In patients with idiopathic venous thrombosis, interleukin-10 is decreased and related to endothelial dysfunction

The aim of this study was to evaluate the levels of anti-inflammatory interleukin-10 and pro-inflammatory cytokines and their relationship to endothelial function in patients with idiopathic venous thrombosis. Forty-nine eligible patients of both sexes with idiopathic venous thrombosis and 48 matched control subjects were studied. Levels of inflammatory markers were determined. Endothelial function was evaluated by ultrasound measurement of the flow mediated dilatation (FMD) of the brachial artery. Compared to the control group, patients with idiopathic venous thrombosis had significantly lower levels of interleukin-10 1.81 pg/ml (1.53–2.21) versus 2.71 pg/ml (1.84–3.65), p < 0.001. Patients also had increased levels of pro-inflammatory cytokines: interleukin-6 2.37 pg/ml (1.59–4.09) versus 2.03 pg/ml (1.49–2.59), p = 0.025, interleukin-8 3.53 pg/ml (2.94–5.30) versus 2.25 pg/ml (1.77–2.90), p < 0.001. Furthermore, decreased FMD was observed in patients: 5.0% (3.9–6.9) versus 12.7% (10.8–15.6), p < 0.001. FMD was related to levels of interleukin-10 (r = 0.33, p = 0.001) and was inversely related to pro-inflammatory cytokines interleukin-6 (r = −0.34, p = 0.001) and interleukin-8 (r = −0.43, p < 0.001). Patients with idiopathic venous thrombosis have decreased levels of IL-10 and increased levels of pro-inflammatory cytokines. This imbalance indicates that in the stable phase of the disease, patients have an increased systemic inflammatory response. This inflammatory response could be the consequence of the disease, but most probably is involved in the pathogenesis of venous thrombosis.     

Genomic distribution of beta papillomaviruses in single eyebrow hair samples and pools of eyebrow hair samples

Human beta papillomaviruses (beta-HPVs) are frequently detected in hairs and the majority of people are infected with multiple beta-HPV genotypes. This study was conducted to investigate for the first time the distribution of beta-HPV genotypes in single hair specimens and to estimate the contribution of a single hair to the beta-HPV profile obtained from a specimen made of multiple hairs pooled together. A total of 85 eyebrow hair specimens, representing 64 single hairs and 21 pools of hairs, obtained from 21 immunocompetent individuals, were tested using a reverse-line blot-based beta-HPV genotyping assay that allows identification of 25 different beta-HPVs. Overall, beta-HPV DNA was detected in 82/84 (97.6%) samples. The great majority of hair pools (19/21; 90.5%) contained multiple beta-HPVs, the mean number of identified beta-HPV genotypes per hair pool was 5.2 (ranging from 1 to 12). In individual hairs, the great majority of individual hairs (43/63; 68.3%) contained multiple beta-HPVs, the mean number of identified beta-HPV genotypes was 4 (ranging from 1 to 12). Overall, HPV-23 was the most prevalent genotype, followed by HPV-24 and HPV-38. A comparison of beta-HPV genotype distribution in pooled hair specimens and in at least one individual hair within a single patient revealed that 5/20 patients had a complete match between the number and profile of identified genotypes, 2/20 patients had the same/similar number of HPV genotypes but different genotype profile, 9/20 patients had more HPV genotypes identified in pools than in the majority of individual hairs and 4/20 patients had at least one individual hair with more HPV genotypes identified than in the corresponding pool. Our results suggest that beta-HPVs are unevenly distributed over the eyebrows and even pools made of several hairs do not necessarily provide information on the whole spectrum of HPV genotypes present in eyebrows.     

Detection and molecular characterisation of noroviruses and sapoviruses in asymptomatic swine and cattle in Slovenian farms

Acute infectious caliciviral gastroenteritis is a common illness in people all over the world. Two genera of the Caliciviridae family, Norovirus and Sapovirus, which usually cause disease in humans, can also be found in animals where they do not always cause clinical signs of gastroenteritis.To investigate the presence of norovirus (NoV) and sapovirus (SaV) strains in asymptomatic swine and cattle, a total of 525 faecal (406 pigs and 119 cattle) specimens were collected during 2004 and 2005 from 8 pig and 4 cattle farms geographically dispersed across Slovenia. RT-PCRs and sequencing were carried out using primers targeting RdRp and capsid regions of both NoVs and SaVs. NoV positivity was detected in both bovine (2/108 [1.9%]) and porcine (5/406 [1.2%]) faecal specimens while SaV positivity was present only in porcine (29/406 [7.1%]) specimens. All porcine NoV strains (n = 5) detected were attributed to a single farm, while the porcine SaV strains (n = 29) detected came from 5 different farms. Phylogenetic analysis of nucleotide sequences of partial RdRp fragments placed two of the bovine NoV strains in genogroup GIII. Of the 5 porcine NoV strains, 4 clustered with GII.11, while 1 strain showed the presence of GII.18. The majority [24/29, 82.7%] of the porcine SaV strains clustered in GIII within two separate lineages, while 5 strains clustered into recently identified genetic clusters GVII (3 strains), GVIII (1 strain) and unknown (1 strain), respectively.Although NoV and SaV strains in asymptomatic swine and cattle were detected at low levels, they were still phylogenetically placed in a common pattern within both genera showing great genetic variability. There were no detected human-like strains in this study.     

Twenty-five years of the international Bled course for teachers of family medicine in Europe: Glancing back and looking forward

The international Bled course for teacher training has played a central role in faculty development in family medicine for the past 25 years. The course was originally designed to promote faculty development for family medicine teachers in the new academic discipline of family medicine in Slovenia in 1990 and to introduce new topics into the family medicine curriculum. In this background paper, we perform a SCOT analysis (strengths, challenges, opportunities, and threats) of the current course, evaluating participant feedback and reviewing past topics and their impact on local and international teaching programmes. We also review the place of the course in the context of other teacher-training programmes in family medicine in Europe. We found that the structure and learning aims of the Bled course have remained stable over 25 years. It provides a safe, well-structured learning environment for the participants even though the course topic is different every year. The course has had a significant impact on curriculum development and teacher training in Slovenia as well as in many other countries in Europe and beyond. Because of the positive impact of the course and the high degree of satisfaction of the participants and course directors, it seems worthwhile to continue this endeavour. New directions for the course will depend on the learning needs of the participants and the evolving medical curricula in the countries they represent.     

Changes in histamine secretion from mast cells caused by digitalis glycosides.

Cardiotonic glycosides modify histamine secretion from rat mast cells in the following way. (1) Preincubation (30 min) of mast cells with liposoluble glycosides (10(-4) mol/l) increases the spontaneous histamine secretion by about 5%. (2) Preincubation of mast cells with 10(-4) mol/l liposoluble glycosides (digitoxin, digoxin, digitoxigenine) decreases histamine release induced by compound 48/80 in the presence of calcium, whereas the water soluble glycoside, strophanthin G, has no effect on the secretion. (3) Preincubation of mast cells in a calcium-free medium with the glycosides (10(-4) mol/l) has a dual-effect on histamine secretion induced by compound 48/80: water soluble glycosides (strophanthin G and K) potentiate histamine release, whereas the liposoluble glycosides (digitoxin, digitoxigenine) decrease the secretory response. The difference in the activity of different glycosides could be explained by their dual effects, namely an inhibition of Na+K(+)-ATPase which leads to an increase in histamine release, and intracellular action(s) of liposoluble glycosides leading to a decrease of histamine secretion.     

Postulates for validating TLR4 agonists

TLRs play a central role in the innate immune response, recognizing a variety of molecular structures characteristic of pathogens. Although TLR4, together with its co‐receptor myeloid differentiation‐2 (MD‐2), recognize bacterial LPS and therefore Gram‐negative bacterial infections, it also plays a key role in many other pathophysiological processes, including sterile inflammation and viral infection. Specifically, numerous endogenous agonists of TLR4 of notably diverse nature, ranging from proteins to metal ions, have been reported. Direct activation of a single receptor by such a range of molecular signals is very difficult to explain from a structural and mechanistic point of view. It is likely that only a subset of these directly activate the TLR4–MD‐2 complex. We propose three postulates aimed at distinguishing the direct agonists of TLR4 from indirect activators. These postulates are as follows: (i) that the agonist requires the TLR4/MD‐2 receptor complex; (ii) that agonist formed synthetically or in situ must activate the receptor complex in order to eliminate artifacts of contamination by other agonists; and (iii) that a specific molecular interaction between the agonist and TLR4/MD‐2 must be identified. The same type of postulates can be applied to pattern recognition receptors in general.