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1.
Int J Biometeorol ; 62(5): 883-895, 2018 May.
Article in English | MEDLINE | ID: mdl-29299679

ABSTRACT

The production of pasture in Ethiopia was simulated by means of a dynamic model. Most of the country is characterized by a tropical monsoon climate with mild temperatures and precipitation mainly concentrated in the June-September period (main rainy season). The production model is driven by solar radiation and takes into account limitations due to relocation, maintenance respiration, conversion to final dry matter, temperature, water stress, and nutrients availability. The model also considers the senescence of grassland which strongly limits the nutritional value of grasses for livestock. The simulation for the 1982-2009 period, performed on gridded daily time series of rainfall and maximum and minimum temperature with a resolution of 0.5°, provided results comparable with values reported in literature. Yearly mean yield in Ethiopia ranged between 1.8 metric ton per hectare (t ha-1) (2002) and 2.6 t ha-1 (1989) of dry matter with values above 2.5 t ha-1 attained in 1983, 1985, 1989, and 2008. The Ethiopian territory has been subdivided in 1494 cells and a frequency distribution of the per-cell yearly mean pasture production has been obtained. This distribution ranges from 0 to 7 t ha-1 and it shows a right skewed distribution and a modal class between 1.5-2 t ha-1. Simulation carried out on long time series for this peculiar tropical environment give rise to as lot of results relevant by the agroecological point of view on space variability of pasture production, main limiting factors (solar radiation, precipitation, temperature), and relevant meteo-climatic cycles affecting pasture production (seasonal and inter yearly variability, ENSO). These results are useful to establish an agro-ecological zoning of the Ethiopian territory.


Subject(s)
Models, Theoretical , Poaceae/growth & development , Animal Feed , Animal Husbandry , Ethiopia , Rain , Sunlight , Temperature , Tropical Climate
3.
Int J Biometeorol ; 61(4): 761-773, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27714505

ABSTRACT

While the climate of Western Europe has been deeply affected by the abrupt climate change that took place in the late '1980s of the twentieth century, a similar signal is detected only few years later, in 1994, in Georgia. Grapevine phenology is deeply influenced by climate and this paper aimed to analyze how phenological timing changed before and after the climatic change of 1994. Availability of thermal resources in the two climatic phases for the five altitudinal belts in the 0-1250-m range was analyzed. A phenological dataset gathered in two experimental sites during the period 2012-2014, and a suitable thermal dataset was used to calibrate a phenological model based on the normal approach and able to describe BBCH phenological stages 61 (beginning of flowering), 71 (fruit set), and 81 (veraison). Calibration was performed for four relevant Georgian varieties (Mtsvane Kakhuri, Rkatsiteli, Ojaleshi, and Saperavi). The model validation was performed on an independent 3-year dataset gathered in Gorizia (Italy). Furthermore, in the case of variety Rkatsiteli, the model was applied to the 1974-2013 thermal time series in order to obtain phenological maps of the Georgian territory. Results show that after the climate change of 1994, Rkatsiteli showed an advance, more relevant at higher altitudes where the whole increase of thermal resource was effectively translated in phenological advance. For instance the average advance of veraison was 5.9 days for 250-500 m asl belt and 18.1 days for 750-1000 m asl). On the other hand, at lower altitudes, phenological advance was depleted by superoptimal temperatures. As a final result, some suggestions for the adaptation of viticultural practices to the current climatic phase are provided.


Subject(s)
Climate Change/history , Vitis , Altitude , Georgia (Republic) , History, 20th Century , History, 21st Century , Seasons , Temperature
5.
Int J Immunopathol Pharmacol ; 28(1): 129-33, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25816416

ABSTRACT

The most common cause of end stage renal disease is diabetic nephropathy. An early diagnosis may allow an intervention to slow down disease progression. Recently, it has been hypothesized that glutathione-S-transferase (GST) activity may be a marker of severity of chronic kidney disease. In particular, a lower GST activity is present in healthy subjects compared to patients with nephropathy. In the present review we illustrate the scientific evidence underlying the possible role of GST activity in the development of diabetic nephropathy and we analyze its usefulness as a possible early biomarker of this diabetic complication.


Subject(s)
Diabetes Complications/metabolism , Diabetic Nephropathies/metabolism , Glutathione Transferase/metabolism , Biomarkers/metabolism , Humans , Kidney Failure, Chronic/metabolism , Renal Insufficiency, Chronic/metabolism
7.
Atherosclerosis ; 232(2): 260-4, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24468136

ABSTRACT

AIMS: Age is one of the most important determinants of cardiovascular health, therefore the management of cardiovascular diseases (CVD) in elderly people entails great challenge. A possible explanation of vascular senescence process is the mitochondrial damage and dysfunction. We hypothesized that metabolomic profiling would identify biomarkers predicting major cardiovascular events (MACEs) in elderly people, improving the clinical standard cardiovascular risk factors. METHODS AND RESULTS: Targeted-mass-spectrometry-based profiling of 49 metabolites was performed in a group of very old participants (n = 67, mean age = 85 ± 3 years) with a high rate of previous CVD (68%). Principal Component Analysis, Random Survival Forest analysis and Cox proportional hazards regression modeling were used to evaluate the relation between the metabolite factors and recurring MACEs. We tested discrimination ability and reclassification of clinical and metabolomic models. At follow-up (median = 3.5 years), 17 MACEs occurred (5 cardiovascular deaths, 1 nonfatal myocardial infarction, 7 nonfatal strokes and 4 peripheral artery surgeries) (incidence = 7.3% person-years). Metabolite factor 1, composed by medium- and long-chain acylcarnitines, and factor 7 (alanine) were independently associated with MACEs, after adjustment for clinical CV covariates [HR = 1.77 (95%CI = 1.11-2.81, p = 0.016) and HR = 2.18 (95%CI = 1.17-4.07, p = 0.014), respectively]. However, only factor 1 significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 7%, p = 0.01) and correctly reclassifying 41% of events and 37% of non-events resulting in a cNRI = 0.79 (p = 0.005). CONCLUSIONS: Aging mitochondrial dysfunction evaluated by metabolomic profiling is associated with MACEs, independently of standard predictors.


Subject(s)
Aging , Cardiovascular Diseases/blood , Cardiovascular Diseases/metabolism , Metabolomics/methods , Aged , Aged, 80 and over , Biomarkers/blood , Carnitine/analogs & derivatives , Carnitine/blood , Cellular Senescence , Female , Follow-Up Studies , Humans , Male , Metabolic Networks and Pathways , Myocardial Infarction/blood , Principal Component Analysis , Proportional Hazards Models , Reproducibility of Results , Stroke/blood
8.
Int J Biometeorol ; 56(6): 1123-34, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22438052

ABSTRACT

Atmospheric variables play a fundamental role in driving man-managed ecosystems and more specifically in agro-ecosystems, determining the quantity and quality of crop production. On the other hand, climate variability can be seen as the superimposition of gradual and abrupt changes. This paper is focused on European surface air temperature in the period 1951-2010. Analysis of this dataset identified breakpoints that define two homogeneous sub-periods: 1951-1987 and 1988-2010. Thermal resources for crops were analyzed adopting a "normal heat hours" approach. Computation highlighted a general increase in thermal resources in the European continent for crop groups II and III (C3 and C4 plants adapted to high or moderate temperatures), while a decline of thermal resources for crop group I (cold adapted C3) was highlighted in the Mediterranean area. The climate variability justifies a change in the potential latitudinal limits of different groups of crops, representing a fundamental step for crop adaptation to climate change.


Subject(s)
Climate Change/history , Crops, Agricultural , Europe , History, 20th Century , History, 21st Century , Temperature
9.
Exp Lung Res ; 33(6): 289-301, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17694439

ABSTRACT

Abnormality in the fragile histidine triade (FHIT), a candidate tumor suppressor gene located in chromosome region 3 (3p14.2), has been frequently found in multiple tumor types, including lung cancer. In this study, the authors assessed the consistency of DNA microsatellite analysis of induced sputum (IS), as compared to that of blood and plasma. They also evaluated the loss of heterozigosity (LOH) and microsatellite instability (MSI) in 3 different loci, D3S1300, D3S1313, and D3S1234, all internal to the FHIT gene, in IS, blood, and plasma from patients with lung cancer, smokers, and healthy subjects. Eighteen patients with lung cancer (3 females, age mean +/- SD: 63 +/- 7 years), 39 smokers (23 females, age mean +/- SD: 57 +/- 6 years and cigarette pack-years mean +/- SD: 34 +/- 12), and 22 healthy nonsmoking subjects (13 females, age mean +/- SD: 63 +/- 5 years) were studied. DNA was extracted from blood, plasma, and IS, by means of a standard method. Analysis of LOH and MSI were performed using a fluorescent polymerase chain reaction (PCR)-based approach, followed by capillary electrophoresis. The ratios between the peak heights (phs), expressed as random fluorescence units, from plasma/blood (p/b) and induced sputum/blood (is/b) in all three loci were considered. The biases (agreement limits) between the mean ph ratio from p/b and is/b of D3S1300, D3S1313, and D3S1234 were respectively 0.07 (- 0.39 to 0.53), 0.016 (- 0.32 to 0.35), - 0.10 (- 0.51 to 0.30) in the patients; - 0.04 (- 0.52 to 0.43), - 0.06 (- 0.31 to 0.18), - 0.08 (- 0.48 to 0.30) in smokers; and - 0.11 (- 0.40 to 0.17), - 0.05 (- 0.53 to 0.43), - 0.09 (- 0.51 to 0.33) in healthy subjects. LOH and MSI in at least one locus were observed in 55% of patients, in 18% of smokers, and in 4.5% of healthy subjects (P < 0.001). These results showed that IS DNA provided data that were consistent with those from blood and plasma. These findings highlight new prospects for early tumor detection by a noninvasive technique based on the analysis of genetic alterations in induced sputum.


Subject(s)
Acid Anhydride Hydrolases/genetics , DNA, Neoplasm , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , Microsatellite Repeats , Neoplasm Proteins/genetics , Smoking/adverse effects , Sputum/chemistry , Aged , Case-Control Studies , DNA Mutational Analysis , DNA, Neoplasm/analysis , DNA, Neoplasm/blood , Electrophoresis, Capillary , Female , Humans , Loss of Heterozygosity , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Polymerase Chain Reaction , Predictive Value of Tests , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity
10.
Arq. bras. med. vet. zootec ; 59(3): 614-620, jun. 2007. tab
Article in Portuguese | LILACS | ID: lil-461137

ABSTRACT

Determinou-se, por meio de um sistema de monitoramento de suínos em fase de crescimento e em matadouro, a presença de patologias como indicadoras de problemas na população de referência. O estudo foi realizado em uma criação intensiva de ciclo completo, durante nove semanas. Foram determinadas as prevalências dos diagnósticos clínico-patológicos obtidos durante um período de nove semanas. Utilizaram-se cinco grupos de 43 leitões, com pesos de até 19kg, considerados de baixa performance. Estimaram-se, por intervalos de confiança de 95 por cento, as prevalências acumuladas em cada monitoramento. Obteve-se correlação de 0,99 (P<0,0001) entre as prevalências anuais com as nove semanas de estudo, mostrando correspondência com o achado em matadouro. Amostras em semanas alternadas de três grupos de 43 animais são bons indicadores das patologias que afetam os suínos em crescimento, mesmo aquelas de baixa freqüência ou muito letais.


The prevalence of different pathologies as an indicator of health problems in a particular population by means of slaughterhouse monitoring of growing pigs was determined. The work was carried out in an indoor intensive farrow to finish swine farm during 9 weeks. The prevalence of diseases was determined by means of clinical and pathological diagnosis. For the slaughterhouse inspection, five groups of 43 pigs each weighting up to 19kg, considered as poor performers, were put together. These animals were sent to the slaughterhouse and were observed for the presence or absence of skin and joint lesions of arms and legs and also lesions of serous membranes and parenchimal organs. An estimative with a confidence interval level of 95 percent was performed on cumulated prevalence in each monitoring session for 43, 86, 129, 172 and 215 animals. Annual prevalence from clinical and pathological diagnosis and 9-week-period had correlations (r=0.99; P<0.0001) and correspondence with slaughterhouse observations. In conclusion, samplings in alternate weeks of three groups of 43 pigs seem to be a good indicator of pathologies affecting growing swines, even those of very low prevalence or highly lethal.


Subject(s)
Animals , Swine Diseases/epidemiology , Swine Diseases/prevention & control , Environmental Monitoring , Swine , Abattoirs
12.
G Chir ; 25(1-2): 35-8, 2004.
Article in Italian | MEDLINE | ID: mdl-15112759

ABSTRACT

The Authors report the case of a 33-year-old male affected with an asymptomatic schwannoma of the posterior mediastinum, and review the relevant Literature, discussing the difficulties in making the differential diagnosis of the posterior mediastinum lesions, particularly in the pre-clinical phase. Neurogenic tumors represent about 75 percent of all tumors of mediastinum and about one third of all tumors of the mediastinum. They can originate from the peripheral nervous system group, from the sympathetic nervous system group or, in rare cases, from the vagus nerve. In adult patients, they are usually found by chance during radiographic examination of the thorax, and they are usually asymptomatic and benign. During preoperative evaluation, a magnetic resonance examination of rachis should be done to exclude the possibility of intraspinal involvement. If there are no contraindications, the treatment of choice should be surgical resection by means of thoracoscopy or thoracotomy, when size and location of the tumors allow it in order to prevent malignant evolution.


Subject(s)
Mediastinal Neoplasms/diagnosis , Neurilemmoma/diagnosis , Adult , Diagnosis, Differential , Hernia, Inguinal/surgery , Humans , Incidental Findings , Male , Mediastinal Neoplasms/diagnostic imaging , Mediastinal Neoplasms/epidemiology , Mediastinal Neoplasms/surgery , Neurilemmoma/diagnostic imaging , Neurilemmoma/epidemiology , Neurilemmoma/surgery , Peripheral Nervous System Neoplasms/classification , Peripheral Nervous System Neoplasms/diagnosis , Thoracotomy , Tomography, X-Ray Computed
13.
G Chir ; 24(5): 186-8, 2003 May.
Article in Italian | MEDLINE | ID: mdl-12945170

ABSTRACT

Malignant periampullary and ampullary tumors represent an anatomic and clinical entity of complex surgical approach due to the difficulty in setting out an early diagnosis, for the back of symptoms at early stages. The Authors at the Department of Surgery and Medical Technology Applications "F. Durante", University of Rome "La Sapienza", since 1990 to 2001 observed 19 cases. The results of surgical treatment of these tumors are here reported. By the analysis of the cases it is evident that long-term survival if mainly conditioned by prompt diagnosis stage of the tumor, and patient status before the operation.


Subject(s)
Ampulla of Vater , Bile Duct Neoplasms/surgery , Common Bile Duct Neoplasms/surgery , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
14.
J Hum Hypertens ; 17(12): 859-64, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14704730

ABSTRACT

The C(-344)T promoter polymorphism of the human aldosterone synthase (CYP11B2) gene has been associated with hypertension and cardiac hypertrophy, but there were contrasting data. We analysed the genotype/phenotype associations between this polymorphism and cardiovascular variables in a young adult population, where interactions among genes, gene-environment, and acquired ageing-related organ damage are reduced. Anthropometric measurements, blood pressure, heart rate, left ventricular variables (by echocardiography), and carotid artery wall intimal-media thickness (by high-resolution sonography and digitalized morphometry) were taken in 420 white Caucasian students (mean age 23.5 years, s.d. 2.5 years). CYP11B2 alleles were detected by genomic polymerase chain reaction followed by digestion. Taking into account the three possible models of inheritance, we found no differences in the considered variables, except for an independent effect of the C(-344) allele on SBP in males (TT 125.6 (1.6), TC 128.4 (1.2) and CC 130.5 (2.2), mmHg, media (ES), P=0.03), and on interventricular septum thickness in diastole in females (CC 6.98 (0.12) vs TT 6.87 (0.09) and TC 6.87 (0.07), mmHg, P<0.01), in the codominant model. In conclusion, the CYP11B2 C(-344)T polymorphism appears to have a slight role in the cardiovascular phenotype of young healthy adults, even if these genotype/phenotype relationships might change with ageing.


Subject(s)
Alleles , Cardiovascular Diseases/genetics , Cytochrome P-450 CYP11B2/genetics , Adult , Analysis of Variance , Anthropometry , Blood Pressure , Chi-Square Distribution , Female , Genetic Variation , Genotype , Humans , Male , Phenotype , Polymerase Chain Reaction
15.
G Chir ; 23(5): 209-11, 2002 May.
Article in Italian | MEDLINE | ID: mdl-12228974

ABSTRACT

Neurinomas, also referred to as neurilemmomas and schwannomas, are rare benign tumours of the peripheral nerves. A small percentage of these lesions arise from the brachial plexus. The Authors report two cases of schwannoma arising from the brachial plexus. Such lesions, usually asymptomatic, may cause sensitivity alterations or, less frequently, motor deficits in the involved arm. Tumour enucleation, avoiding damage to any of the nervous fascicles, is the treatment of choice.


Subject(s)
Brachial Plexus Neuropathies , Neurilemmoma , Peripheral Nervous System Neoplasms , Brachial Plexus Neuropathies/diagnosis , Brachial Plexus Neuropathies/diagnostic imaging , Brachial Plexus Neuropathies/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neurilemmoma/diagnosis , Neurilemmoma/diagnostic imaging , Neurilemmoma/surgery , Peripheral Nervous System Neoplasms/diagnosis , Peripheral Nervous System Neoplasms/diagnostic imaging , Peripheral Nervous System Neoplasms/surgery , Time Factors , Ultrasonography
16.
G Chir ; 23(11-12): 431-3, 2002.
Article in Italian | MEDLINE | ID: mdl-12652919

ABSTRACT

Hyperthyroidism patients can develop atrial fibrillation (AF) with a frequency range between 10 and 25%. The Authors consider 256 hyperthyroid patients operated in their Department, from 1985 to 2001. Before and after surgery, thyroid examination, routine blood tests and common diagnostic evaluations were performed. The follow-up has been 12 months and during this period a L-Thyroxine (50-200 mg/die) therapy has been arranged. Before surgery 59 patients (23%) showed an AF associated with palpitations (76%), asthenia (66%), tremors (54%) and dyspnea (43%). The onset of AF was less than 1 months in 18% of cases, less than 3 months in 30% and chronic in remaining 52%. The 87% of patients was already pharmacologically treated. All the patients were treated with anticoagulants, with a INR value between 2 and 3. After the surgery, 47% of patients presented a restoration of the sinusal rhythm, while the 53% showed a stronger therapeutic responsiveness to specific antiarrhythmic therapy. Treatment of FA hyperthyroid patients with FA tends to normalize the function of the thyroid gland (euthyroidism). In our experience the restoring of sinusal rhythm usually develops in patients with 50 years of age (45 +/- 5 years), while in older patients AF tends to be resistant to treatment.


Subject(s)
Atrial Fibrillation/etiology , Hyperthyroidism/complications , Hyperthyroidism/surgery , Thyroidectomy , Female , Follow-Up Studies , Humans , Male , Middle Aged
17.
J Hypertens ; 19(12): 2171-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11725160

ABSTRACT

OBJECTIVES AND DESIGN: Angiotensinogen (AGT) gene variants influence angiotensinogen plasma levels in children and young adults. The angiotensinogen promoter (-6)A variant facilitates gene transcription in human tissues and it has been associated with high blood pressure in older adults. A young adult population can be used as a model to study genotype/phenotype associations between AGT (-6) variants and cardiovascular variables. METHODS AND RESULTS: Anthropometric measurements, blood pressure and heart rate were taken in 422 white Caucasian students (mean age 23.5 years, SD 2.5 years). Family history for hypertension, physical activity and smoking history were evaluated. Left ventricular variables were measured by echocardiography. Carotid artery wall intimal-media thickness (IMT) was measured by high resolution sonography and digitalized morphometry. The AGT G(-6)A alleles were evaluated by mutagenically separated polymerase chain reaction controlled by direct sequencing. No significant associations were found between angiotensinogen genotype and blood pressure, cardiac variables [except for deceleration time in females which increased with the number of (-6)A alleles] and IMT. Allele frequencies were similar between the first and third tertile of blood pressure and left ventricular mass, and were also similar between negative or positive family history for hypertension (the last group having significantly higher systolic blood pressure in males, P = 0.04 and diastolic blood pressure in females, P < 0.01). Moreover, no relevant interaction on the cardiovascular variables was found between AGT genotype and body mass index. CONCLUSIONS: The angiotensinogen G(-6)A variants do not affect cardiovascular parameters in young adults, but an effect of this polymorphism on cardiovascular phenotype (and hypertension) in older adults cannot be excluded. Additional factors, associated with ageing, should be present to unleash the supposed unfavourable potential of the (-6)A angiotensinogen variant.


Subject(s)
Alleles , Angiotensinogen/genetics , Cardiovascular Physiological Phenomena , Adult , Blood Pressure , Carotid Arteries/diagnostic imaging , Echocardiography , Genetic Variation , Genotype , Humans , Phenotype , Tunica Intima/diagnostic imaging , Tunica Media/ultrastructure
18.
J Hypertens ; 17(9): 1301-5, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10489108

ABSTRACT

OBJECTIVE AND DESIGN: The clearance receptor for natriuretic peptides (NPRC), a candidate gene for essential hypertension, is highly expressed in adipose tissue, where is nutritionally regulated. The objectives of the present study were to sequence the human 5'-flanking regulatory region of NPRC, to identify allelic variants and their frequencies, and to study the genotype/phenotype correlation in hypertensive patients. METHODS AND RESULTS: Using polymerase chain reaction (PCR) and direct automated sequencing, a biallelic (A/C) polymorphism was detected at position -55 in a conserved promoter element named P1. The novel C(-55) variant makes the promoter sequence identical to the mouse gene and introduces a second Hgal site in the amplified DNA, allowing the genotyping of a large number of subjects. In a random sample of 232 white Caucasians the C(-55) allele was more commonly found (81.7% of all alleles) with 155 CC (66.8%), 69 AC (29.7%) and only eight AA (3.5%) genotypes. Atrial natriuretic peptide (ANP) levels were determined in 84 patients with essential hypertension. In the presence of obesity (body mass index (BMI) > or = 30 kg/m2) the homozygous CC hypertensives (n = 21) had significantly lower plasma ANP (33.6 +/- 11.1 pg/ml) compared with the AC patients (n = 11; 46.8 +/- 15.9 pg/ml; P = 0.01), whereas systolic blood pressure (SBP) and mean blood pressure (MBP) had the opposite association (SBP 163.9 +/- 18.7 versus 150.9 +/- 12.9 and MBP 123.3 +/- 12 versus 114.5 +/- 5.9 mmHg; P< 0.05). The difference in ANP levels were also present when overweight patients (BMI > or = 27 kg/m2) were considered. CONCLUSION: A common 'ancestral' C(-55) variant of the NPRC P1 promoter is associated with lower ANP levels and higher SBP and MBP in obese hypertensives. The C(-55) variant, in the presence of increased adiposity, might reduce plasma ANP through increased NPRC-mediated ANP clearance, contributing to higher blood pressure.


Subject(s)
Atrial Natriuretic Factor/blood , Blood Pressure/genetics , Guanylate Cyclase/genetics , Hypertension/genetics , Obesity/genetics , Obesity/physiopathology , Receptors, Atrial Natriuretic Factor/genetics , Adult , Aged , Alleles , Animals , Body Mass Index , Female , Gene Frequency , Genetic Testing , Genotype , Humans , Hypertension/blood , Male , Mice , Middle Aged , Molecular Sequence Data , Polymerase Chain Reaction , Polymorphism, Genetic/genetics , Promoter Regions, Genetic/genetics , Regulatory Sequences, Nucleic Acid/genetics , Sequence Homology, Nucleic Acid
19.
J Clin Invest ; 99(10): 2538-44, 1997 May 15.
Article in English | MEDLINE | ID: mdl-9153298

ABSTRACT

We have investigated the metabolic actions of recombinant human IGF-1 in mice genetically deficient of insulin receptors (IR-/-). After intraperitoneal administration, IGF-1 caused a prompt and sustained decrease of plasma glucose levels in IR-/- mice. Plasma free fatty acid concentrations were unaffected. Interestingly, the effects of IGF-1 were identical in normal mice (IR+/+) and in IR-/- mice. Despite decreased glucose levels, IR-/- mice treated with IGF-1 died within 2-3 d of birth, like sham-treated IR-/- controls. In skeletal muscle, IGF-1 treatment caused phosphorylation of IGF-1 receptors and increased the levels of the phosphatidylinositol-3-kinase p85 subunit detected in antiphosphotyrosine immunoprecipitates, consistent with the possibility that IGF-1 stimulates glucose uptake in a phosphatidylinositol-3-kinase-dependent manner. IGF-1 receptor phosphorylation and coimmunoprecipitation of phosphatidylinositol3-kinase by antiphosphotyrosine antibodies was also observed in liver, and was associated with a decrease in mRNA levels of the key gluconeogenetic enzyme phosphoenolpyruvate carboxykinase. Thus, the effect of IGF-1 on plasma glucose levels may be accounted for by increased peripheral glucose use and by inhibition of hepatic gluconeogenesis. These data indicate that IGF-1 can mimic insulin's effects on glucose metabolism by acting through its own receptor. The failure of IGF-1 to rescue the lethal phenotype due to lack of insulin receptors suggests that IGF-1 receptors cannot effectively mediate all the metabolic actions of insulin receptors.


Subject(s)
Blood Glucose/metabolism , Hypoglycemia/chemically induced , Insulin-Like Growth Factor I/pharmacology , Receptor, IGF Type 1/metabolism , Receptor, Insulin/deficiency , Animals , Animals, Newborn , Blood Glucose/drug effects , Cell Transformation, Viral , Cells, Cultured , Exons , Fatty Acids, Nonesterified/blood , Heterozygote , Humans , Injections, Intraperitoneal , Insulin-Like Growth Factor I/administration & dosage , Liver/metabolism , Mice , Mice, Knockout , Muscle, Skeletal/metabolism , Phosphorylation , Polymerase Chain Reaction , Receptor, IGF Type 1/biosynthesis , Receptor, Insulin/biosynthesis , Receptor, Insulin/genetics , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology , Simian virus 40
20.
J Hypertens ; 15(12 Pt 2): 1695-9, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9488224

ABSTRACT

OBJECTIVE: Human and rat adipose tissue contain very high levels of natriuretic peptides clearance receptor messenger (m)RNA, and fasting inhibits its gene expression in adipose tissue. In this study we evaluated plasma atrial natriuretic peptide (ANP) and gene expression of biologically active type A natriuretic peptide receptor (NPr-A) and clearance natriuretic peptide receptor (NPr-C) in adipose tissue of obese hypertensive and obese normotensive patients. DESIGN AND METHODS: We studied 27 untreated obese hypertensives, 26 obese normotensives (body mass index > or = 30 kg/m2), 24 non-obese essential hypertensives and 23 lean healthy subjects (body mass index < or = 25 kg/m2). Blood samples were withdrawn for ANP, plasma renin activity and aldosterone radioimmunoassays. Subcutaneous peri-umbilical adipose tissue samples were obtained, by needle aspiration, in 13 obese hypertensives and in 12 obese normotensives and used for RNA extraction. Then, complementary synthesis and semiquantitative polymerase chain reaction (PCR) with primers complementary to sequences of different exons of the genes encoding for NPr-A, NPr-C and beta-actin, were performed. 32P-labeled PCR products were separated by electrophoresis, blotted onto nylon membranes, and the exposed autoradiographic films were analysed by densitometry. NPr signals were normalized by the beta-actin expression level. RESULTS: Plasma ANP was lower in obese hypertensives than in obese normotensives (37.5+/-7 versus 43.2+/-6 pg/ml, P< 0.05), but was higher in non-obese hypertensives than in non-obese normotensives. In contrast, plasma renin activity and aldosterone were higher in the obese hypertensives. Although NPr-A and NPr-C expression were not statistically different between the two obese groups, the NPr-A: NPr-C mRNA ratios were significantly lower in obese hypertensives (P < 0.03). CONCLUSIONS: Our data suggest that in obese hypertensives compared to obese normotensives, the lower NPr-A: NPr-C ratio might determine decreased biological activity and/or an increased clearance of natriuretic peptide in adipose tissue, suggesting that the natriuretic peptide and its receptor system may be important in obesity-related hypertension where ANP levels are lower.


Subject(s)
Adipose Tissue/metabolism , Atrial Natriuretic Factor/blood , Guanylate Cyclase/metabolism , Hypertension/metabolism , Obesity/metabolism , Receptors, Atrial Natriuretic Factor/metabolism , Actins/genetics , Aldosterone/blood , Biopsy, Needle , DNA Primers/chemistry , Female , Gene Expression , Guanylate Cyclase/genetics , Humans , Male , Middle Aged , Polymerase Chain Reaction , RNA, Messenger/metabolism , Receptors, Atrial Natriuretic Factor/genetics , Renin/blood
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