Delayed type of asthmatic response to allergen challenge and cytokines in the peripheral blood

Background: Patients with allergic bronchial asthma can develop various types of asthmatic response to bronchial challenge with allergens, such as immediate (IAR), late (LAR) or delayed (DYAR) response, due to different immunological mechanisms. Objective: The DYAR, beginning within 26- 32 h after the challenge, reaching its maximum between 32 and 48 h and resolving within 56 h (p < 0.001), differs from IAR and LAR regarding the clinical features, diagnostic and immunological parameters. Methods: The repeated DYAR (p < 0.001) in 28 patients was supplemented with recording of cytokine concentrations in the serum before and up to 72 h after the bronchial challenge by means of enzyme-linked immunoassay. Results: The DYAR was accompanied by a significant increase in the serum concentration (p < 0.05) of IL-2 at 24, 36 and 48 h; IL-10 at 12, 24, 36 and 48 h; IL-18 at 12 and 24 h; IFN-γ at 24, 36, 48 and 56 h; G-CSF at 1 and 12 h; TNF-α at 12, 36 and 48 h and TGF-β at 12 and 36 h, and a significant decrease in the concentration (p < 0.05) of IL-7 at 36 and 48 h and IL-12p70 at 12 h, as compared both with the prechallenge and with PBS control values. No significant changes in the serum cytokines were recorded during the PBS controls (p > 0.2). Conclusions: These results support the evidence for an active involvement of the Th(1) cells, neutrophils, monocytes, macrophages, epithelial cells and endothelial cells, upon cooperation of other cell types, in the immunological mechanism(s) underlying the DYAR.     

Decreased serum antioxidant capacity in patients with Wilson disease is associated with neurological symptoms

Background &; Aims

Wilson disease (WD) is an inherited disorder of copper disposition caused by an ATP7B transporter gene mutation, leading to copper accumulation in predisposed tissues. In addition to a genetic predisposition, other factors are likely to contribute to its clinical manifestation. The aim of the study was to assess whether oxidative stress affects the phenotypic manifestation of WD.

Methods

In 56 patients with WD (29 men; 26 with the hepatic form, 22 with the neurologic form, and eight asymptomatic; mean age 38.5?±?12 years), total serum antioxidant capacity (TAC) and inflammatory parameters (hs-CRP, IL-1??, IL-2, IL-6, IL-10, and TNF-??) were analyzed and related to the clinical manifestation, and mutations of the ATP7B gene. The control group for the TAC and inflammatory parameters consisted of 50 age- and gender-matched healthy individuals.

Results

WD patients had a significantly lower TAC (p?Conclusions Data from our study suggest that the increased oxidative stress contributes significantly to the clinical manifestation of WD; as a lower TAC is associated with the neurological symptoms in WD patients.     

Differential effects of intravenous anesthetics on hepatosplanchnic microcirculation in rats: sidestream dark-field imaging study

This study aimed to investigate the effects of intravenous anesthetics on hepatosplanchnic microcirculation in laparotomized mechanically ventilated rats using Sidestream Dark-field (SDF) imaging. Thirty male Wistar rats were divided into 5 groups (n = 6 each). All rats were initially anesthetized with 60 mg/kg pentobarbital (i.p.) for instrumentation. This was followed by either ketamine, propofol, thiopental, midazolam or saline+fentanyl (iv bolus over 5 min and then maintenance over 90 min). SDF imaging of the liver and distal ileum microcirculation was performed at the baseline and at t = 5, 35, 65 and 95 min. In propofol group there was increase of functional sinusoidal density (FSD) following induction (+25%, P < 0.05) and maintenance at t = 95 min (+10.3%, P < 0.05), in ketamine and midazolam group decrease of FSD was observed after induction (-20.4%, P < 0.05; -10.1%, P < 0.05) and during maintenance at t = 65 min (-11.6%, P < 0.05; -11.4%, P < 0.05) when compared to baseline. Following induction with propofol functional capillary density (FCD) of ileal longitudinal muscle layer increased (+10.6%, P < 0.05) and returned to baseline values during maintenance. Ketamine and midazolam decreased FCD of longitudinal layer after induction (-24.6%, P < 0.05; -21.1%, P < 0.05) and remained decreased during maintenance at t = 95 min (-10.8%, P < 0.05; -15.5%, P < 0.05). In thiopental and control group, changes in microcirculatory parameters were not significant throughout the study. In conclusion, intravenous anesthetics affect the hepatosplanchnic microcirculation differentially, propofol has shown protective effect on the liver and intestinal microcirculation.     

Oral Enoximone as an Alternative to Protracted Intravenous Medication in Severe Pediatric Myocardial Failure

Phosphodiesterase 3 inhibitors have been used successfully in pediatric patients with acute or chronic myocardial dysfunction over the last two decades. Their protracted continuous intravenous administration is associated with risk of infectious and thromboembolic complications. Weaning intravenous medication and starting oral angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers can be challenging. We reviewed retrospectively hospital records of 48 patients receiving oral enoximone treatment in a single tertiary pediatric cardiac center between November 2005 and April 2014. Failure to wean from intravenous milrinone infusion and/or intolerance of ACE inhibitors and/or beta-blockers was indications for oral enoximone treatment. Age of the patients ranged between 0.5 and 191 months (median 7.5 months) at the time of starting enoximone treatment. There were 14 patients (29 %) with left ventricular dysfunction due to myocarditis or dilated cardiomyopathy and 34 patients (71 %) with myocardial dysfunction complicating congenital heart disease. Fifteen (44 %) of these 34 patients had left ventricular dysfunction, 13 (38 %) right ventricular dysfunction, and in 6 (18 %) both ventricles were failing. Duration of oral enoximone treatment was between 3 days and 34 months (median of 2.3 months). Myocardial functional recovery allowed for weaning of enoximone treatment in 15 patients (31 %) after 6 days–15 months (median 5 months). No adverse hemodynamic effects were noted. Blood stained gastric aspirates encountered in two patients resolved with concomitant milk administration. Based on our limited experience, oral enoximone is a well-tolerated and promising alternative to intravenous medication and/or other commonly used oral medications in selected pediatric patients with chronic heart failure.     

Multimerization of the p12 domain is necessary for Mason-Pfizer monkey virus Gag assembly in vitro

Mason-Pfizer monkey virus (M-PMV) Gag protein contains a domain p12 that is unique to this virus (simian retrovirus-3) and its close relatives. The alpha-helical N-terminal half of p12, which contains a leucine zipper-like region, forms ordered structures in E. coli and the C-terminal half can form SDS-resistant oligomers in vitro. Together these properties suggest that p12 is a strong protein-protein interaction domain that facilitates Gag-Gag oligomerization. We have analyzed the oligomerization potential of a panel of p12 mutants, including versions containing substituted dimer, trimer, and tetramer leucine zippers, expressed in bacteria and in the context of the Gag precursor expressed in vitro and in cells. Purified recombinant p12 and its mutants could form various oligomers as shown by chemical cross-linking experiments. Within Gag these same mutants could assemble when overexpressed in cells. In contrast, all the mutants, including the leucine zipper mutants, were assembly defective in a cell-free system. These data highlight the importance of a region containing alternating leucines and isoleucines within p12, but also indicate that this domain's scaffold-like function is more complex than small number oligomerization.     

Emergence of West Nile virus lineage 2 in Europe: Characteristics of the first seven cases of West Nile neuroinvasive disease in horses in Austria

We report details of the first seven equine cases of confirmed West Nile neuroinvasive disease in Austria. The cases presented during summer and autumn of 2016 (n = 2), 2017 (n = 3) and 2018 (n = 2). All horses showed gait abnormalities and 6 of 7 horses exhibited fasciculations and/or tremors, and we provide video recordings of these. Three horses also showed cranial nerve involvement. Following rapid improvement, three horses were discharged. Four horses were euthanized due to the severity of clinical signs and subjected to neuropathological examination. West Nile virus (WNV) lineage 2 nucleic acid was detected in 5 of 7 horses, and WNV‐specific neutralizing antibodies in all 7 horses. In addition, serologic evidence of WNV infection was found in two out of fourteen in‐contact horses. Horses may be considered a sentinel species for human WNV infections, integrating human and veterinary medicine and thus contributing to the one health concept.     

Colon resection in elderly patients: comparison of data of a single surgical department with collective data from the Czech Republic

Colorectal cancer is predominantly a disease of elderly people, since over 70% of cases occur in those aged 65 years or older. Clinicians have to frequently decide whether major surgery is justified in elderly patients with a limited life expectancy. Our retrospective study was aimed to compare outcomes of primary surgery for colorectal cancer in the elderly patient population. The evaluated data were collected from the 1st Department of Surgery, Charles University, and from all over the Czech Republic. Patients were divided into three groups: the young-old (21-59 years), the older-old (60-69 years), and the oldest-old (>69 years) patients. In the collective data the youngest and the oldest groups differ significantly in the rate of early postoperative complications (12.3% versus 17.6%, p<0.001). The number of complications associated with the emergency procedures was twice as high compared to elective surgery in all groups (p<0.001). There was no correlation between age and length of hospital stay in the single surgery department. These data suggest that major oncology procedures may be undertaken in older patients in whom operative risk is reasonable, with acceptable rates of complications.