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Biomedical subjects

M Gallardo

Publications and source records attributed to M Gallardo.

At least 19 recordsLinked to original sources

SNCA multiplication is not a common cause of Parkinson disease or dementia with Lewy bodies.

The authors recently have shown that triplication of the alpha-synuclein gene (SNCA) can cause Parkinson disease (PD) and diffuse Lewy body disease within the same kindred. The authors assessed 101 familial PD probands, 325 sporadic PD cases, 65 patients with dementia with Lewy bodies, and 366 neurologically normal control subjects for SNCA multiplication. The authors did not identify any subjects with multiplication of SNCA and conclude this mutation is a rare cause of disease.

Adult↗

Location of Pinacyanol in Micellar Solutions of N-Alkyl Trimethylammonium Bromide Surfactants.

The interaction of pinacyanol (PIN), a cationic dye formed by monomer and dimer species, with three cationic surfactants (DTAB, TTAB, and HTAB) has been studied spectroscopically and by acid-base equilibrium in the micellar concentration range. In the presence of surfactants, the absorption maximum of the two main peaks undergoes bathochromic shifts. The spectral shifts suggest a hydrophobic environment of the chromophore. The presence of micelles favors the monomer species; i.e., it reduces the extent of dimerization. The pK(a) of PIN in micellar medium is similar to the value in pure water. When acid-base equilibrium was considered, the changes in the interfacial pK(a) allowed to us to determine the constant dielectric for the interfacial region (epsilon=69). This led to the conclusion that the dye must be solubilized between the solution and the hydrocarbon chain core, i.e., in the aqueous micellar interface. This location can be explained by a cation-pi interaction between the uncharged ring system of the dye and the cationic headgroups of the surfactants. Copyright 2001 Academic Press.

Journal Article↗

A new hyperrecombination mutation identifies a novel yeast gene, THP1, connecting transcription elongation with mitotic recombination.

Given the importance of the incidence of recombination in genomic instability, it is of great interest to know the elements or processes controlling recombination in mitosis. One such process is transcription, which has been shown to induce recombination in bacteria, yeast, and mammals. To further investigate the genetic control of the incidence of recombination and genetic instability and, in particular, its connection with transcription, we have undertaken a search for hyperrecombination mutants among a large number of strains deleted in genes of unknown function. We have identified a new gene, THP1 (YOL072w), whose deletion mutation strongly stimulates recombination between repeats. In addition, thp1 Delta impairs transcription, a defect that is particularly strong at the level of elongation through particular DNA sequences such as lacZ. The hyperrecombination phenotype of thp1 Delta cells is fully dependent on transcription elongation of the repeat construct. When transcription is impeded either by shutting off the promoter or by using a premature transcription terminator, hyperrecombination between repeats is abolished, providing new evidence that transcription-elongation impairment may be a source of recombinogenic substrates in mitosis. We show that Thp1p and two other proteins previously shown to control transcription-associated recombination, Hpr1p and Tho2p, act in the same "pathway" connecting transcription elongation with the incidence of mitotic recombination.

Animals↗

Electrophoretic properties of dodecyltrimethylammonium bromide micelles in KBr solution.

Charge in ionic micelles determines the trends of their stability and their practical applications. Charge can be calculated from zeta potential (zeta) measurements, which, in turn, can be obtained by Doppler microelectrophoresis. In this study, the electrophoretic properties of dodecyltrimethylammonium bromide (DTAB) in KBr aqueous solution (0-6 mM) were determined by Doppler microelectrophoresis. At very low surfactant concentrations (up to 6 mM), zeta potential was quite constant and due to the ionized monomers (DTA+). Above 6 mM, zeta potential increased to a maximum at surfactant concentrations still below the critical micellar concentration (CMC). This increase could be explained by a formation of nonmicellar aggregates of DTAB. Then, above the CMC, zeta potential underwent an abrupt reduction, which was dependent qualitatively and quantitatively on KBr concentration, and which could be due to an increase of the number of counterions adsorbed on the micelle surface. Calculation of effective micellar charge from zeta potential gave the surface charge density. Comparing this value with the theoretical, obtained from geometrical considerations, a fraction of 0.29 of charged micellar headgroups was obtained when DTAB was in aqueous solution, which is consistent with the value obtained by conductivity measurements.

Bromides↗

Involvement of calcium in ACC-oxidase activity from Cicer arietinum seed embryonic axes.

Both in vivo and in vitro ACC-oxidase activities as well as ethylene production from embryonic axes of chickpea seeds were strongly inhibited by EGTA, a selective extracellular Ca2+ ion chelator, indicating that the influx of Ca2+ is important for enzymatic activity. EGTA inhibition was restored by exogenous Ca2+. Treatments of embryonic axes with either Verapamil and LaCl3 (both Ca2+ channel blockers) or TMB-8 (an intracellular Ca2+ antagonist) provoked an inhibition of both ACC-oxidase activity and ethylene production. These results suggest an involvement of calcium fluxes and intracellular calcium levels in the activity of the last step of the ethylene biosynthetic pathway, which is, in turn, intimately correlated with germination of Cicer arietinum seeds.

Amino Acid Oxidoreductases↗

Influence of Size on Electrokinetic Behavior of Phosphatidylserine and Phosphatidylethanolamine Lipid Vesicles.

The aim of this study was to examine the electrokinetic properties of liposomes containing either phosphatidylethanolamine (PE) or phosphatidylserine (PS). Zeta potential was determined by laser-Doppler microelectrophoresis. The presence of PE enhanced the slight negative charge on the phosphate group of phosphatidylcholine. A linear relation between zeta potential and PE concentration was found. Absolute values of zeta potential were higher in PS liposomes and showed an exponential dependence on the PS content. The electrophoretic mobility depended not only on the percentage of aminophospholipid but also on the size of vesicles. This behavior can be explained by the relaxation effect. From geometrical considerations, it was possible to calculate the theoretical surface charge densities. Comparing experimental with theoretical values, an underestimation of zeta potential was found by the electrokinetic classic theory in the experimental conditions used. Copyright 1998 Academic Press.

Journal Article↗

Growth Hormone (GH) but not IGF-I-Secretion is Stimulated in Aged Rats by Chronic Hexarelin and GHRP-6 administration.

The present studies were designed to investigate in aged rats (22-24 months old) the effectiveness and specificity of acute hexarelin (HEXA) administration on the release of growth hormone (GH), the minimal dose of the peptide that produces the maximal GH secretion and the effects of long term treatment with HEXA or growth hormone releasing peptide (GHRP-6) on plasma levels of GH and IGF-1. To select the appropriate anesthetic to obtain serial blood samples, the GH releasing activity of HEXA (30 µg/kg i.v.) was tested in young rats anesthetized with tribromoethanol and ketamine-xylazine, and the results were compared with those obtained from conscious freely moving rats. When compared to the changes found in conscious rats, the GH-response to HEXA was increased by ketamine-xylazine anesthesia, while it was decreased by tribromoethanol. Therefore, all subsequent experiments were performed in conscious freely moving rats. To determine the minimal effective dose of HEXA and GHRP-6 in aged animals, different doses (5, 10, 20, 40, and 80 µg/kg) of either HEXA or GHRP-6 were administered subcutaneously to young and aged rats. It was found that 20 µg/kg bw of HEXA or GHRP-6 was the minimal dose producing the maximal GH response. Plasma PRL and LH determinations in the animals injected with the minimal dose showed that HEXA and GHRP-6 stimulate the GH release specifically. Based on the results obtained in the latter experiments, young and aged rats were chronically treated with s.c. injections of 20 µg/kg twice a day for 15 or 30 days. At the end of the experiments, animals were acutely tested with s.c. injection of the same dose (20 µg/kg). It was found that both young and aged animals released GH in response to the repeated administration of GH releasing peptides after 15 days of treatment. However, after 30 days of treatment plasma GH did not change when young and aged HEXA treated animals were acutely tested with such peptide, but increased significantly in the GHRP-6 treated animals when they were acutely tested with GHRP-6. In response to the long term treatment with the GH-releasing peptides, plasma IGF-I levels increased in young animals when they were acutely tested with the corresponding peptide. However, plasma IGF-I levels in aged rats were not modified by the acute administration of either HEXA or GHRP-6 after 15 or 30 days of treatment. This study showed that: 1. HEXA and GHRP-6 stimulated GH release in aged rats and the magnitude of GH responses was similar to that in young rats; 2. the minimal dose of HEXA and GHRP-6 resulting in maximal GH response was 20 g/kg and such dose of HEXA specifically stimulated GH secretion in aged rats; 3. fifteen but not 30 days treatment of aged rats with such small dose of HEXA resulted in a similar GH response to subsequent stimulation with the same peptide; 4. plasma IGF-I responses to an acute administration of HEXA or GHRP-6 in rats chronically treated with the same peptide vanished with aging.

Journal Article↗

Determination of polyethylene glycol activated with cyanuric chloride in liposomes.

A simple method was developed for the determination of polyethylene glycol (PEG) 5000 activated with cyanuric chloride attached or adsorbed to the liposome membrane. The procedure is based in the measurement of the absorbance at 234 nm of the triazine ring of cyanuric chloride after disrupting the liposomal structure with CHCl3/MeOH (1/8, v/v). In this medium, the molar absorptivity of the molecule is the highest, and lipid does not interfere with the measurement. This procedure results in a convenient, sensitive, and rapid method for the determination of this kind of activated polyethylene glycol in liposomes. The minimal concentration of PEG measured is 50 microM, and so the method is sufficiently sensitive to quantify PEG 5000 in the minimal amounts used for protecting the liposomes from the action of serum. Values calculated by this method have been compared with those obtained by 1H NMR, and a good correlation between them has been obtained.

Cross-Linking Reagents↗

Physicochemical properties of enrofloxacin.

The physicochemical properties of enrofloxacin, a fluoroquinolone that inhibits the activity of bacterial DNA gyrase, are described. Its spectral, solubility and related physicochemical characteristics are discussed. The dissociation behaviour of enrofloxacin was examined by UV spectrophotometry at 25 degrees C in a series of buffers ranging from pH 1 to 10. The corresponding macro- and microscopic dissociation constants were calculated. The apparent n-octanol-water partition coefficients were measured from pH 2 to 10.

Anti-Infective Agents↗

Regulation of the ASC system and Na+/K + pump activities in brown trout (Salmo trutta) hepatocytes

The present study investigates the regulation of Na+/K+ pump activity and alanine uptake in trout hepatocytes. Pump activity increased when cells were incubated in an amino-acid-free medium, while it was reduced in cells from fasted animals. Short-term exposure (3 h) to glucagon modified the activity of the pump in a complex seasonally dependent pattern: in experiments carried out in autumn and winter there was some inhibition, while in spring the pump was activated by this hormone. Pharmacological modification of levels of two intracellular signal transducers, namely cyclic AMP and Ca2+, always led to a reduction in pump activity. These experiments were conducted in May, when activation of the pump by glucagon exposure occurred. There is no apparent explanation for the mechanism by which this hormone modifies the activity of the pump. Glucagon also regulates the activity of system ASC (a Na+-dependent amino acid carrier with short-chain neutral amino acids as preferred substrates). This regulation also showed a seasonally dependent pattern, although the pattern was opposite to that found for the regulation of Na+/K+ pump activity.

Journal Article↗

[Lithium poisoning].

A case of therapeutic overdosage in a 58-year-old woman is reported. Lithium plasma level was 3.7 mmol.l. All clinical and biological disturbances regressed in 3 days after controlled rehydration only. Aetiology, clinical picture, biological characteristics and treatment according to the severity of the lithium poisoning are discussed.

Bipolar Disorder↗

Angina pectoris following cisplatin, etoposide, and bleomycin in a patient with advanced testicular cancer.

OBJECTIVE: To report a case of angina pectoris associated with chemotherapy for testicular cancer. CASE SUMMARY: An HIV-infected patient with massive retroperitoneal metastases of a mixed embryonal and undifferentiated teratocarcinoma was treated with cisplatin, etoposide, and bleomycin. While the patient was receiving the second course of chemotherapy, he developed several episodes of angina pectoris that responded to nitroglycerin. Coronary angiography excluded structural abnormalities in the coronary arteries. The patient was treated prophylactically with nifedipine during the 2 following courses of chemotherapy with no new ischemic events. DISCUSSION: Coronary vasospasm seemed to be responsible for the angina in this patient. Several pathogenetic mechanisms that could explain these vascular events are discussed, including the possible role of bulky metastatic disease. CONCLUSIONS: The combination of cisplatin, etoposide, and bleomycin for testicular cancer, perhaps associated with bulky metastatic disease, can induce vasospastic phenomena that might be life-threatening.

Adult↗

Design and applications of a new fluorimetric assay of thioguanine in liposomes.

This paper describes the systematic design of a modification that overcomes the difficulties encountered with the original fluorimetric method for thioguanine. It allows the determination of thioguanine alone, as well as in a lipid medium (specifically in liposomes). It consists of an earlier lipid extraction based on liquid-solid extraction cartridges; then the oxidation of thioguanine in the lipid-free solution is performed by adding hydrogen peroxide in pH 4.7 acetate buffer at 50 degrees C for 30 min. A central composite design was used to finally optimize the method. The assay is precise (RSD values were 1.8 and 2.1% for intra-day and between-day precision, respectively). The detection limit was 0.05 microM and the limit of quantitation 0.08 microM.

Hydrogen Peroxide↗