[Indications authorized in Spain of osteoporosis drugs].
Explore the source record for details and available documents.
Drug Utilization↗
Biomedical subjects
A Ubeda
Publications and source records attributed to A Ubeda.
[Nonthermal levels of electric currents applied in capacitive electric transfer therapy provokes partial cytotoxic effects in human neuroblastoma cultures].
The present study investigates the cellular response to weak, sine wave, 0.5-MHz electric currents. The experimental exposure to identical signals at an intensity high enough as to significantly increase the temperature in target tissues, has provided positive responses in clinical treatments of tumors with capacitive electric transfer (CET) thermal therapy. The present results show that the in vitro exposure to CET signals at athermal doses causes cytotoxic effects in human neuroblastoma cells. Such a response seems to be due to signal-induced alterations in the cell cycle. As a whole, the results suggest that the potential therapeutic effects of the CET strategy could be due to the thermal response of the tissues to the currents, added to an athermal response of the cells to the electric current itself.
Cell Division↗
Solid-phase synthesis and inhibitory effects of some pyrido[1,2-c]pyrimidine derivatives on leukocyte formations and experimental inflammation.
A number of pyrido[1,2-c]pyrimidines bearing a nitrogen, oxygen, or sulfur functionality at C-1 were synthesized on solid-phase using the iminophosphorane methodology and tested for their effects on leukocyte functions in vitro and antiinflammatory activity. Compound 5c was found to be a strong scavenger of superoxide anion and an inhibitor of chemiluminescence induced by 12-O-tetradecanoylphorbol 13-acetate in human neutrophils. These pyrido[1,2-c]pyrimidines inhibited the generation of PGE(2) by COX-2 in RAW 264.7 macrophages stimulated with lipopolysaccharide. Compounds 7, 5f, 6, and 8 inhibited enzyme activity, whereas the remaining compounds also acted on the induction phase. In addition, 5a-f, 6, and 7 administered p.o. at a dose of 20 mg/kg showed antiinflammatory activity in the carrageenan mouse paw edema model, where they inhibited PGE(2) levels in inflamed paws without affecting the content of this eicosanoid in stomachs. Inhibition of PGE(2) production and superoxide scavenging may participate in the mechanism of the antiinflammatory action of these pyrido[1,2-c]pyrimidine derivatives.
Animals↗
4-dimethylamino-3',4'-dimethoxychalcone downregulates iNOS expression and exerts anti-inflammatory effects.
Reactive oxygen and nitrogen species contribute to the pathophysiology of inflammatory conditions. We have studied the effects of a novel superoxide scavenger, 4-dimethylamino-3', 4'-dimethoxychalcone (CH11) in macrophages and in vivo. CH11 has been shown to inhibit the chemiluminescence induced by zymosan in mouse peritoneal macrophages and the cytotoxic effects of superoxide. In the same cells, the modulation by superoxide of nitric oxide (NO) production in response to zymosan was investigated. CH11 was more effective than the membrane-permeable scavenger Tiron for inhibition of inducible nitric oxide synthase (iNOS) protein expression and nitrite production. We have shown that CH11 inhibited chemiluminescence in vivo, as well as cell migration, and eicosanoid and tumor necrosis factor-alpha (TNF-alpha) levels in the mouse air pouch injected with zymosan. This chalcone derivative also exerted anti-inflammatory effects in the carrageenan paw oedema.
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
Effect of imidazo[1,2-a]pyrimidine derivatives on leukocyte function.
OBJECTIVE AND DESIGN: A series of six imidazo[1,2-a]pyrimidine (IP) derivatives were evaluated for their effects on leukocyte functions in vitro as well as on the inflammatory response induced by zymosan in the mouse air pouch. MATERIALS AND SUBJECTS: Human neutrophils and murine peritoneal macrophages were used for in vitro assays. Mouse air pouch was performed in Swiss mice. TREATMENT: Test compounds were incubated with either human neutrophils or mouse peritoneal macrophages at concentrations not showing cytotoxic effects. For in vivo experiments, IPs were injected into the air pouch. METHODS: Elastase and myeloperoxidase release, superoxide generation and LTB4 production were assayed in human neutrophils treated with different stimuli. Mouse peritoneal macrophages were stimulated with lipopolysaccharide (LPS), followed by determination of nitrite and PGE2 levels in supernatants. Zymosan was injected into six days-old mouse air pouches. Dunnett's t-test was employed for statistical analysis. RESULTS: All IPs inhibited human neutrophil degranulation with IC50 values in the microM range. IP-1, IP-2 and IP-5 also decreased superoxide generation. In LPS-stimulated macrophages, IP-4 and IP-6 inhibited nitrite production with a moderate reduction in PGE2 generation. In addition, these two compounds at 100 nmol/pouch inhibited leukocyte migration and LTB4 levels in the exudate of the mouse air pouch. CONCLUSIONS: Imidazo[1,2-a]pyrimidines are a class of compounds with antiinflammatory potential.
Animals↗
New sesquiterpene derivatives from the sponge Dysidea species with a selective inhibitor profile against human phospholipase A2 and other leukocyte functions.
Two new sesquiterpene cyclopentenones, dysidenones A and B (2, 3), and a new sesquiterpene aminoquinone, dysidine (4), all containing the same rearranged drimane skeleton, have been isolated from a Dysidea sp. sponge, along with bolinaquinone (1). The structures were established from 2D NMR data. Bolinaquinone (1), dysidine (4), and a 1:1 mixture of dysidenones A and B (2, 3) significantly inhibited human synovial phospholipase A2 (PLA2) at 10 microM. Compound 4, which shows an IC50 value of 2.0 microM, exerts a higher potency and selectivity toward this enzyme than the reference inhibitor manoalide. In addition, all of these compounds modulated at 10 microM other human leukocyte functions such as the degranulation process measured as elastase release and the superoxide production measured by chemiluminescence.
Animals↗
Inhibition of leukocyte functions by the alkaloid isaindigotone from Isatis indigotica and some new synthetic derivatives.
The alkaloid isaindigotone (1a) and seven derivatives have been synthesized to study their influence on several leukocyte functions and the generation of inflammatory mediators. Isaindigotone (1a) was found to be a scavenger of superoxide generated either by the hypoxanthine/xanthine oxidase system or stimulated human neutrophils. Isaindigotone (1a) and its acetylated derivative (1b) also inhibited 5-lipoxygenase activity and leukotriene B(4) production in these cells, whereas none of the compounds affected degranulation. In RAW 264.7 macrophages stimulated with lipopolysaccharide, synthetic derivatives exerted higher inhibitory effects on prostaglandin E(2) (PGE(2)) and nitric oxide (NO) generation when compared with (1a). The presence of an acetoxyl group at C-4' favors the inhibition of NO and PGE(2) production, whereas the fluoro substituent at C-4' or the absence of substituents on the aromatic ring of the benzylidene unit improves the inhibition of PGE(2). Thus, this series of compounds can attenuate the production of mediators relevant to the inflammatory response.
Alkaloids↗
Physiological levels of melatonin enhance gap junction communication in primary cultures of mouse hepatocytes.
Gap junction communication is known to be involved in controlling cell proliferation and differentiation, and seems to play a crucial role in suppression of tumor promotion. Melatonin, a hormone secreted by the pineal gland, has putative oncostatic properties. Intercellular communication through gap junctions was assessed by microinjecting Lucifer yellow fluorescent dye into primary hepatocytes and visualizing the spread of the dye to adjacent neighboring cells using phase contrast/fluorescent microscopy. Treatment of primary hepatocyte cultures with a physiological range of melatonin concentrations for 24 h prior to microinjection resulted in significant enhancement in intercellular communication at 0.2 and 0.4 nmol/L but not at lower (0.1 nmol/L) or higher (0.8 or 1.0 nmol/L) concentrations. A time-dependent study showed that the changes in intercellular communication began 10 h after melatonin treatment and reached a maximum at 12 h of treatment. This nonlinear, functional gap junction response to melatonin occurred in the physiological concentration range detected in blood of mammals during nightly releases of the hormone by the pineal gland. These melatonin levels may affect the ability of gap junction communication to exert cell growth control in vivo. The uneven decline between individuals in nocturnal release of melatonin that occurs with age could identify potentially sensitive subpopulations susceptible to developing pathologies involving alterations in biological processes dependent on gap junction communication.
Analysis of Variance↗
Effect of some hexahydroimidazo[1,2-c]pyrimidines in inflammatory responses involving leucocytes and macrophages.
We have studied the effects of some hexahydroimidazo[1,2-c]pyrimidine derivatives (HIPs) on leucocyte functions in-vitro and we have assayed the anti-inflammatory activity of these compounds in two models of inflammation. All HIPs inhibited the human neutrophil degranulation process and superoxide generation at concentrations in the microM range. In mouse peritoneal macrophages stimulated with lipopolysaccharide, HIP-4 and HIP-5 inhibited nitrite production without affecting prostaglandin E2 (PGE2) accumulation. HIP-4 was also active in the zymosan-injected mouse air pouch model (at 100 nmol/pouch), with significant reductions in leucocyte migration and PGE2 and leukotriene B4 levels in the air pouch exudate. To confirm the anti-inflammatory effects of this compound, we tested HIP-4 orally (10-40 mg kg(-1)) on carrageenan mouse-paw oedema where it exerted a dose-dependent inhibition of paw swelling with significant reductions of myeloperoxidase and elastase activity and PGE2 levels in paw homogenates. This study demonstrates that some HIPs inhibit leucocyte functions and one of these derivatives (HIP-4) shows anti-inflammatory activity when administered by the oral route, which can be related to inhibition of leucocyte migration.
Animals↗
An anti-inflammatory ditriazine inhibiting leukocyte functions and expression of inducible nitric oxide synthase and cyclo-oxygenase-2.
A ditriazine derivative (4,10-dichloropyrido[5,6:4,5]thieno[3,2-d':3, 2-d]-1,2,3-ditriazine (DTD)) inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B(4) production, without any effect on 5-lipoxygenase activity. This compound reduced nitric oxide (NO) and prostaglandin E(2) production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase, cyclo-oxygenase-2 or cyclo-oxygenase-1 was observed. DTD significantly reduced mouse paw oedema induced by carrageenan and also markedly reduced NO and prostaglandin E(2) levels in exudates from 24-h zymosan-stimulated mouse air pouch. Western blot analysis showed that DTD reduced the expression of inducible NO synthase and cyclo-oxygenase-2. Our results indicate that DTD exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E(2) production, which could be due to a decreased expression of inducible NO synthase and cyclo-oxygenase-2.
Animals↗
Synthesis and enzyme inhibitory activities of a series of lipidic diamine and aminoalcohol derivatives on cytosolic and secretory phospholipases A2.
We have synthesised some lipidic diamines and aminoalcohols and examined their behaviour as inhibitors of secretory and cytosolic PLA2. Some structure-activity relationships considerations have been deduced. Compound 14 was a potent and selective inhibitor of cPLA2 and compound 4 showed a dual inhibitory profile against both types of PLA2 while no cytotoxicity at 10 microM on human neutrophils or on murine macrophage line was observed for both.
Amino Alcohols↗
Effects of some isoxazolpyrimidine derivatives on nitric oxide and eicosanoid biosynthesis.
The inhibitory effect of some isoxazolpyrimidine derivatives on iNOS and COX-2 endotoxin induction in mouse peritoneal macrophages has been studied. Three of these compounds inhibited nitrite and PGE2 accumulation in a concentration dependent-manner at microM range. None of these active compounds affected iNOS, COX-2, COX-1 or PLA2 activities, although some reduced iNOS or COX-2 expression. Besides, no effect was observed on human neutrophil inflammatory responses (LTB4 biosynthesis and superoxide or elastase release). Active compounds were assayed by oral administration in the mouse air pouch model, where they inhibited nitrite accumulation without affecting PGE2 levels or leukocyte migration.
Animals↗
Role of color Doppler ultrasonography in the diagnosis of endometriotic cyst.
We studied the role of color Doppler ultrasonography in the distinction between endometriomas and other adnexal masses. Three hundred and fifty-two ovarian lesions were studied, comparing sonographic diagnosis with pathologic findings. On color Doppler sonography, an endometriotic cyst usually appeared as a cystic lesion with diffuse internal echoes and low vascularization. The sensitivity and specificity of color Doppler transvaginal sonography in detecting endometriotic cysts were 91.8% and 95.3%, respectively. The positive and negative predictive values were 95.5% and 91.5%, respectively. In our experience, transvaginal sonography with color Doppler interrogation is a useful technique in the diagnosis of pathologic ovarian conditions, including cystic endometriosis.
Adult↗
Synthesis and pharmacological evaluation of some 8-cyanopyrido[3', 2':4,5]thieno[3,2-d]triazine derivatives as inhibitors of nitric oxide and eicosanoid biosynthesis.
A series of 8-cyanopyrido[3',2':4,5]thieno[3,2-d]-1,2,3-triazines, substituted at C-4 and C-7, were synthesized and evaluated as nitric oxide and prostaglandin E(2) inhibitors in murine peritoneal macrophages stimulated with bacterial endotoxin. Several compounds exhibited considerable activity, compounds 10 and 13 being the most interesting ones with IC(50) values of 11.2 and 3.4 microM on nitrites and 0.9 and 0.6 microM on prostaglandin E(2) production, respectively. None of the examples of pyridothienotriazines that were active at 10 microM showed any effect on inducible nitric oxide synthase, cyclooxygenase-2, and cyclooxygenase-1 enzymes, suggesting that they act by modifiying the level of expression of these inducible enzymes.
Animals↗
Novel anti-inflammatory chalcone derivatives inhibit the induction of nitric oxide synthase and cyclooxygenase-2 in mouse peritoneal macrophages.
In a previous work, we tested a series of chalcone derivatives as possible anti-inflammatory compounds. We now investigate the effects of three of those compounds, CHI, CH8 and CH12, on nitric oxide and prostanoid generation in mouse peritoneal macrophages stimulated with lipopolysaccharide and in the mouse air pouch injected with zymosan, where they showed a dose-dependent inhibition with inhibitory concentration 50% values in the microM range. This effect was not the consequence of a direct inhibitory action on enzyme activities. Our results demonstrated that chalcone derivatives inhibited de novo inducible nitric oxide synthase and cyclooxygenase-2 synthesis, being a novel therapeutic approach for inflammatory diseases.
Animals↗
Morphological changes in hysterectomies after endometrial ablation.
Electrosurgical ablation of the endometrium is a therapeutic choice for those patients having abnormal uterine bleeding. When ablation is followed by a hysterectomy, tissue damage due to thermal effect can be seen. From a total of 350 women with endometrial ablation, 12 required subsequent hysterectomy. The histological features found in these specimens are described and related to the elapsed time between the two surgical procedures. The mean elapsed time between ablation and hysterectomy was 19 +/- 17.3 months. Scarring with formation of additional endometrial cavities was seen in five cases, and endocervical stenosis in two cases. In seven patients, endometrial regrowth was seen at hysterectomy. Necrosis, granulomatous and foreign-body giant cell reaction, eosinophilic infiltrate and pigment-containing macrophages in the myometrium were seen in the long-term post-ablation hysterectomies. Necrosis was seen in short period post-ablation hysterectomies. Six of the seven patients with endometrial regeneration had adenomyosis in the hysterectomy specimen. Endometrial ablation induces thermal effects in the endometrium and granulomatous reaction with foreign-body giant cell reaction, fibrosis and deposition of pigment within macrophages in the myometrium. Adenomyosis is a possible explanation for endometrial regeneration in cases of ablation failure.
Adult↗
Synthesis and anti-inflammatory activity of chalcone derivatives.
Chalcones and their derivatives were synthesized and evaluated for their anti-inflammatory activity. In vitro, chalcones 2, 4, 8, 10 and 13 inhibited degranulation and 5-lipoxygenase in human neutrophils, whereas 11 behaved as scavenger of superoxide. Only four compounds (4-7) inhibited cyclo-oxygenase-2 activity. The majority of these samples showed anti-inflammatory effects in the mouse air pouch model.
Animals↗
Histological features of the contralateral ovary in patients with unilateral ovarian cancer: a case control study.
OBJECTIVE: Most of the surface epithelial-stromal tumors of the ovary are thought to arise from epithelial inclusion cysts, thus these cysts, and the original surface epithelium, are precursor lesions of ovarian carcinoma. MATERIAL AND METHODS: The histological features in contralateral ovary from 20 patients with unilateral ovarian carcinoma were compared with 20 ovaries of patients without ovarian pathology and with 12 normal ovaries of women with contralateral benign ovarian pathology. RESULTS: Cortical invaginations were more frequent and numerous in ovaries of patients with contralateral ovarian carcinoma. The presence of cortical invaginations and epithelial inclusion cysts showed correlation in patients with cancer and in those without ovarian pathology, but there were no differences in the number of inclusion cysts when the three groups were compared. Mild cytological atypia was detected more frequently in the surface epithelium of contralateral ovaries of patients with ovarian carcinoma. Ovarian size, cortical thickness, stromal hyperplasia, psammoma bodies, and surface papillae did not show differences when comparing patients with cancer and control groups. CONCLUSION: Cortical invaginations, a previous step in the formation of epithelial inclusion cysts, can also play an important role in the genesis of ovarian carcinoma.
Adult↗