Time- and Dose-Dependent Effects of Chronic Wound Fluid on Human Adult Dermal Fibroblasts

BACKGROUND Wound healing is a biologic process that is altered in patients affected by chronic venous ulcers. The wound microenvironment is reflected in the chronic wound fluid (CWF), an exudate containing serum components and tissue-derived proteins.
OBJECTIVES We investigated the effects of increasing doses of CWF collected from patients suffering from chronic venous ulcers on human adult dermal fibroblasts cultured in vitro and the relationship among CWF effects and treatment length.
METHODS Fibroblasts were treated with 60, 240, and 720 μg/mL CWF for 3 and 7 days. We evaluated cell proliferation and viability by MTT and Trypan blue assay, cell morphology by light microscopy, F-actin microfilaments organization by tetramethylrhodamine B isothiocyanate-conjugated phalloidin, α-smooth muscle actin expression by immunofluorescence, and senescence-associated β-galactosidase activity.
RESULTS CWF induced an increase in cell proliferation in the first 3 days of treatment. In contrast, at 7 days, a strong decrease in cell viability was observed. These changes were related to a cytoskeletal F-actin reorganization and not to fibroblast–myofibroblast differentiation nor to changes in cellular senescence.
CONCLUSIONS This study shows a dose-dependent and biphasic effect of CWF on dermal fibroblasts, suggesting that a continuous exposure to chronic wounds microenvironment may induce late cellular dysfunctions possibly involved in the delayed wound healing.     

Parental presence,clowns or sedative premedication to treat preoperative anxiety in children: what could be the most promising option?

Background and Objectives: A significant number of children undergo surgery experience high levels of anxiety in the presurgical period. The aim of this study is to investigate which intervention is more effective in reducing preoperative anxiety. Methods/Materials: The sample was composed of 75 subjects (aged 5–12 years) who had to undergo minor day surgery. Children were randomly assigned to: the Clowns group (N = 25) accompanied to the preoperative room by the clowns and by a parent; Premedication group (N = 25) premedicated with oral midazolam and accompanied to the preoperative room by one parent; or the Control group (N = 25) only accompanied by one parent. Anxiety in the preoperative period was measured by using the Modified Yale Preoperative Anxiety Scale (m‐YPAS). Parental anxiety was measured by using the State‐Trait Anxiety Inventory (STAI Y‐1/Y‐2). Results: The Clown group was significantly less anxious during the induction of anesthesia compared with Premedication group and Control group. There were not any significant differences between Control group and Premedication group. There was an increased level of anxiety in the induction room in comparison with the waiting room: this difference was statistically significant for Control group and Premedication group, whereas it was not significant in Clown group. Conclusions: PPIA+clown intervention is more effective in reducing anxiety in children during the preoperative period than PPIA alone or PPIA+oral midazolam.     

Familial adult-onset Pompe disease associated with unusual clinical and histological features

The adult-onset form of Pompe disease had a wide clinical spectrum, ranging from asymptomatic patients with increased CK to muscle cramps and pain syndrome or rigid-spine syndrome. In addition clinical severity and disease progression are greatly variable. We report on a family with 3 siblings characterized by an unusual adult-onset Pompe disease including dysphagia and weakness of tongue, axial and limb-girdle muscles, in association with atypical globular inclusions in muscle fibres. Our study confirms the great clinical and histological variability of adult-onset Pompe disease and further supports the need of careful evaluation of bulbar function in patients affected by this pathology.Key words: Pompe disease, globular inclusions, bulbar symptomsGlycogen storage disease type II (Pompe disease or acid maltase deficiency) is a rare autosomal recessive muscular disorder characterized by deficiency of acidalfa glucosidase (GAA), determining accumulation of glycogen in the lysosomes, mainly in cardiac and skeletal muscle cells. Typical phenotypes of glycogenosis type II include the severe classic infantile form, characterized by severe muscle weakness and hypertrophic cardiomyopathy, almost invariably fatal by 12 months, a "non-classic" form presenting between 1 and 2 years of age and the lateonset form, presenting at any time after the age of 1 year, including juvenile and adult-onset subtypes, which are considered as part of a continuous clinical spectrum (1). In particular the adult-onset form presents with slowly progressive proximal lower limb and/or paraspinal muscle weakness, often followed by restrictive respiratory failure, which could be life-threatening, as it is in infants and children (2). However the clinical spectrum of adultonset form is wide, ranging from asymptomatic patients with increased CK to muscle cramps and pain syndrome or rigid-spine syndrome (2, 3). Furthermore clinical severity and disease progression is greatly variable.We report on a family with 3 siblings with an unusual adult-onset Pompe disease clinically characterized by weakness of bulbar, axial and limb-girdle muscles in association with atypical histopathological changes.     

Role of Thromboxane A2 Receptor on the Effects of Oxidized LDL on Microvascular Endothelium Nitric Oxide,Endothelin‐1, and IL‐6 Production

Objective: The aim of this study was to determine to what extent thromboxane A₂ (TP) receptor mediates the effect of oxidated low‐density lipoprotein (LDL) on nitric oxide (NO), interleukin (IL)‐6, and endothelin‐1 (ET‐1) release by microvascular endothelial cells. Methods: Endothelial nitric oxide synthase (eNOS), nitrites and nitrates (NO₂/NO₃), ET‐1, and IL‐6 production were measured following human microvascular endothelial cell 1 exposure to isoprostane‐8‐epi‐PGF_2α (F₂IP), a natural agonist of the TP receptor present in oxidized LDL, or native, low‐, or medium‐oxidized LDL either with the TP‐receptor blocker, SQ29.548, or its vehicle. Results: F₂IP and both native and oxidized LDL enhanced NO₂/NO₃. F₂IP through the TP receptor stimulated eNOS (eight‐fold), while the oxidized LDL effect (two‐to five‐fold) was only partially prevented by SQ29.548. While LDL concentration and degree of oxidation synergistically and independent of SQ29.548 stimulated IL‐6, F₂IP had no effect. F₂IP induced a modest (+50%) increase in ET‐1. LDL, independent of concentration or degree of oxidation, stimulated (+120%) ET‐1 production, and this effect was only partially attenuated by SQ29.548. Conclusions: In microvascular endothelial cells, LDL concentration and degree of oxidation synergistically stimulate NO and IL‐6 production, but only NO release is largely mediated by the TP receptor. LDL facilitates ET‐1 release independent of concentration and degree of oxidation; TP‐receptor stimulation is only partially responsible for this effect.     

Hypertrophy of mucosa and serosa in the obstructed intestine of rats

After a surgically induced partial obstruction of the small intestine (ileum) in adult rats there is an accumulation of ingesta and a progressive enlargement of the lumen accompanied by wall thickening: over a period of 2–3 wk the circumference of the hypertrophic intestine increases by a factor of 2·7 and the thickness of the musculature increases more than threefold, while the length of the ileum (measured at the mesenteric attachment) remains unchanged. The villi become markedly larger and more elongated in the circumferential direction, and have a greater separation between one another. The number of villi per unit surface is markedly reduced but the number of villi per unit length of ileum, whilst appearing to show a small increase, was not significantly altered. The component epithelial cells (absorptive cells) appear unchanged in morphology and size (height). The microvilli of the epithelial cells have the same appearance, size (height) and packing density in the control and the hypertrophic ileum. Glands of Lieberkühn, Peyer's patches and single lymphatic follicles constituting the Peyer's patches are significantly increased in size in the hypertrophic intestine. The serosal surface of the hypertrophic ileum, in spite of the great expansion, remains regularly covered by mesothelial cells; these are much larger than in the controls and have an altered distribution of their microvilli.     

Menopause-related blood pressure increase and its relationship to age and body mass index: the SIMONA epidemiological study

BACKGROUND: Menopause is commonly associated with some blood pressure (BP) rise, but cross-sectional or longitudinal studies completed so far were often too small and were unable to indicate whether this BP increase is really dependent on menopause, or was caused by age or changes in body mass index (BMI). METHODS AND RESULTS: The SIMONA study (Study on Hypertension Prevalence in Menopause in the Italian population) was a large cross-sectional study on 18 326 women of age range 46-59 years, consecutively seen by 302 practitioners all over Italy, and representing 60% of the women of that age in the National Health care list of those doctors. BP was measured three times in the seated position by the same automatic machine, and demographic and clinical data were taken. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were slightly but significantly higher in postmenopausal than premenopausal and perimenopausal women, but so were age and BMI. Within seven biannual strata, differences in age and BMI were minimized, but SBP/DBP remained significantly higher (by 3.4/3.1 mmHg) in postmenopausal than in premenopausal subjects in the youngest stratum (46-47 years), and was also significantly higher in the stratum 48-49 years. The differences remained significant after the exclusion of 1809 women with surgical menopause or 695 women with cardiovascular disease. Even when the confounding effects of age, BMI, smoking and contraceptive or replacement therapies were excluded by analysis of covariance, menopause was significantly and positively associated with SBP and DBP (approximately 2 mmHg difference in the age range 46-49 years). CONCLUSION: Menopause is associated with a slightly but significantly higher BP, even after adjustment for age and BMI, as well as other confounding factors, but the association is evident only in the younger end of the age range related to menopause.     

Hand movements at 3 months predict later hemiplegia in term infants with neonatal cerebral infarction

Aim The aim of this study was to explore the predictive value of quantitative assessment of hand movements in 3‐month‐old infants after neonatal stroke. Method Thirteen infants born at term (five females, eight males; mean gestational age 39.4wks, SD 1.19, range 37–41wks; mean birthweight 3240g, SD 203, range 2900–3570g) with neonatal arterial ischaemic cerebral infarction, and 13 healthy infants (mean gestational age 39.1wks, range 37–41wks, SD 1.26; mean birthweight 3190g, SD 259, range 2680–3490g) were enrolled in the study. The absolute frequency and the asymmetry of global hand opening and closing, wrist segmental movements, and independent digit movements were assessed from videotapes recorded at around 12 weeks. Neurological outcome was assessed when the infants were at least 18 months old using Touwen’s neurological examination. Results Five of the 13 infants with neonatal stroke had normal neurological development, and eight had hemiplegia. Asymmetry of wrist segmental movements and the absolute frequency of independent digit movements were significantly different between infants with and without hemiplegia (p=0.006 and p=0.008, respectively). No differences were found in global hand movements. Interpretation We propose that the observed abnormalities of hand movements are the result of two different mechanisms: direct disruption of the corticospinal projection to the spinal cord, and altered modulation of the central pattern generators of general movements.     

An overview of systematic reviews on cannabis and psychosis: Discussing apparently conflicting results

Issues . Cross‐sectional surveys have revealed that cannabis is the most widely used illicit substance in Western countries. Cannabis intoxication can lead to acute, transient psychotic symptoms and the short‐term exacerbation of pre‐existing psychotic symptoms. However, controversy exists about whether cannabis can actually cause long‐term psychosis. Approach . We summarised the findings of systematic reviews on the association between cannabis use and psychosis, searching MEDLINE, EMBASE and CINAHL up to August 2007. We assessed the methodological quality, selected the better quality reviews and analysed reasons for discordant results. Key Findings . We included five systematic reviews. Four of the reviews performed a meta‐analysis and showed a consistent association between cannabis use and psychosis; the fifth review considered psychological problems more broadly, did not perform a meta‐analysis and reported an inconsistent association. The reasons for discordance were: different outcomes (psychosis vs. psychological problems), different inclusion criteria for primary studies and different methods for summarising the results. Implications . This overview shows a consistent association between cannabis use and psychotic symptoms, though it is not possible to draw firm conclusions about a causal relationship. Reverse causality and residual confounding cannot be excluded. An interaction with other environmental and genetic factors is difficult to ascertain. Conclusion . We conclude that there is insufficient knowledge to determine the level of risk associated with cannabis use in relation to psychotic symptoms and that more information is needed on both the risks of cannabis use and the benefits of preventive interventions to support evidence‐based approaches in this area.[Minozzi S, Davoli M, Bargagli AM, Amato L, Vecchi S, Perucci CA. An overview of systematic reviews on cannabis and psychosis: Discussing apparently conflicting results. Drug Alcohol Rev 2009]