Receptor-mediated exopolysaccharide perception controls bacterial infection.

Surface polysaccharides are important for bacterial interactions with multicellular organisms, and some are virulence factors in pathogens. In the legume-rhizobium symbiosis, bacterial exopolysaccharides (EPS) are essential for the development of infected root nodules. We have identified a gene in Lotus japonicus, Epr3, encoding a receptor-like kinase that controls this infection. We show that epr3 mutants are defective in perception of purified EPS, and that EPR3 binds EPS directly and distinguishes compatible and incompatible EPS in bacterial competition studies. Expression of Epr3 in epidermal cells within the susceptible root zone shows that the protein is involved in bacterial entry, while rhizobial and plant mutant studies suggest that Epr3 regulates bacterial passage through the plant's epidermal cell layer. Finally, we show that Epr3 expression is inducible and dependent on host perception of bacterial nodulation (Nod) factors. Plant-bacterial compatibility and bacterial access to legume roots is thus regulated by a two-stage mechanism involving sequential receptor-mediated recognition of Nod factor and EPS signals.

Separate norovirus outbreaks linked to one source of imported frozen raspberries by molecular analysis, Denmark, 2010-2011.

Norovirus outbreaks occur frequently in Denmark and it can be difficult to establish whether apparently independent outbreaks have the same origin. Here we report on six outbreaks linked to frozen raspberries, investigated separately over a period of 3 months. Norovirus from stools were sequence-typed; including extended sequencing of 1138 bp encompassing the hypervariable P2 region of the capsid gene. Norovirus was detected in 27 stool samples. Genotyping showed genotype GI.Pb_GI.6 (polymerase/capsid) with 100% identical sequences. Samples from five outbreaks were furthermore identical over the variable capsid P2 region. In one outbreak at a hospital canteen, frozen raspberries was associated with illness by cohort investigation (relative risk 6·1, 95% confidence interval 3·2-11). Bags of raspberries suspected to be the source were positive for genogroup I and II noroviruses, one typable virus was genotype GI.6 (capsid). These molecular investigations showed that the apparently independent outbreaks were the result of one contamination event of frozen raspberries. The contaminated raspberries originated from a single producer in Serbia and were originally not considered to belong to the same batch. The outbreaks led to consultations and mutual visits between producers, investigators and authorities. Further, Danish legislation was changed to make heat-treatment of frozen raspberries compulsory in professional catering establishments.

Repetitive natriuresis and blood pressure. Long-term calcium entry blockade with isradipine.

The long-term effects (3.5 months) of a new calcium entry blocker of the 1-4-dihydropyridine class, isradipine (PN 200-110), on renal hemodynamics and excretional parameters were investigated in 10 essential hypertensive subjects (World Health Organization Classes I and II). Blood pressure and renal vascular resistance fell significantly (p less than 0.001), and a slight increase in glomerular filtration rate and renal plasma flow was seen (p less than 0.05). Output of fluid from the proximal tubules, measured as clearance of lithium and uric acid, increased significantly (p less than 0.01 and p less than 0.05, respectively), and a compensatory increase in absolute reabsorption of sodium beyond the proximal tubular level accompanied by an increase in clearance of potassium was noted. A 40% increase in the resultant clearance of sodium (p less than 0.01) and an increase in diuresis (p less than 0.05) followed the morning dose of isradipine after 3.5 months of treatment. Changes in blood pressure were significantly correlated with changes in absolute proximal reabsorption of sodium (r = 0.81), excretion of sodium (r = -0.64), and diuresis (r = -0.80). Thus, the natriuretic properties of calcium entry blockers may be more important for the long-term antihypertensive effect than the vasodilator effect per se. A model for renal sodium handling following treatment with calcium entry blockers was proposed. Although a causal relationship is not implied, isradipine induced a sustained, repetitive postdose effect on proximal fluid output, net natriuresis, and diuresis, that was intimately related to the long-term blood pressure-regulating response.

DNA binding sites recognised in vitro by a knotted class 1 homeodomain protein encoded by the hooded gene, k, in barley (Hordeum vulgare).

The homeodomain of the knotted classes of transcription factors from plants differs from the well characterized Antp/En type homeodomains from Drosophila at key amino acid residues contributing to the DNA binding. A cDNA, Hvh21, derived from the hooded gene and encoding a full length homolog of knotted1 from maize was isolated from barley seedlings and expressed as a maltose binding protein fusion in E. coli. The purified HvH21-fusion protein selected DNA fragments with 1-3 copies of the sequence TGAC. Gel shift experiments showed that the TGAC element was required for binding and the results further indicate that the HvH21-fusion protein binds DNA as a monomer.

Differential effects of isradipine and atenolol on peripheral hemodynamics and arterial compliance.

In a double-blind parallel-group randomized study, 28 patients with essential hypertension (World Health Organization class I/II) were allocated in equal numbers to one of two groups for treatment with either isradipine 5 to 20 mg twice daily or atenolol 50 to 100 mg once daily. At the end of the study, 12 patients were evaluable in the isradipine group and nine in the atenolol group. Assessments at baseline and after 20 weeks of treatment included arterial and venous compliance, mean peripheral perfusion pressure, heart rate, and digital vascular resistance using photoplethysmography. Isradipine had a direct relaxing effect on the arterioles, revealed by a significant increase in arterial compliance and a concomitant normalization of the digital vascular resistance. Atenolol had no significant effect on these parameters but, as expected, it lowered the heart rate, which was not affected by isradipine in the long term. The venous compliance remained low in both groups and, since isradipine--unlike atenolol--is known to have venodilating properties in vitro, its lack of effect in vivo is most likely due to reflex activation of sympathetically mediated venous tone. Because of the preference of isradipine for the arterial side of the peripheral vascular tree, the mean peripheral perfusion pressure remained higher in this group than in the atenolol group, although central systemic blood pressure was lowered equally and satisfactorily in both groups.

Long-term effects of isradipine on blood pressure and renal function.

The hemodynamic and renal effects of isradipine were investigated in 10 hypertensive patients treated for 3.5 months and in a further nine patients treated for two years. Both groups achieved significant and sustained reductions in systolic blood pressure/diastolic blood pressure (-15 percent/-12 percent and -15 percent/-20 percent, respectively; p less than 0.001). Renal parameters were investigated two to three hours after the morning dose of isradipine, using a water-loading procedure. After 3.5 months of treatment, the glomerular filtration rate and renal plasma flow showed small increases (+6 percent and +9 percent, respectively, p less than 0.05), whereas, after two years, these changes were no longer present (+4 percent and 0 percent). Clearance of sodium and uric acid was increased by 40 percent (p less than 0.01) and 21 percent (p less than 0.01), respectively, after 3.5 months, and by 45 percent (p less than 0.05) and 23 percent (p less than 0.01), respectively, after two years. Lithium clearance studies revealed the natriuretic effect to be located in the proximal tubule. After 3.5 months, a significant relationship was found between the blood pressure response and the change in sodium excretion, but this relationship also was no longer present after two years. In conclusion, because of a maintained blood pressure-lowering effect while preserving renal function, and sustained natriuretic and uricosuric actions, isradipine can be considered a promising agent in the long-term treatment of arterial hypertension.

Multicenter, double-blind comparison of doxazosin and atenolol in patients with mild to moderate hypertension.

In a double-blind multicenter study, the new alpha 1-adrenoceptor inhibitor doxazosin was compared with atenolol for efficacy, safety and effect on serum lipids. One hundred and twenty-six patients with mild to moderate hypertension were randomly assigned to receive either doxazosin (n = 63) or atenolol (n = 63). The mean final dosages, administered once daily, to obtain 24-hour blood pressure (BP) control were doxazosin 12 mg (range 1 to 16) and atenolol 91.8 mg (range 50 to 100). Of 12 doxazosin and 7 atenolol patient withdrawals from the study, 7 doxazosin and 4 atenolol patients withdrew for treatment-related reasons. No statistically significant differences between treatment groups were found after 20 weeks in changes from baseline in standing and sitting BPs measured 24 hours after administration. Sitting BP (systolic/diastolic) was reduced by 10.5/9.8 mm Hg after doxazosin treatment and by 10.9/10.7 mm Hg after atenolol therapy. Standing BP was reduced by 8.8/7.7 mm Hg after doxazosin administration and 9.7/9.3 mm Hg after treatment with atenolol. Supine BP was measured in a small cohort of the study population, and doxazosin had a smaller effect than atenolol. After 20 weeks of treatment, both drugs reduced heart rate with atenolol producing a statistically significantly greater decrease than doxazosin (standing, doxazosin 5 beats/min, atenolol 16.2 beats/min, p less than 0.001; sitting, doxazosin 5 beats/min, atenolol 13.1 beats/min, p less than 0.001). Side effects were reported by 37 patients receiving doxazosin therapy and 34 patients receiving atenolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Normal serum levels of calcitonin gene-related peptide (CGRP) in mild to moderate essential hypertension.

Calcitonin gene-related peptide (CGRP), a highly potent vasodilator, is expressed from the calcitonin-gene and has been localized to nerve fibers of the cardiovascular system, suggesting involvement in the physiologic regulation of vascular tone. In this investigation serum concentrations of CGRP were measured in patients with untreated mild to moderate essential hypertension (WHO I-II) and compared with concentrations in sex- and age-matched normal controls to assess a possible relationship between changes in concentrations of CGRP and this condition. The study showed no significant difference in concentrations of CGRP between patients and the normotensive controls. However, a weak but significant positive correlation was found between systolic (SBP), diastolic (DBP), mean blood pressures (MBP), and circulating concentrations of CGRP when calculated for all individuals included in the study. No correlation was found between heart rates (HR) and concentrations of CGRP. In the normotensive control group, but not in patients with hypertension, a significant positive correlation was present between body weights and concentrations of CGRP. These findings do not support the hypothesis that low expression of CGRP plays a causal role in essential hypertension, but the results do not exclude a potential receptor defect for CGRP to be involved in the disease.

Anticoagulant therapy in deep venous thrombosis. A randomized controlled study.

Ninety patients with venographically proven deep venous thrombosis(DVT) but without clinical signs of pulmonary embolism(PE) were randomized into two different treatment regimens to compare the safety and efficacy of continuous intravenous heparin and oral anticoagulant(AC) treatment versus non-AC treatment. All patients in the two treatment groups were actively mobilized from the day of admission and wore graduated compressing stockings. In the non-AC-group the patients were treated with phenylbutazone for ten days. Treatment with heparin was maintained for 6 days and oral AC treatment was given from the third day and continued for 3 months. Venography was repeated after 30 days. A perfusion-ventilation lung scan was performed on day 1-2, 10 and 60. In fifty-nine patients a revenography was performed, twenty nine in the AC-group and thirty in the non-AC group. For distal veins regression was found in nine and eight respectively (4.4% in favour of AC, 95% confidence limit 27.5% to -18.7%) and in proximal veins regression was found in five and eight, respectively (10.9% in favour of AC, 95% confidence limit 32.0% to -10.1%). No difference in lung scans was found after 10 days (0.8% in favour of AC, 95% confidence limit 21.5% to -19.9%) or after 60 days (3.3% in favour of non-AC treatment, 95% confidence limit 21.8% to -28.5%). In the AC group the incidence of bleeding complications was 8.3%. No side-effects of phenylbutazone was found. The present controlled clinical study demonstrated no effect of AC-treatment on DVT progression in actively mobilized patients wearing graduated compressing stockings when compared to a non-AC treated group receiving analgetic therapy with phenylbutazone. However, the patient population of the study is relatively small with wide confidence intervals for differences between groups. Before more general recommendations can be made, a large scale placebo-controlled study is needed to evaluate the possible effect of AC-treatment in DVT patients, who can be mobilized from the first day.

Combined actions of isradipine and captopril on renal function in hypertension.

The object of this study was to test the hypothesis that the natriuretic and uricosuric effect of calcium-entry blockers could be mediated through antagonism of angiotensin II dependent intrarenal mechanisms. The antihypertensive efficacy, haemodynamic and excretional effects of superimposed calcium blockade with isradipine were investigated in seven hypertensives with unsatisfactorally controlled blood pressure with captopril 50 mg twice daily. Glomerular filtration rate (GFR) and renal plasma flow (RPF), clearances (C) of sodium (Na), potassium (K), uric acid (UA) and lithium (Li), were measured before and after a low-dose bolus of isradipine, i.v. Subsequently, measurements were repeated during constant i.v. infusion of a higher dose with definite systemic haemodynamic effects. After 4 months of combined treatment with isradipine and captopril renal investigations were carried out again. The low isradipine dose induced a slight but statistically significant increment in CNa (22% +/- 28) and heart rate (4% +/- 4), whereas no other variables changed significantly. Infusion of the high isradipine dose caused a pronounced fall in renal vascular resistance (27% +/- 14), systolic (8% +/- 2) and diastolic blood pressure (17% +/- 5). RPF increased significantly (15% +/- 18) whereas no changes were noted in GFR, filtration fraction and urinary albumin excretion rate. In spite of the pronounced fall in BP during the high dose infusion, significant increments in natriuresis (91% +/- 63) and diuresis (41% +/- 27) were induced. The natriuresis was caused by a proximal tubular action as indicated by increased CLi and CLi/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Bepridil versus verapamil in stable angina pectoris--a controlled clinical trial.

The calcium antagonist bepridil (bepridil monohydrochloride monohydrate, Org 5730, Cordium) was investigated in comparison with verapamil in a double-blind cross-over design in patients with angina pectoris. Exercise parameters, frequency of anginal attacks, consumption of nitroglycerin and subjective preference were analysed for 36 patients. The exercise capacity, estimated by exercise time and total work load during standard bicycle testing, was significantly more improved with bepridil treatment than with verapamil treatment. No significant differences were observed in frequencies of anginal attack, consumption of nitroglycerin and subjective preference. Side effects were mild and equally divided over both treatment groups.

Evaluation of a new semi-automated screening method for the detection of Salmonella in foods within 24 h.

A new method for the detection of Salmonella in foods and feeds, 'The EiaFoss Salmonella Method' has been performance tested in comparison with a traditional technique, the Rappaport-Vassiliadis cultural procedure, as reference method. The new method is based on a two step enrichment procedure (19 and 3 h) using two different pre-enrichment broths (Salmonella enrichment broth, SEB I and SEB II) for raw and processed foods, followed by an automated enzyme immunoassay (EIA) carried out in the 'EiaFoss analyser'. A total of 161 food and nine feed samples were investigated. Only naturally contaminated samples were used. Viable Salmonella were recovered in 30 samples using either method. When using the EiaFoss Salmonella Method 13% more samples (27:24) were proved salmonella-positive compared with the reference method. The explanation for the better performance of the EiaFoss Salmonella Method is discussed and attributed in part to better enrichment procedures when using SEB I or SEB II.

[Acetylsalicylic acid in the treatment of arterial thromboembolic diseases. 1. Pharmacologic aspects]. / Acetylsalicylsyrebehandling ved arterielle trombo-emboliske sygdomme. 1. Farmakologiske aspekter.

The possible antithrombotic potential of acetyl salicylic acid (ASA) has been established in recent years and the preparation has been employed extensively in ischaemic cardiac disease and cerebrovascular conditions. The inhibiting effect of ASA on platelet function by means of blocking of cyclo-oxygenase is mentioned and, similarly, the presumed role in thrombosis development and atherogenesis is mentioned. ASA's pharmacokinetics are illustrated with emphasis on optimal anti-thrombotic ASA dosage, in particular, in relation to the effects of the preparation on the thromboxan A2 (TxA2)/prostacyclin (PGI2)-ratio. This is probably best achieved by means of low oral dosage in the form of sustained-release ASA formulation where the inhibition of platelet function probably occurs mainly in the presystemic circulation. It is concluded that a daily dosage of 80-100 mg ASA ensures effective and rapid inhibition of TxA2 production. Administration of 30-50 mg ASA daily results in a corresponding blockage of TxA2 production but not until after treatment for three to four days.

[Acetylsalicylic acid in the treatment of arterial thromboembolytic diseases. 2. Clinical documentation]. / Acetylsalicylsyrebehandling ved arterielle tromboemboliske sygdomme. 2. Klinisk dokumentation.

A review of the literature is undertaken to account for the current status of acetylsalicylic acid (ASA) in the treatment of patients with arterial thrombo-embolic conditions. Employment of ASA monotherapy has been documented to be effective in clinically controlled investigations in patients with unstable angina pectoris, transient cerebral ischaemia, coronary by-pass and femoro-popliteal endarterectomy and introduction of vascular prostheses and, in addition, in primary and secondary prophylaxis of acute myocardial infarction (AMI). In combination with dipyridamol, ASA has been found to be effective in secondary AMI prophylaxis, coronary by-pass operation and in peripheral arteriosclerosis. In patients with cardiac valvular prostheses, conventional anticoagulation therapy must still constitute the basic treatment but dipyridamol may be employed to increase the antithrombotic efficacy of the treatment. The dosage of ASA in the majority of works has been about 1,000 mg daily while isolated investigations have shown good effect from doses as low as 60 mg daily. It appears to be important for the efficacy of the treatment with platelet inhibitors in the above-mentioned conditions that treatment is instituted rapidly and, in connection with operative intervention, preferably preoperatively. In other clinical conditions such as preeclampsia, hypertension in pregnancy, diabetic angiopathy and nephropathy, membranoproliferative glomerulonephritis and arterio-venous shunts with haemodialysis, treatment with ASA appears to be effective but documentation in extensive clinically-controlled investigations is not yet available. The duration of treatment with ASA in arterial thrombo-embolic disease does not appear to be illustrated unanimously in the articles published but, as the atherosclerotic lesion is not influenced by ASA, there are indications for life-long therapy.

Left ventricular contractile function after distal protection in primary percutaneous coronary intervention: results from the Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction trial.

BACKGROUND: Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function. METHODS: Patients with STEMI were randomly referred within 12 h for PCI with (N = 312) or without distal protection (N = 314). Left ventricular (LV) contractile function was assessed with echocardiography 8 months after PCI. Global LV myocardial wall motion index (WMI) was calculated as the average wall motion score of all myocardial segments. The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI were also recorded. RESULTS: The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI was 7.1% after distal protection and 5.7% after conventional treatment (p = 0.17). WMI improved by 4.1% at 8 months in patients treated with distal protection compared to patients receiving conventional PCI (p < 0.01). In myocardium supplied by a culprit artery treated by distal protection regional LV function was 9-11% higher than myocardial regions treated conventionally ( p < 0.02). CONCLUSIONS: Routine use of distal protection during primary PCI is associated with a significant improvement in LV contractile function, with no detectable impact on intermediate term clinical outcome.