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Biomedical subjects

M Colombo

Publications and source records attributed to M Colombo.

At least 19 recordsLinked to original sources
PubMed2006

Modeling cross correlations within a many-assets market.

A simple model for simulating cross correlations of a many-assets market is discussed. Correlations between assets are initially considered within the context of the well-known one-factor model, in which a driving term common to all stocks is present. The results are compared to those of real market data corresponding to a set of 445 stocks taken from the Standard and Poors 500 index. The model is further extended by introducing a stochastic volatility within each time series using an autoregressive scheme. This artificial market reproduces the empirically observed fat tails in the distribution function of logarithmic price variations and, more important, leads to additional cross correlations between the time series, in better agreement with the real market behavior.

Journal Article↗
PubMed2005

Validity and reliability of the Italian version of the Chronic Liver Disease Questionnaire (CLDQ-I) for the assessment of health-related quality of life.

BACKGROUND: The Chronic Liver Disease Questionnaire is a specific health-related quality of life assessment designed for patients with liver diseases. AIM: The aim of this paper is to report on the validity, reliability and sensitivity to change of the Italian version (Chronic Liver Disease Questionnaire-I) in subjects with HCV infection. SUBJECTS: The Chronic Liver Disease Questionnaire-I was administered to 350 subjects with HCV infection together with the World Health Organization Quality of Life Assessment, abbreviated version, a generic quality of life assessment. METHODS: The instrument was translated from English, backtranslated and reviewed in focus groups in the framework of a large multicentre study. Exploratory factor analysis identified five factors accounting for 65% of the variance of Chronic Liver Disease Questionnaire-I items and only partially overlapping with those found in the original version. RESULTS: The Chronic Liver Disease Questionnaire-I proved to discriminate between subjects with and without comorbid diseases at baseline (t-test = 3.59, p < 0.001). Test-retest reliability was moderate (ICC = 0.60). The Chronic Liver Disease Questionnaire-I was sensitive to change in patients who deteriorated after one month of treatment. Change in the overall Chronic Liver Disease Questionnaire-I score in deteriorated patients was correlated with changes in World Health Organization Quality of Life Assessment, abbreviated version scores in the physical, psychological and environment, but not in the social area. CONCLUSIONS: The Italian version of Chronic Liver Disease Questionnaire is a valid and reliable instrument to be used in cross-sectional and longitudinal studies.

Chronic Disease↗
PubMed2005

Protein and m-RNA expression of farnesyl-transferases, RhoA and RhoB in rat liver hepatocytes: action of perillyl alcohol and vitamin A in vivo.

We analysed the action, in rats in vivo, of the protein isoprenylation inhibitor perillyl alcohol (POH) and that of vitamin A, alone or in association, on m-RNA and protein expression of farnesyltransferases (FTases alpha and beta subunits) and their protein substrates RhoA and RhoB, in isolated hepatocytes. Combined administration of POH and vitamin A induced a sharp decrease in FTase alpha protein after 96 h, suggesting an involvement not only of farnesyltransferases but also of geranylgeranyltransferases, which share the FTase alpha protein. FTase beta protein did not decrease. POH plus vitamin A, in contrast with POH or vitamin A alone, induced a decrease in RhoB protein, probably because of different cleavages. No modification was observed in RhoA protein. Vitamin A alone increased RhoB m-RNA and protein expression. As one of the functions of RhoB is cell polarisation, these data support our previous hypothesis of a polarised transport of vitamin A from hepatocytes to hepatic stellate cells. As the behaviours of m-RNAs and proteins in this study were often different, cytoplasmic metabolic pathways must be considered for the parameters studied. The behaviour of Rho B, which is thought to have an antioncogene function, is discussed in view of its isoprenylated forms in the membranes. These preliminary findings stress the need, when studying the association of two isoprenoids in cancer therapy, to consider normal as well as tumour-bearing animals.

Alkyl and Aryl Transferases↗
PubMed2005

Interferon-alpha suppresses liver cell proliferation in patients with chronic hepatitis C virus infection.

SUMMARY: Interferon (IFN) therapy has been shown to reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C, including virological nonresponders (NR). Whether IFN suppresses liver cell proliferation, i.e. the relevant risk factor for HCC, is unknown. The aim of the study was to evaluate the effect of IFN therapy on liver cell proliferation in chronic hepatitis C. The proliferating cell nuclear antigen-labelling index (PCNA-LI) was assessed prior to and at the end of therapy in the liver of 29 patients with chronic hepatitis C who received 3 MU IFN-alpha2b thrice weekly for 24-48 weeks. Overall, the median value of PCNA-LI was significantly reduced from 2.6% to 1.1% at the end of therapy (P < 0.0001). At baseline, PCNA-LI median values were similar in the 15 virological responders compared with the 14 NRs (2.3%vs 3.4%, P = 0.121) and at the end of therapy, median changes of PCNA-LI (-1.4%vs-1.1%, P = 0.089) were also similar although there was a higher decline of the proliferation index in responders with respect to NRs at the end of therapy (0.7%vs 1.6%, P = 0.004). In the two groups, the rate of fibrosis score reduction was also similar (7%vs 20%, P = 0.326). In contrast, the histological activity index was more often reduced in responders than in NRs both at the >or=2 and >or=4 points reduction level (80%vs 36%, P = 0.02 and 53%vs 14%, P = 0.03, respectively). The study showed a significant suppression of liver cell proliferation in IFN-treated patients with chronic hepatitis C. Although the strongest IFN effect was observed in virological responders, a reduction of proliferative activity was also seen in virological NRs.

Adult↗
PubMed2005

Hepatitis C reactivation in patients with chronic infection with genotypes 1b and 2c: a retrospective cohort study of 206 untreated patients.

BACKGROUND: We previously described hepatitis reactivation in two carriers of the hepatitis C virus (HCV) genotype 2c. AIM: To assess the relationship between HCV genotypes and risk of hepatitis reactivation, we studied the course of aminotransferases in patients infected with the two relevant genotypes in Italy. PATIENTS: A cohort of 100 patients with genotype 2c chronic hepatitis and 106 with genotype 1b were subjected to surveillance. METHODS: Hepatitis reactivation was defined as an alanine aminotransferase (ALT) value > or =400 IU/l or a maximum/minimum ALT ratio value of > or =8. RESULTS: Over a period of 71 (24-144) months, one or more flares of ALT (201-2200 IU/l, 6-90 months' duration) occurred in 31 patients with genotype 2c and in eight patients with genotype 1b (rates of flares: 55.6 per 1000 person years for genotype 2c v 15.0 for genotype 1b; p=0.001). On repeat biopsy, hepatic fibrosis increased by more than 2 points in 10/16 patients examined either during or after an ALT flare compared with 7/36 flare free patients (63% v 19%; p=0.003). Hepatitis flares were significantly associated with genotype 2c (odds ratio 6.48 (95% confidence interval 2.57-16.35)) but not with sex, age, modality or duration of infection, baseline ALT values or histological severity of hepatitis, hepatitis other than HCV, or reinfection. CONCLUSIONS: Genotype 2c carriers are at high risk of hepatitis reactivation, suggesting that virus genetic heterogeneity is important in the natural history of HCV, questioning the linearity of hepatic fibrosis progression during hepatitis C.

Adult↗
PubMed2004

Polymorphisms of the interleukin-1beta gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro.

OBJECTIVE: To investigate the role of interleukin-1beta (IL-1beta) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age. METHODS AND RESULTS: A total of 406 patients with myocardial infarction (MI) at young age, frequency-matched for age, sex, and recruitment center, with 419 healthy population-based controls and 134 patients with ischemic stroke at young age, matched by age and sex, with 134 healthy population-based controls, were studied. Subjects carrying the TT genotype of the -511C/T IL-1beta polymorphism showed a decreased risk of MI (odds ratio [OR], 0.36; 95% CI, 0.20 to 0.64) and stroke (OR, 0.32; 95% CI, 0.13 to 0.81) after adjustment for conventional risk factors. In both studies, the T allele showed a codominant effect (P=0.0020 in MI; P=0.021 in stroke). Mononuclear cells from volunteers carrying the T allele showed a decreased release of IL-1beta and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1beta during cell stimulation resulted in a marked reduction of tissue factor activity expression. CONCLUSIONS: -511C/T IL-1beta gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.

Adolescent↗
PubMed2004

The impact of cognitive impairment on the rehabilitation process in geriatrics.

A study has been carried out in our geriatric rehabilitation wards, to know better the role of cognitive dysfunction in treatment outcome and processing, mainly functional recovery and comorbidity. We analyzed 478 frail inpatients, 2/3 of them were females, aged 78.7 + 9.2 years, consecutively admitted to the unit. Assessment of cognitive function was performed by the mini mental state examination (MMSE), of functional status by Barthel index (BI), of co-morbidity by cumulative illness rating scale (CIRS) both at the admission and discharge for each patient, together with the usual clinical parameters and social outcome. More than one people in three lived alone and showed some communication problems; one in seven needed modifications in food preparation or nutritional system;more than one in five had pressure sore >/= 2 (EPUAP = European Pressure Ulcers Advisory Panel classification). The mean (+/- SD) levels of the admitted were: MMSE = 20 +/- 7.2; BI total score = 45.5 +/- 28.9; CIRS class = 4 +/- 2, CIRS severity score = 1.9 +/- 0.4. Of the patients, 74.5% were discharged to home. Mean functional gain was 20 points at BI: 65.6 +/-30.7; MMSE improved to 21.6 +/- 7.1 (p = 0.00005 for both comparisons, by Wilcoxon test).MMSE was positively correlated to BI (r = 0.6, p = 0.0005) and negatively correlated (p =0.0005) to CIRS comorbidity (r = -0.33) and severity (r = -0.26), and to age (r = -0.38, p =0.0005) both at admission and at discharge. MMSE at admission was correlated neither to functional gain, nor to improvement of clinical indicators, nor to measures of functional and clinical efficiency. MMSE at discharge showed similar results. In a stepwise multiple correlation analysis, taking the gain in BI as the dependent variable, while BI, serum albumin level, MMSE, CIRS severity and comorbidity indexes at admission as independent variables, MMSE together with BI admission total score and CIRS severity index retained a strong association with functional gain, whilst admission serum albumin levels and CIRSindex lost it. Consistently with some literary data, we showed the actual possibility of functional and clinical gains for people cared in a geriatric rehabilitation ward, all through a wide range of MMSE score, including subnormal scores. Poor cognitive status bears heavily on frailty, but does not hamper the outcomes of genuine rehabilitative efforts in geriatrics.

Aged↗
PubMed2004

Bacterial communities and enzyme activities of PAHs polluted soils.

Three soils (i.e. a Belgian soil, B-BT, a German soil, G, and an Italian agricultural soil, I-BT) with different properties and hydrocarbon-pollution history with regard to their potential to degrade phenanthrene were investigated. A chemical and microbiological evaluation of soils was done using measurements of routine chemical properties, bacterial counts and several enzyme activities. The three soils showed different levels of polycyclic aromatic hydrocarbons (PAHs), being their contamination strictly associated to their pollution history. High values of enzyme activities and culturable heterotrophic bacteria were detected in the soil with no or negligible presence of organic pollutants. Genetic diversity of soil samples and enrichment cultures was measured as bands on denaturing gradient gel electrophoresis (DGGE) of amplified 16S rDNA sequences from the soil and enrichment community DNAs. When analysed by Shannon index (H'), the highest genetic biodiversity (H'=2.87) was found in the Belgian soil B-BT with a medium-term exposition to PAHs and the poorest biodiversity (H'=0.85) in the German soil with a long-term exposition to alkanes and PAHs and where absence, or lower levels of enzyme activities were measured. For the Italian agricultural soil I-BT, containing negligible amounts of organic pollutants but the highest Cu content, a Shannon index=2.13 was found. The enrichment of four mixed cultures capable of degrading solid phenanthrene in batch liquid systems was also studied. Phenanthrene degradation rates in batch systems were culture-dependent, and simple (one-slope) and complex (two-slope) kinetic behaviours were observed. The presence of common bands of microbial species in the cultures and in the native soil DNA indicated that those strains could be potential in situ phenanthrene degraders. Consistent with this assumption are the decrease of PAH and phenanthrene contents of Belgian soil B-BT and the isolation of phenanthrene-degrading bacteria. From the fastest phenanthrene-degrading culture C(B-BT), representative strains were identified as Achromobacter xylosoxidans (100%), Methylobacterium sp. (99%), Rhizobium galegae (99%), Rhodococcus aetherovorans (100%), Stenotrophomonas acidaminiphila (100%), Alcaligenes sp. (99%) and Aquamicrobium defluvium (100%). DGGE-profiles of culture C(B-BT) showed bands attributable to Rhodococcus, Achromobacter, Methylobacterium rhizobium, Alcaligenes and Aquamicrobium. The isolation of Rhodococcus aetherovorans and Methylobacterium sp. can be consistent with the hypothesis that different phenanthrene-degrading strategies, cell surface properties, or the presence of xenobiotic-specific membrane carriers could play a role in the uptake/degradation of solid phenanthrene.

Bacteria↗
PubMed2004

GnRH antagonists and mild ovarian stimulation for intrauterine insemination: a randomized study comparing different gonadotrophin dosages.

BACKGROUND: The precise role of GnRH antagonists in the armamentarium of drugs for stimulation of ovulation associated with intrauterine insemination remains to be clarified. In this study, we have compared two different protocols employing GnRH antagonists in order to determine the lower effective dose of gonadotrophins to use. METHODS: Sixty-six couples with unexplained infertility or moderate male subfertility were recruited. Starting on day 3 of the cycle, 32 patients were randomized to receive 50 IU of recombinant FSH per day, whereas 34 were treated with 50 IU of recombinant FSH on alternate days. Women received the GnRH antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a leading follicle > or =14 mm in mean diameter was visualized, until HCG administration. Insemination was performed 34 h after HCG injection. RESULTS: The regimen with daily recombinant FSH was associated with a lower rate of mono-ovulation (53.3% versus 78.8%, P=0.06) but also with a higher clinical pregnancy rate per initiated cycle (34.4% versus 5.9%, P=0.005). CONCLUSIONS: A protocol of recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and safe regimen for ovulation induction associated with intrauterine insemination.

Adult↗
PubMed2004

Hepatitis C in haemophilia: lights and shadows.

Hepatitis C is a major cause of morbidity and mortality in haemophiliacs who received clotting factor concentrates before the availability of virus-inactivated factors in the mid-1980s. Early studies gave conflicting indications as to the severity of hepatitis C (originally termed non-A non-B hepatitis), as mild, slowly progressive hepatitis was documented in several infants and young adults with haemophilia who were examined with repeat liver biopsies, whereas more progressive hepatitis and cirrhosis was documented in others. One major point of dispute was whether these discrepancies could in part be accounted for by epidemiological differences among studies, as hepatitis C acquired early in life may initially run a benign course and later worsen owing to spontaneous recrudescence of hepatitis or interference with such comorbidity factors as alcohol abuse or infection with the human immunodeficiency virus (HIV). In the mid 1990s, the latter infection overshadowed hepatitis C as a cause of death in this patient population. Because hepatocellular carcinoma is emerging as an important complication in haemophiliacs with long-standing hepatitis C virus (HCV) infection who survived HIV infection, and because of recent advances in treating HIV, morbidity and mortality associated with chronic hepatitis C have regained emphasis amongst haemophiliacs. The development of newer interferon-based therapies provides an opportunity for modifying the natural history of HCV infection in a substantial number of haemophilic patients.

Adult↗
PubMed2004

Sustained suppression of hepatitis C virus by high doses of interferon and ribavirin in adult hemophilic patients.

BACKGROUND: In a recent randomized controlled study, only a minority (15%) of adult hemophiliacs with chronic HCV achieved a sustained virologic response to treatment with interferon (IFN) and ribavirin given at standard doses. STUDY DESIGN AND METHODS: Whether the therapeutic response might be improved in these patients by increasing the doses of IFN was evaluated. Thirty-four previously untreated, adult hemophiliacs with chronic HCV but negative for HIV were investigated. There were 33 men and 1 woman, aged 21 to 60 years (mean, 36). Twenty-three patients (68%) had genotype 1, and median serum HCV-RNA was 473 x 10(3) IU per L (range, 3.6-2145). Patients were treated with IFN at 5 million units (MU) thrice weekly for 6 months, followed by 3 mol/L for 6 additional months in combination with daily oral doses of 1 or 1.2 g of ribavirin. RESULTS: A total of 33 patients (97%) completed the study; one patient withdrew because of treatment-related symptoms. Treatment dosage had to be reduced in 20 patients (59%). By intention-to-treat analysis, 14 patients (41%) had a sustained virologic response, particularly those infected by HCV genotype 2 or 3 (70% vs. 29% with genotype 1 or 4, p < 0.05). Sustained response rates were similar in the 13 compliant patients and the 20 patients who had to reduce IFN and/or ribavirin doses (54% vs. 35%). CONCLUSIONS: High-dose IFN therapy plus ribavirin provided high rates of sustained virologic responses in adult hemophiliacs with chronic HCV, even if side-effects led to dose reduction in half of these patients.

Adult↗
PubMed2004

A 24-month survey on root canal treatment performed by NiTi engine driven files and warm gutta-percha filling associated system.

AIM: Techniques based on NiTi engine driven files for shaping and warm gutta percha for obturing the root canal space are becoming more and more popular. Aim of this paper is to evaluate, by a clinical longitudinal study, the type of sealing and the outcome of endodontic treatment, performed by new Profile and Thermafil technique, in teeth with or without periapical lesions. METHODS: A total of 122 teeth in 64 patients were consecutively enrolled in the study; 63 teeth had normal periapical status (Group A) and 59 teeth had periapical lesion (Group B). Endodontic therapy was carried out by Profile .04 and Profile .06 NiTi engine driven files and the obturation was made by Thermafil, a filling technique based on heated gutta-percha surrounding a plastic carrier. The type of sealing was evaluated by a score (A best - D worst) and the type of healing was classified as complete, incomplete and failure according to previous published data. The radiographical outcome of the teeth was evaluated by independent observers after 24 months. Data were analysed by non parametric statistics. RESULTS: At the end of the study, 115 teeth (59 group A and 56 group B) were examined. The quality of sealing was evaluated and some differences were reported comparing different types of teeth. The radiographic outcome was evaluated and 94.9% showed to be completely healed in group A and 48.2% in group B (p=0.0001). CONCLUSION: The technique based on NiTi engine driven files and Thermafil heated gutta-percha has shown, after 24 months, results which were comparable to other root canal shaping and filling methods.

Adult↗
PubMed2003

Treatment of primary sclerosing cholangitis with low-dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey.

BACKGROUND: Data concerning the usefulness and type of drugs employed to treat patients with primary sclerosing cholangitis are controversial. Ursodeoxycholic acid has been shown to be a useful agent, however the drug dosage and its effect on the clinical course are still under debate. AIM: To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis. METHODS: We retrospectively analysed data from 86 patients with primary sclerosing cholangitis from eight centres in Italy between 1987 and 1997: 69 were treated with ursodeoxycholic acid (8-13 mg/kg/day), while 17 received symptomatic treatment and served as controls. The effect of therapy was evaluated by standard liver function tests and symptom analysis. RESULTS: Ursodeoxycholic acid treatment was associated with significant improvement in serum alkaline phosphatase (735+/-833 vs. 519+/-448 U/l, p<0.001), gamma-glutamyl transpeptidase (401+/-352 vs. 234+/-235 U/l, p<0.001), aspartate aminotransferase (87+/-70 vs. 56+/-42 U/l, p=0.001), alanine aminotransferase (146+/-139 vs. 76+/-73 U/l, p<0.001), and total bilirubin (1.88+/-2.44 vs. 1.76+/-4.12 U/l, p=0.01); there was also amelioration of fatigue (p=0.007), jaundice (p=0.002), and body weight loss (p=0.002). CONCLUSIONS: Ursodeoxycholic acid, at a dose of 8-13 mg/kg/day was beneficial for the general condition and liver biochemistry of patients with primary sclerosing cholangitis; high-dose ursodeoxycholic acid treatment requires further evaluation.

Adult↗
PubMed2003

Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population.

AIMS: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries.

Adult↗
PubMed2003

A prospective study of blood alpha-fetoprotein messenger RNA as a predictor of hepatocellular carcinoma in patients with cirrhosis.

Blood alpha-fetoprotein messenger RNA (AFP mRNA) is thought to be a marker of hepatocellular carcinoma (HCC). Its value as a predictor of HCC in patients at risk is not known. A series of 201 patients with compensated cirrhosis (114 men, mean age 58 years) underwent surveillance with semi-annual ultrasound and serum alpha-fetoprotein measurements. Total RNA was extracted from peripheral blood mononuclear cells collected at different intervals and AFP mRNA was retrotranscribed and amplified by nested polymerase chain reaction. Ten patients with HCC and 30 blood donors were used as controls. Three patients with HCC, 39 with cirrhosis under surveillance and four blood donors circulated AFP mRNA (30, 20 and 13%, NS). During 50 months of surveillance, 27 patients with cirrhosis developed HCC: the tumour was detected more often in patients with higher than normal baseline serum AFP (> or =7 IU/L) than in those with normal AFP levels (21%vs 9%, P = 0.02). The incidence of HCC was the same in patients with and without AFP mRNA at baseline (15%vs 14%). In 53 patients, AFP mRNA was re-tested after 6-25 months of surveillance. HCC developed in two of 11 (18%) who were initially AFP mRNA positive and later became negative, in none of those who were initially negative and later became positive and in two of 39 (5%) who remained persistently negative. In conclusion, blood AFP mRNA is not a sensitive predictor of HCC in patients with compensated cirrhosis.

Aged↗
PubMed2003

Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat.

Stevioside, a glycoside present in the leaves of the plant, Stevia rebaudiana Bertoni (SrB), has acute insulinotropic effects in vitro. Its potential antihyperglycemic and blood pressure-lowering effects were examined in a long-term study in the type 2 diabetic Goto-Kakizaki (GK) rat. Rats were fed 0.025 g x kg(-1) x d(-1) of stevioside (purity > 99.6%) for 6 weeks. An intra-arterial catheter was inserted into the rats after 5 weeks, and conscious rats were subjected to arterial glucose tolerance test (2.0 g x kg(-1)) during week 6. Stevioside had an antihyperglycemic effect (incremental area under the glucose response curve [IAUC]): 985 +/- 20 (stevioside) versus 1,575 +/- 21 (control) mmol/L x 180 minutes, (P <.05), it enhanced the first-phase insulin response (IAUC: 343 +/- 33 [stevioside] v 136 +/- 24 [control] microU/mL insulin x 30 minutes, P <.05) and concomitantly suppressed the glucagon levels (total AUC: 2,026 +/- 234 [stevioside] v 3,535 +/- 282 [control] pg/mL x 180 minutes, P <.05). In addition, stevioside caused a pronounced suppression of both the systolic (135 +/- 2 v 153 +/- 5 mm Hg; P <.001) and the diastolic blood pressure (74 +/- 1 v 83 +/- 1 mm Hg; P <.001). Bolus injections of stevioside (0.025 g x kg(-1)) did not induce hypoglycemia. Stevioside augmented the insulin content in the beta-cell line, INS-1. Stevioside may increase the insulin secretion, in part, by induction of genes involved in glycolysis. It may also improve the nutrient-sensing mechanisms, increase cytosolic long-chain fatty acyl-coenzyme A (CoA), and downregulate phosphodiesterase 1 (PDE1) estimated by the microarray gene chip technology. In conclusion, stevioside enjoys a dual positive effect by acting as an antihyperglycemic and a blood pressure-lowering substance; effects that may have therapeutic potential in the treatment of type 2 diabetes and the metabolic syndrome.

Animals↗