complicações
20.
Percept Mot Skills ; 50(3 Pt 2): 1239-46, 1980 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7413398

RESUMO

20 right-handed males judged the duration of small and large colored circles, which were briefly exposed in the left, center, and right visual fields. Perceived duration was a logarithmic function of exposure duration and a positive function of size and chromaticity. Over-all accuracy was equivalent in the left and right visual fields, but the effects of chromaticity and duration on subjects' judgments were asymmetrical. These and other findings suggest a two-process model of time perception in which there is right hemispheric control over a visual information processor and left hemispheric control over a timer.


Assuntos
Percepção de Cores , Dominância Cerebral , Percepção do Tempo , Humanos , Masculino , Percepção de Tamanho , Campos Visuais
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