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P Rojas

Publications and source records attributed to P Rojas.

At least 19 recordsLinked to original sources
PubMed2006

Cyclin D2 and cyclin D3 play opposite roles in mouse skin carcinogenesis.

D-type cyclins are components of the cell-cycle engine that link cell signaling pathways and passage throughout G1 phase. We previously described the effects of overexpression cyclin D1, D2 or D3 in mouse epidermis and tumor development. We now asked whether cyclin D2 and/or cyclin D3 play a relevant role in ras-dependent tumorigenesis. Here, we described the effect of cyclin D3 and cyclin D2 overexpression in mouse skin tumor development. Notably, overexpression of cyclin D3 results in reduced tumor development and malignant progression to squamous cell carcinomas (SCC). Biochemical analysis of keratinocytes shows that overexpression of cyclin D3 results in strong reduction of cyclin D2 and its associated kinase activity. Furthermore, we found that reinstatement of cyclin D2 level in the cyclin D3/cyclin D2 bigenic mice results in a complete reversion of the inhibitory action of cyclin D3. Supporting these results, ablation of cyclin D2 results in reduced tumorigenesis and malignant progression. On the other hand, overexpression of cyclin D2 results in an increased number of papillomas and malignant progression. We conclude that cyclin D3 and cyclin D2 play opposite roles in mouse skin tumor development and that the suppressive activity of cyclin D3 is associated with cyclin D2 downregulation.

Animals↗
PubMed2005

Nutritional and hormonal control of lipolysis in isolated gilthead seabream (Sparus aurata) adipocytes.

We examined the effects of diet composition and fasting on lipolysis of freshly isolated adipocytes from gilthead seabream (Sparus aurata). We also analyzed the effects of insulin, glucagon, and growth hormone (GH) in adipocytes isolated from fish fed with different diets. Basal lipolysis, measured as glycerol release, increased proportionally with cell concentration and time of incubation, which validates the suitability of these cell preparations for the study of hormonal regulation of this metabolic process. Gilthead seabream were fed two different diets, FM (100% of fish meal) and PP (100% of plant protein supplied by plant sources) for 6 wk. After this period, each diet group was divided into two groups: fed and fasted (for 11 days). Lipolysis was significantly higher in adipocytes from PP-fed fish than in adipocytes from FM-fed fish. Fasting provoked a significant increase in the lipolytic rate, about threefold in isolated adipocytes regardless of nutritional history. Hormone effects were similar in the different groups: glucagon increased the lipolytic rate, whereas insulin had almost no effect. GH was clearly lipolytic, although the relative increase in glycerol over control was lower in isolated adipocytes from fasted fish compared with fed fish. Together, we demonstrate for the first time that lipolysis, measured in isolated seabream adipocytes, is affected by the nutritional state of the fish. Furthermore, our data suggest that glucagon and especially GH play a major role in the control of adipocyte lipolysis.

Adipocytes↗
PubMed2004

Testicular torsion and its effects on the spermatogenic cycle in the contralateral testis of the rat.

The aim of the present study was to evaluate the effects of unilateral testicular torsion on the contralateral testis with respect to the stages of the cycle of the seminiferous epithelium (CSE). Fifty-five male Wistar rats, 60 days old, were used. The animals were divided into 11 groups. Groups 1-5 were subjected to unilateral testicular torsion from 3 to 48 h, followed by detorsion. Groups 6-10 had unilateral orchiectomies after unilateral testicular torsion for 3 to 48 h. Animals constituting group 11 served as the control sham-operated group. All animals were killed after 2 months. The percentage of affected tubules (tubules showing pathological changes) in the contralateral testis was estimated based on the CSE stages. In the torsion/detorsion group, the percentage of affected tubules was significantly greater (58.6%) than in torsion/orchiectomy group (48.0%). Stages VI-XI of the spermatogenic cycle were the most affected when compared with the rest of the stages in each experimental group (P <0.05). These results show that stages VI-XI of the spermatogenic cycle, the stages associated with low antioxidant capacities, are the most sensitive to the effects of testicular torsion on the contralateral testis.

Animals↗
PubMed2003

Dissection of K+ currents in Caenorhabditis elegans muscle cells by genetics and RNA interference.

GFP-promoter experiments have previously shown that at least nine genes encoding potassium channel subunits are expressed in Caenorhabditis elegans muscle. By using genetic, RNA interference, and physiological techniques we revealed the molecular identity of the major components of the outward K+ currents in body wall muscle cells in culture. We found that under physiological conditions, outward current is dominated by the products of only two genes, Shaker (Kv1) and Shal (Kv4), both expressing voltage-dependent potassium channels. Other channels may be held in reserve to respond to particular circumstances. Because GFP-promoter experiments indicated that slo-2 expression is prominent, we created a deletion mutant to identify the SLO-2 current in vivo. In both whole-cell and single-channel modes, in vivo SLO-2 channels were active only when intracellular Ca2+ and Cl- were raised above normal physiological conditions, as occurs during hypoxia. Under such conditions, SLO-2 is the largest outward current, contributing up to 87% of the total current. Other channels are present in muscle, but our results suggest that they are unlikely to contribute a large outward component under physiological conditions. However, they, too, may contribute currents conditional on other factors. Hence, the picture that emerges is of a complex membrane with a small number of household conductances functioning under normal circumstances, but with additional conductances that are activated during unusual circumstances.

Animals↗
PubMed2001

Neuroprotective effect of acute and chronic administration of copper (II) sulfate against MPP+ neurotoxicity in mice.

Neurodegenerative effects of MPP+, the main metabolite of MPTP include dopamine (DA) depletion and enhanced lipid peroxidation (LPO) in mice striata, both associated to free radicals overproduction. Since copper is related to several antioxidant enzymes, we tested its neuroprotective effect against MPP+-induced neurotoxicity (20 microg/3 microl). CuSO4 pretreatment was administrated by either acute (2.5 mg/kg, i.p.) or chronic (350 or 700 mg/l doses through drinking water, for 30 days) schemes. Acute administration blocked MPP+-induced striatal LPO only when administered 16 or 24 hours before MPP+, and prevented the DA-depleting effect only at 24 hours. Chronic CuSO4 prevented the LPO increase, and blocked the DA depletion only at the higher dose used (700 mg/l). Neuroprotective effect of CuSO4 was dependent on the dose and the time of pretreatment, which suggest that this lag could be related with mechanisms of activation or synthesis of copper-dependent proteins responsible of cellular defense against MPP+.

1-Methyl-4-phenylpyridinium↗
PubMed2001

EGb761 blocks MPP+-induced lipid peroxidation in mouse corpus striatum.

EGb761 has been suggested to be an antioxidant and free radical scavenger. Excess generation of free radicals, leading to lipid peroxidation (LP), has been proposed to play a role in the damage to striatal neurons induced by 1-methyl-4-phenylpyridinium (MPP+). We investigated the effects of EGb761 pretreatment on MPP+ neurotoxicity. C-57 black mice were pretreated with EGb761 for 17 days at different doses (0.63, 1.25, 2.5, 5 or 10 mg/kg) followed by administration of MPP+, (0.18, 0.36 or 0.72 mg/kg). LP was analyzed in corpus striatum at 30 min, 1 h, 2 h and 24 h after MPP+ administration. Striatal dopamine content was analyzed by HPLC at the highest EGb761 dose at 2 h and 24 h after MPP+ administration. MPP+-induced LP was blocked (100%) by EGb761 (10 mg/kg). Pretreatment with EGb761 partially prevented (32%) the dopamine-depleting effect of MPP+ at 24 h. These results suggest that supplements of EGb761 may be effective at preventing MPP+-induced oxidative stress.

1-Methyl-4-phenylpyridinium↗
PubMed2001

Community environmental health assessment in Peru's desert hills and rainforest.

Peru's expanding population and rapid urbanization--a result of migration to its largest cities--have stressed the country's public services infrastructure and the provision of public health and environmental health services. In response, the Ministry of Health established the General Directorate of Environmental Health (DIGESA), the branch charged with assuring adequate environmental health services to populations in rural and urban areas. The magnitude of the environmental health problems in peri-urban settlements, however, has exceeded the capacity of DIGESA to respond. The Urban Environmental Health Project is an effort to develop the ability of local communities to address these problems

Community Health Planning↗
PubMed2001

[Diabetes mellitus induced by olanzapine. A case report].

Atypical antipsychotics are widely used in psychotic disorders, refractory to conventional neuroleptic agents. They induce minimal extra pyramidal side effects, probably due to their greater affinity for certain dopaminergic receptors. However, this polyreceptor affinity may be responsible for the development of other side effects. We report a 48 years old male drinker and addicted to cocaine, that after two months of Olanzapine use, developed a severe diabetes mellitus with fasting blood glucose values reaching 514 mg/dl. When he was admitted to the hospital, physical examination was normal and his body mass index was 28 kg/m2. Olanzapine was discontinued and blood glucose values gradually returned to normal. After two months of follow up, the patient is on dietary treatment and with a fasting glucose of 132 mg/dl.

Antipsychotic Agents↗
PubMed2000

Kinetic characterization of calcium uptake by the rat liver Golgi apparatus.

We carried out a kinetic characterization of the Ca(2+)active transport in the rat liver Golgi Apparatus (GA) membrane. Calcium accumulation by vesicles of a GA enriched fraction was found to be a function of both Ca(2+)and ATP-Mg concentrations, it was inhibited by 2 microm thapsigargin but not stimulated by 3 microm calmodulin. The kinetic parameter values obtained for the GA Ca(2+)pump were: J(max)of 3.96 nmol/mg min, K(m)for Ca(2+)of 0.150 microm and two K(m)'s for ATP of 1.14 microm and 519 microm. These results were almost identical to those obtained for the endoplasmic reticulum (ER) fraction, indicating that the GA Ca(2+)pump is a sarco/endoplasmic reticulum (SERCA) P-type, analogous-if not identical-to that present in the ER.

Adenosine Triphosphate↗
PubMed2000

Changes of metallothionein I + II proteins in the brain after 1-methyl-4-phenylpyridinium administration in mice.

1-methyl-4-phenylpyridinium (MPP+) is a drug that induces a Parkinson's-like syndrome in several species. Oxidative stress resulting from either excess generation or reduced scavenging of free radicals has been proposed to play a role in its neurotoxicity. It has been suggested that metallothionein (MT) protects against oxidative damage of the central nervous system produced by overproduction of free radicals. This study examined the effect of MPP+ on metallothionein I+II protein content in different brain regions. NIH mice were injected with MPP+ (4.5, 9.0 or 18 microg/3 microl) into their right lateral ventricle. Corpus striatum, cerebellum, midbrain, frontal cortex and hippocampus were dissected out and their metallothionein concentrations were analyzed by radioimmunoassay. MPP+ reduced the concentration of MT I+II proteins (38%) only in the striatum. The results suggest that changes in MT I+II content may be associated with MPP+ neurotoxicity.

1-Methyl-4-phenylpyridinium↗
PubMed2000

MPTP decreases MT-I mRNA in mouse striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a drug that induces parkinsonism in humans and non-human primates. Free radicals are thought to be involved in its mechanism of action. Recently, metallothionein has been proposed to play a role as a scavenger of free radicals. In the present work, we studied the effect of MPTP neurotoxicity on brain metallothionein-I (MT-I) mRNA expression. Male C-57 black mice were treated with MPTP (30 mg/kg, i.p., daily) for 3 or 5 days. All animals were killed by cervical dislocation 7 days after the last MPTP dose. The brains were removed quickly and immediately frozen, and quantitative in situ hybridization was performed using MT-I cDNA probe. MT-I mRNA content in striatum, a region which is known to be highly predisposed and sensitive to MPTP-induced oxidative stress, decreased by 30% (3 days) and 39% (5 days) respectively, after the last MPTP administration. These results suggest that MT-I gene expression is decreased in MPTP neurotoxicity. It is suggested that the reduction of MT, an anti-oxidant and a free radical scavenger, in the striatum by MPTP enables the neurotoxin to exert maximal oxidative damage to the striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Diagnosis of Chlamydia pneumoniae in community-acquired pneumonia in children in Chile.

UNLABELLED: The incidence of Chlamydia pneumoniae in community-acquired pneumonia in children was studied prospectively in 112 children aged 1 mo to 14 y. Diagnosis of C. pneumoniae was performed by polymerase chain reaction (PCR) on nasopharyngeal aspirates and serology by the microimmunofluorescence test on a single serum specimen. Three (2.7%) cases of pneumonia due to this agent were diagnosed by both PCR and serology. C. pneumoniae was not found in any of 62 children below 5 y of age. In the age group 5-8 y, only 1/30 (3%) was found positive, and in the age group 9-14 y, C. pneumoniae was diagnosed in 2/20 (10%) children. CONCLUSION: Although the number of enrolled patients is small, and the diagnostic techniques used may have some limitations, the results of this study suggest that C. pneumoniae.plays a minor role in the aetiology of pneumonia in children less than 9 y of age in our country. However, it should be considered as a potential agent in pneumonia in older children.

Adolescent↗
PubMed2000

Relationship between plasma ammonia concentration and beta-N-acetylhexosaminidase isoenzyme activities in liver cirrhosis.

Ammonia is known to increase the secretion of beta-N-acetylhexosaminidase (Hex) to the extracellular medium in cultured human fibroblasts and Hep G2 cells. We examined 35 patients with liver cirrhosis and the results revealed a significant increase for the plasma activities of total Hex and its isoenzymes Hex A and Hex B (p < 0.001). The partial correlations, with other biochemical markers of liver injury constant, between plasma ammonia concentration and the activity (r = 0.658) and the proportion in percentage of the Hex B isoenzyme (r = 0.692) were statistically significant (p < 0.001). The increased concentration of ammonia could explain, at least partially, an increased secretion of Hex B isoforms to the plasma in patients with liver disease.

Adult↗
PubMed1999

Metallothionein-I and -II knock-out mice are not more sensitive than control mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.

Oxidative stress, resulting from either excess generation or reduced scavenging of free radicals, has been proposed to play a role in damaging striatal neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity. Metallothionein (MT) is a scavenger of oxygen-derived free radicals and it has been suggested that MT protects against oxidative damage in the central nervous system. In the present study we compared MT-I and -II null mice (MT-null) and the parental strain with intact metallothionein genes (control mice) to determine whether the absence of MT protein alters MPTP neurotoxicity. Control and MT-null mice were treated with MPTP at different doses (30, 40 and 50 mg/kg, i.p.) for 11 days. Seven days after the last dose, brains were removed and dopamine (DA) and homovanillic acid (HVA) contents were analyzed in striatum and midbrain by high pressure liquid chromatography (HPLC). Striatal DA content in MPTP-treated control mice was reduced by 53, 74 and 84% after 30, 40 and 50 mg/kg, respectively. Similar decreases were observed in MT-null mice treated with MPTP. MT-null mice were not more sensitive than control mice to MPTP neurotoxicity. The data suggest that MT-I and -II proteins do not play a role in protecting against MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1999

Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit.

Maxi-K channels consist of a pore-forming alpha subunit and a regulatory beta subunit, which confers the channel with a higher Ca(2+) sensitivity. Estradiol bound to the beta subunit and activated the Maxi-K channel (hSlo) only when both alpha and beta subunits were present. This activation was independent of the generation of intracellular signals and could be triggered by estradiol conjugated to a membrane-impenetrable carrier protein. This study documents the direct interaction of a hormone with a voltage-gated channel subunit and provides the molecular mechanism for the modulation of vascular smooth muscle Maxi-K channels by estrogens.

Animals↗
PubMed1999

Plateletpheresis efficiency: a comparison of the spectra LRS and AMICUS separators.

BACKGROUND: Optimizing the yields of plateletpheresis by increasing collection efficiencies may provide several benefits: to patients, by increasing the dose in single-donor platelet (SDP) units; to the collection center, by increasing the percentage of components that may be split into double units; and/or to the donor, by reducing the duration of donation. STUDY DESIGN AND METHODS: A prospective, randomized study was undertaken to compare the efficiency of platelet collection in paired donations by 21 donors on two cell separators (Spectra LRS, version [v] 5.1; and AMICUS, v2.37). The order of donation was randomly assigned; donations were performed at least 2 weeks apart. A fixed blood volume (4000 mL) was processed by utilizing standard protocols. Findings were confirmed in a retrospective, matched study that compared the two separators by using fixed collection times (90 min). RESULTS: The AMICUS and Spectra LRS separators consistently produced white cell-reduced (<1 x 10(6) white cells) components. The AMICUS harvested 32 percent more platelets on average (median, 4.9 x 10(11); range, 1.5-8.7 x 10(11)) than the Spectra LRS (median, 3.7 x 10(11); range, 2.1-7.7 x 10(11)) (p = 0.03), with mean times of 71.5 and 66.0 minutes (p = 0.03), respectively, to process 4000 mL. Mild donor reactions tended to be more common on the AMICUS separator, which used significantly more ACD (median 482 mL vs. 389 mL; p<0.0001) than on the Spectra LRS. CONCLUSIONS: The AMICUS separator harvested more platelets per unit of blood volume processed than the Spectra LRS. Possible benefits include increased dose in each single-donor unit, increased double-unit harvests, and/or shorter donation time.

Cell Separation↗