Isolation, partial characterisation and immunomodulating activities of polysaccharides from Vernonia kotschyana Sch. Bip. ex Walp

The roots from Vernonia kotschyana Sch. Bip. ex Walp. (Baccharoides adoensis var. kotschyana (Sch. Bip. ex Walp.) M.A. Isawumi, G.El-Ghazaly & B. Nordenstam) (Asteraceae) are used in Malian folk medicine for the treatment of gastritis, gastro duodenal ulcers, as an aid to ameliorate digestion and as a wound healing remedy. Since a common feature among these conditions is related to immune responses, immunomodulating activities of fractions isolated from both the 50 degrees C and the 100 degrees C water extracts from Vernonia kotschyana were investigated in this study. The active principles were identified as acidic polysaccharide fractions, containing pectic arabinogalactan type II structures, which showed both complement fixing ability and T-cell independent induction of B-cell proliferation in vitro. Some activity was also observed on macrophages. The present study may provide additional support for the popular use of this plant to improve intestinal health.     

Antiepileptic drug treatment of children at a referral centre for epilepsy—Does admission make a difference?

PurposeTo study the antiepileptic drug treatment of children at a referral centre for epilepsy, including a follow-up study three months after discharge.Material and methodsThe study includes children admitted to The National Centre for Epilepsy in Norway. Data were collected from the medical records of 261 children, and a questionnaire regarding the pharmacological treatment was sent to their parents three months after discharge.ResultsThe most common reasons for admission to the referral centre were medical and diagnostic evaluation. New antiepileptic drugs were used more frequently than old, in 251 and 158 cases, respectively. 53 and 54% were using polytherapy at admission and discharge, respectively. Levetiracetam, valproate and lamotrigine were the most frequently used antiepileptic drugs before, during, and after the stay at the centre. Levetiracetam was the only drug being more frequently used at discharge/three months after discharge than at admission. Dosage adjustments were made in 83% of the patients following measurement of serum concentrations and clinical evaluation.According to the parents the number of adverse effects had been reduced by 20% three months after discharge. Likewise 40% stated that their children experienced better seizure control, and 47% that their family experienced a better everyday life after the stay.ConclusionClose comprehensive follow-up of children admitted to the referral centre, with main focus on optimalization of the pharmacological treatment, is of importance regarding quality of life aspects both to the children and their families.     

Increase in the Complement Activation Product C4d and the Terminal Complement Complex sC5b-9 Is Associated with Disease Severity and a Fatal Outcome in Necrotizing Soft-Tissue Infection

The hyperinflammatory burden is immense in necrotizing soft-tissue infection (NSTI). The complement system is a key during the innate immune response and may be a promising target to reduce the inflammatory response, potentially improving the clinical outcome. However, complement activation and its association to disease severity and survival remain unknown in NSTI. Therefore, we prospectively enrolled patients with NSTI and sampled blood at admission and once daily for the following 3 days. Plasma C4c, C4d, C3bc, and C3dg and the terminal complement complex (TCC) were evaluated using ELISA techniques. In total, 242 patients were included with a median age of 62 years, with a 60% male predominance. All-cause 30-day mortality was 17% (95% confidence interval [CI] 13–23) with a follow-up of >98%. C4c and C3dg were negatively correlated with Simplified Acute Physiology Score II (Rho −0.22, p < 0.001 and Rho −0.17, p = 0.01). Patients with septic shock (n = 114, 47%) had higher levels of baseline TCC than those in non-shock patients (18 vs. 14, p < 0.001). TCC correlated with the Sequential Organ Failure Assessment (SOFA) score (Rho 0.19, p = 0.004). In multivariate Cox regression analysis (adjusted for age, sex, comorbidity, and SOFA score), high baseline C4d (>20 ng/mL) and the combination of high C4d and TCC (>31 arbitrary units/mL) were associated with increased 30-day mortality (hazard ratio [HR] 3.26, 95% CI 1.56–6.81 and HR 5.12, 95% CI 2.15–12.23, respectively). High levels of both C4d and TCC demonstrated a negative predictive value of 0.87. In conclusion, we found that in patients with NSTI, complement activation correlated with the severity of the disease. High baseline C4d and combination of high C4d and TCC are associated with increased 30-day mortality. Low baseline C4d or TCC indicates a higher probability of survival.     

Language lateralization and cognitive control across the menstrual cycle assessed with a dichotic-listening paradigm

Lateralization has been shown to vary across the menstrual cycle, however, the underlying mechanisms are not fully understood, and results are inconsistent. Additionally, it has been suggested that estradiol enhances cognitive control. By modulating attention in a consonant-vowel dichotic listening test, the current study aims to investigate the effects of cycle-related changes on language lateralization (non-forced condition), as well as the effects of estradiol-modulated cognitive control (forced left condition) on the ear advantage. Fifteen women and fifteen men tested three times on the dichotic listening test, women once in menstrual, follicular, and luteal phase (verified by hormone assays). Whereas the results from the non-forced and forced-right condition remained stable, results from the forced left condition changed across the cycle, where women in the follicular phase compared to both menstrual and luteal phases showed a stronger left ear advantage, i.e. better cognitive control performance. The increase in performance from menstrual to follicular phase correlated negatively with increase in estradiol levels, indicating a shift from a stimulus-driven right ear advantage (indicating a left hemispheric asymmetry for language) when estradiol levels were low toward a cognitively controlled left ear advantage when estradiol levels were high. This finding strongly suggests an active role of estradiol on cognitive control. The study further suggests that the degree of cognitive control demands of a given task is important to consider when investigating lateralization across the menstrual cycle.     

Adherence to a Healthy Nordic Food Index Is Associated with a Lower Risk of Type-2 Diabetes—The Danish Diet,Cancer and Health Cohort Study

Background: Type-2 diabetes (T2D) prevalence is rapidly increasing worldwide. Lifestyle factors, in particular obesity, diet, and physical activity play a significant role in the etiology of the disease. Of dietary patterns, particularly the Mediterranean diet has been studied, and generally a protective association has been identified. However, other regional diets are less explored. Objective: The aim of the present study was to investigate the association between adherence to a healthy Nordic food index and the risk of T2D. The index consists of six food items: fish, cabbage, rye bread, oatmeal, apples and pears, and root vegetables. Methods: Data was obtained from a prospective cohort study of 57,053 Danish men and women aged 50–64 years, at baseline, of whom 7366 developed T2D (median follow-up: 15.3 years). The Cox proportional hazards model was used to assess the association between the healthy Nordic food index and risk of T2D, adjusted for potential confounders. Results: Greater adherence to the healthy Nordic food index was significantly associated with lower risk of T2D after adjusting for potential confounders. An index score of 5−6 points (high adherence) was associated with a statistically significantly 25% lower T2D risk in women (HR: 0.75, 95%CI: 0.61–0.92) and 38% in men (HR: 0.62; 95%CI: 0.53–0.71) compared to those with an index score of 0 points (poor adherence). Conclusion: Adherence to a healthy Nordic food index was found to be inversely associated with risk of T2D, suggesting that regional diets other than the Mediterranean may also be recommended for prevention of T2D.     

Comparison of different commercial methods for HPV detection in follow-up cytology after ASCUS/LSIL, prediction of CIN2-3 in follow up biopsies and spontaneous regression of CIN2-3

Objective

Different Human Papilloma Virus (HPV) tests are currently used. An integrated comparison of the Amplicor, Cobas4800, PreTect HPV-Proofer and APTIMA HPV tests has not been done.

Methods

We compared the high-risk HPV detection power of these HPV tests in 528 consecutive population-based follow-up Liquid-Based Cytology samples (LBC) after ASCUS/LSIL index cytology. Their sensitivity and specificity to detect HPV in LBC, their predictive values of histopathologic CIN2–3 in follow-up punch biopsies and CIN2–3 regression in the subsequent cones was assessed. The HPV subtypes detected by the Linear Array genotyping-test (LA), PreTect HPV-Proofer and Cobas4800 were also compared. The follow-up histopathology was consensus expert-reviewed and Ki67/p16-supported. The predictive values of the HPV results in LBC by the different tests for presence of CIN2–3 in follow-up biopsies, and regression in subsequent cones, was assessed.

Results

Amplicor, Cobas4800 and APTIMA show good agreement for HPV-positivity/negativity. PreTect HPV-Proofer has many discrepancies versus any of the other methods. The sensitivities for Amplicor, Cobas4800 and APTIMA to detect CIN2–3 were very high (96–100%), but rather low for PreTect HPV-Proofer (53%). Specificity in case of CIN1 or less in follow-up biopsies of Amplicor and Cobas4800 is lower than APTIMA and highest for PreTect HPV-Proofer. HPV subtyping by LA agreed in 90% with Cobas4800 but 70% with PreTect HPV-Proofer.

Conclusions

The Amplicor, Cobas4800 and APTIMA give comparable results but PreTect HPV-Proofer differs from the other tests, with low sensitivity but higher specificity. None of the methods predicted regression of CIN2–3.     

Effects of the 5-HT4 receptor agonist RS67333 and paroxetine on hippocampal extracellular 5-HT levels

The 5-HT₄ receptor modulates activity of serotonergic neurons and is a new potential target for antidepressant treatment. This microdialysis study evaluated the effect of the 5-HT₄ receptor agonist, RS67333, on extracellular serotonin (5-hydroxytryptamine, 5-HT) and 5-HIAA levels in rat ventral hippocampus during chloral hydrate anaesthesia, and explored the ability of RS67333 to augment the effect of the selective serotonin reuptake inhibitor paroxetine. The effect of RS67333 was examined after acute and subchronic (3 days) administration. Acute RS67333 (1.5 mg/kg i.v.) had no effect on extracellular 5-HT or 5-HIAA levels, while acute paroxetine (0.5 mg/kg i.v.) increased 5-HT levels by 299 ± 16% and decreased 5-HIAA levels by 25 ± 4%. Administration of RS67333 80 min after paroxetine caused an additional transient increase in 5-HT levels (to 398 ± 52% of baseline). Subchronic RS67333 administration (1.5 mg/kg i.p.) increased basal 5-HT levels by 73 ± 15% and decreased 5-HIAA levels by 27 ± 13%. In conclusion, the 5-HT₄ receptor agonist RS67333 augmented the acute effect of paroxetine on extracellular 5-HT levels in the ventral hippocampus, and after 3 days increased basal hippocampal 5-HT levels.     

Detection of parvovirus B19 NS1-specific antibodies by ELISA and western blotting employing recombinant NS1 protein as antigen

Human parvovirus B19 (B19) encodes a number of nonstructural proteins, including the major protein, NS1, and two structural proteins, VP1 and VP2. The use of denatured NS1 in enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) assay has provided an opportunity to study some of the immunologic properties of NS1, but the results have been equivocal and the diagnostic sensitivity poor, probably because of the absence of conformational epitopes. Various viral isolates and baculovirus vectors were employed to produce recombinant B19 NS1 under nondenaturing conditions for the first time. To assess the antigenicity of purified B19 NS1, the reaction patterns of 252 samples were compared by B19 NS1 and VP2 ELISA. In sera from individuals with past infection (VP2 IgG-positive), the use of this new antigen increased significantly the sensitivity of ELISA compared with WB (78% vs. 33%, P = 0.001), contradicting perpetuated claims that B19 NS1 IgG is detected primarily in patients with arthralgia or chronic infection. Previous reports of the absence of NS1 IgG during the initial phase of infection (< 6 weeks) were proved incorrect by the detection of NS1 IgG in 60% of samples from patients recently infected by B19. Including conformational epitopes in the ELISA increases the diagnostic sensitivity, although immunologically, a temporal (years) attenuation of NS1 antibodies appears to take place. This novel diagnostic tool may be useful as a supplement in case of borderline results by VP2 ELISA and for monitoring the efficacy of future capsid-based B19 vaccines.