PubMed Health⌕ Search

Biomedical subjects

R Briones

Publications and source records attributed to R Briones.

At least 19 recordsLinked to original sources

Applications of electron spin resonance and spin trapping in tropical parasitic diseases.

Free radicals may be reaction intermediates in biological systems in more situations than are presently recognized. However, progress in detecting such species by Electron Spin Resonance (ESR) has been relatively slow. ESR is a very sensitive technique for free radical detection and characterization. It can be used to investigate very low concentrations of radicals provided that they are stable enough for their presence to be detected. For unstable radicals special techniques have to be employed. One of these methods is called Spin Trapping. Parasitic diseases in tropical and subtropical areas constitute a major health and economic problem. The range of antiparasitic drugs varies widely in structural complexity and action at the subcellular and molecular levels. However, a number of these drugs are thought to exert their action by generating free radicals. Most of the free radical producing drugs used against parasites are: quinones, naphtoquinones, quinone-imines, aminoquinolines, N-oxides and nitroheterocyclic compounds. This review summarizes some of the more relevant achievements of ESR and Spin Trapping applications in parasitic diseases studies. The use of ESR spectroscopy to obtain relevant information about free radical characterization and the analysis of the mechanisms of action of drugs involved in several parasitic diseases is also presented.

Antiparasitic Agents↗

Pancreas islet transplantation in patients with type 1 diabetes mellitus after kidney transplantation.

Diabetic patients with end-stage renal disease have a high mortality rate. A combined kidney-pancreas transplant is associated with greater life expectancy. Pancreas islet transplantation is an alternative involving a lower degree of morbidity. We present two patients, of 41 and 37 years of age, with a long history of diabetes mellitus (C-peptide negative), both with a previous kidney transplant, who had been treated with 22 and 28 U of insulin/d, respectively. Both patients had frequent episodes of unawareness hypoglycemia. Pancreatic islets were infused to a total of 7809 and 19,180 IE/kg, respectively. Basal posttransplant C peptide levels were 2.9 and 1.3 ng/mL. After the implant, one patient required occasional doses of insulin, and the other patient more than 50% reduced dose. After the first implant neither patient had any episodes of unawareness hypoglycemia. HbA1c at 4 months were 6.2% and 6.9%. There were no transplant-related complications.

Adult↗

Release and functional role of neuropeptide Y as a sympathetic modulator in human saphenous vein biopsies.

Transmural electrical stimulation of the sympathetic nerve endings of human saphenous vein biopsies released two forms of NPY identified chromatographically as native and oxidized peptide. The release process is dependent on extracellular calcium, the frequency, and the duration of the stimuli. While guanethidine reduced the overflow of ir-NPY, phenoxybenzamine did not augment NPY release, but increased that of noradrenaline. Oxidized NPY, like native NPY, potentiated the noradrenaline and adenosine 5'-triphospahate-induced vasoconstriction, an effect blocked by BIBP 3226 and consonant with the RT-PCR detection of the mRNA encoding the NPY Y1 receptor. These results highlight the functional role of NPY in human vascular sympathetic reflexes.

Adenosine Triphosphate↗

Electrochemical and microsomal production of free radicals from 1,2,5-oxadiazole N-oxide as potential antiprotozoal drugs.

The electron spin resonance (ESR) spectra of free radicals obtained by electrolytic or microsomal reduction of several potential antiprotozoal 1,2,5-oxadiazoles were characterized and analyzed. Ab initio molecular orbital calculations were performed to obtain the optimized geometries and the theoretical hyperfine constant was carried out using ZINDO semiempirical methodology. Density functional theory was used to rationalize the reduction potentials of these compounds.

Antiprotozoal Agents↗

Pharmacological identification of P2X1, P2X4 and P2X7 nucleotide receptors in the smooth muscles of human umbilical cord and chorionic blood vessels.

To ascertain the role of extracellular adenosine 5'-triphosphate (ATP) receptors in human placenta circulation, we identified and pharmacologically characterized the P2X receptor population in its superficial vessels. Total RNA was extracted from segments of chorionic and umbilical arteries and veins of terminal placentae delivered by vaginal or Caesarian births. Polymerase chain reaction (PCR), followed by sequencing of the products, identified the presence of P2X 1, 4, 5, 6, and 7mRNAs in smooth muscle from chorionic and umbilical arteries and veins. Umbilical vessels proximal to the fetus expressed the same population of P2X subtypes, except for the P2X(5), but additionally expressed the P2X(2). Rings of chorionic vessels contracted upon addition of nucleotides and analogs with the following relative rank order of potencies in arteries and veins: alpha,beta-methyleneATP>beta,gamma-methyleneATP>PNP>ATP=diBzATP>2-MeSATP>ADP>AMP; in umbilical vessels alpha,beta-methyleneATP was at least 100-fold more potent than ATP. Nucleotide potency was less than that of PGF(2alpha) or endothelin-2, but had the same magnitude as serotonin. ATP-desensitized receptors evidenced cross desensitization to alpha,beta-methyleneATP, 2-MeSATP and diBzATP, effect not observed when desensitization was elicited by alpha,beta-methyleneATP, confirming the presence of various P2X receptor subtypes in the smooth muscles of these vessels. The vasocontractile efficacy of alpha,beta-methyleneATP was unaltered by endothelium removal, while that of ATP was significantly attenuated and those elicited by 2-MeSATP were blunted, indicating the presence of additional endothelial nucleotide receptors. These results suggest that P2X receptors participate in the humoral regulation of placental blood flow.

Adenosine Triphosphate↗

Effect of natural and modified zeolite addition on anaerobic digestion of piggery waste.

The effect of natural and modified zeolites on the anaerobic degradation of acetate and methanol was evaluated by the determination of specific methane productivity (SMP) in batch minidigesters of 50 mL at doses of 0.01, 0.05 and 0.1 g of zeolite/g of VSS. The effects of the different zeolite concentrations were determined by the results of the SMP. A kinetic characterization with data of accumulated methane gas volume was also carried out. In the second phase of the study, the effects of natural and nickel zeolite concentrations were tested with piggery waste in laboratory scale digesters of 2.5 L operating at semi continuous mode, by increasing the organic load applied from 0.2 to 22.0 g TCOD/d corresponding to organic loading rates (OLR) of 0.1-8.8 g TCOD/l x d. A greater effect of modified zeolite on SMP was observed, with an increase of 8.5 times with magnesium zeolite, 4.4 times with cobalt zeolite and 2.8 times with nickel zeolite. Two phases were defined in the kinetic study and an increase of more than 2 times the apparent constant of digesters with modified zeolites was observed in the second phase when compared to unmodified natural zeolite. Modified natural zeolite addition to digesters can allow an increase in the potential biodegradability of piggery waste solid fraction and/or a considerable reduction of digestion volume.

Acetates↗

Mutation Arg336 to Lys in Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase originates an enzyme with increased oxaloacetate decarboxylase activity.

Saccharomyces cerevisiae phosphoenolpyruvate (PEP) carboxykinase catalyzes one of the first reactions in the biosynthesis of carbohydrates. Apart from the physiologically important reaction, the enzyme also presents low oxaloacetate decarboxylase and pyruvate kinase-like activities. Data from the crystalline structure of homologous Escherichia coli PEP carboxykinase suggest that Arg(333) may be involved in stabilization of enolpyruvate, a postulated reaction intermediate. In this work, the equivalent Arg(336) from the S. cerevisiae enzyme was changed to Lys or Gln. Kinetic analyses of the varied enzymes showed that a positive charge at position 336 is critical for catalysis of the main reaction, and further suggested different rate limiting steps for the main reaction and the secondary activities. The Arg336Lys altered enzyme showed increased oxaloacetate decarboxylase activity and developed the ability to catalyze pyruvate enolization. These last results support the proposal that enolpyruvate is an intermediate in the PEP carboxykinase reaction and suggest that in the Arg336Lys PEP carboxykinase a proton donor group has appeared.

Arginine↗

Electron spin resonance studies and theoretical quantum calculations of free radicals generated from anthracenetrione by electrochemical and microsomal reduction.

The ESR spectra of radicals obtained by electrolytic reduction of 4,4-dimethylanthracene-1,9,10 (4H)-trione (1) and the regioisomeric quinones 8-acetyloxymethyl-4,4,5-trimethyl- (2), and 5-acetyloxy-methyl-4,4,8-trimethyl-(4H)-1,9,10-anthracenetrione (3) were measured in DMSO and analyzed by quantum chemical calculations. The electrochemistry of these compounds was characterized using cyclic voltammetry, in DMSO and DMF solvents and compared with nifurtimox. The quinones were also reduced by microsomal NADPH-cytochrome P-450 reductase and the corresponding radicals species were also detected by ESR spectroscopy. AMI, INDO, and ADF calculations were performed to obtain the optimized geometries, theoretical hyperfine constants, and spin distributions, respectively. Density functional theory was used to rationalize the reduction potential of these compounds.

Anthracenes↗

Carotid occlusive disease: primary care of patients with or without symptoms.

Of the half-million strokes that occur each year in the United States, 20 to 30% can be directly linked to carotid occlusive disease. The degree of stenosis involving the carotid bifurcation is an important predictor of stroke risk. Asymptomatic disease may be diagnosed on routine physical exam or screening of the carotid bifurcation in patients with risk factors for ischemic strokes. Symptomatic disease includes transient ischemic attacks, stroke in evolution, and complete stroke. Duplex ultrasound scanning is the standard test for the initial evaluation of carotid artery disease. Patients undergoing surgery should also have magnetic resonance angiography or an angiogram of the carotid vessels. Stroke prevention includes lifestyle modification such as cessation of smoking, strict dietary and medical management of hyperlipidemia, diabetes, and hypertension. Antiplatelet, anticoagulant, and thrombolytic therapy can be used where indicated.

Aged↗

Managing pressure ulcers: a multisite CQI challenge.

Think preventing and tracking pressure ulcers is expensive? Treatment may cost more. The Nurse Executive Council of VHA Alabama partnered with KCI USA, Inc., to implement a CQI project to manage pressure ulcer incidence.

Alabama↗

Effect of Somatostatin on TSH levels in non-toxic sporadic goiter.

Somatostatin (SS-14; growth hormone-release inhibiting hormone) was infused into eight patients with non-toxic sporadic goiter and into eleven normal control subjects. Each patient was given 150 microgram(s) of somatostatin as an intravenous bolus and 350 microgram(s) by infusion over a period of 60 minutes. Somatostatin did not lower the basal TSH levels as compared to the pre-infusion levels in this type of goiter, but produced a decrease in the TSH response to TRH during and after the infusion.

Adult↗

Single pedicle microvascular transfers of the serratus anterior and latissimus dorsi muscles in rats.

In the rat, the serratus anterior and latissimus dorsi muscles receive axial vascular pedicles from the thoracodorsal artery. This anatomy was confirmed by dissections, and 10 microvascular transfers of the latissimus-serratus flap on a common pedicle were performed with a 90% success rate. The flaps had an average weight of 1.8 g. This flap is a reliable small animal model for microvascular muscle transplants and contains sufficient tissue to be used in multiple biochemical assays.

Animals↗

Cholesterol increase in mitochondria: a new method of cholesterol incorporation.

In this study, we report a new method for cholesterol incorporation in mitochondria. This method is based on the coupling of cholesterol to bovine serum albumin (BSA) to form a structure with a spherical shape (designated C-BSA-C). The results show that C-BSA-C induces a specific cholesterol incorporation in mitochondria without interference from BSA. The cholesterol increase is complete in 1 minute, and is dose-related and pH-dependent. Temperature also has an effect. In mitochondria from dog adrenal glands, pregnenolone biosynthesis induced by C-BSA-C is increased, indicating that only cholesterol is transferred to the membrane.

Animals↗

Evidence for the involvement of dithiol groups in mitochondrial calcium transport: studies with cadmium.

The effect of cadmium on some functions of mitochondria isolated from kidneys of rat was studied. Addition of cadmium chloride to mitochondria induced stimulation of both State 4 respiratory rate and ATPase activity, which are prevented by the addition of ruthenium red. We also show that cadmium inhibits competitively calcium translocation; this inhibitory effect of cadmium is reverted by the addition of dithiothreitol. From these results, it is proposed that, similarly to Ca2+, cadmium penetrates mitochondria and binds to a membrane dithiol group, which is essential for the translocation of the cation.

Animals↗

Amygdaloid kindling during rapid eye movement (REM) sleep in cats.

Development of amygdaloid kindling was analyzed during REM sleep and during wakefulness. Daily evolution of electrographic and behavioral changes was significantly delayed in REM kindled rats. The number of kindling trials required to reach the first generalized convulsive seizure was also significantly increased in comparison with awake kindled animals. Changes in sleep organization were measured under REM kindling conditions. A significant increase in total sleep time and in the percentage of light slow-wave sleep was found during the kindling process. No significant sleep changes were observed in REM-established kindling. REM inhibitory influence over epileptogenesis is discussed.

Amygdala↗

Purkinje cell responses to a cerebral penicillin-induced epileptogenic focus in the cat.

A penicillin focus was induced in the postcruciate region of the cerebral cortex of the cat. Analyzing the Purkinje cell unit responses to consecutive interictal paroxysms, 60% of the cells studied (total number, 148) were found to respond with activation and 25%, with deactivation; the others were not uniform in their responses. These different response patterns were attributed to the high patchy topographic relation between the cerebral cortex and the cerebellar system as well as to the two basic patterns of neural activity, which are generated in the epileptic focus (activation), and its periphery (inhibition). The climbing fiber response to the interictal paroxysms was observed in only 41% of the Purkinje cells of the tuber vermis. This was interpreted as an interference of the epileptic interictal propagation at the inferior olivary complex level. An increase in the simple action potential discharge frequency was found during the ictal phase in intermedial regions of the cerebellar cortex in contrast with the more lateral regions, which showed a decrease; this pattern was inverted during the postictal depression phase. A tentative explanation is made relative to the different functions of the intermedial and lateral cerebellum. During ictal and postictal depression phases, no significant changes were found in the climbing fiber activity.

Action Potentials↗

Brain content of leu5- and met5-enkephalin changes independently during the development of kindling in the rat.

Brain content of leucine-enkephalin and methionine-enkephalin changes independently during kindling of the amygdala. Both peptides were measured after 4, 8, 15 and 21 days of stimulation. Leu-enkephalin showed a progressive increase during the kindling: the results on the 4th day did not differ significantly from the controls, whereas those on the 8th day displayed an increase only in the stimulated left hemisphere and those on the 15th day showed an increase in both hemispheres. This increase was also seen after 21 days of stimulation. In contrast, Met-enkephalin was not modified during the early stages of kindling, but was found to be increased after the animals had presented five or more generalized seizures. These results show that Leu-enkephalin is related to the development of kindling, whereas Met-enkephalin levels change only as a consequence of the generalized seizures.

Amygdala↗

Amygdaloid kindling enhances the enkephalin content in the rat brain.

Established amygdaloid kindling causes an increase in the immunoassayable content of both Leuenkephalin and Met-enkephalin in the rat brain. Control and sham-operated (electrode implanted but not stimulated) rats do not show statistically significant differences in brain enkephalin content, while kindled rats show a 40% enkephalin increase in both hemispheres. The present finding is in agreement with several lines of evidence and suggest that enkephalins may play a role in epileptic seizures.

Amygdala↗