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P Rojas

Publications and source records attributed to P Rojas.

At least 37 records · Page 2Linked to original sources
PubMed1999

[High prevalence of undiagnosed primary hyperaldosteronism among patients with essential hypertension].

BACKGROUND: Classically, primary hyperaldosteronism was diagnosed in no more than 1% of patients with hypertension, when hypokalemia was used as the screening test. However, numerous patients with primary hyperaldosteronism do not have hypokalemia and the disease remains undiagnosed. AIM: To assess the prevalence of normokalemic primary hyperaldosteronism among patients classified as having essential hypertension. PATIENTS AND METHODS: One hundred hypertensive patients with a blood pressure over 145/95 were studied. Plasma aldosterone and plasma renin activity were measured in all. A primary hyperaldosteronism was diagnosed when high aldosterone levels (over 16 ng/dl) and low plasma renin activity (below 0.5 ng/ml/h) coexisted in two blood tests or the aldosterone/plasma renin activity ratio was over 50. A probable primary hyperaldosteronism was diagnosed when the ratio was between 25 and 50 and these patients were subjected to a Fludrocortisone test to confirm the diagnosis. A dexametasone suppression test was done to discard glucocorticoid remediable aldosteronism. An adrenal TAC scan was done to all patients with primary hyperaldosteronism. RESULTS: A diagnosis of primary hyperaldosteronism was reached in ten patients. Seven had elevated aldosterone and low plasma renin activity. In three the diagnosis was confirmed with the fludrocortisone test. All ten patients had normal serum potassium levels. Dexametasone suppression test was positive in three patients, that normalized their blood pressure levels. Adrenal TAC scans showed an adenoma in one patient and hyperplasia in another. CONCLUSIONS: Primary hyperaldosteronism is more frequent than previously thought, it is overlooked when hypokalemia is used as the screening test and it can only be diagnosed measuring plasma aldosterone and renin activity.

Aldosterone↗
PubMed1998

Metallothionein, neurotrophins and selegiline in providing neuroprotection in Parkinson's disease.

The finding that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) elicits parkinsonism in human beings suggests that endogenous or xenobiotic neurotoxic compounds may be involved in the etiology of Parkinson's disease (PD). We have shown that cerebrospinal fluid (CSF) of newly diagnosed and drug untreated patients with PD contains a low molecular weight substance(s) which inhibits the growth and function of dopaminergic neurons in culture. In addition, selegiline in a dosage below the level that inhibits monoamine oxidase B (MAO-B), protects dopaminergic neurons in culture against toxic factor(s) present in the CSF of patients with PD, and the said effect is mediated via elaboration of brain-derived neurotrophic factor (BDNF). In view of the fact that 6-hydroxydopamine (6-OHDA) or MPTP causes parkinsonism by generating free radicals, and inducers of metallothionein (MT) isoforms avert the said neurotoxicity, we intended to learn whether MT isoforms were capable of scavenging free radicals. By employing electron spin resonance spectroscopy (ESR), we examined for the first time the free radical scavenging effects of MT-I and MT-II isoforms on four types of free radicals. Solutions of 0.15 mM of MT-I and 0.3 mM of MT-II scavenged the 1,1-diphenyl-2-picrylhydrazyl radicals completely. Furthermore, they were able to scavenge hydroxyl radicals generated in a Fenton reaction. Moreover, MT-I scavenged almost 90% of the superoxide generated by the hypoxanthine and xanthine oxidase system, while MT-II could only scavenge 40%. By using 2,2,6,6-tetramethyl-4-piperidone as a "spin-trap" for the reactive oxygen species (containing singlet oxygen, superoxide and hydroxyl radicals) generated by photosensitized oxidation of riboflavin, and measuring the relative signal intensities of the resulting stable nitroxide adduct, 2,2,6,6-tetramethyl-4-piperidone-1-oxyl, we observed that MT-II could scavenge 92%, while MT-I could completely scavenge all the reactive species generated. The results of this investigation are interpreted to suggest that selegiline by preventing the generation of free radicals, MT isoforms by scavenging free radicals, and neurotrophins by rescuing dopaminergic neurons are capable of attenuating oxidative stress and of providing neuro-protection in PD.

Journal Article↗
PubMed1997

Effect of p-chlorophenylalanine (PCPA) on sleep and monoamines content in the brain of a lizard species.

Administration of PCPA, a specific inhibitor of serotonin synthesis, induced a significant decrease of total sleep time in the lizard Ctenosaura pectinata. This effect was exerted on both quiet sleep and active sleep, but it was more intense on active sleep. Reduction in the amount of active sleep was due to a decrease in the number of the episodes not in their mean duration, since this parameter increased significantly from 5.97 s, under control conditions, to 11.77 s, 10.66 s and 8.85 s at 24, 48 and 72 h after PCPA injection, respectively. Neurochemical analysis showed a significant decrease in the amount of serotonin in the analyzed brain stem structures 12 h after PCPA administration. The possible participation of serotonergic mechanisms in the regulation of reptilian sleep is discussed.

Animals↗
PubMed1997

Metallothionein inducers protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in mice.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a drug that induces parkinsonism in human and non-human primates. Free radicals are thought to be involved in its mechanism of action. Recently, the participation of metallothionein as scavenger of free radicals has been proposed. In this work, we studied the effect of metallothionein inducers in MPTP neurotoxic action. Male swiss albino mice were pretreated either with cadmium (1 mg/kg) or dexamethasone (5 mg/kg), two well-known inducers of metallothionein synthesis, and 5 hours later with an MPTP administration (30 mg/kg). Treatment schedule was repeated daily for either 3 or 5 consecutive days. All animals were killed 7 days after the last administration, and striatal dopamine and homovanillic acid contents were analyzed as an end-point of MPTP neurotoxicity. Striatal dopamine content of cadmium plus MPTP-treated animals (3-days) increased by 32%, and 48% (5-days) vs MPTP-alone animals. Dexamethasone plus MPTP-treated group also showed increased dopamine levels 28% (3-days) and 43% (5-days). MPTP treatment reduced striatal metallothionein concentration (49% vs control animals). Dexamethasone and cadmium increased metallothionein concentrations in MPTP-treated groups, by 77% and 82% respectively. Results suggest that metallothionein induction provide a significant resistance factor against the deleterious effect of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

Biological monitoring for mercury within a community with soil and fish contamination.

To assess the impact of elevated levels of inorganic mercury in soil and dust and organic mercury in fish, biological monitoring was conducted among Native Americans living next to an inactive mercury mine in Clear Lake, California. Of resident tribal members, 46% (n = 56) participated in biomonitoring. Urine mercury levels are equivalent to background, indicating that soil and dust exposures among study participants are not substantial. The average blood organic mercury level among study participants is 15.6 +/- 8.8 micrograms/l (n = 44), which is higher than levels reported by others among those who do not consume fish (2 micrograms/l). Consistent with results from other studies, a correlation between fish consumption and blood organic mercury is observed (p = 0.03). The margin between observed and established adverse effect levels for adults is examined for blood organic mercury and found to be less than 10-fold for 20% of the study population. Protective public health efforts for the study population and other similarly exposed populations, notably those who consume commercial fish products, are considered.

Adult↗
PubMed1996

The antioxidant properties of zinc and metallothionein.

Support for the hypothesis that metallothionein isoforms participate in intracellular defense against reactive oxygen and nitrogen species is derived from observations that substances causing oxidative stress, such as ethanol and iron, and agents involved in inflammatory processes, such as interleukin-1 and tumour necrosis factor alpha, induce the synthesis of metallothionein. Moreover, animals deficient in metallothionein isoforms exhibit greater susceptibility to oxidative stress; metallothionein genes are transcriptionally activated in cells and tissues during oxidative stress; and over expression of metallothionein reduces the sensitivity of cells and tissues to free radical-induced injury. In this study, we have shown that the i.c.v. administration of ZnSO4 increases the synthesis of metallothionein I mRNA and metallothionein II mRNA. In addition, the i.c.v. administration of ZnSO4 enhances the concentration of zinc and in direct proportion the synthesis of metallothionein mRNAs. Agents known to generate free radicals and to cause oxidative stress such as 6-hydroxydopamine, iron, hydrogen peroxide, and various alcohols lead to induction of metallothionein in the hippocampal neurons in primary culture and in Chang liver cells in culture. In view of the fact that zinc and 6-hydroxydopamine induce the level of brain metallothionein and its mRNAs and zinc and metallothionein concentrations vary in different regions of the brain, it is postulated that metallothionein may play a major role in nullifying the iron-mediated generation of free radicals and in protecting against oxidative stress in the brain.

Animals↗
PubMed1996

6-Hydroxydopamine-mediated induction of rat brain metallothionein I mRNA.

Oxidative stress, resulting either from excess generation or reduced scavenging of free radicals, has been proposed to play a role in damaging striatal neurons in Parkinson's disease. Since metallothionein is able to regulate the intracellular redox potential, we have undertaken a group of experiments to learn whether or not 6-hydroxydopamine, which generates free radicals and is toxic to dopaminergic neurons, could alter the levels of zinc and metallothionein in the brain. The lesioning of the rat striatum with 6-hydroxydopamine (8.0 micrograms in 4 microliter 0.02% ascorbic acid) resulted in a reduction in the levels of zinc and metallothionein in the striatum but not other brain regions tested. However, the intracerebroventricular administration of 6-hydroxydopamine, in a dosage regimen that does not lesion catecholaminergic pathways but causes oxidative stress, enhanced dramatically the level of metallothionein I mRNA in some brain areas such as hippocampus, arcuate nucleus, choroid plexus, and granular layer of cerebellum, but not in the caudate putamen. The results of these studies are interpreted to suggest that zinc or metallothionein are altered in conditions where oxidative stress has taken place. Moreover, it is proposed that areas of brain, such as striatum containing high concentrations of iron, but low levels of inducible metallothionein are particularly vulnerable to oxidative stress.

Animals↗
PubMed1995

Expression of the subunits of protein kinase CK2 during oogenesis in Xenopus laevis.

Northern-blot analysis of RNAs from different tissues demonstrated that the mRNA for the protein kinase CK2 alpha subunit is very abundant in the ovary of Xenopus laevis. The competitive reverse-PCR technique has been used to quantitate the mRNA for both CK2 alpha and CK2 beta subunits during oogenesis. The results obtained using eight different animals consistently show an increment of 2-3-fold in the mRNA for both subunits in vitellogenic oocytes (stages II-VI). Each stage-VI oocyte contains approximately 5 x 10(-7) molecules CK2 alpha mRNA and 1 x 10(-7) molecules CK2 beta mRNA. These amounts are considerably higher than many other mRNAs analyzed in these cells. Activity measurements of CK2 using casein or a specific model peptide revealed increments of about 10-12-fold during oogenesis, and also indicated that the amount of enzyme in the nucleus accounted for 15-30% of the total enzyme in the oocyte at all stages. Western-blot analysis of CK2 alpha indicated that the amount of this protein subunit also increased during oogenesis in a parallel fashion with the increment of enzymic activity.

Animals↗
PubMed1995

Short-term manganese pretreatment partially protects against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces parkinsonism in human and non-human primates. Its mechanism of action is not fully elucidated. Recently, the participation of trace metals, such as manganese, on its neurotoxic action has been postulated. In this work, we studied the effect of manganese administration on the neurochemical consequences of MPTP neurotoxic action. Male Swiss albino mice were treated with manganese chloride (MnCl2.4H2O; 0.5 mg/ml or 1.0 mg/ml of drinking water) for 7 days, followed by three MPTP administrations (30 mg/kg, intraperitoneally). Seven days after the last MPTP administration, mice were sacrificed and dopamine and homovanillic acid contents in corpus striatum were analyzed. Striatal concentration of dopamine was found increased by 60% in mice pretreated with 0.5 mg/ml and 52% in the group treated of 1.0 mg/ml as compared versus animals treated with MPTP only. Homovanillic acid content in both groups treated with manganese was the same as those in control animals. The results indicate that manganese may interact with MPTP, producing an enhancement of striatal dopamine turnover, as the protective effect of manganese was more pronounced in the metabolite than in the neurotransmitter.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Expression and regulation of brain metallothionein.

Many, but not all, zinc-containing neurons in the brain are a subclass of the glutamatergic neurons, and they are found predominantly in the telencephalon. These neurons store zinc in their presynaptic terminals and release it by a calcium-dependent mechanism. These "vesicular" pools of zinc are viewed as endogenous modulators of ligand- and voltage-gated ion channels. Metallothioneins (MTs) are low molecular weight zinc-binding proteins consisting of 25-30% cysteine, with no aromatic amino acids or disulfide bonds. The areas of the brain containing high contents of zinc such as the retina, the pineal gland, and the hippocampus synthesize unique isoforms of MT on a continuous basis. The four MT isoforms are thought to provide the neurons and glial elements with mechanisms to distribute, donate, and sequester zinc at presynaptic terminals; or buffer the excess zinc at synaptic junctions. In this cause, glutathione disulfide may participate in releasing zinc from MT. A similar nucleotide and amino acid sequence has made it difficult to obtain cDNA probes and antibodies capable of distinguishing indisputably among MT isoforms. MT-I and MT-II isoforms are found in the brain and in the peripheral tissues; MT-III isoform, possessing an additional seven amino acids, is expressed mostly in the brain and to a very minute extent in the intestine and pancreas; whereas MT-IV isoform is found in tissues containing stratified squamous epithelial cells. Since MTs are expressed in neurons that sequester zinc in their synaptic vesicles, the regulation of the expression of MT isoforms is extremely important in terms of maintaining the steady-state level of zinc and controlling redox potentials. The concentration of zinc has been shown to be altered in an extensive number of disorders of the central nervous system, including alcoholism. Alzheimer-type dementia, amyotrophic lateral sclerosis, Down's syndrome, epilepsy, Friedreich's ataxia, Guillaine-Barré syndrome, hepatic encephalopathy, multiple sclerosis, Parkinson's disease, Pick's disease, retinitis pigmentosa, retinal dystrophy, schizophrenia, and Wernicke-Korsakoff syndrome. The status of MT isoforms and other low molecular weight zinc-binding proteins in these conditions, diseases, disorders, or syndromes is being delineated at this time. Since several of these disorders, such as amyotrophic lateral sclerosis, are associated with oxidative stress, and since MT is able to prevent the formation of free radicals, it is believed that cytokine-induced induction of MT provides a long-lasting protection to avert oxidative damage.

Amino Acids↗
PubMed1995

Depletion of copper and manganese in brain after MPTP treatment of mice.

The mechanism of action of MPTP, a parkinsonism-inducing drug has been related to trace metals as a result of the observed potentiation of the neurotoxic action of the drug when diethyldithiocarbamate is concurrently administered. Diethyldithiocarbamate is a well-known chelator of trace metals, particularly copper. In the present study we analyzed the concentrations of copper and manganese in four brain regions of mice treated with neurotoxic doses of MPTP, in order to further substantiate the relationship between trace metals of MPTP-induced neurotoxicity. Male Swiss albino mice were administered with MPTP (30 mg/kg) for either three or five days. Seven days after the last MPTP administration, they were sacrificed and the content of manganese and copper in the following regions was determined by graphite furnace atomic absorption spectrophotometry: cortex, cerebellum, midbrain and corpus striatum. Results indicate a significant depletion of manganese in corpus striatum (19.5% versus control) in the mice treated with MPTP for 5 days. Copper was also found to be decreased in corpus striatum (17.3% in mice treated for 3 days and 51.3% in mice treated for 5 days). Midbrain copper was depleted by 42.9% in the group of mice treated for 5 days with MPTP. Results indicate that MPTP induced a diminution of both copper and manganese in corpus striatum, suggesting that this alteration could be related to MPTP mechanism of action.

Animals↗
PubMed1993

Increased striatal lipid peroxidation after intracerebroventricular MPP+ administration to mice.

Mice received different doses intracerebroventricularly of MPP+ (1-methyl-4-phenylpyridinium ion), the active metabolite of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a drug which induces a Parkinson model in rodents. Two indexes of lipid peroxidation were monitored at different times after administration: 1) production of thiobarbituric acid-reactive substances and 2) formation of lipid fluorescence products. A regional-selective overproduction of thiobarbituric acid-reactive substances was observed in corpus striatum and midbrain, but not in frontal cortex, cerebellum nor hippocampus. Enhancement was 70% and 198% at 30 and 60 min. in striatum and 88% at 30 min. in midbrain, when compared with respective controls injected intracerebroventricularly with saline solution. MPP+ also induced lipid fluorescence products formation enhancement in corpus striatum. This increase was dose-dependent in the range of MPP+ doses which induced striatal dopamine depletion. Striatal LFP formation was found increased 24 hr after MPP+ administration (38% vs control), indicating long-lasting lipid peroxidation overproduction. These results suggest that lipid peroxidation might be involved in the neurotoxic effects of MPP+ in vivo.

1-Methyl-4-phenylpyridinium↗
PubMed1992

Trisomy 8: an additional case with unique manifestations [correction].

We report on an infant with multiple congenital anomalies and mosaic trisomy 8 [corrected]. Clinical findings are presented, and compared with those of the 24 cases previously reported. Some unusual characteristics found in this patient include macrocephaly, an extreme degree of palatal hypoplasia, and abnormally shaped long bones.

Abnormalities, Multiple↗