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Biomedical subjects

D Díaz

Publications and source records attributed to D Díaz.

17 recordsLinked to original sources

Contrasting effects of Cd2+ and Co2+ on the blocking/unblocking of human Cav3 channels.

Inorganic ions have been used widely to investigate biophysical properties of high voltage-activated calcium channels (HVA: Ca(v)1 and Ca(v)2 families). In contrast, such information regarding low voltage-activated calcium channels (LVA: Ca(v)3 family) is less documented. We have studied the blocking effect of Cd2+, Co2+ and Ni2+ on T-currents expressed by human Ca(v)3 channels: Ca(v)3.1, Ca(v)3.2, and Ca(v)3.3. With the use of the whole-cell configuration of the patch-clamp technique, we have recorded Ca2+ (2 mM: ) currents from HEK-293 cells stably expressing recombinant T-type channels. Cd2+ and Co2+ block was 2- to 3-fold more potent for Ca(v)3.2 channels (EC50 = 65 and 122 microM, respectively) than for the other two LVA channel family members. Current-voltage relationships indicate that Co2+ and Ni2+ shift the voltage dependence of Ca(v)3.1 and Ca(v)3.3 channels activation to more positive potentials. Interestingly, block of those two Ca(v)3 channels by Co2+ and Ni2+ was drastically increased at extreme negative voltages; in contrast, block due to Cd2+ was significantly decreased. This unblocking effect was slightly voltage-dependent. Tail-current analysis reveals a differential effect of Cd2+ on Ca(v)3.3 channels, which can not close while the pore is occupied with this metal cation. The results suggest that metal cations affect differentially T-type channel activity by a mechanism involving the ionic radii of inorganic ions and structural characteristics of the channels pore.

Cadmium↗

Double cationic propargylation: from linear to polycyclic ethers.

[reaction: see text]. The trapping of cations generated from Co2(CO)6-bispropargylic alcohols provided diethers in good yield. The procedure is also valid when two vicinal acetylenes are present. The methodology can be applied to the synthesis of symmetrical or unsymmetrical linear or cyclic propargylic ethers. The use of substrates with a stereochemically defined secondary nucleophilic alcohol provided cyclic ethers with a high degree of stereocontrol.

Journal Article↗

Localization of glutamate-cysteine ligase mRNA and protein in mouse kidney and induction with methylmercury.

Methylmercury (MeHg) is a toxicant that targets the kidney among other tissues. MeHg accumulates in the kidney, where it indirectly produces oxidative stress due to glutathione depletion and leakage of reactive oxygen species from the mitochondria. Glutathione is believed to have an important role in protecting the kidney against MeHg toxicity, and MeHg exposure is known to result in the induction of GSH synthesis through the upregulation of the enzyme glutamate-cysteine ligase (GLCL). GLCL, the rate-limiting enzyme in GSH synthesis, is composed of two subunits, a large catalytic (GLCLc) and a smaller regulatory (GLCLr) subunit. In this study we show that GLCLc and GLCLr mRNAs and GLCLc protein are localized in the paracortical region of the mouse kidney, the area of the kidney with the highest MeHg concentration, and that the upregulation of these mRNAs induced by MeHg is also located to the same region. This supports the role of GLCL in protection against MeHg toxicity in the kidney.

Animals↗

Tissue specific changes in the expression of glutamate-cysteine ligase mRNAs in mice exposed to methylmercury.

Glutamate-cysteine ligase (GLCL), the rate-limiting enzyme in glutathione (GSH) synthesis is composed of two subunits, a catalytic (GLCLc) and a regulatory subunit (GLCLr). These two subunits are known to be differentially regulated in vitro, in different cell types and in response to various xenobiotic exposures. In this study, we examined whether these two subunits can also be differentially regulated in vivo. We found that GLCLc and GLCLr are differentially regulated at the transcriptional level in a tissue-dependent manner in female mice treated with methylmercury (MeHg). MeHg caused a downregulation of both subunit mRNAs in the liver, upregulation of both subunit mRNAs in the kidney and upregulation of only the catalytic subunit mRNA in the small intestine of female mice treated with a single dose of MeHg (6 mg/kg) by intraperitoneal injection. These results suggest that GLCLc and GLCLr can be differentially regulated in vivo, and that this regulation is tissue dependent in the mouse.

Animals↗

[Diagnosis of tuberculosis meningitis by detection of adenosine deaminase activity and amplification of nucleotide sequences with PCR].

Tuberculous meningitis (TBM) is the most severe and lethal form of tuberculosis. The rapid bacteriological diagnosis with the conventional techniques is nearly impossible in TBM. There for many patients are treated with anti-TBC drugs without a definitive diagnosis. A more fast and accurate diagnostic method is necessary, in order to initiate the treatment on time to prevent the irreversible neurologic sequel or death. We evaluated the use of two rapid methods: Adenosine deaminase activity (ADA) and polymerase chain reaction (PCR) for IS6110 and mtp40 sequences on cerebrospinal fluid (CSF) from chronic meningitis patients. For ADA activity > 8.0 U/L the sensibility and specificity was 80% and 91%. PCR sensibility was 80% and specificity 97%. ADA activity and PCR on CSF could be specially useful as complementary tools in the early diagnosis of TBM.

Adenosine Deaminase↗

Merosin-deficient congenital muscular dystrophy associated with abnormal cerebral cortical gyration: an autopsy study.

We report clinical, biopsy and autopsy findings in a merosin-deficient congenital muscular dystrophy (CMD) infant with abnormal cortical gyration. Brain showed polymicrogyria and occipital agyria with marginal neuroglial heterotopia and inferior vermis hypoplasia. There was a normal pattern of myelination consistent with early age. Laminin alpha 2 chain was also absent in myocardium, brain pial-glial membrane, brain and skin blood vessels as well as intramuscular and skin nerves. Occasional basal lamina gaps were found in muscle fibres but not in brain-blood vessels. This is the first autopsy study in a merosin-deficient CMD case with abnormal cortical gyration.

Autopsy↗

Study of the binding in an aqueous medium of inclusion complexes of several cyclodextrins involving fenoprofen calcium.

Interactions among fenoprofen calcium and alpha-, beta-, gamma- and hydroxypropyl-beta-cyclodextrins (HP-beta-CD) were evaluated in aqueous solution by UV/vis and fluorescence direct spectroscopies and monodimensional (1D) 1H-NMR. Different UV/vis and fluorescence emission spectra were obtained to study the apparent binding constants (K) to define the most appropriate cyclodextrin to form the inclusion complexes (IC). beta-CD and HP-beta-CD clearly fit the magnitude of stability constant data of the complexes to take into account the pharmaceutical technology interest.

Anti-Inflammatory Agents, Non-Steroidal↗

Solubility, 1H-NMR, and molecular mechanics of mebendazole with different cyclodextrins.

The solubility behavior and binding constants (Kass) of mebendazole with alpha-, beta-, gamma-, and hydroxypropyl-beta-cyclodextrins (HP-beta-CD) have been investigated in simulated intestinal juice by the Higuchi and Connors method. AL diagrams have been obtained. The equilibrium has also been studied in simulated gastric fluid with HP-beta-CD. The phase solubility, 1H-NMR, and molecular mechanics studies revealed the formation of a 1:1 complex.

Antinematodal Agents↗

Binding, molecular mechanics, and thermodynamics of cyclodextrin inclusion complexes with ketoprofen in aqueous medium.

The purpose of this work was to study the interaction forces involved in the inclusion processes of ketoprofen with several cyclodextrins and to assess the best cyclodextrin for complexing this anti-inflammatory drug. The behavior of the inclusion complexes of ketoprofen with alpha-, beta-, and gamma-cyclodextrins was studied by UV-VIS direct spectroscopy, 1H NMR, and molecular mechanics. Thermodynamic parameters for the binding processes were obtained from the temperature variations in binding constants, which manifest that "nonclassical" hydrophobic interactions are the main forces involved in these inclusion processes. Binding constants show that beta- and gamma-cyclodextrins form more stable 1:1 complexes with ketoprofen than does alpha-cyclodextrin. 1H NMR spectra show that the inclusion degree depends on the size of the internal diameter of cyclodextrin. The geometries calculated on the bases of molecular mechanics for these three-dimensional models indicate high stability.

Anti-Inflammatory Agents, Non-Steroidal↗

Complexation and solubility behavior of albendazole with some cyclodextrins.

The main purpose of this work was to study the albendazole-cyclodextrins complexation equilibrium and to propose a suitable excipient to improve the solubility behavior and dissolution rate of albendazole. The complexation of albendazole with four cyclodextrins, alpha-CD, beta-CD, gamma-CD, and hydroxypropylated (HP)-beta-CD, has been studied by using electronic absorption spectroscopy and molecular mechanics. The equilibrium was studied at pH 7.5 under various temperature conditions, and at pH 1.8 with HP-beta-CD at 298 K. The albendazole binding constant was the greatest for the HP-beta-CD. Both the un-ionized (Alb) and the ionized species (AlbH+) were shown to interact with HP-beta-CD. The studies at different temperatures suggest that the hydrophobic effect is the most important driving force in these systems. Moreover, the dissolution rate studies with beta- and HP-beta-CDs in the buffered aqueous solution at pH 7.5 have been accomplished and the dissolution rate was observed to increase with the cyclodextrin concentration. The solubility behavior was studied with the Higuchi and Connors method. The phase solubility and direct spectroscopy methods reveal a 1:1 inclusion complex in all of the studied cases. Molecular mechanics data show the most probable structure of the complexes.

Albendazole↗

Molecular structure and gas chromatographic retention behavior of the components of Ylang-Ylang oil.

Using quantitative structure-retention relationships (QSRR) methodologies the Kovats gas chromatographic retention indices for both apolar (DB-1) and polar (DB-Wax) columns for 48 compounds from Ylang-Ylang essential oil were empirically predicted from calculated and experimental data on molecular structure. Topological, geometric, and electronic descriptors were obtained for model generation. Relationships between descriptors and the retention data reported were established by linear multiple regression, giving equations that can be used to predict the Kovats indices for compounds present in essential oils, both in DB-1 and DB-Wax columns. Factor analysis was performed to interpret the meaning of the descriptors included in the models. The prediction model for the DB-1 column includes descriptors such as Randic's first-order connectivity index (1X), the molecular surface (MSA), the sum of the atomic charge on all the hydrogens (QH), Randic's third-order connectivity index (3X) and the molecular electronegativity (chi). The prediction model for the DB-Wax column includes the first three descriptors mentioned for the DB-1 column (1X, MSA and QH) and the most negative charge (MNC), the global softness (S), and the difference between Randic's and Kier and Hall's third-order connectivity indexes (3X-3XV).

Chromatography, Gas↗

Modulation of human papillomavirus type 16 mRNA in cervical invasive carcinoma patients by interferon-alpha therapy.

Mechanisms by which interferon produces papilloma regression remain largely unknown. We analyzed biopsies from three cervical invasive carcinoma patients treated with interferon-alpha (IFN-alpha) administered both topically and i.m. for 15 days. All specimens contained human papillomavirus (HPV-16) DNA as determined by polymerase chain reaction using specific HPV-16 E7 primers. Interestingly, in two patients. HPV-16 mRNA expression was reduced (44% and 67%, respectively) after IFN treatment. Upregulation of 2-5 A synthetase and PKR mRNA levels were indicative of the IFN effect. A larger study should be initiated to see whether IFN-alpha modulates the HPV-16 mRNA levels in tumor biopsies from cervical carcinoma patients.

Antiviral Agents↗

[Effect of antibiotic prophylaxis with vancomycin on methicillin-resistant Staphylococcus aureus infection following liver transplantation].

An epidemic outbreak of Methicillin-resistant Staphylococcus Aureus (MRSA) infections affecting liver transplantation patients was detected in our hospital. In this study we describe the special characteristics of the infections and the results of prophylactic treatment with Vancomycin. Between april 1990 and december 1991, 47 patients with mean age of 54.4 +/- 10 years underwent liver transplantation. The patients were included in two chronological groups: 1) Group I: 20 patients not treated prophylactically with Vancomycin; 2) Group II: 27 consecutive patients treated with Vancomycin. Systematical cultures of body fluids for bacteria and fungi were done in every patient, and were repeated after 24 hours. The cultures were repeated again in case of sepsis. Group I patients had a significantly higher frequency of MRSA infections than group II patients. Furthermore, in patients with MRSA infection, independently of the group, duration of transplantation (p < 0.01), reoperations (p < 0.001) and prophylactic treatment with Vancomycin (p < 0.001) were significative factors. In conclusion, Vancomycin appears to be an elective prophylactic antibiotic in case of high risk of MRSA sepsis after liver transplantation.

Adult↗

Effects of subconjunctival methylprednisolone on the blood aqueous barrier following cataract surgery.

The aim of this double-blind randomized study was to assess the effect of subconjunctival methylprednisolone hemisuccinate (MH) on the recovery of the blood aqueous barrier (BAB) following uncomplicated cataract surgery performed by the same surgeon in normal eyes. Fifty eyes of fifty patients (28 female, 22 male, mean age 72.3 +/- 11.2 years) were randomized into two groups: group 1 received a subconjunctival injection of MH (40 mg in 0.5 cc) at the end of the surgery and group 2 did not. All patients were free of other ocular or systemic diseases known to alter the BAB and were not taking any anti-inflammatory medications. Postoperative treatments were similar in both groups. The patients were submitted to laser flare photometry 30 minutes to one hour after mydriasis with a drop of tropicamide preoperatively and on the first, second and seventh day and then one month and six months following surgery. No difference in aqueous flare was seen between the two groups on any of postoperative visits. These data suggest that subconjunctival MH has no beneficial effect in postoperative BAB permeability following uncomplicated cataract surgery in normal eyes.

Aged↗

A descriptive-exploratory study of outcome and some biopsychosocial characteristics of drug dependent veterans in Puerto Rico.

OBJECTIVE: The authors attempted to correlate outcomes with various significant biopsychosocial variables in drug dependent veterans receiving outpatient treatment at San Juan V.A.M.C. METHODS: The clinical charts of 120 inactive patients were examined using a 50 item questionnaire. The data was processed and analyzed using the EpiInfo v.5 computer program. The outcome of the patients was measured using a Goal Attainment Scale Technique with demonstrated validity and reliability. RESULTS: The patients retention in treatment for 12 or more visits and its relationship to good outcomes was the most significant finding of this study (P < 0.00000000, 80.5% of patients improved). Only 5% of patients with 3 or less visits showed positive outcomes. Another variable associated with good outcomes was a supportive wife (P < 0.02). HIV reactivity was strongly correlated with IV drug use (P < 0.037). CONCLUSIONS: The strong correlation of the retention of patients in treatment for 12 or more visits and good outcomes should alert clinicians and policy makers as to the importance of available and effective treatments in the fight against substance abuse and mental health problems. This study also showed that a supportive family member is usually the best social asset that patients and therapists have in their fight for sobriety.

Adult↗