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Biomedical subjects

Leonardo A Sechi

Publications and source records attributed to Leonardo A Sechi.

At least 37 records · Page 2Linked to original sources
PubMed2005

The renin-angiotensin-aldosterone system, glucose metabolism and diabetes.

In diabetes mellitus (DM), the circulating renin-angiotensin system (RAS) is suppressed, but the renal tissue RAS is activated. Hyperglycemia increases tissue angiotensin II (Ang II), which induces oxidative stress, endothelial damage and disease pathology including vasoconstriction, thrombosis, inflammation and vascular remodeling. In early DM, the type 1 Ang II (AT(1)) receptor is upregulated but the type 2 Ang II (AT(2)) receptor is downregulated. This imbalance can predispose the individual to tissue damage. Hyperglycemia also increases the production of aldosterone, which has an unknown contribution to tissue damage. The insulin resistance state is associated with upregulation of the AT(1) receptor and an increase in oxygen free radicals in endothelial tissue caused by activation of NAD(P)H oxidase. Treatment with an AT(1) receptor blocker normalizes oxidase activity and improves endothelial function. An understanding of the tissue renin-angiotensin-aldosterone system, which is a crucial factor in the progression of tissue damage in DM, is imperative for protection against tissue damage in this chronic disease.

Aldosterone↗
PubMed2005

Alcohol-induced endothelial changes are associated with oxidative stress and are rapidly reversed after withdrawal.

BACKGROUND: Although heavy alcohol drinkers are at an increased risk of developing cardiovascular events, moderate alcohol intake is associated with reduced incidence of cardiovascular death. This paradox might reflect a dose-related effect of different alcohol intakes on endothelial function and this, in turn, might depend on changes in oxidative stress. METHODS: We tested the effects of alcohol withdrawal in heavy alcohol consumers and compared the plasma levels of endothelin-1, nitric oxide, plasminogen activator inhibitor-1, von Willebrand factor, malondialdehyde, and intracellular glutathione with those of alcoholics that did not modify their alcohol intake and teetotalers. In human endothelial cells that had been cultured for 2 weeks in the presence of different concentrations of ethanol, we assessed the same parameters after withdrawal of ethanol exposure. RESULTS: Alcohol increased the levels of endothelin-1, nitric oxide, and plasminogen activator inhibitor-1 and decreased the levels of von Willebrand factor both in vivo and in vitro. These changes were dose dependent, rapidly reversed after withdrawal of exposure, and associated with the presence of increased oxidative stress as indicated by increased levels of both malondialdehyde and intracellular glutathione. Blockade of oxidative stress by incubation of endothelial cells in the presence of oxidants' scavengers prevented the alcohol-induced functional modifications of the endothelium. CONCLUSIONS: Alcohol affects endothelial function with an effect that is mediated by an activated oxidative stress and is rapidly reversed after withdrawal. Dose-related endothelial responses to different alcohol intakes might translate in either vascular protection or vascular damage.

Adult↗
PubMed2005

New risk factors for atherosclerosis in hypertension: focus on the prothrombotic state and lipoprotein(a).

Although adequate control of blood pressure is of basic importance in cardiovascular prevention in hypertensive patients, correction of additional risk factors is an integral part of their management. In addition to classical risk factors, epidemiological research has identified a number of other conditions that might significantly contribute to cardiovascular risk in the general population and might achieve specific relevance in patients with high blood pressure. In fact, more than 20% of patients with premature cardiovascular events do not have any of the traditional risk factors and, although effective intervention on blood pressure and additional risk factors has significantly reduced cardiovascular morbidity and mortality, the contribution to stroke, coronary artery disease and renal failure is still unacceptably high. Evaluation of new risk factors may further expand our capacity to predict atherothrombotic events when these factors are included along with the traditional ones in the assessment of global cardiovascular risk in hypertensive patients. Because it could be anticipated that the role of these novel factors will become increasingly evident in the future, researchers with an interest in hypertension and physicians dealing with problems related to cardiovascular prevention should give them appropriate consideration. This review summarizes the basic biology and clinical evidence of two emerging risk factors that are reciprocally related and contribute to the development and progression of organ damage in hypertension: the prothrombotic state and lipoprotein(a).

Animals↗
PubMed2005

PCR-based detection of the Mycobacterium tuberculosis complex in urine of HIV-infected and uninfected pulmonary and extrapulmonary tuberculosis patients in Burkina Faso.

To evaluate a one-tube nested PCR-based analysis of urine for diagnosing pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in Bobo-Dioulasso, Burkina Faso, a prospective analysis of urine samples from HIV- and non-HIV-infected adults with PTB and EPTB (case patients) and with pathology other than tuberculosis (TB) (control patients) was performed. Three groups of patients were classified as microbiological-positive and -negative PTB and EPTB on the basis of clinical signs and microbiological results. Urine from patients was analysed using the DNA extraction and Sechi's methods, both modified, for the detection of Mycobacterium tuberculosis. The sensitivity, specificity, positive predictive value and negative predictive value were calculated. The sensitivity of the test for the microbiological-positive PTB, microbiological-negative PTB and EPTB was 40.5 % (88/217), 66.7 % (20/30) and 57.1 % (48/84), respectively. The specificity was 98.2 %. Differences were observed in the two populations infected and not infected by HIV. This method is not appropriate for detection of new TB cases in the routine laboratory, but it can be useful for cases where the clinical and bacteriological diagnosis of TB is not conclusive.

Adolescent↗
PubMed2005

Detection and Isolation of Mycobacterium avium subspecies paratuberculosis from intestinal mucosal biopsies of patients with and without Crohn's disease in Sardinia.

OBJECTIVES: Sardinia is an island community of 1.6 million people. There are also about 3.5 million sheep and one hundred thousand cattle in which Johne's disease and Mycobacterium avium subspecies paratuberculosis infection are endemic. The present study was designed to determine what proportion of people in Sardinia attending for ileocolonoscopy with or without Crohn's disease were infected with this pathogen. METHODS: Mycobacterium avium subspecies paratuberculosis was detected by IS900 PCR on DNA extracts of fresh intestinal mucosal biopsies as well as by isolation in culture using supplemented MGIT media followed by PCR with amplicon sequencing. RESULTS: Twenty five patients (83.3%) with Crohn's disease and 3 control patients (10.3%) were IS900 PCR positive (p = 0.000001; Odds ratio 43.3). Mycobacterium avium subspecies paratuberculosis grew in cultures from 19 Crohn's patients (63.3%) and from 3 control patients (10.3%) (p = 0.00001; Odds ratio 14.9). All patients positive by culture had previously been positive by PCR. Mycobacterium avium subspecies paratuberculosis first appeared in the liquid cultures in a Ziehl Neelsen (ZN) staining negative form and partially reverted through a rhodamine-auramine positive staining form to the classical ZN positive form. This resulted in a stable mixed culture of all 3 forms illustrating the phenotypic versatility of these complex chronic enteric pathogens. CONCLUSIONS: Mycobacterium avium subspecies paratuberculosis was detected in the majority of Sardinian Crohn's disease patients. The finding of the organism colonizing a proportion of people without Crohn's disease is consistent with what occurs in other conditions caused by a primary bacterial pathogen in susceptible hosts.

Adolescent↗
PubMed2005

Patients with pulmonary tuberculosis develop a strong humoral response against methylated heparin-binding hemagglutinin.

Reactivities of human sera against selected recombinant Mycobacterium tuberculosis antigens were assessed by enzyme-linked immunosorbent assay. The results obtained indicate that patients with tuberculosis (TB) do not develop a strong humoral response against PE_PGRS and PPE proteins or against the Ag85B and heparin-binding hemagglutinin (HBHA) recombinant antigens. Conversely, purified methylated HBHA was strongly recognized by sera obtained from TB patients compared to controls.

Antibodies, Bacterial↗
PubMed2005

Mycobacterium avium subsp. paratuberculosis, genetic susceptibility to Crohn's disease, and Sardinians: the way ahead.

The present study was performed to determine what proportion of people in Sardinia with or without Crohn's disease were infected with Mycobacterium avium subspecies paratuberculosis and had a preponderance of allelic variants of Nod 2, an intracellular protein involved in Crohn's disease susceptibility. Genetic analysis of the alleles of the NOD 2/CARD 15 gene (ins C 3020, G 908 R, and R 702 W alleles), linked to susceptibility or genetic predisposition to Crohn's disease in humans, was carried out on specimens from 37 Crohn's disease patients and 34 patients without Crohn's disease. Our results show that more than 70 percent of people in Sardinia with Crohn's disease carry at least one of the susceptibility-associated NOD 2/CARD 15 alleles and were infected with Mycobacterium avium subspecies paratuberculosis.

Crohn Disease↗
PubMed2005

Analysis of genomic downsizing on the basis of region-of-difference polymorphism profiling of Mycobacterium tuberculosis patient isolates reveals geographic partitioning.

Mycobacterium tuberculosis, the etiological agent of tuberculosis, has lost many coding and noncoding regions in its genome during the course of evolution. We performed region-of-difference (RD) analysis using PCR-based genotyping of 131 M. tuberculosis clinical isolates obtained from four different countries, namely, India, Peru, Libya, and Angola. Our studies revealed that RD patterns are often distinct for strains circulating in specific geographical regions and can be used to trace the descent and spread of an isolate from its original reservoir. We describe our findings, which show that no single isolate from the four countries (n = 131) had all the 15 RDs either deleted or retained. Tuberculosis-specific deletion 1 (TbD1) was found to be conserved in 23% of the Indian isolates, indicating their possible ancient origin. RD9 was the most conserved region, RD11 was predominantly deleted, and RD6 was the most variable among the isolates in our collection irrespective of their geographic region. In contrast to earlier reports, our results demonstrate that the deletion of RD1 does not correlate with a decrease in the virulence potential of M. tuberculosis, as Indian isolates (n = 30) examined by us were from diseased individuals and yet had lost the RD1 region. Our results further illustrated that the intactness of the RD5 region may be associated with increased virulence of the organism. This study highlights that the RDs in M. tuberculosis genomes are geographically distributed and specific and may possibly be associated with virulence spectrum.

Angola↗
PubMed2005

Plasma adiponectin is decreased in nonalcoholic fatty liver disease.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with obesity and metabolic syndrome. The recently discovered hormone adiponectin is produced by adipose tissue, and low plasma adiponectin is considered a key factor in the development of the insulin resistance underlying metabolic syndrome. Animal studies suggest that adiponectin may protect against non-alcoholic steatohepatitis, but direct evidence in humans is lacking. We therefore conducted this study to assess the relationship between plasma adiponectin and nonalcoholic fatty liver disease to explore its role in the pathogenesis of this disease. DESIGN AND METHODS: We measured plasma adiponectin and anthropometric, biochemical, hormonal and metabolic correlates in a group of 17 NAFLD patients with diagnosis confirmed by biopsy, and 20 controls with comparable age, body-mass index and sex. Furthermore we compared plasma adiponectin in patients with simple steatosis and steatohepatitis. RESULTS: Plasma adiponectin was significantly lower in NAFLD patients than controls (5.93+/-0.45 vs 15.67+/-1.60ng/ml). Moreover, NAFLD patients were significantly more insulin resistant while having similar serum leptin. Adiponectin was similar in simple steatosis and in steatohepatitis (6.16+/-0.78 vs 5.69+/-0.49ng/ml). An inverse correlation was observed between adiponectin and homeostatic model assessment (HOMA) of insulin resistance (P = 0.008), while adiponectin did not correlate with serum transaminases and lipid values. CONCLUSIONS: These data support a role for low circulating adiponectin in the pathogenesis of NAFLD and confirm the strict association between reduced adiponectin production by adipose tissue, NAFLD and insulin resistance.

Adiponectin↗
PubMed2004

PER-1 type beta-lactamase production in Acinetobacter baumannii is related to cell adhesion.

BACKGROUND: Recently, the dissemination of ESBL (PER-1) among Acinetobacter isolates was reported in Turkish hospitals. We investigated the presence and the association of various virulence determinants in 20 Acinetobacter baumannii isolates, of which 13 were blaPER-1 positive. MATERIAL/METHODS: Virulence tests were slime and hemolysin production, gelatinase and protease activity, biofilm formation, and Caco2 cell adhesion. RAPD analysis was also performed with ERIC primers. RESULTS: None of the strains was positive for slime or hemolysin production and gelatinase or protease activity. A total of 16 strains, five of which were PER-1 gene negative, formed a biofilm on polymer surfaces. There was no relation between the presence of the PER gene and biofilm formation. On the other hand, nine strains (all PER-1 gene positive) were positive in adhesion experiments to Caco2 cell lines. All PER-negative strains were negative for cell adhesion. CONCLUSIONS: This study indicates the existence of a relation between PER-1 gene and cell adhesion in Acinetobacter strains.

Acinetobacter baumannii↗
PubMed2004

AmpliBASE MT: a Mycobacterium tuberculosis diversity knowledgebase.

AmpliBASE MT is an online databank of high-resolution DNA fingerprints representing fluorescent amplified fragment length polymorphism (FAFLP) profiles or amplitypes developed for the Mycobacterium tuberculosis complex strains from 48 different countries. AmpliBASE MT is based on a relational database management system that is hyperlinked to visualize genotyping results in the form of DNA fingerprint images for individual strains. A flexible search system based on systematic comparisons of fragment sizes in base pairs allows inter-laboratory comparison of FAFLP profiles. Besides this, the database also displays previously published data on IS6110 profiles, spoligotypes, MIRU-VNTRs and large sequence polymorphisms along with the FAFLP records that will give the overall comparisons. Being the first of its kind, AmpliBASE MT is expected to be a very helpful tool in strengthening the concept of 'geographic genomics' and will be very helpful to molecular epidemiologists and those interested in diagnostic development for tuberculosis.

DNA Fingerprinting↗
PubMed2004

Aeromonas caviae keratitis associated with contact lens wear.

OBJECTIVE: We report the first case of bilateral contact lens-related Aeromonas caviae keratitis associated with A. caviae contamination of the contact lens case. The presence of virulence factors produced by Aeromonas species was also investigated. DESIGN: Case report. INTERVENTION AND TESTING: Conjunctival swabs and corneal scrapings from both eyes were inoculated for culture. The contact lens case was also cultured. The isolate was analyzed for the presence of virulence properties, such as gelatinase and protease production. The presence of virulence genes, such as the cytolytic enterotoxin (AHCYTOEN) and type IV Aeromonas pilus (tap) genes, was investigated using polymerase chain reaction. The susceptibility of A. caviae to 6 commercial contact lens disinfecting solutions was tested. MAIN OUTCOME MEASURES: Culture results, protease activity, and gelatinase production were analyzed. Polymerase chain reaction amplification products were visualized in ethidium bromide-stained agarose gel. Bacterial growth after exposure to contact lens disinfecting solutions was assessed. RESULTS: Aeromonas caviae was grown bilaterally from the conjunctiva, cornea, and contact lens case. The organism showed protease and gelatinase production. Polymerase chain reaction amplification revealed that the A. caviae strain contained the AHCYTOEN and tap virulence genes. Incubation for the minimum recommended time with all tested disinfecting solutions was effective in killing A. caviae. CONCLUSIONS: Aeromonas caviae should be considered a possible etiologic agent of contact lens-associated keratitis. The presence of virulence factors may be important in determining corneal infection. Commercial contact lens disinfecting solutions, along with proper lens case hygiene, may be effective in preventing A. caviae keratitis in soft contact lens wearers.

Adult↗
PubMed2004

The cag pathogenicity island of Helicobacter pylori is disrupted in the majority of patient isolates from different human populations.

The cag pathogenicity island (cag-PAI) is one of the major virulence determinants of Helicobacter pylori. The chromosomal integrity of this island or the lack thereof is speculated to play an important role in the progress of the gastroduodenal pathology caused by H. pylori. We determined the integrity of the cag-PAI by using specific flanking and internally anchored PCR primers to know the biogeographical distribution of strains carrying fully integral cag-PAI with proinflammatory behavior in vivo. Genotypes based on eight selected loci were studied in 335 isolates obtained from eight different geographic regions. The cag-PAI appeared to be disrupted in the majority of patient isolates throughout the world. Conservation of cag-PAI was highest in Japanese isolates (57.1%). However, only 18.6% of the Peruvian and 12% of the Indian isolates carried an intact cag-PAI. The integrity of cag-PAI in European and African strains was minimal. All 10 strains from Costa Rica had rearrangements. Overall, a majority of the strains of East Asian ancestry were found to have intact cag-PAI compared to strains of other descent. We also found that the cagE and cagT genes were less often rearranged (18%) than the cagA gene (27%). We attempted to relate cag-PAI rearrangement patterns to disease outcome. Deletion frequencies of cagA, cagE, and cagT genes were higher in benign cases than in isolates from severe ulcers and gastric cancer. Conversely, the cagA promoter and the left end of the cag-PAI were frequently rearranged or deleted in isolates linked to severe pathology. Analysis of the cag-PAI genotypes with a different biogeoclimatic history will contribute to our understanding of the pathogen-host interaction in health and disease.

Antigens, Bacterial↗
PubMed2004

Molecular genotyping of a large, multicentric collection of tubercle bacilli indicates geographical partitioning of strain variation and has implications for global epidemiology of Mycobacterium tuberculosis.

Tuberculosis continues to be a major killer disease, despite an all-out effort launched against it in the postgenomic era. We describe here the population structure of Mycobacterium tuberculosis strains, as revealed by a chromosome-wide scan of fluorescent amplified fragment length polymorphisms (FAFLPs), for more than 1,100 independent isolates from 11 different countries. The bacterial strains were genotyped based on a total of 136 +/- 1 different FAFLP markers at the genome sequence interface, with details on IS6110 profiles, drug resistance status, clinicopathological observations, and host status integrated into the analysis process. The strains were found to cluster with possible geographic affinities, including the parameters of host species type, IS6110 profile, and drug susceptibility status. Of the five most commonly amplified fragment sets (or amplitypes), type A predominated in strains of mixed origin, deposited in The Netherlands; type B was exclusively observed for Indian isolates; type C was found mainly in strains from Peru and Australia; and types D and E predominated in European strains from France and Italy. The amplitypes were independent of certain large sequence polymorphisms representing two important deletions, TbD1 and Rd9. It appears that M. tuberculosis has a high genomic diversity with a possible geographic evolution. This may have occurred due to specific genomic deletions and synonymous substitutions selected rigorously against host defenses and environmental stresses on an evolutionary timescale. The genotypic data reported here are additionally significant for genotype-phenotype correlations and for determining whether pathogen diversity is a reflection f the host population diversity.

DNA Transposable Elements↗
PubMed2003

Quinoxalin-2-ones. Part 5. Synthesis and antimicrobial evaluation of 3-alkyl-, 3-halomethyl- and 3-carboxyethylquinoxaline-2-ones variously substituted on the benzo-moiety.

A new series of 3-alkyl-, 3-trifluoromethyl-, 3-carboxyethyl- and 3-bromomethylquinoxaline-2-ones and 2,3-bis(bromomethyl)quinoxalines bearing Cl, CF3, morpholine on the benzo-moiety, were synthesised and submitted to a preliminary in vitro evaluation for antibacterial and anticandida activities. Results of the screening showed that compounds 9b, 14b and 19b (MIC=62.5 microg/ml) and 10b (MIC=15.6 microg/ml) were the most active against Vibrio alginolyticus.

Anti-Bacterial Agents↗