Repeated treatment with dithranol induces a tolerance reaction in keratinocytes in vitro

Summary The hyperproliferative human keratinocyte line (HaCaT) was tested for dithranol tolerance (tachyphylaxis) at the cellular level. At day 4 after seeding, keratinocytes were treated with 0.3 or 1.0 M dithranol. Data were compared with those from experiments including additional pretreatments with 0.3 M at day 3, or at days 1 and 3. Protein content, DNA synthesis and protein synthesis (incorporation of ³H-thymidine and ¹⁴C-amino acids per protein) were determined at 24, 48 and 72 h after the last drug exposure. Protein content of attached cells decreased in relation to dose and frequency of treatments. Inhibition of DNA and protein synthesis (38.2% and 32.3%, respectively) also occurred 24 h after a single treatment with 0.3 M dithranol, but was only 18.4% and 9.1% after pretreatment twice with 0.3 M dithranol. This tolerance reaction in vitro, after repeated dithranol exposure of human keratinocytes, may be explained by a selective loss of drug-sensitive cells.This study was supported in part by the W.-Doerenkamp-Foundation. B. F. from the Department of Dermatology, Albert Szent-Györgyi Medical University of Szeged, Hungary, is a fellow of the Alexander-von-Humboldt-Foundation. On the occasion of the 65th birthday of Prof. Dr. Dr. h. c. G. K. Steigleder     

Extracellular signal‐regulated kinase (ERK) is involved in LPS‐induced disturbances in intestinal motility

Background Lipopolysaccharide (LPS) is a causative agent of sepsis. A relationship has been described between LPS, free radicals, and cyclooxygenase‐2 (COX‐2). Here, we investigate the role of extracellular signal‐regulated kinase (ERK) mitogen‐activated protein kinases (MAPK) in the effect of LPS on intestinal motility, oxidative stress status, and COX‐2 expression. Methods Rabbits were injected with (i) saline, (ii) LPS, (iii) U0126, an ERK MAPK inhibitor, or (iv) U0126+LPS. Duodenal contractility was studied in an organ bath with acetylcholine, prostaglandin E₂, and KCl added. Neuromuscular function was assessed by electrical field stimulation (EFS). Neurotransmitter blockers were used to study the EFS‐elicited contractile response. The formation of products of oxidative damage to proteins (carbonyls), lipids, [malondialdehyde (MDA), and 4‐hydroxyalkenals (4‐HDA)] was quantified in plasma and intestine. The protein expression of phospho‐ERK (p‐ERK), total ERK, and COX‐2 in the intestine was measured by western blot, and p‐ERK was localized by immunohistochemistry. Key Results Acetylcholine, prostaglandin E₂, and KCl‐induced contractions decreased with LPS. Electrical field stimulation induced a neurogenic contraction that was reduced by LPS. Lipopolysaccharide increased p‐ERK and COX‐2 expression and the levels of carbonyls and MDA+4‐HDA. U0126 blocked the effect of LPS on acetylcholine, prostaglandin E₂, KCl, and EFS‐induced contractions, the levels of carbonyls and MDA+4‐HDA and p‐ERK and COX‐2 expression. Phospho‐ERK was detected mostly in the neurons of the myenteric and submucosal ganglia. Conclusions & Inferences We can suggest that ERK is involved in the mechanism of action of LPS in the intestine.     

Irritable bowel syndrome and risk of colorectal cancer: a Danish nationwide cohort study

Background:

Little is known about the risk of colorectal cancer among patients with irritable bowel syndrome (IBS).

Methods:

We conducted a nationwide cohort study using data from the Danish National Registry of Patients and the Danish Cancer Registry from 1977 to 2008. We included patients with a first-time hospital contact for IBS and followed them for colorectal cancer. We estimated the expected number of cancers by applying national rates and we computed standardised incidence ratios (SIRs) by comparing the observed number of colorectal cancers with the expected number. We stratified the SIRs according to age, gender, and time of follow-up.

Results:

Among 57 851 IBS patients, we identified 407 cases of colon cancer during a combined follow-up of 506 930 years (SIR, 1.14 (95% confidence interval (CI): 1.03–1.25) and 115 cases of rectal cancer, corresponding to a SIR of 0.67 (95% CI: 0.52–0.85). In the first 3 months after an IBS diagnosis, the SIR was 8.42 (95% CI: 6.48–10.75) for colon cancer and 4.81 (95% CI: 2.85–7.60) for rectal cancer. Thereafter, the SIRs declined and 4–10 years after an IBS diagnosis, the SIRs for both colon and rectal cancer remained below 0.95.

Conclusion:

We found a decreased risk of colorectal cancer in the period 1–10 years after an IBS diagnosis. However, in the first 3 months after an IBS diagnosis, the risk of colon cancer was more than eight-fold increased and the risk of rectal cancer was five-fold increased. These increased risks are likely to be explained by diagnostic confusion because of overlapping symptomatology.     

Why do festival goers drink? Assessment of drinking motives using the DMQ‐R SF in a recreational setting

Introduction and Aims. The aim of this study is to confirm the four‐dimensional structure and other measurement properties of the Drinking Motives Questionnaire Revised Short Form (DMQ‐R SF) among young Hungarian adults in a recreational setting. Design and Methods. In a ‘Health Tent’ at Europe's biggest music and cultural festival, 390 attendees (mean age 23.6, SD = 4.4) completed the DMQ‐R SF and answered other alcohol‐related questions. Data were analysed by confirmatory factor analysis, repeated measures anova and structural equation modelling. Results. The results confirmed the good measurement properties of the DMQ‐R SF in terms of factor loadings, model fit and internal consistency. These statistics were similar for men and women. For both genders, social motives were the most frequently indicated motivational dimension, followed by coping, conformity and enhancement. Social motives were consistently related to drinking, and coping to alcohol‐related problems. Discussion and Conclusions. It seems that the DMQ‐R SF is a useful instrument for measuring the motivation to engage in drinking in recreational settings, such as parties, clubs and festivals, where hard‐to‐reach target groups vulnerable to risky drinking behaviour are present, but time for filling out questionnaires is restricted.[Németh Z, Kuntsche E, Urbán R, Farkas J, Demetrovics Z. Why do festival goers drink? Assessment of drinking motives using the DMQ‐R SF in a recreational setting. Drug Alcohol Rev 2011;30;40–46]     

Atrofia renal izquierda y abocamiento ureteral a vesícula seminal. tratamiento quirúrgico laparoscópico

Renal atrophy with an ectopic drainage of the ureter is an uncommon malformation. Zinder described in 1914 a cystic dilation of the seminal vesicle in association with an ipsilateral renal agenesis. Usually, these patients present lower urinary tract symptoms with perineal discomfort and fever. The most accurate diagnosis is given by the MRI, while CT and ultrasonography are less precise.We present a case of a patient who goes into hospital because of left lumbar pain and urinary sepsis data, whose CT detects an ectopic drainage of the left uereter in the seminal vesicle. He underwent a successful laparoscopic surgical treatment.     

Validity of reliability: comparison of interrater reliabilities of psychopathological symptoms

We have tested the stability of interrater reliability of psychiatric symptoms over a quarter of century using 2 rating scales. Interrater reliabilities of items of 2 psychiatric rating scales employed by 2 consecutive follow-ups were compared. Interrater reliabilites proved to be by and large stable. Interrater reliability depends on the standard deviation of the items scores. In addition to the traditional approach, a new statistical method for unifying the assessments from multiple raters is also presented. Using this method, we demonstrated that probabilities of correct ratings are higher in the absence of manifest symptoms, or in the presence of symptoms, as compared with cases characterized by middle scores. To interpret the relationships revealed in the setting of the experiment, we introduce for its theoretical designation the term "validity of reliability." It is recommended for evaluation of results of rating scales in the context of psychiatric nosology.     

A comparison of factors associated with collagen metabolism in different skeletal muscles from dystrophic (mdx) mice: impact of pirfenidone

Skeletal muscles in mdx mice exhibit differential degrees of pathological changes and fibrosis. The purpose of this study was to examine differences in various indices of collagen metabolism in skeletal muscles with widely different functions and activity profiles in mdx mice, and to determine whether pirfenidone would attenuate the development of fibrosis. Mice in the pirfenidone group were orally fed pirfenidone (500 mg/kg) daily for 4 weeks. Marked differences were noted in hydroxyproline concentration between muscles, which could not be explained solely by the level of type I collagen and transforming growth factor-beta1 (TGF-beta1) mRNA. In normal mice, matrix metalloproteinase (MMP)-2 mRNA was significantly higher in the gastrocnemius than in the diaphragm or genioglossus muscles, suggesting that collagen degradation plays an important role in regulating collagen accretion in skeletal muscle. In mdx mice, the levels of both MMP-2 and MMP-9 mRNA were significantly elevated relative to control, although the response was muscle specific. Pirfenidone treatment resulted in a significant reduction in the level of hydroxyproline concentration across all muscles, although the effect was small. Results from this study reveal intrinsic dissimilarities in collagen metabolism between functionally different skeletal muscles. Moreover, the pharmacological use of pirfenidone may be beneficial in preventing fibrosis in muscular dystrophy.