Dietary fibers, prebiotics, and exopolysaccharides produced by lactic acid bacteria: potential health benefits with special regard to cholesterol-lowering effects.

The gastrointestinal (GIT) microbiota, which plays a crucial role in human health, is influenced by a number of factors including diet. Consumption of specific dietary ingredients, such as dietary fibers and prebiotics, is an avenue by which the microbiota can be positively modulated. These substances may also reduce serum cholesterol levels through various mechanisms. Interest has increased in methods of reducing blood cholesterol level, because dyslipidemia is recognized as a contributory risk factor for the development of cardiovascular diseases. Several drugs have been developed for the treatment of hypercholesterolemia; however, undesirable side effects were observed, which have caused concerns about their long-term therapeutic use. Alternatively, many nonpharmacological approaches were tested to reduce elevated serum cholesterol levels. Dietary fibers and prebiotics have particularly beneficial effects on the GIT microbiome, and can also reduce serum cholesterol level through various mechanisms. Lactic acid bacteria (LAB) are potentially capable of synthesizing different polysaccharides, e.g. exopolysaccharides (EPS), which may play a role as prebiotics. LAB-based EPS have the potential to affect the gastrointestinal microbiome and reduce cholesterol. However, as dietary fibers comprise a complex group of substances with remarkably diverse structures, properties, and impacts, EPS also differ greatly and show a multitude of beneficial health effects. This review discusses the current knowledge related to the effects of dietary fibers and prebiotics on the human GIT microbiome, the prebiotic properties of EPS produced by LAB, and the health-promoting benefits of these polymers with special emphasis being given to cholesterol lowering.

Basal insulin peglispro versus insulin glargine in insulin-naïve type 2 diabetes: IMAGINE 2 randomized trial.

AIMS: To compare, in a double-blind, randomized, multi-national study, 52- or 78-week treatment with basal insulin peglispro or insulin glargine, added to pre-study oral antihyperglycaemic medications, in insulin-naïve adults with type 2 diabetes. MATERIAL AND METHODS: The primary outcome was non-inferiority of peglispro to glargine with regard to glycated haemoglobin (HbA1c) reduction (margin = 0.4%). Six gated secondary objectives with statistical multiplicity adjustments focused on other measures of glycaemic control and safety. Liver fat content was measured using MRI, in a subset of patients. RESULTS: Peglispro was non-inferior to glargine in HbA1c reduction [least-squares (LS) mean difference: -0.29%, 95% confidence interval (CI) -0.40, -0.19], and had a lower nocturnal hypoglycaemia rate [relative rate 0.74 (95% CI 0.60, 0.91); p = .005), more patients achieving HbA1c <7.0% without nocturnal hypoglycaemia [odds ratio (OR) 2.15 (95% CI 1.60, 2.89); p < .001], greater HbA1c reduction (p < .001), and more patients achieving HbA1c<7.0% [OR 1.97 (95% CI 1.57, 2.47); p < .001]. Total hypoglycaemia rate and fasting serum glucose did not achieve statistical superiority. At 52 weeks, peglispro-treated patients had higher triglyceride (1.9 vs 1.7 mmol/L). alanine transaminase (34 vs 27 IU/L), and aspartate transaminase levels (27 vs 24 IU/L). LS mean liver fat content was unchanged with peglispro at 52 weeks but decreased 3.1% with glargine [difference: 2.6% (0.9, 4.2); p = .002]. More peglispro-treated patients experienced adverse injection site reactions (3.5% vs 0.6%, p < .001). CONCLUSIONS: Compared with glargine at 52 weeks, peglispro resulted in a statistically superior reduction in HbA1c, more patients achieving HbA1c targets, less nocturnal hypoglycaemia, no improvement in total hypoglycaemia, higher triglyceride levels, higher aminotransferase levels, and more injection site reactions.

The effect of paternal and maternal history of diabetes mellitus on the development of gestational diabetes mellitus.

BACKGROUND: There is an ongoing debate whether maternal diabetes is a more important risk factor for gestational diabetes (GDM) development than paternal diabetes. AIM: To describe the risk of GDM associated with paternal and maternal diabetes, and to further characterise GDM women with maternal diabetes. SUBJECTS AND METHODS: Case-control study within a population-based GDM screening program in an urban area of Hungary in 2002-2003. All GDM women (no.=133) and an age-matched control group (no.=135) with a mean age of 31 years was evaluated. Blood pressure, anthropometric data, and blood glucose values from a 75 g Oral Glucose Tolerance Test (OGTT) were recorded at 24-28 weeks of gestation. Family history data were by self-report. RESULTS: Known paternal diabetes was not related to GDM risk [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.35-2.00]. Known maternal diabetes (OR 2.90, 95% CI 0.99-8.49) and diabetes in the maternal line (OR 2.83, 95% CI 1.16-6.89) were both related to GDM after adjustment for body mass index (BMI). GDM women with known maternal diabetes had a higher BMI, 31.6 [9.1] kg/m2 median [interquartile range], than GDM women with or without diabetes in the maternal line, 26.1 [4.9] and 26.3 [6.1] kg/m2, respectively, while figures for fasting glucose during OGTT were 5.2 [0.7] vs 4.4 [1.1] vs 4.9 [0.8] mmol/l respectively (all p<0.05). CONCLUSIONS: Maternal history of diabetes and history of diabetes in the maternal line seems to be a stronger predictor of GDM than paternal history.

Mating type loci inFusarium: structure and function.

Sex in fungi is regulated by highly dissimilar mating type loci named idiomorphs. The genus Fusarium harbours both sexual as well as esexual species and each appears to contain one or the other idiomorph. The structure of these loci is highly conserved, suggesting a cryptic sexual cycle in these socalled asexual species. Alternatively, idiomorphs could regulate additional hitherto unrecognized biological processes. Such processes could be elucidated by expression profiling using mutants disrupted in their mating type loci.

Gestational diabetes: current aspects on pathogenesis and treatment.

Gestational diabetes (GDM) is a carbohydrate intolerance resulting in hyperglycaemia of variable severity with onset or first recognition during pregnancy. The incidence of GDM is between 0.15-15%, which corresponds to the prevalence of type 2 diabetes and IGT in a given country.--The predominant pathogenic factor in GDM could be the inadequate insulin secretion. If GDM is not properly treated the risk of adverse maternal (preeclampsia) and fetal (large-for-gestational-age infant, macrosomia, birth trauma, cesarean section, still-birth) outcome increases. Hypertension is more prevalent in GDM, and GDM is diagnosed more frequently in women with chronic hypertension.--In order to screen for disturbances of carbohydrate metabolism during pregnancy a simple method suitable for all pregnant women would be desirable, however no such method is available at present. According to the latest WHO recommendation the screening for GDM should be performed universally with the standard 75 g oGTT evaluating only the 2-hour blood glucose values or together with the fasting ones. The latter could provide even an exact diagnosis of the carbohydrate metabolic state.--To manage GDM the first step prompt after diagnosis is to educate adequate dietary needs. If the blood sugar values in spite of an adequate diet exceed the desirable target values, insulin treatment has to be initiated.--GDM is a predictor of diabetes (mainly type 2) later in life. The cumulative incidence of type 2 diabetes is about 50% at 5 years. This review of the current literature including our own experience strongly supposes that prior GDM is also a predictor or even an early manifestation of the metabolic (insulin resistance) syndrome. By all means GDM is a cardiovascular risk factor that could be screened to prevent late complications. The previously presented evidence also strongly suggests that yearly check-ups for women with previous GDM are inevitably important.

Expression of cmg1, an exo-beta-1,3-glucanase gene from Coniothyrium minitans, increases during sclerotial parasitism.

During sclerotial infection of Sclerotinia sclerotiorum the mycoparasite Coniothyrium minitans penetrates through the host cell wall, which contains beta-1,3-glucan as its major component. A PCR-based strategy was used to clone a beta-1,3-glucanase-encoding gene, designated cmg1, from a cDNA library of the fungus. The nucleotide and deduced amino acid sequences of this gene showed high levels of similarity to the sequences of other fungal exo-beta-1,3-glucanase genes. The calculated molecular mass of the deduced protein (without the predicted 24-amino-acid N-terminal secretion signal peptide) was 83,346 Da, and the estimated pI was 4.73. Saccharomyces cerevisiae INVSc1 expressing the cmg1 gene secreted a approximately 100-kDa beta-1,3-glucanase enzyme (as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) into the culture medium. N-terminal sequence analysis of the purified recombinant enzyme revealed that the secreted enzyme starts at Ala-32, seven amino acids downstream from the predicted signal peptidase cleavage site. The purified recombinant glucanase inhibited in vitro mycelial growth of S. sclerotiorum by 35 and 85% at concentrations of 300 and 600 microg x ml(-1), respectively. A single copy of the cmg1 gene is present in the genome of C. minitans. Northern analyses indicated increases in the transcript levels of cmg1 due to both carbon starvation and the presence of ground sclerotia of S. sclerotiorum; only slight repression was observed in the presence of 2% glucose. Expression of cmg1 increased during parasitic interaction with S. sclerotiorum.

Blood pressure response to standing in the diagnosis of autonomic neuropathy: the EURODIAB IDDM Complications Study.

Autonomic neuropathy is associated with poor prognosis. Cardiovascular reflexes are essential for the diagnosis of autonomic nerve dysfunction. Blood pressure response to standing is the most simple test for the evaluation of sympathetic integrity, however it is still discussed which diagnostic criteria of abnormal response should be considered as optimal. The EURODIAB IDDM Complications Study involved the examination of randomly selected Type 1 diabetic patients from 31 centres in 16 European counties. Data from 3007 patients were available for the present evaluation. Two tests of autonomic function (response of heart rate /R-R ratio/ and blood pressure from lying to standing) just as the frequency of feeling faint on standing up were assessed. R-R ratio was abnormal in 24% of patients. According to different diagnostic criteria of abnormal BP response to standing (>30 mmHg, >20 mmHg, and >10 mmHg fall in systolic BP), the frequency of abnormal results was 5.9%, 18% and 32%, respectively (p < 0.001). The frequency of feeling faint on standing was 18%, thus, it was identical with the prevalence of abnormal blood pressure response to standing when >20 mmHg fall in systolic blood pressure was considered as abnormal. Feeling faint on standing correlated significantly with both autonomic test results (p < 0.001). A fall >20 mmHg in systolic blood pressure after standing up seems to be the most reliable criterion for the assessment of orthostatic hypotension in the diagnosis of autonomic neuropathy in patients with Type 1 diabetes mellitus.

Targets and reality: a comparison of health care indicators in the U.S. (Pittsburgh Epidemiology of Diabetes Complications Study) and Hungary (DiabCare Hungary).

OBJECTIVE: In the U.S., both primary care and specialist physicians share in the care of type 1 diabetic patients, often in an informal collaboration. In Hungary, however, type 1 diabetic patients are generally managed in special centralized diabetes units. These different treatment settings may lead to different health care practices and outcomes. To determine if this is true, diabetes care indicators and complications were compared across representative study populations from the 2 countries. RESEARCH DESIGN AND METHODS: The Pittsburgh Epidemiology of Diabetes Complications Study (EDC) is a prospective cohort of childhood-onset type 1 diabetic patients. DiabCare Hungary, a multicenter cross-sectional study, was developed for quality control purposes and provides a nationwide data set of diabetic patients. We identified 2 comparable populations (EDC, n = 416; DiabCare, n = 405) in terms of age (> or =14 years) and age at onset (<17 years). RESULTS: EDC patients were less likely to receive diabetes education (P<0.0001), see an ophthalmologist (P<0.0001), be treated by diabetologists (P<0.0001), or perform self-monitoring of blood glucose (P<0.0001). They were more likely to use conservative insulin regimens (i.e., 1-2 injections/day, P<0.0001) and have a higher glycated hemoglobin (P< 0.0001). DiabCare patients more often experienced severe hypoglycemia (P<0.01) and had a lower prevalence of proliferative retinopathy (P<0.0001), legal blindness (P<0.05), and albuminuria (> or =30 mg/day P<0.01). No significant differences in macrovascular complications were seen, although rates were generally low CONCLUSIONS: These data suggest that the 2 populations differ by their diabetes care practices, degree of glycemic control, and microvascular complication status.

Different risk factors of microangiopathy in patients with type I diabetes mellitus of short versus long duration. The EURODIAB IDDM Complications Study.

AIMS/HYPOTHESIS: To identify factors associated with early development of and late protection from microvascular complications in subjects with Type I (insulin-dependent) diabetes mellitus. METHODS: The frequency of microvascular complications and their relation to risk factors were studied in 300 Type I diabetic subjects with short duration of disease (< or = 5 years) compared with 1062 subjects with long duration (> or = 14 years). Microvascular disease was defined as the presence of either retinopathy (assessed from centrally-graded retinal photographs) or urinary albumin excretion rate of more than 20 micrograms/min. RESULTS: The prevalence of microvascular disease was 25% in the short duration group. In the long duration group 18% had no evidence of microvascular complications. In the short duration group factors associated with early development of complications were cigarette smoking and a family history of hypertension. Subjects free of microvascular complications in spite of long duration of diabetes had better glycaemic control, lower blood pressure, better lipid profile and lower von Willebrand factor levels. CONCLUSION/INTERPRETATION: At the early stages of Type I diabetes, cigarette smoking and genetic susceptibility to hypertension are important risk factors for microvascular complications. At a later stage, additional risk factors are poorer glycaemic control, higher blood pressure, and an unfavourable lipid profile possibly associated with endothelial dysfunction. Many of these factors are amenable to long-term intervention which should be started as soon as possible in the course of the disease.

Molecular standardization of mating type terminology in the Gibberella fujikuroi species complex.

Mating type in the Gibberella fujikuroi species complex is controlled by a single locus with two alleles and is usually identified following sexual crosses with standard, female-fertile tester isolates. The mating type alleles have been arbitrarily designated "+" and "-" within each biological species, and the nomenclature is tied to the standard tester strains. We developed a pair of PCR primers that can be used to amplify a unique fragment of one of the mating type alleles (MAT-2) from at least seven of the biological species in this species complex. Based on the amplification pattern, we propose a replacement for the existing, arbitrary +/- terminology that is presently in use. The new terminology is based on DNA sequence similarities between the mating type allele fragments from the biological species of the G. fujikuroi species complex and the corresponding fragments from other filamentous ascomycetes.

[Detection of antibodies against pancreatic islet cells in clinical practice]. / Hasnyálmirigy-szigetsejt elleni antitestek vizsgálata a klinikai gyakorlatban.

Development of diabetes mellitus caused by pancreatic beta-cell destruction of autoimmune origin is the result of a long lasting process. The most easily examinable feature of this stage is the occurrence of the islet cell antibodies. The sera which are positive for islet cell cytoplasmic antibodies (ICA), examined by indirect immunofluorescence, contain a mixture of antibodies. The glutamic acid decarbocylase (GAD), the tyrosin phosphatase (IA2), the insulin, and the GM2-1 glycolipid can be the targets of these antibodies. One can routinely examine the ICA, the GADA, the IA2 antibodies. The detection of antibodies against insulin (IAA) and GM-2-1 glycolipid is not invented in the routine laboratory work. The aim of the authors was the evaluation of clinical significance of occurrence of islet cell antibodies: one hundred and eighteen nondiabetic children an adult human being without known diabetic first degree relatives and 366 type 1 diabetic children and adult patients served as controls. The authors evaluated the predictive value of the different islet cell antibodies to the development of type 1 diabetes mellitus in 596 nondiabetic children with type 1 diabetic first degree relatives. The authors looked for markers of beta-cell destruction among sera of 320 diabetics manifested after 30 years of age with at least half a year of non-insulin-dependency and in the sera of 68 females suffered from gestational diabetes after 0-14 years of the index pregnancy. Finally the authors report 7 cases in which the examination of islet cell antibodies helped the diagnosis and classification of diabetes mellitus. Indirect immunofluorescence method was used for the detection of ICA, radioimmunoassay for that of GADA and IA2 antibodies. There was no positive reaction for ICA and GADA in the nondiabetic population without diabetic first degree relatives. Among the freshly diagnosed type 1 diabetic children 39% were positive for only ICA, 44% for only GADA and 80% for any antibodies. Among the freshly manifested type 1 diabetic adults ICA positivity only was observed in 21%, GADA positivity only in 7.1% and 93% for any antibodies. From the 595 nondiabetic children with type 1 diabetic first degree relatives 23 were positive for ICA, from whom 5 became diabetic during a two years observation period. These diabetic children had multiplex autoantibodies besides ICA. One child from this group, who was negative for ICA became diabetic, too. Among type 2 diabetic patients 13% were positive for ICA alone, 17% were positive for GADA alone and 27% were positive for any antibodies. The insulin dependency manifested in a short time was associated with antibody positivity. Among the gestational diabetics 10 were found positive for ICA. From them, 7 were type 1 diabetics, and 3 were type 2 diabetics at the time of the detection of antibodies. The authors suggest the need of determination of islet cell antibodies in the group of nondiabetic first degree relatives of type 1 diabetic patients (ICA, GADA, IA2 and IAA), in the group of non-insulin-dependent diabetics (ICA and GADA) as a screening for later insulin dependency, and in gestational diabetes after delivery (ICA) as screening for type 1 diabetes mellitus.

Homologous transformation of Trichoderma hamatum with an endochitinase encoding gene, resulting in increased levels of chitinase activity.

A 42-kDa endochitinase encoding gene, Tham-ch, was cloned by screening the genomic library of Trichoderma hamatum strain Tam-61 with a PCR-amplified chitinase sequence from the same fungus. Tham-ch with its own regulatory sequences was reintroduced into the host strain. The integration of the transforming construct was stable only in one copy. Homologous integration occurred in nine transformants, while non-homologous integration was detected in one transformant. All but one transformant expressed higher levels of chitinase activity in comparison to the wild-type recipient strain; the maximum level of increase was 5-fold. Duplicating the copy number of the highly conserved approximately 42-kDa endochitinase encoding gene appears to be one potential means by which the biocontrol capability of the Trichoderma species might be improved.

DNA amplification polymorphisms of Mucor piriformis.

Mucor piriformis can cause postharvest decay in various fruits and vegetables stored at low temperatures. Thirty isolates of this fungus, collected from infected fruit, were subjected to random amplified polymorphic DNA (RAPD) analysis. Seven different 10-bp primers were used to determine the type and extent of intraspecific genetic polymorphisms. Nineteen composite amplification types were identified, indicating a higher degree of variability than found in previous isoenzyme studies. Numerical analysis with the UPGMA technique revealed three clusters, which correlated with the mating competency of the isolates or their place of origin. These results demonstrate that RAPD analysis can identify isolates and subspecific populations of M. piriformis.

Biological and molecular characterisation of potential biocontrol strains of Trichoderma.

Thirty-four strains of seven species of Trichoderma isolated from various fungal sources were compared for direct mycoparasitic activity (MPA), chitinase production and antibiotic activity (ANA) in order to choose the most appropriate partners for a strain-breeding programme. Within species genetic differences were also assesses in T. hamatum, T. harzianum and T. viride by means of random amplification of polymorphic DNA (RAPD). Endochitinase activities of the Trichoderma strains ranged between 20.4 and 1264.5 units/g dry weight of mycelium. The correlation between MPA and chitinase activity was not unambiguous and no correlation existed between MPA and ANA. The RAPD patterns of T. viride strains were highly variable, while isolates of T. harzianum proved to be more uniform; T. hamatum revealed remarkable intraspecific divergence. All these three comprised certain pairs of strains that are promising participants of a strain-improving programme, since their strong genetic affinities offer good changes for combining their contrasted biocontrol traits.