Vasopressin, when added to norepinephrine, was not associated with increased predicted mortality after cardiac surgery

BACKGROUND AND AIMS: Arginin vasopressin (AVP) is a potent vasoconstrictor which has been used in vasodilatory shock when therapy with catecholamines and fluids has failed. In this study we evaluated the association of AVP with organ failure and mortality in cardiac surgical patients suffering from vasodilatory shock refractory to norepinephrine (NE) treatment. MATERIAL AND METHODS: Cardiac surgical patients who received AVP in addition to NE (N=33, AVP-group) and 33 control patients (NE group) who were treated with an equal dose of NE compared with AVP patients when AVP infusion started. Data on preoperative risk factors according to EuroSCORE and predicted mortality calculated by logistic EuroSCORE were collected preoperatively. Data on hemodynamics, organ dysfunctions, length of intensive care unit stay and mortality were collected. RESULTS: EuroSCORE did not differ between the groups, AVP:10.4 +/- 3.9 vs. NE 8.9 +/- 4.0. Observed 30 day mortality was lower than predicted in both groups, AVP: 7 (21.7%) vs. predicted mortality 25.9% and NE: 2 (6.1%) vs. 16.0%, respectively. There were more renal complications (36.4% vs. 9.1%, p = 0.008) and infections (30.3% vs. 3.0%, p = 0.003) in patients receiving AVP. Cardiovascular complications did not differ between the groups. CONCLUSIONS: In this prospectively observed cohort of cardiac surgical patients, AVP did not increase mortality predicted by Euroscore. Anyhow renal and infection complications were common.     

The omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis

The omptins are a family of enterobacterial surface proteases/adhesins that share high sequence identity and a conserved beta-barrel fold in the outer membrane. The omptins are multifunctional, and the individual omptins exhibit differing virulence-associated functions. The Pla plasminogen activator of Yersinia pestis contributes by several mechanisms to bacterial invasiveness and the systemic, uncontrolled proteolysis in plague. Pla proteolytically activates the human proenzyme plasminogen and inactivates the antiprotease alpha2-antiplasmin, and its binding to laminin localizes the uncontrolled plasmin activity onto basement membranes. These properties enhance bacterial migration through tissue barriers. Pla also degrades circulating complement proteins and functions in bacterial invasion into human epithelial cells. PgtE of Salmonella enterica and OmpT of Escherichia coli have been shown to degrade cationic antimicrobial peptides from epithelial cells or macrophages. PgtE and SopA of Shigella flexneri appear important in the intracellular phases of salmonellosis and shigellosis, whereas functions of OmpT have mainly been associated with protein degradation in E. coli cells. The differing virulence roles and functions have been attributed to minor sequence variations at the surface-exposed regions important for substrate recognition, to the dependence of omptin functions on lipopolysaccharide, and to the different regulation of omptin expression.     

Tacrine restores cholinergic nicotinic receptors and glucose metabolism in alzheimer patients as visualized by positron emission tomography

Three patients with Alzheimer's disease, a 68-year-old woman with mild dementia and 2 men (aged 64 and 72 years) with moderate dementia were treated orally with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine), 80 mg daily, for several months. The patients were investigated using positron emission tomography (PET) prior to, and after 3 weeks and 3 months of treatment. The PET studies involved a multi-tracer system consisting of [¹⁸F]-fluoro-deoxy-glucose (¹⁸F-FDG) (tracer for glucose metabolism); ¹¹C-butanol (cerebral blood flow) and (S)(−)- and (R)(+)-[N-¹¹C-methyl]-nicotine (nicotinic receptors; cholinergic neural activity). Tacrine treatment increased the uptake of ¹¹C-nicotine to the brain. Significant reduced difference in uptake between the two enantiomers (S)(−)- and (R)(+)¹¹C-nicotine was observed in the frontal and temporal cortices after tacrine treatment in all three patients. The kinetic analysis indicated increased binding of (S)(−)¹¹C-nicotine in brain compatible with a restoration of nicotinic cholinergic receptors. The most pronounced effect was observed after 3 weeks and 3 months treatment in the patient with mild dementia. An increase in cerebral glucose utilization was found in the 68-year-old patient with mild dementia but also slightly in the 64-year-old man with moderate dementia when treated with tacrine for 3 months. Tacrine administration did not affect cerebral blood flow. The PET data obtained after 3 weeks of tacrine treatment was paralleled by improvement in neuropsychological performance. This study shows in vivo by PET neurochemical effects induced in brain by treatment with tacrine to Alzheimer patients. Intervention with tacrine in the early course of the disease might be necessary for clinical improvement.     

Identification of Two Laminin-Binding Fimbriae, the Type 1 Fimbria of Salmonella enterica Serovar Typhimurium and the G Fimbria of Escherichia coli, as Plasminogen Receptors

Escherichia coli strains carrying recombinant plasmids encoding either the type 1 fimbria of Salmonella enterica serovar Typhimurium or the G fimbria of E. coli exhibited binding of human ¹²⁵I-Glu-plasminogen and enhanced the tissue-type plasminogen activator-catalyzed conversion of plasminogen to plasmin. Purified type 1 or G fimbriae similarly bound plasminogen and enhanced its activation. The binding of plasminogen did not involve the characteristic carbohydrate-binding property of the fimbriae but was inhibited at low concentrations by the lysine analog -aminocaproic acid. Because these fimbrial types bind to laminin of basement membranes (M. Kukkonen et al., Mol. Microbiol. 7:229–237, 1993; S. Saarela et al., Infect. Immun. 64:2857–2860, 1996), the results demonstrate a structural unity in the creation and targeting of bacterium-bound proteolytic plasmin activity to basement membranes.     

Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation

Background Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. Objective Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy‐prone infants. Methods In a randomized double‐blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C‐reactive protein (CRP), total IgA and IgE, food‐specific IgA, IgG, and IgE, IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α, and IFN‐γ. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. Results Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL‐10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17–0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16–0.87), P=0.023] at age 2 years, when adjusted with probiotic use. Conclusion The association of CRP with a decreased risk of eczema at 2 years of age in allergy‐prone children supports the view that chronic, low‐grade inflammation protects from eczema. Probiotic‐induced low‐grade inflammation was characterized by elevation of IgE, IgA, and IL‐10, the changes typically observed in helminth infection‐associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.     

Cyanobacteria produce a high variety of hepatotoxic peptides in lichen symbiosis

Lichens are symbiotic associations between fungi and photosynthetic algae or cyanobacteria. Microcystins are potent toxins that are responsible for the poisoning of both humans and animals. These toxins are mainly associated with aquatic cyanobacterial blooms, but here we show that the cyanobacterial symbionts of terrestrial lichens from all over the world commonly produce microcystins. We screened 803 lichen specimens from five different continents for cyanobacterial toxins by amplifying a part of the gene cluster encoding the enzyme complex responsible for microcystin production and detecting toxins directly from lichen thalli. We found either the biosynthetic genes for making microcystins or the toxin itself in 12% of all analyzed lichen specimens. A plethora of different microcystins was found with over 50 chemical variants, and many of the variants detected have only rarely been reported from free-living cyanobacteria. In addition, high amounts of nodularin, up to 60 μg g(-1), were detected from some lichen thalli. This microcystin analog and potent hepatotoxin has previously been known only from the aquatic bloom-forming genus Nodularia. Our results demonstrate that the production of cyanobacterial hepatotoxins in lichen symbiosis is a global phenomenon and occurs in many different lichen lineages. The very high genetic diversity of the mcyE gene and the chemical diversity of microcystins suggest that lichen symbioses may have been an important environment for diversification of these cyanobacteria.     

Sensation and sexual arousal in circumcised and uncircumcised men

IntroductionResearch, theory, and popular belief all suggest that penile sensation is greater in the uncircumcised as compared with the circumcised man. However, research involving direct measurement of penile sensation has been undertaken only in sexually functional and dysfunctional groups, and as a correlate of sexual behavior. There are no reports of penile sensation in sexually aroused subjects, and it is not known how arousal affects sensation. In principle, this should be more closely related to actual sexual function.AimThis study therefore compared genital and nongenital sensation as a function of sexual arousal in circumcised and uncircumcised men.MethodsTwenty uncircumcised men and an equal number of age-matched circumcised participants underwent genital and nongenital sensory testing at baseline and in response to erotic and control stimulus films. Touch and pain thresholds were assessed on the penile shaft, the glans penis, and the volar surface of the forearm. Sexual arousal was assessed via thermal imaging of the penis.ResultsIn response to the erotic stimulus, both groups evidenced a significant increase in penile temperature, which correlated highly with subjective reports of sexual arousal. Uncircumcised men had significantly lower penile temperature than circumcised men, and evidenced a larger increase in penile temperature with sexual arousal. No differences in genital sensitivity were found between the uncircumcised and circumcised groups. Uncircumcised men were less sensitive to touch on the forearm than circumcised men. A decrease in overall touch sensitivity was observed in both groups with exposure to the erotic film as compared with either baseline or control stimulus film conditions. No significant effect was found for pain sensitivity.ConclusionThese results do not support the hypothesized penile sensory differences associated with circumcision. However, group differences in penile temperature and sexual response were found. Payne K, Thaler L, Kukkonen T, Carrier S, and Binik Y. Sensation and sexual arousal in circumcised and uncircumcised men.     

Toxicity of Freshwater Sediments in the Vicinity of an Old Sawmill: Application of Three Bioassays

Toxicity of contaminated sediments collected from an old sawmill area and the downstream river-lake system was assessed with three different bioassays. Survival and growth were used as endpoints in subchronic (10-day) test with Chironomus riparius and growth and reproduction in long-term (28-day) test with Lumbriculus variegatus. A microbial bioluminescent direct contact assay, the Flash test, was also included in the test set to measure acute toxicity. In every bioassay, sediment from a pool of the sawmill was found to be toxic, and some adverse effects were found in other sediments as well. The bioassays were then compared to chemical analysis results, which showed the presence of several toxicants. These results could not, however, be directly connected to any individual toxicant, nor did they show any obvious trend downstream from the mill. Received: 5 June 2000/Accepted: 26 October 2000     

Toxicokinetics of 2,4,5-Trichlorophenol and Benzo(a)pyrene in the Clam Pisidium amnicum: Effects of Seasonal Temperatures and Trematode Parasites

Several biotic and abiotic stress factors may affect aquatic organisms simultaneously. However, not much is known about the effects of, e.g., low temperatures and parasite infections on the toxicokinetics of organic hydrophobic chemicals. Here we studied the accumulation and depuration of [¹⁴C]2,4,5-trichlorophenol (TCP) and [³H]benzo(a)pyrene (BaP) in the sediment-dwelling freshwater clam Pisidium amnicum. Experiments were made in October (+15°C), April (+4°C), and July (+15°C) both with uninfected clams and clams infected with Bunodera luciopercae (Trematoda). The accumulation rate for both chemicals was slower at 4°C than at 15°C. The depuration of TCP was biphasic, and the slowest depuration occurred at 4°C. For BaP, the depuration was very slow and monophasic at all temperatures. The highest BCFs for both chemicals were found in July at 15°C. Surprisingly, the BCFs for TCP were higher in April at 4°C than in October at 15°C. For BaP, no steady-state was reached in April. Differences in chemical toxicokinetics between the infected and uninfected clams were only minor. However, for both chemicals a trend of slightly lower BCFs in the infected clams was found. In conclusion, low temperatures modify the toxicokinetics of organic chemicals in P. amnicum and the effects depend on hydrophobicity of the chemical. The effects of parasites on toxicokinetics seem to be small. Received: 4 November 1999/Accepted: 29 March 2000