Hepatic Function and Fibrinolysis in Patients with Hereditary Angioedema Undergoing Long-Term Treatment with Tranexamic Acid

Prophylactic treatment with antifibrinolytic agents, epsilon-aminocapriod and tranexamic acid, reduces the incidence and severits of attacks in patients with hereditary angioedema. Long-term ellectivenessor risk of antifibrinolytic agents has not been established. Sixteen patients needing continuous prophylaxis because of frequency and severity of attacks were treated with tranexamic acid. In four patients this treatment was ineffective and the drug was withdrawn after 2 months. A remission or reduction in the frequency or serverity of attacks was observed in 12 patients treated for a period ranging from 8 to 34 months. Hepatic tests and blood fibrinolytic activity were not influenced by long term oral treatment with tranexamic acid.     

The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth

Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of alpha/beta-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase.     

Peripheral amplification of sweating – a role for calcitonin gene-related peptide

Neuropeptides are the mediators of neurogenic inflammation. Some pain disorders, e.g. complex regional pain syndromes, are characterized by increased neurogenic inflammation and by exaggerated sudomotor function. The aim of this study was to explore whether neuropeptides have a peripheral effect on human sweating. We investigated the effects of different concentrations of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and substance P (SP) on acetylcholine-induced axon reflex sweating in healthy subjects (total n = 18). All substances were applied via dermal microdialysis. The experiments were done in a parallel setting: ACh alone and ACh combined with CGRP, VIP or SP in various concentrations were applied. Acetylcholine (10⁻² m ) always elicited a sweating response, neuropeptides alone did not. However, CGRP significantly enhanced ACh-induced sweating ( P < 0.01). Post hoc tests revealed that CGRP in physiological concentrations of 10⁻⁷–10⁻⁹ m was most effective. VIP at any concentration had no significant effect on axon reflex sweating. The duration of the sweating response ( P < 0.01), but not the amount of sweat, was reduced by SP. ACh-induced skin blood flow was significantly increased by CGRP ( P < 0.01), but unaltered by VIP and SP. The results indicate that CGRP amplifies axon reflex sweating in human skin.     

Obesity and asthma, what are the links?

PURPOSE OF REVIEW: Obesity is a major cause of morbidity accounting for approximately 300 000 deaths each year and about 7% of the health care budget with an economic impact greater than US dollar 100 billion annually in the United States. Obesity and its sequelae such as cardiovascular disease, diabetes, arthritis or cancer have been on the rise over the last decades. The parallel time trend with an increasing prevalence of asthma has induced a lively debate about a potential link between both conditions. RECENT FINDINGS: A number of prospective studies have shown that weight gain can antedate the development of asthma. Effect modification by sex may occur as some studies have shown effects of body mass index on asthma only among females. However, sex differences are not consistent. Several hypotheses have been proposed to explain the epidemiological associations including alterations in airway mechanics and immune responses, hormonal influences and genetic factors. SUMMARY: There is evidence that obesity and overweight are associated with the development of asthma. Yet, the mechanisms underlying this relation are unclear. Weight reduction among asthmatic patients can result in improvements of lung function demonstrating the potential clinical impact of the findings.     

Low elementary movement speed is associated with poor motor skill in Turner's syndrome

The article aims to discriminate between 2 features that in principle both may be characteristic of the frequently observed poor motor performance in girls with Turner's syndrome (TS). On the one hand, a reduced movement speed that is independent of variations in spatial accuracy demands and therefore suggests a problem in motor execution. On the other hand, a disproportional slowing down of movement speed under spatial-accuracy demands, indicating a more central problem in motor programming. To assess their motor performance problems, 15 girls with TS (age 9.6-13.0 years) and 14 female controls (age 9.1-13.0 years) were tested using the Movement Assessment Battery for Children (MABC). In additionally, an experimental procedure using a variant of Fitts' graphic aiming task was used to try and disentangle the role of spatial-accuracy demands in different motor task conditions. The results of the MABC reestablish that overall motor performance in girls with TS is poor. The data from the Fitts' task reveal that TS girls move with the same accuracy as their normal peers but show a significantly lower speed independent of task difficulty. We conclude that a problem in motor execution is the main factor determining performance differences between girls with TS and controls.     

Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression

We tested the hypothesis that PTEN inactivation may stratify cancer progression risk among putative endometrial hyperplasias, classified prognostically by means of the morphometric D score (DS). The DS, calculated from 3 morphometric variables measured in routine hematoxylin-eosin-stained endometrial biopsy slides, is the most sensitive and specific method of endometrial cancer risk prediction currently available. Clinical outcomes of 103 women with endometrial hyperplasia on biopsy were tallied according to the DS. Seven (7/103; 7%) patients with carcinoma during follow-up were all distributed within the high-risk prognostic group (ie, DS <1 = endometrial intraepithelial neoplasia [EIN]) (7/21; 33% progression). None of the 82 cases with a DS higher than 1 progressed. All cases that progressed were PTEN null, indicating that this genotype is capable of further stratifying cancer progression risk in hyperplasias irrespective of histological categorization. However, only 16% of the PTEN-null cases progressed. When PTEN expression pattern was combined with EIN, the prognostic power was greatly increased (specificity from 63% for PTEN and 85% for EIN to 93% when combined; positive predictive value from 16% and 33% to 50%). We conclude that loss of PTEN expression is the first biomarker in EIN that increases the accuracy of the prognostic DS to predict cancer progression risk. Unless endometrial hyperplasias are stratified by histological morphometric D-Score, PTEN has a low positive predictive value.     

Development of a Cell Patterning Technique Using Poly(Ethylene Glycol) Disilane

A simple technique for controlling cell adhesion on glass substrates by surface modification using a commercially available poly(ethylene glycol) (PEG) disilane, which can bind directly to glass in a single step, in combination with photolithographic micropatterning, was developed, characterized, and evaluated for patterning of HepG2 hepatoma cells and 3T3 fibroblasts. The optimal concentration of PEG-disilane for surface modification was 5 mM, and patterning of strongly adherent cells such as HepG2 required the chelation of divalent metal cations in order to inhibit nonspecific binding and cell aggregation. Whereas the average thickness of the PEG-disilane layer was 18±3.5 nm, the perimeters of patterned areas of exposed glass exhibited ridges of average height 857±50 nm, which may have aided in constraining cell spreading and migration. Although unpatterned PEG-treated substrates were hydrophilic (contact angle 46±1°), micropatterned surfaces behaved as if they were somewhat hydrophobic (contact angle 90°), necessitating special protocols for preventing deleterious dewetting of cells. For optimized protocols, the probability of adhesion of HepG2 cells to a patterned area of exposed glass was almost 15 times higher than the probability of adhesion to a PEG-treated background region of equal area. Our technique is useful for short- to intermediate-term patterning of cell or tissue morphology, e.g., for investigation of the effects of cell–cell interactions or cell geometry.     

Reproductive risk factors in unilateral and bilateral renal agenesis

ABSTRACT  Renal agenesis (RA) appears to be a multifactorial condition with combined genetic and environmental influences. We performed a retrospective case-control study of reproductive history of 26 isolated RA live births cases referred to Sicilian Registry of Congenital Malformations. A statistical significant association for birth weight if we considered all RA together and for bilateral RA alone, an increasing risk for maternal age only in the bilateral RA subgroup and a male predominance both for unilateral and bilateral RA was found. Our results show that some reproductive risk factors may be associated with RA, moreover differences found between subgroups indicate that some risk factors may be different in unilateral and bilateral RA. The association between reproductive risk factors and RA may reflect pathogenetic interaction between genetic and environmental factors. Nevertheless further studies are needed to clarify these associations and to explore the role of perinatal factors in the etiology of renal agenesis. In fact if prenatal or perinatal risk factors are in a causal chain influencing the risk for developing RA, then these data could have important implications in the prevention or treatment of this condition.     

Variability in acquired resistance of Pasteurella and Mannheimia isolates from the nasopharynx of calves, with particular reference to different herd types

To measure the level of antimicrobial resistance in potential bovine respiratory pathogens at different production types, nasal swabs were collected from 57 calves of 13 dairy herds, 150 calves of 9 beef cattle herds, and 289 calves of 5 high-density veal calf herds and investigated for the presence of Pasteurellaceae. All calves were less than 6 months old. Susceptibilities of the Pasteurella and Mannheimia isolates to eight antimicrobials were determined using an agar dilution method. P. multocida (37.3%) and hemolytic Mannheimia organisms (M. haemolytica sensu lato) (6.3%) were the most frequently detected organisms. The overall prevalence of isolates resistant to at least one antimicrobial from the dairy, beef, and veal calves were 17.6% (6/34), 21.9% (14/64), and 71.9% (64/89), respectively. In isolates obtained on the veal calf herds, acquired resistance to ampicillin, oxytetracycline, potentiated sulfonamides, gentamicin, tilmicosin, and enrofloxacin was frequently present, and 32.6% of these isolates were resistant to more than two of the tested antimicrobials. Resistance to ceftiofur and florfenicol was not detected. A substantial within-herd variability of species diversity and resistance profiles among isolates belonging to the genera Pasteurella and Mannheimia was found among the isolates of the veal calf farms.