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1.
Ralf Berger Jurandir Marcondes Ribas Filho Osvaldo Malafaia Paulo Afonso Nunes Nassif Eduardo Nascimento Silva Alfredo Benjamin Duarte da Silva Milka Takejima Marcelo Augusto de Souza Pedro Henrique de Paula Mrio Rodrigues Montemor Netto Lucia de Noronha 《Acta cirúrgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia》2021,36(5)
2.
Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats. 总被引:3,自引:0,他引:3
N Jelovac P Sikiric R Rucman M Petek A Marovic D Perovic S Seiwerth S Mise B Turkovic G Dodig P Miklic G Buljat I Prkacin 《European journal of pharmacology》1999,379(1):19-31
A gastric pentadecapeptide, BPC 157, with the amino acid sequence, Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, MW 1419, known to have a variety of protective effects in gastrointestinal tract and other organs, was recently shown to particularly affect dopamine systems. For instance, it blocks the stereotypy produced acutely by amphetamine in rats, and the development of haloperidol-induced supersensitivity to amphetamine in mice. Consequently, whether pentadecapeptide BPC 157, that by itself has no cataleptogenic effect in normal animals, may attenuate the immediate effects of neuroleptics application, particularly catalepsy, was the focus of the present report. Prominent catalepsy, otherwise consistently seen in the mice treated with haloperidol (0.625, 1.25, 2.5, 5.0 and 10.0 mg/kg b.w., i.p.) and fluphenazine (0.3125, 0.625, 1.25, 2.5 and 5.0 mg/kg b.w., i.p.) after 1.5, 3, 4.5, 6 and 7.5 h following administration, was markedly attenuated when pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w., i.p.) was coadministered with the neuroleptic. The number of cataleptic mice was markedly lower throughout most of the experimental period. Moreover, on challenge with lower doses of neuroleptics, catalepsy appearance was postponed and the mice, otherwise cataleptic since the earliest period, became cataleptic later, not before 3 or 4.5 h after neuroleptic administration, especially if protected with higher pentadecapeptide dose. Besides catalepsy, coadministration of the pentadecapeptide BPC 157, given in the above mentioned doses, reduced not only catalepsy but somatosensory disorientation (for 7.5 h after administration of a neuroleptic, assessed at intervals of 1.5 h, by a simple scoring system [0-5]) in haloperidol- or fluphenazine-challenged mice as it did in mice treated with sulpiride (20, 40, 80 and 160 mg/kg b.w., i.p.) or with clozapine (25, 50 and 100 mg/kg b.w., i.p.), in which case catalepsy was absent. In other experiments, considering the gastric origin of this pentadecapeptide, the focus was shifted to the evidence that a dose of haloperidol, cataleptogenic due to dopamine receptors blockade, induces gastric ulcers in rats. Coadministration of pentadecapeptide BPC 157 (10 microg, 10 ng, 1.0 ng, 100 pg/kg b.w., i.p.) to rats completely inhibited the lesions otherwise regularly evident 24 h after haloperidol (5.0 mg/kg b.w., i.p.) in control rats (18 of 20 rats had gastric lesions). This activity accompanied the antagonism of the haloperidol catalepsy in rats (assessed at 60-min intervals from I to 5 h after haloperidol), when 10-microg- or 10-ng regimens were given (lower doses could not influence catalepsy). Together, these findings indicate that pentadecapeptide BPC 157 fully interacts with the dopamine system, both centrally and peripherally, or at least, that BPC 157 interferes with some steps involved in catalepsy and/or ulcer formation. 相似文献
3.
4.
An-Sofie Schoonjans Fabienne Marchau Bernard P. Paelinck Lieven Lagae Arnold Gammaitoni Milka Pringsheim 《Current medical research and opinion》2017,33(10):1773-1781
Objective: Dravet syndrome (DS) is a rare, treatment-resistant epilepsy syndrome for which current treatment regimens are often ineffective. Fenfluramine is currently in development for treatment of DS, based on reports in the 1980s and 1990s of its anti-epileptic activity in pediatric patients with intractable epilepsy. However, fenfluramine was withdrawn from global markets in 1997 following reports of its association with pulmonary hypertension and heart valve disease in adult patients treated for obesity. This review was conducted to assess cardiac safety of fenfluramine when used at lower doses for treatment of DS.Methods: Pubmed was searched for clinical studies of fenfluramine in obese adults who reported incidence of heart valve disease. These data were reviewed against published results from Belgian patients with DS who have been treated with low-dose fenfluramine for up to 28 years.Results: Nine controlled studies of fenfluramine and related compounds (dexfenfluramine and/or phentermine) which assessed incidence and severity of cardiac valve disease in 3,268 treated patients and 2,017 control subjects have been reported. Mild or greater aortic valve regurgitation was found in 9.6% of treated patients compared with 3.9% of control subjects, and moderate or greater mitral valve regurgitation was found in 3.1% of treated patients and 2.5% of control subjects. Nineteen DS patients have been treated for up to 28 years with 10–20?mg/day fenfluramine, with no clinical signs or symptoms of cardiac valve disease or pulmonary hypertension. Slight and clinically unimportant changes in valve structure have been seen on echocardiography in five patients at some time during the observation period.Conclusions: A different benefit-risk relationship appears to be emerging when fenfluramine is used at low doses for extended periods in young patients with DS. Continued cardiac assessments during ongoing Phase 3 clinical trials will provide additional safety information for this potential new and effective treatment. 相似文献
5.
Branko Filipović Branka Šošić‐Jurjević Vladimir Ajdžanović Jasmina Pantelić Nataša Nestorović Verica Milošević Milka Sekulić 《Journal of anatomy》2013,222(3):313-320
Androgen deficiency is one of the major factors leading to the development of osteoporosis in men. Since calcitonin (CT) is a potent antiresorptive agent, in the present study we investigated the effects of androgen deficiency and subsequent testosterone and estradiol treatment on CT-producing thyroid C cells, skeletal and hormonal changes in middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One group of Orx rats received 5 mg kg−1 b.w. testosterone propionate (TP) subcutaneously, while another group was injected with 0.06 mg kg−1 b.w. estradiol dipropionate (EDP) once a day for 3 weeks. A peroxidase–antiperoxidase method was applied for localization of CT in the C cells. The studies included ultrastructural microscopic observation of these cells. The metaphyseal region of the proximal tibia was measured histomorphometrically using an imagej public domain image processing program. TP or EDP treatment significantly increased C cell volume (Vc), volume densities (Vv) and serum CT concentration compared with the Orx animals. Administration of both TP and EDP significantly enhanced cancellous bone area (B.Ar), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and reduced trabecular separation (Tb.Sp). Serum osteocalcin (OC) and urinary Ca concentrations were significantly lower after these treatments in comparison with Orx rats. These data suggest that testosterone and estradiol treatment in Orx middle-aged rats affect calcitonin-producing thyroid C cells, which may contribute to the bone protective effects of sex hormones in the rat model of male osteoporosis. 相似文献
6.
Huang ZM Chinen M Chang PJ Xie T Zhong L Demetriou S Patel MP Scherzer R Sviderskaya EV Bennett DC Millhauser GL Oh DH Cleaver JE Wei ML 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(2):553-558
Protein-trafficking pathways are targeted here in human melanoma cells using methods independent of oncogene mutational status, and the ability to up-regulate and down-regulate tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to cis-diaminedichloroplatinum II (cDDP, cis-platin), carboplatin, dacarbazine, or temozolomide together with velaparib, an inhibitor of poly (ADP ribose) polymerase 1, is increased by up to 10-fold by targeting genes that regulate both protein trafficking and the formation of melanosomes, intracellular organelles unique to melanocytes and melanoma cells. Melanoma cells depleted of either of the protein-trafficking regulators vacuolar protein sorting 33A protein (VPS33A) or cappuccino protein (CNO) have increased nuclear localization of cDDP, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity. Depleted cells also exhibit a decreased proportion of intracellular, mature melanosomes compared with undepleted cells. Modulation of protein trafficking via cell-surface signaling by binding the melanocortin 1 receptor with the antagonist agouti-signaling protein decreased the proportion of mature melanosomes formed and increased cDDP sensitivity, whereas receptor binding with the agonist melanocyte-stimulating hormone resulted in an increased proportion of mature melanosomes formed and in decreased sensitivity (i.e., increased resistance) to cDDP. Mutation of the protein-trafficking gene Hps6, known to impair the formation of mature melanosomes, also increased cDDP sensitivity. Together, these results indicate that targeting protein-trafficking molecules markedly increases melanoma treatment sensitivity and influences the degree of melanosomes available for sequestration of therapeutic agents. 相似文献
7.
Maarit Jaana Korhonen Pekka Tiittanen Helena Kastarinen Arja Helin‐Salmivaara Milka Hauta‐aho Maria Rikala Risto Huupponen 《Basic & clinical pharmacology & toxicology》2018,123(2):195-201
Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person‐years of exposure to warfarin‐only and 60,253 years of exposure to warfarin‐with‐statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin‐with‐statin compared to warfarin‐only and to allow multiple episodes per patient and time‐dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable‐adjusted RR = 0.98, 95% CI 0.89–1.07) or to simvastatin (RR = 1.01, 95% CI 0.91–1.11) with warfarin compared to exposure to warfarin‐only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization. 相似文献
8.
I. Perovic M. Milovanovic D. Stanic L. Burazer D. Petrovic N. Milcic-Matic G. Gafvelin M. van Hage R. Jankov T. Cirkovic Velickovic 《Clinical and experimental allergy》2009,39(3):435-446
Background Treating allergies with modified allergens is an approach to make the treatment safer and more efficient. Art v 1 is the most prominent allergen of mugwort pollen and a significant cause of hayfever around Europe. The aim of this study was to reduce the allergenicity of Art v 1 by acetylation, and to investigate the capacity of the modified protein to generate blocking antibodies.
Methods The reduction of allergenicity of Art v 1 following acetylation was monitored by immunoblot, ELISA inhibition using a pool of sera from mugwort pollen allergic patients, basophil activation assay and by skin prick testing of mugwort-allergic patients. Rabbits were immunized against Art v 1 and acetylated Art v 1 (acArt v 1) and the rabbit antisera were tested for their capacity to block human IgE binding in ELISA. Human T cell proliferation against Art v 1 and acArt v 1 was examined in peripheral blood mononuclear cells (PBMCs) of mugwort pollen allergic patients and cytokine release in PBMC cultures was monitored.
Results Acetylation of Art v 1 gave a derivative of reduced allergenicity in the in vitro and ex vivo tests applied. The skin test reactivity to acArt v 1 was significantly reduced in 19 patients when compared with the reactivity to Art v 1. Rabbit antibodies to acArt v 1 and Art v 1 showed similar capacity to block human IgE binding to Art v 1 in inhibition ELISA. Both proteins were able to induce proliferation of PBMCs and CD3/CD4+ cells of mugwort-allergic patients. Release of IL-5 was significantly reduced in cultures stimulated with acArt v 1.
Conclusions Art v 1 modified by acetylation had a significantly reduced allergenicity in vitro and in vivo , while its immunogenicity was retained. Modification of allergens by acetylation could be a new strategy for allergen-specific immunotherapy. 相似文献
Methods The reduction of allergenicity of Art v 1 following acetylation was monitored by immunoblot, ELISA inhibition using a pool of sera from mugwort pollen allergic patients, basophil activation assay and by skin prick testing of mugwort-allergic patients. Rabbits were immunized against Art v 1 and acetylated Art v 1 (acArt v 1) and the rabbit antisera were tested for their capacity to block human IgE binding in ELISA. Human T cell proliferation against Art v 1 and acArt v 1 was examined in peripheral blood mononuclear cells (PBMCs) of mugwort pollen allergic patients and cytokine release in PBMC cultures was monitored.
Results Acetylation of Art v 1 gave a derivative of reduced allergenicity in the in vitro and ex vivo tests applied. The skin test reactivity to acArt v 1 was significantly reduced in 19 patients when compared with the reactivity to Art v 1. Rabbit antibodies to acArt v 1 and Art v 1 showed similar capacity to block human IgE binding to Art v 1 in inhibition ELISA. Both proteins were able to induce proliferation of PBMCs and CD3/CD4
Conclusions Art v 1 modified by acetylation had a significantly reduced allergenicity in vitro and in vivo , while its immunogenicity was retained. Modification of allergens by acetylation could be a new strategy for allergen-specific immunotherapy. 相似文献
9.
Miroslav L. Djordjevic Dusan Stanojevic Marta Bizic Vladimir Kojovic Marko Majstorovic Svetlana Vujovic Alexandar Milosevic Gradimir Korac Sava V. Perovic 《The journal of sexual medicine》2009,6(5):1306-1313
IntroductionMetoidioplasty represents one of the variants of phalloplasty in female transsexuals. Its main characteristic is that it is a one-stage procedure. It involves lengthening and straightening of hypertrophied clitoris to create a neophallus, urethral lengthening to enable voiding while standing, and scrotal reconstruction with insertion of testicle prostheses.AimOur aim is to describe our technique and highlight its advantages.MethodsBetween September 2002 and April 2007, 82 female transsexuals, aged 18–54 years (mean age 31) underwent one-stage metoidioplasty. Clitoris is lengthened and straightened by division of clitoral ligaments and short urethral plate. Urethroplasty is done with combined buccal mucosa graft and genital skin flaps. Scrotum is created from labia majora in which two testicle prostheses are inserted. Simultaneously, female genitalia are removed.Main Outcome MeasuresPatients' personal satisfaction about sensitivity and length of neophallus, possibility to void in standing position, real length of reconstructed urethra as well as complication rate comparing to other published data.ResultsThe median follow-up was 32 months (range 14–69). The mean neophallic length was 5.7 cm (range 4–10). Voiding in standing position was reported in all patients, while dribbling and spraying were noticed in 23 cases and solved spontaneously. There were two urethral strictures and seven fistulas that required secondary minor revision. All patients reported preserved sensation and normal postoperative erection. Testicle prostheses rejection was not observed in any of the patients.ConclusionsMetoidioplasty is a single-stage and time-saving procedure. It could be an alternative to total phalloplasty in female transsexuals who do not wish to have sexual intercourse. Also, it represents a first step in cases where additional augmentation phalloplasty is required. Djordjevic ML, Stanojevic D, Bizic M, Kojovic V, Majstorovic M, Vujovic S, Milosevic A, Korac G, and Perovic SV. Metoidioplasty as a single stage sex reassignment surgery in female transsexuals: Belgrade experience. J Sex Med 2009;6:1306–1313. 相似文献
10.