scholarly journals Activity of the New Triazole Derivative Albaconazole against Trypanosoma (Schizotrypanum) cruzi in Dog Hosts

2004 ◽  
Vol 48 (11) ◽  
pp. 4286-4292 ◽  
Author(s):  
Paulo Marcos da Matta Guedes ◽  
Julio A. Urbina ◽  
Marta de Lana ◽  
Luis C. C. Afonso ◽  
Vanja M. Veloso ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Protozoan Parasite ◽  
Term Treatment ◽  
Natural Resistance ◽  
Clinical Use ◽  
Triazole Derivative ◽  
Long Term Treatment ◽  
Proliferative Assay

ABSTRACT Albaconazole is an experimental triazole derivative with potent and broad-spectrum antifungal activity and a remarkably long half-life in dogs, monkeys, and humans. In the present work, we investigated the in vivo activity of this compound against two strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease, using dogs as hosts. The T. cruzi strains used in the study were previously characterized (murine model) as susceptible (strain Berenice-78) and partially resistant (strain Y) to the drugs currently in clinical use, nifurtimox and benznidazole. Our results demonstrated that albaconazole is very effective in suppressing the proliferation of the parasite and preventing the death of infected animals. Furthermore, the parasitological, PCR, serological, and proliferative assay results indicated parasitological cure indices of 25 and 100% among animals inoculated with T. cruzi strain Y when they were treated with albaconazole at 1.5 mg/kg of body weight/day for 60 and 90 days, respectively. On the other hand, although albaconazole given at 1.5 mg/kg/day was very effective in suppressing the proliferation of the parasite in animals infected with the Berenice-78 T. cruzi strain, no parasitological cure was observed among them, even when a longer treatment period (150 doses) was used. In conclusion, our results demonstrate that albaconazole has trypanocidal activity in vivo and is capable of inducing radical parasitological cure, although natural resistance to this compound was also indicated. Furthermore, the compound can be used in long-term treatment schemes (60 to 150 days) with minimal toxicity and thus represents a potentially useful candidate for the treatment of human Chagas' disease.

scholarly journals Sunitinib treatment promotes metastasis of drug-resistant renal cell carcinoma via TFE3 signaling pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Luchao Li ◽  
Shuo Zhao ◽  
Zhengfang Liu ◽  
Nianzhao Zhang ◽  
Shuo Pang ◽  
...  
Keyword(s):  
Renal Cell ◽  
Cell Cancer ◽  
Acquired Resistance ◽  
Resistant Cell ◽  
Term Treatment ◽  
Acquired Drug Resistance ◽  
Sunitinib Treatment ◽  
Long Term Treatment

AbstractReceptor tyrosine kinase (RTK) inhibitors, such as sunitinib and sorafenib, remain the first-line drugs for the treatment of mRCC. Acquired drug resistance and metastasis are the main causes of treatment failure. However, in the case of metastasis Renal Cell Cancer (mRCC), which showed a good response to sunitinib, we found that long-term treatment with sunitinib could promote lysosome biosynthesis and exocytosis, thereby triggering the metastasis of RCC. By constructing sunitinib-resistant cell lines in vivo, we confirmed that TFE3 plays a key role in the acquired resistance to sunitinib in RCC. Under the stimulation of sunitinib, TFE3 continued to enter the nucleus, promoting the expression of endoplasmic reticulum (ER) protein E-Syt1. E-Syt1 and the lysosomal membrane protein Syt7 form a heterodimer, which induces ER fragmentation, Ca2+ release, and lysosomal exocytosis. Lysosomal exocytosis has two functions: pumping sunitinib out from the cytoplasm, which promotes resistance to sunitinib in RCC, releasing cathepsin B (CTSB) into the extracellular matrix (ECM), which can degrade the ECM to enhance the invasion and metastasis ability of RCC. Our study found that although sunitinib is an effective drug for the treatment of mRCC, once RCC has acquired resistance to sunitinib, sunitinib treatment will promote metastasis.

Biocompatibility of Charcoal Hemoperfusion. Effects of Long-Term Treatment on Lymphocyte Characteristics and Function

1986 ◽  
Vol 9 (5) ◽  
pp. 301-304 ◽  
Author(s):  
S. Stefoni ◽  
A. Nanni Costa ◽  
G. Liviano D'Arcangelo ◽  
M. Biavati ◽  
S. lannelli ◽  
...  
Keyword(s):  
Antigen Expression ◽  
Term Treatment ◽  
T Cell Subsets ◽  
Long Term Treatment ◽  
Circulating Lymphocytes ◽  
And Function ◽  
Charcoal Hemoperfusion

Biocompatibility of charcoal hemoperfusion was studied in a group of 15 uremic patients, evaluating the effects of long-term treatment on some structural and functional parameters of circulating lymphocytes: in vivo distribution of T-cell subsets; surface T3, T4 and T8 antigen expression, in vivo and in vitro DNA synthesis. A comparative analysis was performed with patients on conventional dialysis using cuprophan membranes.

The Successful Long-Term Treatment of Age Related Erectile Dysfunction with hSlo cDNA in Rats In Vivo

2003 ◽  
Vol 170 (1) ◽  
pp. 285-290 ◽  
Author(s):  
A. MELMAN ◽  
W. ZHAO ◽  
K.P. DAVIES ◽  
R. BAKAL ◽  
G.J. CHRIST
Keyword(s):  
Erectile Dysfunction ◽  
Term Treatment ◽  
Age Related ◽  
Long Term Treatment

scholarly journals Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats

2006 ◽  
Vol 189 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Martina Böttner ◽  
Julie Christoffel ◽  
Hubertus Jarry ◽  
Wolfgang Wuttke
Keyword(s):  
Serum Levels ◽  
Term Treatment ◽  
Prolactin Secretion ◽  
Gnrh Receptor ◽  
Female Rats ◽  
Pituitary Function ◽  
Ovx Rats ◽  
Long Term Treatment

Hormone replacement therapy (HRT) has been used for several decades to treat menopausal discomforts. However, in the light of recent studies that draw attention to the potential hazards of conventional HRT, various attempts have been undertaken to search for alternatives to classical HRT. Phytoestrogens are claimed to be capable of positively influencing menopausal symptoms, including hot flushes. We designed a long-term study of 3 months to assess the effects of subcutaneous and orally fed 17β-estradiol (E2), as well as the actions of resveratrol (RES) on pituitary function in female rats. Our results have demonstrated that RES binds with a 10-fold lower affinity to estrogen receptor (ER)-α than to ERβ. The data from the in vivo study revealed that a dosage of 5 μg and 50 μg RES/kg bodyweight per day given to ovariectomized (OVX) rats achieved serum levels of 1.0 and 8.1 μM respectively. Long-term treatment of OVX rats with RES revealed no estrogenic potential on pituitary function in vivo as assessed by LH and prolactin secretion and by regulation of mRNAs for LHα, LHβ, and GnRH receptor. Subcutaneous treatment with E2 in silastic capsules exerted stronger effects on LH and prolactin secretion, as well as on LHβ, LHα, GnRH receptor, and ERβ mRNA regulation compared with orally applied estradiol benzoate despite comparable serum levels. Levels of aryl hydrocarbon receptor (AhR) mRNA in the pituitary were increased following OVX and attenuated by long-term E2 treatment, whereas RES did not modulate AhR mRNA expression.

Opposite Effects of Captopril on Angiotensin I-Converting Enzyme ‘Activity’ and ‘Concentration’; Relation between Enzyme Inhibition and Long-Term Blood Pressure Response

1981 ◽  
Vol 60 (5) ◽  
pp. 491-498 ◽  
Author(s):  
F. Boomsma ◽  
J. H. B. de Bruyn ◽  
F. H. M. Derkx ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Blood Pressure ◽  
Enzyme Activity ◽  
Inhibitory Effect ◽  
Enzyme Concentration ◽  
Term Treatment ◽  
Converting Enzyme ◽  
Control Value ◽  
Long Term Treatment

1. The relationship between the antihypertensive action of captopril and its inhibitory effect on angiotensin I(ANG I)-converting enzyme has been investigated. Converting enzyme was measured in plasma by its ability to generate hippuric acid from the synthetic substrate hippuryl-l-histidyl-l-leucine. Inhibition by captopril appeared transient on storage of the plasma samples at −20°C, so that measurements in such samples were not a valid index of the effect in vivo. 2. Rapid reversal of captopril's inhibitory effect on ANG I-converting enzyme in plasma was achieved by the addition of N-ethylmaleimide (0.1 mmol/l). In this way an estimate of converting enzyme ‘concentration’ was obtained both in stored and in freshly prepared plasma samples. Measurements of converting enzyme ‘activity’ in freshly prepared samples, in the absence of N-ethylmaleimide, were used as an index of inhibition in vivo. 3. In eight hypertensive subjects ANG I-converting enzyme ‘concentration’ did not change after a single oral 100 mg dose of captopril. Long-term treatment of 10 hypertensive subjects with captopril was associated with a gradual increase in converting enzyme ‘concentration’ from 29 ± 2 to 47 ± 3 m-units/ml (mean ± sem) over a period of several weeks. In contrast, captopril caused a rapid fall of converting enzyme ‘activity’. 4. Abrupt withdrawal of captopril after long-term treatment caused a gradual decrease in ANG I-converting enzyme ‘concentration’ to the control value. In contrast, converting enzyme ‘activity’ rose rapidly and became equal to enzyme ‘concentration’ 2 days after the drug had been stopped. 5. The concentration of enzymatically active renin in plasma rose from 13 ± 3 to 81 ± 34 μ-units/ml during long-term captopril treatment (mean ± sem). Blood pressure fell from 168 ±4/108 ± 3 to 140 ± 3/90 ± 3 mmHg and had not returned to the control value in the first week after the drug had been stopped, despite the fact that circulating active renin and ANG I-converting enzyme ‘activity’ were elevated. 6. It is concluded that long-term inhibition of ANG I-converting enzyme by captopril is associated with an increased plasma concentration of this enzyme. The results also suggest that the level of converting enzyme ‘activity’ in plasma is not the only factor that determines the long-term effect of captopril on blood pressure.

Plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-containing superoxide dismutase in alcoholics treated with disulfiram

1986 ◽  
Vol 70 (4) ◽  
pp. 365-369 ◽  
Author(s):  
Michael Öhman ◽  
Stefan L. Marklund
Keyword(s):  
Superoxide Dismutase ◽  
Chronic Alcoholism ◽  
Term Treatment ◽  
Extracellular Superoxide Dismutase ◽  
Healthy Controls ◽  
Efficient Inhibitor ◽  
Long Term Treatment

1. Disulfiram has long been used in the treatment of chronic alcoholism. It is in vivo partially reduced to diethyldithiocarbamate, which is an efficient inhibitor of Cu, Zn-containing superoxide dismutase both in vitro and in vivo. The recently described extracellular superoxide dismutase is even more sensitive to diethyldithiocarbamate than Cu, Zn-superoxide dismutase. 2. To test for the possibility that long term treatment with disulfiram leads to inhibition of the superoxide dismutases, plasma extracellular superoxide dismutase and erythrocyte Cu, Zn-superoxide dismutase were determined in 12 disulfiram-treated alcoholics, and compared with 11 non-treated alcoholics and 19 healthy controls. 3. Plasma extracellular superoxide dismutase was moderately reduced (about 20%) in the disulfiram-treated alcoholics as compared with the non-treated alcoholics and the healthy controls. No effect of disulfiram treatment on erythrocyte Cu, Zn-superoxide dismutase activity was demonstrated.

Role of antiglucocorticoid RU 486 on dexamethasone-induced hypertension in rats

1989 ◽  
Vol 256 (5) ◽  
pp. E682-E685 ◽  
Author(s):  
M. Kalimi
Keyword(s):  
Blood Pressure ◽  
Term Treatment ◽  
Sprague Dawley ◽  
Ru 486 ◽  
Sprague Dawley Rats ◽  
Long Term Treatment ◽  
Term Administration ◽  
Slight Elevation

This study was conducted to investigate whether hypertension induced by long-term in vivo administration of dexamethasone in rats could be prevented by the newly synthesized potent antiglucocorticoid drug RU 486. Subcutaneous implantation of 5 mg of dexamethasone pellets in Sprague-Dawley rats resulted in a rapid increase in the blood pressure that remained elevated during the 3 wk of experimental observation. RU 486 (50 mg) administered alone surprisingly showed slight elevation of blood pressure over untreated control animals. However, the blood pressure leveled off to control levels over the next 2 wk. Interestingly, a 50-mg RU 486 pellet implanted along with 5 mg of dexamethasone effectively prevented the dexamethasone-induced increase in blood pressure. RU 486 administered together with dexamethasone prevented dexamethasone-induced diuresis and urinary Na+ excretion. However, RU 486 was unable to reverse the weight loss or involution of thymus observed by long-term treatment with dexamethasone alone. No abnormalities were found in either kidneys or hearts in any of the treated groups under microscopic examination. These results suggest that RU 486 successfully prevented the hypertension produced by the long-term administration of dexamethasone in male Sprague-Dawley rats.

EVIDENCE FOR PLASMIN-MEDIATED FIBRINOLYSIS AFTER /RELEASE OF TISSUE PLASMINOGEN ACTIVATOR BY DESMOPRESSIN INFUSION

1987 ◽  
Author(s):  
G D O Lowe ◽  
J T Douglas ◽  
M Small ◽  
C Kluft ◽  
C D Forbes
Keyword(s):  
Plasminogen Activator ◽  
Venous Blood ◽  
Term Treatment ◽  
Fibrin Plate ◽  
Long Term Treatment ◽  
Post Infusion ◽  
Control Of Diabetes ◽  
High Level

A relationship between tPA activity and plasmin-mediated fibrinolysis in vivo (plasma levels of Bβ15-42-containing peptides) has been suggested by our previous studies: inverse correlations of Bβ15-42 levels with obesity and triglyceride levels (both associated with high tPA inhibition) in an epidemiological study; and increased levels of Bβ15-42 following improved control of diabetes, or treatment with oral or intramuscular stanozolol (which decrease tPA inhibition). The aim of the present study was to establish whether or not intravenous infusion of desamino-D-arginine vasopressin (DDAVP, desmopressin) is followed by increases in plasmin-mediated fibrinolysis in vivo (plasma Bβ15-42 levels). Desmopressin (0.3 μg/kg body weight) was infused intravenously over 15 mins in 22 subjects. Venous blood was obtained by separate venepuncture before and 15 mins after the end of the infusion, for assay of plasminogen activator activity of the euglobulin fraction on fibrin plates, tPA activity, and Bβ15-42 levels (RIA,IMCO). 18 subjects showed normal increases in fibrin plate lysis and in tPA activity after desmopressin (median tPA activity 120 mU/ml pre-, 5000 mU/ml post-infusion, p<0.001). In these 18 subjects, Bβ15-42 levels rose significantly (median 1.5pmol/ml pre-, 4.2 pmol/ml post-infusion, p<0.001). Four subjects showed no significant increases in fibrin plate lysis or in tPA activity after desmopressin (non-responders): all had significantly elevated levels of tPA-inhibition. In these 4 subjects no increases in Bβ15-42 levels were observed. In one nonresponder, who suffered a large myocardial infarction due to angiographic thrombosis with no atheroma at the age of 22 years, long-term treatment with stanozolol normalised the high level of tPA-inhibition, as well as the fibrin plate lysis and tPA activity responses to desmopressin: Bβ15-42 level then showed a normal response after desmopressin infusion (2.2 to 5 pmol/ml). We conclude that desmopressin infusion increases plasmin-mediated fibrinolysis in vivo, but only in the presence of normal increases in tPA activity.

Sign in / Sign up

Export Citation Format

Share Document