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Biomedical subjects

C Perez

Publications and source records attributed to C Perez.

At least 37 records · Page 2Linked to original sources
PubMed2001

Adult Still's disease associated with Mycoplasma pneumoniae infection.

Adult Still's disease (ASD) is a systemic inflammatory disorder of unknown origin. Several reports have suggested a triggering infection in ASD. We describe a case of ASD associated with acute Mycoplasma pneumoniae infection. The close temporal relationship between ASD and acute infection strongly suggests that M. pneumoniae triggered ASD. We suggest that M. pneumoniae should be added to the list of infectious agents that may play a role in its etiology.

Adolescent↗
PubMed2001

Recent strategies in the development of new human cytomegalovirus inhibitors.

Human cytomegalovirus (HCMV) is one of the most common opportunistic infections in immunucompromised individuals, such as AIDS patients and organ transplant recipients, and is the most frequent congenital viral infection in humans. Despite a reduction of the incidence of AIDS-related opportunistic infections in patients under highly active antiretroviral treatment, attention should be paid to the HCMV risk factor in these individuals. Furthermore, HCMV may have an important role in atherosclerosis. Existing antiviral treatments for the HCMV infection suffer from poor bioavailability, toxicity, and limited effectiveness, mainly due to the development of drug resistance. Fortunately there are novel and potentially very effective new compounds undergoing pre-clinical and clinical evaluation. This review provides an overview in the last five years of new HCMV inhibitors (chemical structures, SAR, and new mechanisms of action) with the aim to provide new clues for the development of future drugs against this opportunistic virus.

AIDS-Related Opportunistic Infections↗
PubMed2001

Expression of a reporter gene after microinjection of mammalian artificial chromosomes into pronuclei of bovine zygotes.

The introduction of mammalian artificial chromosomes (ACs) into zygotes represents an alternative, more predictive technology for the production of recombinant proteins in transgenic animals. The aim of these experiments was to examine the effects of artificial chromosome microinjection into bovine pronuclei on embryo development and reporter gene expression. Bovine oocytes aspirated from 2-5 mm size follicles were matured in vitro for 22 hr. Mature oocytes were fertilized in vitro with frozen- thawed bull spermatozoa. Artificial chromosome carrying either beta-galactosidase (Lac-Z) gene or green fluorescence protein (GFP) gene were isolated by flow cytometry. A single chromosome was microinjected into one of the two pronuclei of bovine zygotes. Sham injected zygotes served as controls. Injected zygotes were cultured in G 1.2 medium for 7 days. Hatched blastocysts were cultured on blocked STO cell feeder layer for attachment and outgrowth of ICM and trophectoderm cells. The results showed a high zygote survival rate following LacZ-ACs microinjection (74%). However, the blastocyst development rate after 7 days of culture was significantly lower than that of sham injected zygotes (7.5 vs. 22%). Embryonic cells positive for Lac-Z gene were detected by PCR in three of nine outgrowth colonies. In addition, GFP gene expression was observed in 15 out of 85 (18%) embryos at the arrested 2-cell stage to blastocyst stage. Six blastocysts successfully outgrew, three outgrowths were GFP positive for up to 3 weeks in culture. We conclude that the methodology for artificial chromosome delivery into bovine zygotes could lead to viable blastocyst development, and reporter gene expression could be sustained during pre-implantation development.

Animals↗
PubMed2001

Nocardiosis revealed by thyroid abscess in a liver--kidney transplant recipient.

Nocardiosis is a life-threatening infection, particularly among immunocompromised patients, which usually affects lungs, skin and central nervous system. We report a case of disseminated nocardiosis revealed by suppurative thyroiditis in a liver-kidney transplant recipient with poor nutritional status at the time of infection. Nocardia Asteroides was isolated from fine-needle aspiration material of the thyroid abscess. Clinical manifestations resolved after surgical drainage of the thyroid abscess, prolonged antibiotherapy and diminution of immunosuppressive regimen. Clinicians should be aware of this entity, as Nocardia Asteroides may need more than 5 days of culture to be isolated.

Abscess↗
PubMed2001

Glucose facilitation of cognitive performance in healthy young adults: examination of the influence of fast-duration, time of day and pre-consumption plasma glucose levels.

RATIONALE: Previous investigations have demonstrated increased performance after the administration of a glucose-load on certain aspects of cognitive functioning in healthy young adults. Generally these studies have used a procedure where participants were tested in the morning after an overnight fast. OBJECTIVE: The aim of the present study was, for the first time, to investigate the glucose cognitive facilitation effect under more natural testing times and with shorter duration of the previous fast. METHODS: Measures of verbal and non-verbal memory performance were compared under different fasting intervals (2-h fast versus overnight fast), times (morning versus afternoon) and glycaemic conditions (glucose versus aspartame drinks) in healthy young participants. RESULTS: There was a significant glucose facilitation effect on long-term verbal memory performance. In addition, glucose significantly enhanced long-term spatial memory performance. The effect of glucose was essentially equivalent whether it was given after an overnight fast or a 2-h fast following breakfast or lunch. There was no effect of drink and time of day on working memory performance. CONCLUSIONS: The results of this study further support the hypothesis that glucose administration can enhance certain aspects of memory performance in healthy young adults. More significantly, the findings indicate that this cognitive facilitation effect persists under more naturalistic conditions of glucose administration and is not restricted to long fast durations or morning administration.

Adolescent↗
PubMed2001

"In vitro" antifungal activity of protease inhibitors.

In the last five years, as HAART has become standard therapy in HIV seropositive or AIDS patients, changes have been noted in the numbers and types of opportunistic fungal infections in these cohorts of patients. Particularly, oropharyngeal candidiasis have become rare in HIV infected patients since the introduction of new anti-HIV drugs of the protease inhibitors type. At the Immunology Institute of the Universidad Central de Venezuela the most frequent protease inhibitors (PIs) used for the treatment of these patients have been: Nelfinavir (Viracept, Roche), Indinavir (Crixivan Merck), Ritonavir (Norvir, Abbott), Saquinavir (Fortovase, Roche). Recently, we observed that recurrent candidiasis was less frequent and no Candida could be isolated in our patients. A direct relation to the PIs was suspected. In order to assess the "in vitro" antifungal activity of the afore mentioned protease inhibitors on Candida sp., we used both the well diffusion test and the NCCLS broth microdilution test to assay 100 Candida sp. isolates from HIV seropositive or AIDS patients with syntomatic oropharyngeal Candida infection. In general, the data obtained with the well diffusion test were in agreement with those obtained by the broth microdilution test. All 100 isolates were susceptible to Saquinavir and 32 were susceptible to Indinavir using the NCCLS microdilution test, while 97 were susceptible to Saquinavir and 52 to Indinavir by the well diffusion test. From 17 C. albicans resistant to fluconazole, all were susceptible to Saquinavir by the NCCLS micromethod and 16 by the well diffusion test. Our results showed anticandidal activity "in vitro" of PIs, mainly Saquinavir.

AIDS-Related Opportunistic Infections↗
PubMed2001

Anti-HIV-1 activity of benzothiadiazine dioxide.

Antiviral assays carried out on the potent benzothiadiazine dioxide (BTD) human cytomegalovirus (HCMV) inhibitors have led us to find marginal but selective anti-HIV-1 activity. Specific pharmacological studies, such as time of addition experiments and assays on specific viral strains with mutations on its reverse transcriptase, have indicated that BTD compounds act as non-nucleoside reverse transcriptase inhibitors. Theoretical calculations showed a butterfly conformation for the active derivatives that are compatible with their mechanism of action. Therefore, BTD derivatives can be considered as potential lead compounds for the treatment of opportunistic HCMV infections in immunocompromised individuals such as AIDS patients.

Antiviral Agents↗
PubMed2001

Pharmacological effects of elenoside, an arylnaphthalene lignan.

Acute toxicity (24 h) and general behavior in mice of a lignan from Justicia hyssopifolia, a beta-D-glucoside (elenoside), was studied, and the cytotoxic activity was performed. Elenoside (arylnaphthalene lignan) in mice showed a moderate toxicity order (305 mg/kg) and central depressive properties at doses of 25, 50, and 100 mg/kg. It also displayed cytotoxic activity in a range of concentration of 10(-5)-10(-4) M when studied in the human tumor cell line panel of the US National Cancer Institute (NCI). The results indicated that elenoside has central depressant effects, and the cytotoxic activity of elenoside suggests that this compound and its genin derivatives merit further investigation as antitumoral drugs.

Animals↗
PubMed2001

Distal third fibular aneurysmal bone cyst: en bloc resection and proximal third fibular reconstruction.

Treatment of aneurysmal bone cysts (ABCs) located in the distal third fibula adjacent to the growth plate, can be problematic. The first choice of treatment for these lesions has been cyst curettage and bone graft. Complications include the high recurrence rate, possible growth-plate injury, and possible ankle instability associated with that treatment led to the development of other surgical options. We used en bloc resection and proximal third fibular bone reconstruction to treat an 8-year-old female patient with a distal third fibular ABC close to the growth plate. There was no recurrence, growth-plate injury, or ankle instability at 30-month follow-up.

Bone Cysts, Aneurysmal↗
PubMed2001

[Iron deficiency anemia due to stromal tumor of the ileum].

Iron-deficiency anemia occurs in 3.5 to 5.3% of adult men and postmenopausal women. Occult gastrointestinal bleeding is the cause in the vast majority of cases. After endoscopic examinations have ruled out lesions in colon and upper gastrointestinal tract, 5 to 20% of those patients remain without diagnosis. Angiodysplasias and tumors are the most common causes of occult bleeding arising from the small bowel. Their diagnosis requires complex studies with quite low yield. However, it is necessary to perform them when anemia becomes severe or persistent. We report the case of a male patient with severe and persistent iron-deficiency anemia who had a stromal gastrointestinal tumor located in the ileum.

Anemia, Iron-Deficiency↗
PubMed2000

p44/SSL1, the regulatory subunit of the XPD/RAD3 helicase, plays a crucial role in the transcriptional activity of TFIIH.

In order to unravel the mechanism that regulates transcription of protein-coding genes, we investigated the function of the p44 subunit of TFIIH, a basal transcription factor that is also involved in DNA repair. We have shown previously that mutations in the C terminus of the XPD helicase, another subunit of TFIIH, prevent its regulation by p44 (Coin, F., Bergmann, E., Tremeau-Bravard, A., and Egly, J. M. (1999) EMBO 18, 1357-1366). By using a site-directed mutagenesis approach within the p44 region from amino acids 66 to 200, we indicate how a decrease in the interaction between p44 and XPD results in a decrease of the XPD helicase activity and leads to a defect in the first steps of the transcription reaction, namely the first phosphodiester bond formation and promoter clearance. We thus provide some explanation for the transcriptional defect found in SSL1 mutated yeast (Wang, Z., Buratowski, S., Svejstrup, J. Q., Feaver, W. J., Wu, X., Kornberg, R. D., Donahue, T. F., and Friedberg, E. C. (1995) Mol. Cell. Biol. 15, 2288-2293). Moreover, this study shows how the activity of the the cyclin-dependent kinase-activating kinase associated with TFIIH complex in stimulating transcription is mediated in part by p44/XPD interaction.

Adenosine Triphosphatases↗
PubMed2000

Benzothiadiazine dioxide dibenzyl derivatives as potent human cytomegalovirus inhibitors: synthesis and comparative molecular field analysis.

The benzothiadiazine dioxide (BTD) derivatives are potent nonnucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship study of these compounds, we have now synthesized N,N- and N,O-dibenzyl derivatives with different para-substituents (alkyl, phenyl, electron-donating, electron-withdrawing) in the phenyl ring of the benzyl moieties. The antiviral activity against HCMV (AD-169 strain) was also experimentally measured showing IC(50) values between 2.5 and 50 microM. Comparative molecular field analysis (CoMFA) was employed to generate a model, based upon 32 diverse BTD derivatives, to delineate structural and electrostatic features important for enhanced activity against HCMV. The steric (van der Waals) interactions with the receptor majoritary describes the variation in antiviral activity among the inhibitors. Finally, the CoMFA model was used to design two sets of novel BTD derivatives. Synthesis and subsequent anti-HCMV evaluation of these compounds enabled us to maintain the activity of this new kind of HCMV inhibitors.

Antiviral Agents↗
PubMed2000

Nonnucleoside human cytomegalovirus inhibitors: synthesis and antiviral evaluation of (chlorophenylmethyl)benzothiadiazine dioxide derivatives.

A second generation of benzothiadiazine dioxide (BTD) derivatives was synthesized employing benzylation reactions mainly. The chlorophenylmethyl BTD derivatives showed activity against human cytomegalovirus (HCMV) with IC(50) values ranging from 3 to 10 microM. Their 50% cytotoxic concentrations were often >200 microM to lung fibroblast HEL cell proliferation and between 20 and 35 microM for lymphocyte CME cell growth. When cytotoxicity for cell morphology was considered, the minimum cytotoxic concentration for the different BTD derivatives varied between 5 and 200 microM. Some of the anti-HCMV compounds also showed activity against HIV-1 and HIV-2. The chlorophenylmethyl derivative 21 was active against a variety of HCMV clinical isolates from patients with different clinical manifestations and fully maintained its activity against a ganciclovir-resistant HCMV strain. The dibenzyl BTD derivatives did not inhibit HCMV protease, and preliminary pharmacological experiments revealed that their anti-HCMV action stems from interference with an early stage of the viral replicative cycle.

Animals↗
PubMed2000

A synthetic hydroxy acid that shows tubular-shaped structure in solid-state and ionophoric activity in phospholipid bilayers

[formula: see text] In this contribution, we describe the ability of compound (+/-)-1b and six molecules of water to form in solid-state hexameric aggregates, which self-assemble to give hollow tubular structures. Single-crystal X-ray analysis shows that these tubes are open-ended, with irregular shape and internal van der Waals pore diameter between 6 and 9 A. In addition, transmembrane sodium transport activity was also assessed for (+/-)-1b using dynamic Na(+)-NMR technique.

Journal Article↗