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Biomedical subjects

N Perez

Publications and source records attributed to N Perez.

At least 55 records · Page 3Linked to original sources
PubMed1998

Antiproliferative effects and mechanism of action of SCH 56592 against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies.

We have investigated the antiproliferative effects of SCH 56592, a new experimental triazole, against Trypanosoma (Schizotrypanum) cruzi, the etiological agent of Chagas' disease in Latin America. SCH 56592 blocked the proliferation of the epimastigote form of the parasite in vitro at 30 nM, a concentration 30- to 100-fold lower than that required with the reference compounds ketoconazole and itraconazole. At that concentration all the parasite's endogenous sterols (ergosterol, 24-ethyl-cholesta-5,7,22-trien-3 beta-ol, and its 22-dihydro analogs), were replaced by methylated sterols (lanosterol and 24-methylene-dihydrolanosterol), as revealed by high-resolution gas chromatography coupled with mass spectrometry. This indicated that the primary mechanism of action of the drug was inhibition of the parasite's sterol C-14 alpha demethylase. Against the clinically relevant intracellular amastigote form, grown in cultured Vero cells at 37 degrees C, the MIC of SCH 56592 was 0.3 nM, again 33- to 100-fold lower than that of ketoconazole or itraconazole. In a murine model of acute Chagas' disease, SCH 56592 given at > or = 10 mg/kg of body weight/day for a total of 43 doses allowed 85 to 100% survival and 90 to 100% cure of the surviving animals, as verified by parasitological, serological, and PCR-based tests, while ketoconazole given at 30 mg/kg day allowed 60% survival but only 20% cure. In a murine model of chronic Chagas' disease, SCH 56592 was again more effective than ketoconazole, providing 75 to 85% protection from death, with 60 to 75% parasitological cures of the surviving animals, while no parasitological cures were observed with ketoconazole. The results indicate that SCH 56592 is the most powerful sterol biosynthesis inhibitor ever tested against T. cruzi and may be useful in the treatment of human Chagas' disease.

Animals↗
PubMed1998

[Treatment using percutaneous arterial embolization of post-traumatic priapism in children].

High flow rate priapism was diagnosed in a 14-year-old adolescent 5 days after a fall onto the perineum. Highly selective embolization of the 2 internal pudendal arteries was performed with gelatin (SPONGEL). Rapid resolution of the priapism as well as return of normal erection were observed within 48 hours. Doppler ultrasound revealed a high flow rate and identified the side of the traumatized artery. Endovascular embolization allows effective treatment of traumatic arteriocavernous fistula.

Accidental Falls↗
PubMed1997

[Angioplasty of renal artery stenoses before surgical treatment of subrenal abdominal aortic lesions].

PURPOSE: To evaluate the results of the association of a percutaneous transluminal renal angioplasty before a surgical revascularization of the infra-renal aorta. PATIENTS AND METHODS: Percutaneous transluminal angioplasty of one (n = 12) or two (n = 2) renal arteries have been performed in 14 patients (11 hypertensive and one with azotemia), 2 to 240 days (mean 54) before infra-renal aortic surgery (aneurysms: 8, occlusive disease: 6). RESULTS: 15 of the 16 dilatations were completely technically successful (residual stenosis less than 20%), with one groin hematoma treated medically. Mean duration of the surgical intervention were 137 minutes (occlusive disease) and 147 minutes (aneurysm). In the post-operative course were noted resolutive infections in two patients, and one death because of myocardial infarction. At the end of the follow-up (3 to 60 months, mean 32), all of the 13 patients alive had improved in terms of vascular disease. Hypertension was improved for 2 patients, stable for 10, worse for 1. Creatinine serum level was stable for 12 patients, and the renal insufficient was worsened. CONCLUSION: Combined percutaneous transluminal renal angioplasty and aortic revascularization seems to be reliable and safe; it can be an alternative to a simultaneous aortic and renal revascularization, notably for high-risk patients.

Aged↗
PubMed1997

Cure of renovascular hypertension by percutaneous occlusion of a large idiopathic renal arteriovenous fistula. Case report.

Percutaneous balloon occlusion of a large hypertensive idiopathic renal arteriovenous fistula is reported. A lumbar thrill was noted in a 52-year-old hypertensive woman. Intravenous digital substraction angiography identified the lesion. After arteriographic assessment a percutaneous embolisation was performed with a releasable balloon positioned on a coaxial micro-catheter. Immediate post-procedural angiographic control demonstrated complete occlusion with a small segmental area of renal hypoperfusion. The lumbar thrill disappeared. Normalisation of the blood pressure was noted two days later and confirmed eight months later. Persistent occlusion of the fistula was angiographically confirmed, whereas the area of renal hypoperfusion had partially decreased. Releasable balloon percutaneous embolisation appears to be a safe alternative to surgery in the treatment of large renal arteriovenous fistulas.

Angiography, Digital Subtraction↗
PubMed1996

Cure of short- and long-term experimental Chagas' disease using D0870.

Chagas' disease, a protozoan infection by the kinetoplastid Trypanosoma cruzi, constitutes a major public health problem in Latin America. With the use of mouse models of both short- and long-term forms of the disease, the efficacy of D0870, a bis-triazole derivative, was tested. D0870 was able to prevent death and induced parasitological cure in 70 to 90 percent of animals, in both the short- and long-term disease. In contrast, currently used drugs such as nifurtimox or ketoconazole prolonged survival but did not induce significant curing effects. D0870 may be useful in the treatment of human long-term Chagas' disease, a condition that is currently incurable.

Animals↗
PubMed1996

Treatment of chronic, nonhealing abdominal wound in a liquid environment.

A 66-year-old woman with an abdominal wound caused by infected synthetic mesh had failed to heal in spite of many surgical attempts to close the wound. A sealed transparent vinyl chamber was glued to the periphery of the wound and antibiotics in high concentrations (up to 2,500 times the minimum inhibitory concentration) were delivered through the chamber. The wound fluid in the chamber was used for analysis of microbial activity, concentration of residual antibiotics, and growth factor activity. After 10 weeks of treatment, the wound was closed and has not recurred in 24 months.

Abdominal Injuries↗
PubMed1995

Prostate cancer screening practices: differences between clinic and private patients.

How often prostate cancer screening tests are conducted in general practice is unknown. It is known that at the primary care level, health care delivered to uninsured and Medicaid patients and to privately insured patients differs. We investigated the frequency of digital rectal examination and prostate-specific antigen testing in a clinic (an internal medicine clinic) and a faculty private practice population at The Mount Sinai Hospital over a period of one year. A total of 165 male patients over 40 years of age were asked to respond to a survey questionnaire; 142 interviews were completed (62 private and 80 clinic). Chart and computer database review were used to record the last serum prostate-specific antigen test performed. There was no difference in age distribution between the two groups. The private practice patients were more likely to be insured and college educated, whereas the clinic patients were more likely to have no more than an eighth-grade education and to receive Medicaid. The two groups did not differ in frequency of digital examination within the past year. Private patients were six times more likely than clinic patients to have had prostate-specific antigen screening and seven times more likely to receive both of the recommended prostate screening tests within the past year. Results also showed that 25% of all patients were not screened for cancer by digital rectal examination. Study of a larger population is recommended to further corroborate these findings.

Adult↗
PubMed1995

[Evolution of serum creatinine level 48 hours after angioplasty for renal artery stenosis in 91 patients].

To determine variations of serum creatinine level immediately after percutaneous angioplasty for renal artery stenosis. After technical success of unilateral or bilateral percutaneous angioplasty for renal artery stenosis in 91 patients (mean age 62.7 years) in whom ioxaglate was always used (90 to 300 ml, mean 195), serum creatinine levels immediately before and 48 hours after dilatation were compared. In the whole population, no significant variation was observed in the overall population. No significant difference was observed between unilateral and bilateral renal angioplasty. The volume of contrast media did not influence creatinine level, nor did iodine injection performed during (n = 4) or more than 3 days before angioplasty. A significant difference was observed with or without diabetes mellitus (n = 15, p = 0.05). In patients without diabetes mellitus technically successful percutaneous angioplasty for renal artery stenosis when using ioxaglate do not significant alter serum creatinine level 48 hours later.

Adolescent↗
PubMed1994

An environmentally regulated receptor for diamine oxidase modulates human endothelial cell/fibroblast histamine degradative uptake.

Human vascular endothelial cells and fibroblasts express a cell-surface degradative pathway for the multifunctional mediator histamine, which employs a receptor for the metabolic enzyme diamine oxidase (DAO) and results in cellular accumulation of the final metabolite methylimidazoleacetic acid. We demonstrate recognition and regulatory properties of DAO receptors as a function of cellular environmental conditions. Fast and slow ligand binding receptor populations bind DAO at 4 degrees C maximally in 1 and 7 h, respectively; upon warming cells to 37 degrees C both populations participate in degradative uptake of histamine accumulated as methylimidazoleacetic acid. Bound DAO is displaced by heparin with 24-fold greater potency than dextran sulfate, implicating structural specificity of heparin-like glycosaminoglycan moieties as a critical factor in initial receptor/enzyme interaction at fast and slow sites. Receptor-bound DAO is retained under mildly acidic conditions characteristic of early to mid endocytic intracellular compartments and thus could recycle to the plasma membrane intact after internalization. DAO initially bound to receptors in whole cells is retained through cell disruption/membrane fractionation procedures, but DAO binds poorly to isolated membrane fractions or presolubilized receptors, suggesting that the geometry of DAO binding components is not readily maintained upon cell disruption unless DAO is already bound. Cells down-regulate their complement of DAO receptors upon prolonged exposure to DAO. In cells plated at high density, half of the bound DAO becomes nondisplaceable by heparin within 15 min at 37 degrees C, a time consistent with receptor internalization, whereas cells plated at low density retain all bound DAO in a heparin-sensitive state. The protein kinase C activator phorbol 12-myristate 13-acetate modulates DAO receptor number by 35% and total histamine degradative uptake by > 2-fold. Thus this pathway is subject to regulation at the levels of DAO receptor numbers, their state of cell-surface display, and additional cellular elements of the degradative pathway with which the DAO receptors interface.

Amine Oxidase (Copper-Containing)↗
PubMed1993

Mechanisms of protein degradation in Trypanosoma cruzi.

Proteolysis of endogenous proteins may play a key role in the adaptation of T. cruzi to the different host environments to which it is exposed during its complex life cycle. For this reason, we have attempted to study the intracellular pathways of protein degradation in the non infective epimastigotes form (EP strain) of T. cruzi. Following intracellular proteolysis by pulse chase experiments with 35 S methionine, we observed a significant inhibition (50%) of the degradation of endogenous proteins in log phase parasites in the presence of inhibitors of lysosomal functions, such as chloroquine and E 64. A significant increase in proteolysis was observed in stationary phase parasites which was reverted to log phase values by supplementing the chase medium with 0.5% glucose or 10% serum, or in the presence of chloroquine. Under this condition of nutritional stress, we could observe an increase in the activity of acid proteases. A significant increase in the degradation rates was observed when abnormal proteins were induced in the parasite by amino acid analogs and puromycin. This increase was not affected by E 64, suggesting the participation of non lysosomal mechanisms in the degradation of rapidly degradable abnormal proteins. Under these conditions, we could observe an increase in high molecular weight conjugates of ubiquitin with respect to endogenous proteins. These results suggest the importance of lysosomal mechanisms in the degradation of cellular proteins in nutritional optimal conditions and during nutritional deprivation, and the possible involvement of the ubiquitin system in the degradation of high turnover proteins.

Animals↗
PubMed1992

Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases.

The balance between levels of metalloproteinases and their corresponding inhibitors is a critical factor in tumor invasion and metastasis. Down-regulation of the activity of these proteases was achieved by transfection of invasive and metastatic rat cells with the complementary DNA for metalloproteinase inhibitor/tissue inhibitor of metalloproteinase 2 (MI/TIMP-2), a novel inhibitor of metalloproteinases recently described. (Y. A. DeClerck et al., J. Biol. Chem., 264: 17445-17453, 1989; W. G. Stetler-Stevenson et al., J. Biol. Chem., 264: 17374-17378, 1989). Secretion of functional MI/TIMP-2 protein in stably transfected cells resulted in a marked decrease in metalloproteinase activity. Partial suppression of the formation of lung colonies after i.v. injection in nude mice was observed in a transfected clone expressing high levels of MI/TIMP-2. Production of MI/TIMP-2 in four clones markedly reduced tumor growth rate in vivo after s.c. injection and completely suppressed local tissue invasion. Thus, down-regulation of metalloproteinase activity has a striking effect on local invasion and partially suppresses hematogenous metastasis.

Animals↗
PubMed1992

Abnormal muscle and skin mitochondria in family with myoclonus, ataxia, and deafness (May and White syndrome).

A mother and two of her daughters had deafness and cortical reflex myoclonus; the mother also had mild truncal ataxia. Muscle and skin biopsy specimens revealed abundant ragged-red fibres and abnormal mitochondria. The son of one of the daughters had sensorineural deafness. Three other grandchildren were asymptomatic. The two daughters also had diabetes mellitus, hypertension and cardiomyopathy. Another daughter died of renal failure. The mother lost her hearing in her 70s, one daughter in her 30s, and the other daughter and the grandson in their 20s. The mother has had transient episodes (24-48 hours) of temporal disorientation, severe action myoclonus, and ataxia for about eight years. This is the first reported family with inherited deafness, myoclonus, and ataxia with mitochondrial pathology.

Adolescent↗