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1.
J Neonatal Perinatal Med ; 15(2): 311-316, 2022.
Article in English | MEDLINE | ID: mdl-34974442

ABSTRACT

BACKGROUND: Neonatal hypoglycemia management in the first 48 hours is guided by the American Academy of Pediatrics (AAP) and Pediatric Endocrine Society (PES) recommendations. Our aim was to determine the incidence of hypoglycemia via point of care test (POCT) on the 2nd day of life (DOL) among healthy, asymptomatic neonates regardless of risk factors. METHODS: In this prospective observational study, preprandial point of care glucose concentration was measured on the 2nd DOL in 150 healthy, asymptomatic neonates in the newborn nursery. We used 50 mg/dl (2.8 mmol/L) as the hypoglycemia threshold based on PES recommendations. RESULTS: The incidence of hypoglycemia on the second DOL was 10% among asymptomatic neonates (no risk factors = 8%; late preterm birth (LPT) + small for gestational age (SGA) = 16%; large for gestational age (LGA) + infant of diabetic mother (IDM) = 6%). SGA + LPT neonates accounted for the majority of the hypoglycemic cases (53.3%) and exhibited a trend towards the lowest glucose concentration (p = 0.09). CONCLUSION: The incidence of hypoglycemia on DOL 2 among asymptomatic neonates is high and of unclear significance in the absence of dedicated neurodevelopmental follow-up.


Subject(s)
Hypoglycemia , Infant, Newborn, Diseases , Premature Birth , Blood Glucose , Child , Female , Glucose , Humans , Hypoglycemia/diagnosis , Hypoglycemia/epidemiology , Infant , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Infant, Small for Gestational Age , Pregnancy
2.
Acta Virol ; 63(1): 96-102, 2019.
Article in English | MEDLINE | ID: mdl-30879318

ABSTRACT

The presence of porcine astroviruses in diarrheic and healthy pigs has been reported, however, the consequences of the astrovirus infection during the weaning process have not been described. In this study, eight healthy conventional newly-weaned piglets were used to evaluate effects of astrovirus infection during the first five days. Four piglets were infected with the porcine astrovirus PoAstV/PUJP5 strain and the other four represented the control group. Body weight, rectal temperature, diarrhea and other clinical signs were monitored every 24 hours. The results showed that all animals gained body weight, the occurrence of mild diarrhea on the 3rd day post-infection, and the astroviral presence in diarrheic samples. On the 5th day post-infection all the piglets were euthanized and then intestinal and extra-intestinal tissues were analyzed for the presence of PoAstV/PUJP5. The cytoplasmic antigen of PoAstV/PUJP5 was observed in the enterocytes of infected piglets from jejunum, ileum, colon and in inflammatory cells from mesenteric lymph nodes. In addition, villi atrophy, fusion, epithelial hyperplasia and incipient virus detection in mesenteric lymph were observed. RNAemia could not be proved. This study shows for the first time the effects of porcine astrovirus infection on conventional newly-weaning piglets. Keywords: porcine astrovirus; newly-weaned piglets.


Subject(s)
Adenoviruses, Porcine , Astroviridae Infections , Swine Diseases , Animals , Astroviridae Infections/pathology , Astroviridae Infections/veterinary , Swine , Swine Diseases/pathology , Weaning
3.
Springerplus ; 5(1): 2068, 2016.
Article in English | MEDLINE | ID: mdl-27995045

ABSTRACT

The diamondback moth (Plutella xylostella) is a major pest of broccoli crops in Colombia. To control P. xylostella, we evaluated the interaction of Beauveria bassiana Bb9205 and Metarhizium anisopliae Ma9236 with Heterorhabditis bacteriophora HNI0100 and its bacterial symbiont Photorhabdus luminescens HNI0100. We used antagonism and disk diffusion assays with fungal extracts to test the interaction between symbiotic bacterium and fungi. P. luminescens inhibited the growth of B. bassiana and M. anisopliae up to 40% by the secretion of secondary metabolites, whereas fungal extracts did not inhibit P. luminescens; this explains the in vivo interactions of these biological control agents. To test the interaction between fungi and nematodes, we first inoculated the fungi followed by the nematodes on different days (0, 2, 4, and 6). We identified the type of interaction using the formula by Nishimatsu and Jackson (J Econ Entomol 91:410-418, 1998) and established that on days 0, 2 and 4 there was an antagonistic interaction, while a synergistic interaction occurred on day 6. Therefore, the use of the interaction between H. bacteriophora HNI0100 with M. anisopliae Ma9236 and B. bassiana Bb9205 is an innovative alternative for the control of P. xylostella.

4.
Mucosal Immunol ; 9(3): 702-17, 2016 05.
Article in English | MEDLINE | ID: mdl-26376364

ABSTRACT

CD163 is a macrophage scavenger receptor with anti-inflammatory and pro-inflammatory functions. Here, we report that alveolar macrophages (AMΦs) from asthmatic subjects had reduced cell-surface expression of CD163, which suggested that CD163 might modulate the pathogenesis of asthma. Consistent with this, house dust mite (HDM)-challenged Cd163(-/-) mice displayed increases in airway eosinophils and mucous cell metaplasia (MCM). The increased airway eosinophils and MCM in HDM-challenged Cd163(-/-) mice were mediated by augmented CCL24 production and could be reversed by administration of a neutralizing anti-CCL24 antibody. A proteomic analysis identified the calcium-dependent binding of CD163 to Dermatophagoides pteronyssinus peptidase 1 (Der p1). Der p1-challenged Cd163(-/-) mice had the same phenotype as HDM-challenged Cd163(-/-) mice with increases in airway eosinophils, MCM and CCL24 production, while Der p1 induced CCL24 secretion by bone marrow-derived macrophages (BMMΦs) from Cd163(-/-) mice, but not BMMΦs from wild-type (WT) mice. Finally, airway eosinophils and bronchoalveolar lavage fluid CCL24 levels were increased in Der p1-challenged WT mice that received adoptively transferred AMΦ's from Cd163(-/-) mice. Thus, we have identified CD163 as a macrophage receptor that binds Der p1. Furthermore, we have shown that HDM-challenged Cd163(-/-) mice have increased eosinophilic airway inflammation and MCM that are mediated by a CCL24-dependent mechanism.


Subject(s)
Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Asthma/immunology , Chemokine CCL24/metabolism , Eosinophils/immunology , Macrophages, Alveolar/immunology , Receptors, Cell Surface/metabolism , Respiratory Mucosa/pathology , Animals , Antibodies, Neutralizing/administration & dosage , Antigens, CD/genetics , Antigens, Dermatophagoides/immunology , Antigens, Dermatophagoides/metabolism , Antigens, Differentiation, Myelomonocytic/genetics , Arthropod Proteins/immunology , Arthropod Proteins/metabolism , Cell Movement , Cells, Cultured , Chemokine CCL24/immunology , Cysteine Endopeptidases/immunology , Cysteine Endopeptidases/metabolism , Humans , Macrophages, Alveolar/transplantation , Metaplasia , Mice , Mice, Inbred C57BL , Mice, Knockout , Pyroglyphidae , Receptors, Cell Surface/genetics
5.
Springerplus ; 4: 620, 2015.
Article in English | MEDLINE | ID: mdl-26543755

ABSTRACT

Strategus aloeus L (Coleoptera: Scarabaeidae), known as "Little bull" or oil palm "chiza" is a limiting pest in palm plantation in Cesar Colombia. Its management is based on pesticide use or old palm removal in renewal lots. Therefore, other alternatives are being sought out. Entomopathogenic nematodes isolated from the Colombian Andean region were evaluated. Under laboratory conditions S. aloeus third instar larvae exposure to 160 infective juveniles (IJs) per/cm(2) Steinernema sp3 JCL027, S. feltiae SCT125, S. websteri JCL006, S. colombiense SNI0198, Heterorhabditis bacteriophora HNI0100, H. bacteriophora HASA702, H. indica SL0708 (n = 20) was evaluated under a completely randomized design. The experiment was repeated three times on different dates. Significant differences were observed (F = 11.127, df = 7. 24, p = 0.0054), registering mortality between 3 and 14 days. Steinernema sp3 JCL027 was the strain producing the highest mortality rate (19.3 ± 8 %), followed by H. bacteriophora HNI0100 (5.2 ± 9 %). Thus, we evaluated Steinernema sp3 JCL0270 using a randomized design at 0, 160, 290, 420, 550, 680, 810 IJs/cm(2) (n = 12). The experiment was repeated three times on different dates. Significant differences were found among treatments (44 ± 5 %, F = 14.676; df = 6. 21, p = 0.001), with 680 IJs/cm(2) producing the highest mortality followed by 810 IJs/cm(2) (22 ± 5 %). In conclusion, this alternative must be further explored in search of pesticide use and cost reduction, in addition to young palm loss in a plantation.

6.
Water Sci Technol ; 71(4): 503-10, 2015.
Article in English | MEDLINE | ID: mdl-25746640

ABSTRACT

Results of the start-up and maturation phases of a full-scale, high-rate anaerobic pond bioreactor (HRAPB)(®) plus improved facultative ponds (IFPs) to treat municipal wastewater are presented (CODt: 759 mg L⁻¹, CODf: 219 mg L⁻¹, S-SO(4)(2-): 102 mg L⁻¹, and Cr⁺: 1,500 µgL⁻¹). The start-up of the HRAPB(®) comprised, first, the application of a selective pressure increasing up-flow velocity rates. Second, batch stages between successive rates were allowed until 70% of the initial CODf was removed. The IFPs were left in batch and ended when in-pond Chlorophyll-a concentration reached 800 µgL⁻¹. Subsequently, the system underwent gradual maturation and reached effluent concentrations of CODt: 223 mg L⁻¹, CODf: 50 mg L⁻¹, and Cr⁺: 60 µgL⁻¹. The actual efficiency of the system compared with the expected design efficiency was lower given the characteristics of the influent wastewater biochemical oxygen demand/chemical oxygen demand ratios < 0.4, presence of Cr⁺ >1,000 µgL⁻¹, and variations in both conductivity (500-4,500 µScm⁻¹) and pH (6.5-10.5 units). Nonetheless, the system exhibited an adaptation state in less than 1.5 months and yielded an ST/SV ratio of 0.46, and specific methanogenic activity of 0.43 g-CH4-CODg⁻¹SV⁻¹d⁻¹ for HRAPB(®); the in-pond Chlorophyll-a was on average 1,200 µgL⁻¹ in the IFPs, which demonstrated the robustness of these eco-technologies in tropical conditions.


Subject(s)
Bioreactors , Ponds , Waste Disposal Facilities , Waste Disposal, Fluid/methods , Wastewater/chemistry , Biological Oxygen Demand Analysis , Cities
7.
Univ. sci ; 19(3): 277-285, sep.-dic. 2014. ilus, tab
Article in English | LILACS-Express | LILACS | ID: lil-735237

ABSTRACT

The diamondback moth (Plutella xylostella) is a major pest of broccoli worldwide. It mainly causes leaf defoliation and generates annual losses of 80%. In this study we evaluated the susceptibility of P. xylostella to entomopathogens Heterorhabditis bacteriophora HNI0100, Beauveria bassiana Bb9205 and Metarhizium anisopliae Ma9236. The methodology was based on the inoculation of third instar larvae of P. xylostella with 5x10/ 1x10², 3x10², 6x10² and 1,2x10³ IJs/cm² of H. bacteriophora HNI0100 and evaluated them after 24, 48 and 72 h and 1x10(4), 1x10(5), 1x10(6), 1x10(7) and 1x10(8) con/cm² of B. bassiana Bb9205 and M. anisopliae Ma9236, which were evaluated during two weeks. At a dose of 1,2 x10³ JIs/cm², P. xylostella had a susceptibility to H. bacteriophora HNI0100 of 91,66%. Similarly, B. bassiana Bb9205 and M. anisopiae Ma9236 had a mortality of 95,33 and 99,67% at 1x10(5) con/cm². The results suggest that the use of strains of entomopathogenic nematodes and fungi is an innovative alternative for the control of P. xylostella. However, studies on the interaction of nematodes and fungi and Plutella xylostella are necessary.


La palomilla dorso de diamante (Plutella xylostella) es una de las principales plagas del cultivo de brócoli (Brassica oleracea) en el mundo. El principal daño es la defoliación de las hojas, generando pérdidas anuales del 80%. El objetivo de este estudio fue evaluar la susceptibilidad de P. xylostella a los entomopatógenos Heterorhabditis bacteriophora HNI0100, Beauveria bassiana Bb9205 y Metarhizium anisopliae Ma9236. La metodología se basó en la inoculación de 5x10¹, 1x10², 3x10², 6x10² y 1,2x10³ JIs/cm² en larvas de tercer instar de P. xylostella evaluada a las 24, 48 y 72 h y 1x10(4), 1x10(5), 1x10(6), 1x10(7) y 1x10(8) con/cm² de B. bassiana y M. anisopliae evaluadas durante dos semanas. Los resultados mostraron que P. xylostella fue susceptible a H. bacteriophora HNI0100 con una tasa de mortalidad del 91,66% a dosis de 1,2x10³ JIs/cm². Así mismo, B. bassiana Bb9205 y M. anisopliae Ma9236 generaron 95,33 y 99,67% de mortalidad con la dosis de 1x10(5) con/cm². El uso de nematodos y hongos entomopatógenos es una alternativa innovadora para el control de P. xylostella, sin embargo, se requiere estudiar su interacción para el control de este insecto plaga.


A mariposa dorso de diamante Plutella xxylostella é uma das principais pragas do cultivo dos brócolos (Brassica oleraceà) no mundo. O principal dano é o desfolhamento das folhas, gerando perdas anuais de 80%. O objetivo deste estudo foi avaliar a suceptibilidade da P. xylostella aos entomopatógenos Heterorhabditis bacteriophora HNI0100, Beauveria bassiana Bb9205 e Metarhizium anisopliae Ma9236. A metodologia baseou-se na inoculação de 5x10¹, 1x10², 3x10², 6x10² y 1,2x10³ JIs/cm² em larvas do terceiro instar de P. xylostella avaliada às 24, 48 e 72 h e 1x10(4), 1x10(5), 1x10(6), 1x10(7) e 1x10(8) con/cm² de B. bassiana e M. anisopliae avaliadas durante 2 semanas. Os resultados mostraram que P. xylostella foi susceptível a H. bacteriophora HNI0100 com uma taxa de mortalidade de 91,66% com a dose de 1,2x10³ JIs/ cm². Desta forma, B. bassiana Bb9205 e M. anisopliae Ma9236 geraram 95,33 é 99,67% de mortalidade com a dose de 1x10(5) con/cm². O uso de estirpes colombianas de nematóides e fungos entomopatógenos é uma alternativa inovadora para o controlo de P. xylostella. Ainda se requer estudar a interação entre fungos e nematóides em Plutella xylostella.

8.
Eureka (Asunción, En línea) ; 10(1): 55-67, 2013. ilus, tab
Article in Spanish | LILACS | ID: lil-695883

ABSTRACT

El objetivo principal de esta investigación es determinar la correlación entre el Bienestar Social y la Participación Política en adultos pertenecientes a una Comunidad Rural de Minga Guazú, Alto Paraná. La muestra está conformada por 70 adultos, sin discriminación de sexo. Se aplicó un diseño descriptivo y correlacional. El análisis de datos se realizó a través del Coeficiente de Correlación Lineal R de Pearson, obteniendo una relación positiva entre las dos escalas relacionadas. Se concluye que el Bienestar Social está ligado al grado de Participación Política que presenta la Comunidad Rural participante.


The main objective of this research is to determine the correlation between Social Welfare and Political Participation in adults belonging to a Rural Community from Minga Guazu, Alto Parana. The sample consisted of 70 adults, regardless of sex. We used a descriptive and correlational design. Data analysis was performed using the linear correlation coefficient R Pearson, obtaining a positive relationship between the two scales related. We conclude that Social Welfare is linked to the grades of political participation presented by the participant Rural Community.

9.
Exp Clin Endocrinol Diabetes ; 120(4): 248-51, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21922457

ABSTRACT

OBJECTIVE: Mitochondrial dysfunction and oxidative stress in insulin responsive tissues is implicated in the pathogenesis of type 2 diabetes. Whether these perturbations extend to other tissues and contribute to their pathophysiology is less well established. The objective of this study was to investigate platelet mitochondria to evaluate whether type 2 diabetes associated mitochondrial dysfunction is evident in circulating cells. METHOD: A pilot study of mitochondrial respiratory function and proteomic changes comparing platelets extracted from insulin sensitive (n=8) and type 2 diabetic subjects (n=7). RESULTS: In-situ platelet mitochondria show diminished oxygen consumption and lower oxygen-dependent ATP synthesis in diabetic vs. control subjects. Mass spectrometric identification and confirmatory immunoblot analysis identifies induction of the mitochondrial anti-oxidant enzymes superoxide dismutase 2 and thioredoxin-dependent peroxide reductase 3 in platelets of diabetic subjects. As oxidative stress upregulates anti-oxidant enzymes we assessed mitochondrial protein carbonylation as an index of oxidative-stress. Platelets of diabetic subjects exhibit significantly increased protein carbonylation compared to controls. CONCLUSIONS: As platelets are anuclear fragments of megakaryocytes, our data suggest that the bone marrow compartment in type 2 diabetic subjects is exposed to increased mitochondrial oxidative stress with upregulation of nuclear-encoded antioxidant mitochondrial enzymes. This 'stress-signature' in platelets of diabetic subjects is associated with a diminution of their mitochondrial contribution to energy production and support that mitochondrial perturbations in type 2 diabetes extends beyond the classical insulin responsive tissues. Platelets, as "accessible human tissue", may be useful to measure the mitochondrial modulatory effects of emerging anti-diabetic therapeutics.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Heat-Shock Proteins/metabolism , Mitochondria/physiology , Protein Processing, Post-Translational , Adult , Antioxidants/pharmacology , Blood Platelets/metabolism , Blood Platelets/physiology , Blood Platelets/ultrastructure , Case-Control Studies , Cell Respiration/drug effects , Cell Respiration/physiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Female , Heat-Shock Proteins/analysis , Humans , Male , Middle Aged , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondrial Proteins/analysis , Mitochondrial Proteins/metabolism , Oxidative Stress/drug effects , Oxidative Stress/physiology , Oxygen Consumption/drug effects , Oxygen Consumption/physiology , Pilot Projects , Protein Processing, Post-Translational/drug effects , Proteomics/methods
10.
Kidney Int ; 70(10): 1847-57, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17021608

ABSTRACT

Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We aimed to discover biomarkers in urinary exosomes to detect acute kidney injury (AKI), which has a high mortality and morbidity. Animals were injected with cisplatin. Urinary exosomes were isolated by differential centrifugation. Protein changes were evaluated by two-dimensional difference in gel electrophoresis and changed proteins were identified by mass spectrometry. The identified candidate biomarkers were validated by Western blotting in individual urine samples from rats subjected to cisplatin injection; bilateral ischemia and reperfusion (I/R); volume depletion; and intensive care unit (ICU) patients with and without AKI. We identified 18 proteins that were increased and nine proteins that were decreased 8 h after cisplatin injection. Most of the candidates could not be validated by Western blotting. However, exosomal Fetuin-A increased 52.5-fold at day 2 (1 day before serum creatinine increase and tubule damage) and remained elevated 51.5-fold at day 5 (peak renal injury) after cisplatin injection. By immunoelectron microscopy and elution studies, Fetuin-A was located inside urinary exosomes. Urinary Fetuin-A was increased 31.6-fold in the early phase (2-8 h) of I/R, but not in prerenal azotemia. Urinary exosomal Fetuin-A also increased in three ICU patients with AKI compared to the patients without AKI. We conclude that (1) proteomic analysis of urinary exosomes can provide biomarker candidates for the diagnosis of AKI and (2) urinary Fetuin-A might be a predictive biomarker of structural renal injury.


Subject(s)
Acute Kidney Injury/urine , Blood Proteins/urine , Proteomics/methods , Reperfusion Injury/urine , Acute Kidney Injury/etiology , Acute Kidney Injury/pathology , Adult , Aged , Aged, 80 and over , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology , Biomarkers/urine , Cell Membrane/metabolism , Cisplatin/adverse effects , Cisplatin/pharmacology , Female , Humans , Kidney/drug effects , Kidney/injuries , Kidney/pathology , Male , Middle Aged , Models, Animal , Rats , Reperfusion Injury/etiology , Reperfusion Injury/pathology , alpha-2-HS-Glycoprotein , alpha-Fetoproteins/urine
11.
Histol Histopathol ; 16(4): 1057-60, 2001 10.
Article in English | MEDLINE | ID: mdl-11642725

ABSTRACT

It has been proposed that tumor suppressor genes may have a role in the mechanisms of proliferation and differentiation during human placental development. The Retinoblastoma gene family is a well known family of tumor suppressor genes. Many studies have pointed out a role of this family not only in cell cycle progression, but also during development and differentiation. On the light of these observations we have investigated the immunohistochemical expression pattern of the Retinoblastoma family members, p107 and Rb2/p130 in human placenta samples in first trimester and full-term placental sections. p107 and pRb2/p130 showed the most abundant expression levels during the first trimester of gestation and progressively declined to being barely detectable in the placenta by late gestation. These results indicate that the expression of the above genes is modulated during placental development and suggest a mechanism for controlling trophoblast proliferation.


Subject(s)
Genes, Retinoblastoma/genetics , Genes, Tumor Suppressor , Nuclear Proteins/biosynthesis , Nuclear Proteins/genetics , Phosphoproteins/biosynthesis , Phosphoproteins/genetics , Placenta/metabolism , Proteins , Retinoblastoma Protein/metabolism , Adult , Decidua/metabolism , Female , Humans , Immunohistochemistry , Pregnancy , Retinoblastoma-Like Protein p107 , Retinoblastoma-Like Protein p130 , Trophoblasts/metabolism
12.
Eur J Ophthalmol ; 11(3): 218-22, 2001.
Article in English | MEDLINE | ID: mdl-11681498

ABSTRACT

PURPOSE: To describe ophthalmic complications after nasal and sinus surgery. METHODS: Four cases with orbital complications were retrospectively selected from among more than 2000 cases of orbital pathologies. RESULTS: Motility disturbances due to extraocular muscle injury occurred in two patients after intranasal ethmoidectomy and in one patient after a Caldwell-Luc procedure. In the fourth case an orbital apex syndrome was noted after intranasal ethmoidectomies. CONCLUSIONS: Ophthalmic complications may occur after nasal and sinus surgery, even using an endoscopic procedure. Successful handling of these complications could be reached by on their early recognition and treatment.


Subject(s)
Eye Injuries/etiology , Nasal Polyps/surgery , Ocular Motility Disorders/etiology , Oculomotor Muscles/injuries , Orbit/injuries , Orbital Fractures/etiology , Adult , Eye Injuries/diagnosis , Eye Injuries/surgery , Female , Humans , Middle Aged , Ocular Motility Disorders/diagnosis , Ocular Motility Disorders/surgery , Orbital Fractures/diagnosis , Orbital Fractures/surgery , Postoperative Complications , Retrospective Studies , Tomography, X-Ray Computed , Visual Acuity
15.
Toxicol Lett ; 120(1-3): 369-77, 2001 Mar 31.
Article in English | MEDLINE | ID: mdl-11323196

ABSTRACT

The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is a key regulator in cholesterol biosynthesis and HMG CoA reductase inhibitors (statins) have become a widely prescribed family of lipid lowering agents. Cholesterol synthesis occurs predominantly in liver which is the target organ of statins. We studied the effects of fluvastatin (Lescol), a member of the statin family, on hepatic protein regulation. Male F344 rats treated with 0.8 mg/kg per day fluvastatin or 24 mg/kg per day fluvastatin for 7 days showed treatment-related changes in 58 liver proteins (P<0.005). Major effects were evident in the cholesterol biosynthesis pathway including the induction of enzymes upstream and downstream of the target enzyme HMG CoA reductase. Treatment also triggered alterations in key enzymes of carbohydrate metabolism and was associated with changes in a heterogeneous set of cellular stress proteins involved in cytoskeletal structure, calcium homeostasis and protease activity. The latter set of protein alterations indicates that hepatotoxicity is associated with high-dose treatment. Based on the results it is suggested that HMG-CoA synthase and isopentenyl-diphosphate delta-isomerase may be explored as alternative drug targets and that the induction levels of these enzymes may serve as a measure of potency of individual statin drugs. It is proposed that efficacy and cellular stress markers discovered in this study may be used in a high throughput screen (HTS) assay format to compare efficiently and accurately the therapeutic windows of different members of the statin family.


Subject(s)
Cholesterol/biosynthesis , Fatty Acids, Monounsaturated/toxicity , Hydroxymethylglutaryl-CoA Reductase Inhibitors/toxicity , Indoles/toxicity , Liver/drug effects , Proteins/metabolism , Animals , Carbohydrate Metabolism , Fluvastatin , Lipid Metabolism , Liver/metabolism , Male , Proteome , Rats , Rats, Inbred F344
16.
Electrophoresis ; 21(11): 2129-37, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10892724

ABSTRACT

Lovastatin is a lipid lowering agent that acts by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a key regulatory enzyme in cholesterol biosynthesis. In this study the pattern of gene network regulation induced in hepatic proteins as a response to lovastatin treatment was analyzed by proteomics. In livers of male F344 rats treated with 1.6 mg/kg/day lovastatin or 150 mg/kg/day lovastatin for seven days, 36 proteins were found to be significantly altered (p<0.001) in relation to treatment. The changed proteins were classified according to their cellular function and participation in biochemical pathways. The following observations were made: (i) inhibition of HMG-CoA reductase provoked a regulatory response in the cholesterol synthesis pathway including the induction of cytosolic HMG-CoA synthase and of isopentenyl-diphosphate delta-isomerase, (ii) manipulation of the lipid metabolism triggered alterations in key enzymes of the carbohydrate metabolism, and (iii) lovastatin treatment was associated with signs of toxicity as reflected by changes in a heterogeneous set of cellular stress proteins involved in functions such as cytoskeletal structure, calcium homeostasis, protease inhibition, cell signaling or apoptosis. These results present new insights into liver gene network regulations induced by lovastatin and illustrate a yet unexplored application of proteomics to discover new targets by analysis of existing drugs and the pathways that they regulate.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Liver/drug effects , Lovastatin/pharmacology , Proteins/metabolism , Proteome , Amino Acids/metabolism , Animals , Apoptosis , Biotransformation , Calcium/metabolism , Carbohydrate Metabolism , Cholesterol/metabolism , Cytoskeleton/metabolism , Electrophoresis, Gel, Two-Dimensional , Gene Expression Regulation/drug effects , Homeostasis , Liver/metabolism , Male , Mass Spectrometry/methods , Nucleotides/metabolism , Oxidative Stress , Proteins/genetics , Rats , Rats, Inbred F344 , Signal Transduction
17.
Boll Soc Ital Biol Sper ; 76(1-2): 5-11, 2000.
Article in English | MEDLINE | ID: mdl-11449823

ABSTRACT

Kinematics variables of pointing movements where assessed in five adult subjects exposed acutely (30 min) and chronically (10 days) to a low O2 mixture (13.5% O2 in N2). Amplitude of displacement did not vary in both experimental conditions but movement duration markedly increased compared to pre and post exposure conditions. While in acute hypoxia the times of acceleration and deceleration are almost equal, in chronic hypoxia deceleration time exceeded of 100 ms the time of acceleration. The time from the peak acceleration to the peak of deceleration ("switch" time) increased in both experimental conditions and was about 50% of the movement duration. This time lengthening at hypoxia may be explained either by alteration of propioceptive loops or by a different strategy elaborated by the CNS to generally slow accurate movements.


Subject(s)
Hypoxia/physiopathology , Movement , Adult , Biomechanical Phenomena , Humans , Male
18.
Boll Soc Ital Biol Sper ; 75(11-12): 77-82, 1999.
Article in English | MEDLINE | ID: mdl-11433682

ABSTRACT

We tested whether cutaneous afferents from the skin field close to an upper limb muscular region would carry information to spinal neurons at the onset or at the offset of a voluntary elbow extension movement lasting 1 s. We detected a depression of EMG activity both at onset and at the offset of the reaching movement but in the latter case depression was significantly larger and immediate. The marked depression of EMG activity suggests an inhibition, via spinal neurons, of the descending excitation to the motoneurones supplying the triceps brachii. This spinal control might be a very efficient mechanism for the termination of voluntary movement.


Subject(s)
Elbow/physiology , Motor Neurons/physiology , Radial Nerve/physiology , Spinal Nerves/physiology , Adult , Arm/physiology , Electric Stimulation , Female , Humans , Male , Muscle Contraction/physiology , Reflex, Stretch/physiology
19.
Eur J Histochem ; 41(2): 133-8, 1997.
Article in English | MEDLINE | ID: mdl-9271706

ABSTRACT

Lung cancer is a worldwide problem and in many countires it is the most lethal malignancy. Because relapse is frequent after resection of non small cell lung cancer, an urgent need exists to define prognostic factors which could help in choosing the best therapeutic approach. We performed immunohistochemistry on 60 formalin-fixed paraffin-embedded non small cell lung cancer specimens in order to evaluate the frequency of cyclin D1 overexpression, and to relate it to the degree of malignancy of these tumors and to the overall survival time of the patients. All specimens were positive for cyclin D1 immunostaining. We found cyclin D1 overexpression in 30 (50%) of our specimens, with no significant difference among the different histological types. Cyclin D1 overexpression correlates in a statistical manner with short-term patient survival. Mantel-Cox analysis of these data generated a significant P value = 0.003. The mean survival time and the five-year survival rate also differed statistically. We did not find any statistically significant correlation between cyclin D1 overexpression and histological grading, tumor stage or TNM status. We concluded that cyclin D1 overexpression in 30 patients is a frequent event in non small cell lung cancer pathogenesis and may have prognostic relevance.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Cyclins/metabolism , Lung Neoplasms/metabolism , Oncogene Proteins/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cyclin D1 , Humans , Immunohistochemistry , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Middle Aged , Neoplasm Staging , Prognosis , Survival Rate
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