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1.
Eur J Pharmacol ; 861: 172593, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31401154

RESUMO

We focused on the cyclophosphamide-induced hemorrhagic cystitis (100 mg/kg/day intraperitoneally throughout three days) as a particular NO-system disturbance, and therapy possibilities. We demonstrated that it may be attenuated by subsequent administration of the NOS substrate L-arginine (100 mg/kg/day intraperitoneally), aggravated by NOS-blocker L-NAME (5 mg/kg/day intraperitoneally), all influenced by the stable gastric pentadecapeptide BPC 157 (10 µg/kg/day, 10 ng/kg/day, intraperitoneally or perorally, in drinking water). Regularly, cyclophosphamide dose- and time-dependently induced severe hemorrhagic cystitis lesions, gross lesions, and corresponding urothelial necrosis, vesical edema, erosion, hemorrhage, inflammation, and ulceration, microscopically. The bladder wet weight dramatically increased. Functionally, already after first cyclophosphamide administration, there is an increased leak point pressure. Until the second cyclophosphamide administration, L-arginine consistently attenuated regular cyclophosphamide-induced severe hemorrhagic cystitis lesions, grossly and microscopically, but not functionally. L-NAME aggravated these lesions and eradicated beneficial effect of L-arginine when combined. BPC 157 administration after cyclophosphamide, given in either dose or in either regimen markedly attenuated all cyclophosphamide lesions, grossly, microscopically. The increase of the bladder wet weight was consistently attenuated. Functionally, increased leak point pressure was reversed to the values noted in normal rats. The similar findings were noted in rats that received BPC 157 together with L-NAME or L-arginine, given alone or combined. Thus, the lesions are NO-related based on the administration of L-NAME as well as administration of L-arginine, and their mutual interaction, and counteraction by BPC 157 application. Likewise, we reveal new therapeutic possibilities, emphasizing stable gastric pentadecapeptide BPC 157 and L-arginine, versus L-NAME in rats underwent cyclophosphamide-induced cystitis.


Assuntos
Arginina/farmacologia , Ciclofosfamida/efeitos adversos , Cistite/complicações , Cistite/tratamento farmacológico , Hemorragia/complicações , NG-Nitroarginina Metil Éster/farmacologia , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Arginina/uso terapêutico , Feminino , NG-Nitroarginina Metil Éster/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Proteínas/uso terapêutico , Ratos , Ratos Wistar
2.
Med Sci Monit Basic Res ; 19: 93-102, 2013 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-23478678

RESUMO

BACKGROUND: Since an originally anti-ulcer stable gastric pentadecapeptide BPC 157 (PL 14736) was shown to promote healing of injured striated muscle and smooth muscle in the gastrointestinal tract, we explored its therapeutic potentials for leak point pressure (LPP) recovery in rat stress urinary incontinence (SUI) after transabdominal urethrolysis (TU) and prolonged vaginal dilatation (VD). MATERIAL AND METHODS: During a 7-day period, TU-rats and VD-rats (or healthy rats) received BPC 157, either (i) intraperitoneally, 10 µg/kg or 10 ng/kg, once daily (first administration 30 min after surgery, last 24 h before LPP-testing and sacrifice), or (ii) per-orally, 10 µg/kg in drinking water (0.16 µg/mL, 12 mL/rat/day). Vesicourethral segments were harvested for immunohistochemical evaluation. RESULTS: All BPC 157 regimens counteracted decrease of LPP values in TU-rats and VD-rats. Additionally, BPC 157-TU rats (µg-intraperitoneally or per-orally) and BPC 157-VD rats (µg intraperitoneally) reached LPP values originally noted in healthy rats. Conversely, in healthy rats, BPC 157 did not alter LPP. Immunohistochemical studies revealed higher desmin (delineates striated organization of skeletal muscle), smooth muscle actin, and CD34 (angiogenic marker) positivity within the urethral wall in BPC 157-treated rats vs. controls, as well as overall preserved muscle/connective tissue ratio assessed with Mallory's trichrome staining. CONCLUSIONS: Pentadecapeptide BPC 157, applied parenterally or per-orally, appears to ameliorate the SUI in rat models, improving the otherwise detrimental course of healing after VD and TU, which may be analogous to human injury. These beneficial effects may possibly be selectively used in future strategies for treatment of SUI.


Assuntos
Fragmentos de Peptídeos/uso terapêutico , Proteínas/uso terapêutico , Uretra/efeitos dos fármacos , Incontinência Urinária por Estresse/tratamento farmacológico , Actinas/metabolismo , Administração Oral , Animais , Antiulcerosos/uso terapêutico , Modelos Animais de Doenças , Feminino , Infusões Parenterais , Músculo Liso/patologia , Ratos , Ratos Wistar , Uretra/patologia , Vagina/patologia , Cicatrização
3.
Med Glas (Zenica) ; 9(2): 406-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22926387

RESUMO

Glycated hemoglobin A1C reflects a mean glycemia over the preceding 3 months (erythrocyte life span). In diabetes management, target value is set below 6.5%, to reduce the risk of chronic complications. However, there are different conditions that lead to a shortened lifespan of erythrocytes, resulting in falsely low HbA1C value. Case presented involves a 72-year-old patient with history of diabetes and possible iatrogenic-induced autoimmune hemolytic anemia. Thus, HbA1C may be a screening test for hemolysis in non-diabetic patients with hemolytic anemia, but in diabetic population with hemolytic disease it is considered to be a very poor marker for both, overall glycemia and haemolysis.


Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/análise , Idoso , Anemia Hemolítica Autoimune/etiologia , Biomarcadores/sangue , Glicemia , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Metformina/efeitos adversos , Metformina/uso terapêutico
4.
Regul Pept ; 160(1-3): 26-32, 2010 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-19931318

RESUMO

Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide, efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported, improved muscle crush injury. After an induced traumatic brain injury (TBI) in mice by a falling weight, BPC 157 regimens (10.0microg, 10.0ng/kgi.p.) demonstrated a marked attenuation of damage with an improved early outcome and a minimal postponed mortality throughout a 24h post-injury period. Ultimately, the traumatic lesions (subarachnoidal and intraventricular haemorrhage, brain laceration, haemorrhagic laceration) were less intense and consecutive brain edema had considerably improved. Given prophylactically (30 min before TBI) the improved conscious/unconscious/death ratio in TBI-mice was after force impulses of 0.068 Ns, 0.093 Ns, 0.113 Ns, 0.130 Ns, 0.145 Ns, and 0.159 Ns. Counteraction (with a reduction of unconsciousness, lower mortality) with both microg- and ng-regimens included the force impulses of 0.068-0.145 Ns. A higher regimen presented effectiveness also against the maximal force impulse (0.159 Ns). Furthermore, BPC 157 application immediately prior to injury was beneficial in mice subjected to force impulses of 0.093 Ns-TBI. For a more severe force impulse (0.130 Ns, 0.145 Ns, or 0159 Ns), the time-relation to improve the conscious/unconscious/death ratio was: 5 min (0.130 Ns-TBI), 20 min (0.145 Ns-TBI) or 30 min (0.159 Ns-TBI).


Assuntos
Antiulcerosos/farmacologia , Encéfalo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Animais , Lesões Encefálicas/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos , Fatores de Tempo
5.
Coll Antropol ; 27(2): 735-43, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14746166

RESUMO

The study evaluated antioxidant status in patients with peripheral vascular disease (PVD), with and without concomitant diabetes mellitus (DM). 211 participants were divided into standardized 4 groups: patients with PVD and DM (PVD+DM+), patients with PVD without DM (PVD+DM-), patients without PVD with DM (PVD-DM+) and patients without PVD and DM (PVD-DM-). The diagnosis of PVD was established by Doppler sonography analysis, including determination of the ankle brachial index (ABI), partial pressures along the leg, and CW Doppler sonography at typical locations. Antioxidant status has been evaluated through the colorimetrically assessed serum activity of key antioxidant enzymes: superoxide dismutase (SOD), catalase, and glutathione peroxidase (GLPX) as well as through total antioxidant status (TAS) determination. In PVD+DM- group, as well as PVD-DM+ group, a significantly lower activity of the GLPX, catalase and TAS was found, whereas activity of SOD was significantly higher. There was no statistically significant difference between PVD+DM+ and PVD-DM+ group. Likewise, there was no statistically significant difference between PVD+DM- and PVD-DM-group. This study has shown that there is statistically significant difference in activity of antioxidant enzymes between diabetic and non-diabetic patients, irrespectively of PVD presence. Furthermore, PVD present alone does not alter key antioxidant enzymes activity in comparison with healthy subjects.


Assuntos
Antioxidantes/metabolismo , Catalase/sangue , Angiopatias Diabéticas/metabolismo , Glutationa Peroxidase/sangue , Doenças Vasculares Periféricas/metabolismo , Superóxido Dismutase/sangue , Angiopatias Diabéticas/enzimologia , Humanos , Doenças Vasculares Periféricas/enzimologia
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