Insulin secretion is stimulated by ethanol extract of Anemarrhena asphodeloides in isolated islet of healthy Wistar and diabetic Goto-Kakizaki Rats.

BACKGROUND: The hypoglycemic effect of extract of Anemarrhena asphodeloides has been accounted for by the substance mangiferin which increases insulin sensitivity. The present study aimed to investigate whether an ethanol extract of Anemarrhena asphodeloides would stimulate insulin secretion and if so, further elucidate the mechanism behind this effect. METHODS: Isolated pancreatic islets of normal Wistar rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused to study effect of Anemarrhena asphodeloides extract (TH2) on insulin release. RESULTS: At 3.3 mM glucose, 2, 4, and 8 mg/ml TH2 increased the insulin release of Wistar rat islets 2.5-, 4.1-, and 5.7-fold, respectively (p < 0.05) and of GK rat islets 1.7-, 3.0-, and 6.3-fold, respectively (p < 0.01). Similarly at 16.7 mM glucose, 2, 4 and 8 mg/ml TH2 increased insulin release of Wistar rat islets 1.5-, 2.2-, and 3.8-fold, respectively (p < 0.05) and of GK rat 2.5-, 4.2-, and 11.9-fold, respectively (p < 0.01). In perifusions of islets, TH2 also increased insulin secretion that returned to basal levels when TH2 was omitted from the perifusate. Mangiferin had no effect on insulin secretion of islets. In islets depolarized by 30 mM KCl and B-cell K-ATP channels kept open by 0.25 mM diazoxide, TH2 (8 mg/ml) further enhanced insulin secretion at 3.3 but not at 16.7 mM glucose. Pertussis toxin suppressed the insulin stimulating effect of 2 and 8 mg/ml TH2 by 35 % and 47 % (p < 0.05 and p < 0.001, respectively). CONCLUSIONS: Ethanol extract of the roots of Anemarrhena asphodeloides contains a substance, TH2, that stimulates insulin secretion both at 3.3 and 16.7 mM glucose in islets of normal Wistar and diabetic GK rats. The mechanism behind TH2-stimulated insulin secretion involves an effect on the exocytotic machinery of the B-cell, mediated via pertussis toxin-sensitive Gi- (or Ge-) proteins.     

Recurrence after successful treatment among patients with multidrug-resistant tuberculosis

A retrospective review was conducted of patients with multidrug-resistant tuberculosis (MDR-TB) to elucidate the rate of recurrence after successful treatment. Of 123 MDR-TB patients, 90 were declared as 'cured' or 'treatment completed' after individualised treatment; four (4.4%) experienced recurrence. All patients with recur- rent MDR-TB were documented as 'treatment completed' after treatment. Recurrence of MDR-TB is possible after successful treatment, particularly among those documented as 'treatment completed'.     

Voluntary micturition after intradural nerve anastomosis

ZusammenfassungHintergrund Für den Neurourologen ist eine der größten Herausforderungen die Wiederherstellung der willentlich steuerbaren Miktion bei Patienten mit einer kompletten Querschnittlähmung.Tiermodelle Carlsson u. Sundin publizierten 1968 über die Wiederherstellung der Blasenfunktion durch eine Nervenanastomose oberhalb der spinalen Verletzung . Später wurde im Ratten- und Katzenmodell ein Reflexbogen unterhalb der Querschnittsverletzung durch eine Nervenanastomose erzeugt, wodurch die Blase vermittelt durch einen starken Hautreiz entleert werden kann.Richtungsweisende Forschung In Berichten über Zell- bzw. Gentherapie wurden kleinere Nervendefekte repariert oder Stammzellen i.v. appliziert, um unmittelbar nach der Verletzung die Regeneration positiv zu beeinflussen.Klinische Gegenwart Bereits 1967 wurde über die nervale Rekonstruktion der Harnblase bei Patienten berichtet. In zwei Fällen wurde durch die intradurale Anastomose zwischen Th12 und S2+3 nach 8–12 Monaten die Miktion wieder willkürlich möglich. Durch Modifikation der Op.-Technik wurde neben der sensorischen Reinervation die Wiedererlangung der genitalen Reflexe in 72% der Fälle erreicht. Xiao et al. publizierten bei einem Mindest-Follow-up von 3 Jahren einen 67%igen Miktionserfolg nach einem Jahr mittels eines somatischen Reflexbogens unterhalb der Querschnittsläsion durch Anastomose der Vorderwurzel von L5 auf S2/3 unilateral.Fazit Die Zelltherapie bedarf noch weiterer Fortschritte bis zur Anwendung am Patienten. Schon heute sollte bei ausgewählten Patienten eine Therapie der neurogenen Blase bei Rückenmarkverletzung angeboten werden. Derzeit sollten diese Op.-Techniken, wie am UKT angeboten, nur in Zentren durchgeführt werden, die über entsprechende Erfahrung damit verfügen und ein Follow-up zur Evaluation dieser Techniken gewährleisten können.     

Correlation of antiviral T-cell responses with suppression of viral rebound in chronic hepatitis B carriers: a proof-of-concept study

Despite recent advances in the chemotherapy of chronic hepatitis B (CHB), an effective viral suppression after cessation of therapy has not yet been achieved. To investigate whether hepatitis B virus (HBV)-specific T-cell responses are inducible and can contribute to the viral suppression after cessation of the therapy, we conducted a proof-of-concept study with a DNA vaccine comprising of most HBV genes plus genetically engineered interleukin-12 DNA (IL-12N222L) in 12 CHB carriers being treated with lamivudine (LAM). When the ex vivo and/or cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay was performed, the detectable HBV-specific IFN-gamma secreting T-cell responses were observed at the end of treatment and during a follow-up. These type 1T-cell responses, particularly CD4(+) memory T-cell responses could be maintained for at least 40 weeks after the therapy and correlated with virological responses, but not with alanine aminotransferase elevation. Moreover, DNA vaccination under LAM treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Thus, a combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB.     

Leu7Pro polymorphism in the neuropeptide Y (NPY) gene is associated with impaired glucose tolerance and type 2 diabetes in Swedish men.

The neuropeptide Y (NPY) is a neuropeptide with a role in the regulation of satiety and energy balance of body weight, insulin release, cardiovascular and central endocrine systems. In order to evaluate whether the NPY gene variations contribute to development of type 2 diabetes (T2DM), we have performed a genetic association study for Leu7Pro (T1128 C) polymorphism of the NPY gene in impaired glucose tolerance (IGT) and T2DM. Genotyping experiments for this non-synonymous single nucleotide polymorphism (SNP) in 263 patients with T2DM, 309 subjects with IGT and 469 non-diabetic healthy individuals in Swedish Caucasians were performed by using Dynamic Allele Specific Hybridisation (DASH). We found that the frequencies of the "risk" allele C in the subjects with IGT and the patients with T2DM in Swedish men were 13 % (p = 0.002, OR = 3.70, 1.65 - 8.29 95 % CI) and 10 % (p = 0.007, OR = 4.80, 1.47 - 11.33 95 % CI) respectively, which were significantly higher than the C allele frequency in non-diabetic controls (6 %). Furthermore, we found that the carriers with TC and CC genotypes in the subjects with IGT in Swedish men had significantly higher fasting plasma glucose in comparison with the TT carriers (5.6 +/- 0.7 mmol/l vs. 5.2 +/- 0.7 mmol/l, p = 0.021). The present study thus provides the evidence that Leu7Pro polymorphism in the NPY gene is associated with IGT and T2DM in Swedish men, and indicates that the NPY gene variations contribute to development of T2DM. Questions of gender specificity may be explained by genetic backgrounds, sense of coherence for stress and other factors in environment.     

Lower serum concentration of matrix metalloproteinase-3 in the acute stage of myocardial infarction

OBJECTIVES: The importance of matrix metalloproteinases (MMPs) in the progression and rupture of the atherosclerotic plaque is gaining increasing recognition but the mechanisms are not yet fully understood. The aim of this study was to investigate the significance of MMP-3 in the acute phase of myocardial infarction (MI) and the influence of the -1612 5A/6A MMP-3 gene promoter polymorphism on serum MMP-3 concentration. SUBJECTS: One-hundred and sixty-four patients admitted with ST-elevation MI and receiving thrombolysis treatment were included in this study. Serum MMP-3 was analysed at admission, after 48 h and at 3 months. RESULTS: Serum MMP-3 concentration was significantly increased at 3 months when compared with admission and 48 h (19.5 ng mL(-1) [14.4-24.7] vs. 15.5 ng mL(-1) [10.5-21.8] at admission, P < 0.001; and 14.7 ng mL(-1) [9.9-23.8] at 48 h, P < 0.001). Furthermore, we found the -1612 5A/6A polymorphism to influence the serum concentration of MMP-3 at all time-points: 14.1 ng mL(-1) [10.2-18.8] in 5A/5A; 19.6 ng mL(-1) [15.0-24.4] in 5A/6A; and 24.0 ng mL(-1) [20.1-32.3] in 6A/6A genotype at 3 months (P < 0.001 between all groups). Female patients had lower serum MMP-3 concentration than male patients at all time-points (14.8 ng mL(-1) [9.4-20.8] vs. 19.9 ng mL(-1) [16.0-26.9], P < 0.0001 at 3 months). CONCLUSIONS: Serum concentration of MMP-3 is significantly lower in the acute stage of MI than during recovery and is significantly influenced by -1612 5A/6A genotype and gender. Together with previous findings, these results primarily implicate MMP-3 in atherosclerosis progression rather than in acute MI.     

A new approach for detection of leg movement using segmental electrical impedance changes

The purpose of this paper is to provide a new approach for detection using bio-impedance. This impedance is measured by the four-electrode method. As the impedance changes resulting from ankle, knee, and hip movements depend on electrode placement, we determined the optimal electrode configurations for these movements by searching for high correlation coefficients, large impedance changes, and minimum interference in ten subjects (age: 20?±?4). Our optimal electrode configurations showed very strong relationships between the ankle joint angle and ankle impedance (γ?=???0.913?±?0.03), between the knee joint angle and knee impedance (γ?=?0.944?±?0.02), and between the hip joint angle and hip impedance (γ?=?0.823?±?0.08). This study showed that lower leg movement could be easily measured by the impedance measurement system with two pairs of skin electrodes.     

Accuracy of a first diagnosis of asthma in primary health care

BACKGROUND: In a postal questionnaire study, the prevalence of asthma in southern Sweden has been found to be 5.5%. However, the register prevalence of asthma obtained from the medical records in the same municipality and age groups was found to be only 2.1%. OBJECTIVES: The aims of the study were to investigate whether the low register prevalence of asthma was caused by an underdiagnosis of asthma in primary health care and to validate a first diagnosis of asthma set by GPs in primary health care. METHODS: During a period of 3 months in 1997, all patients seeking care in the primary health care units of the municipality of Lund (population 171 877) with upper or lower airway infections, prolonged cough, allergic rhinitis, fatigue or a first positive diagnosis of asthma were recorded ( n = 3025). RESULTS: In the whole group of 3025 patients, 99 patients were found to have received a diagnosis of asthma for the first time during the study period. The diagnosis was verified in 52 of those 68 patients who attended a follow-up and examination by a respiratory physician. Among the remaining 2926 patients, 221 patients were selected randomly to constitute a control group. In this group, three patients were found to have asthma. Thus, the specificity of an asthma diagnosis set in primary health care was 0.99 [95% confidence interval (CI) 0.99-1.00] and the sensitivity was 0.59 (95% CI 0.31-0.81). CONCLUSIONS: The GPs in this study were good at excluding those who did not have asthma (specificity 99%) but less good in correctly diagnosing those who actually had current asthma (sensitivity 59%), which suggests an underdiagnosis of asthma.