Secretion,blood levels and cutaneous expression of TL1A in psoriasis patients

TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker.     

Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations.

Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr respectively) whereas differences in AUC, t1/2 and Cmax were not significant. The AUC (mean +/- S.D.) values following single dose administration of Cardil and Cardizem were 678.4 +/- 321.5 and 948.6 +/- 580.6 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.89 and 0.44-1.34 respectively. At steady-state a significant difference between Cmax/Cmin and tmax was seen Cmax/Cmin being 4.9 and 3.2 respectively and Tmax being 2.7 +/- 2.0 and 6.0 +/- 2.8 hr respectively, whereas Cmax and AUC did not differ significantly. The AUC (mean +/- S.D.) values in steady state of Cardil and Cardizem were 880.1 +/- 399.8 and 1056.8 +/- 509.8 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.96 and 0.66-1.26 respectively. Although the observed ratios AUCCardil/AUCCardizem in both the single-dose and the steady-state study do not differ significantly from 1.0, the confidence limits exceed the acceptable values given by Poulsen & Juul (personal communication 1990) (a 20% decrease or increase of the ratio to 0.8 or 1.2).     

Cisplatinum Dose Dependent Response in Germ Cell Cancer Evaluated by Tumour Marker Modelling

This study presents an analysis on longitudinal tumour marker series in twenty-two patients with non-seminomatous germ cell cancers treated with cisplatinum (DDP) based combination chemotherapy. Series of alphafoetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) were analyzed applying a dynamic mathematical marker model. The model analysis provided quantitated values for growth rate and treatment response in the marker producing cells. The analysis showed that LDH had to be above 2 000 U/l to be a trustworthy tumour marker. HCG producing cells tended to grow faster than AFP producing cells, and were 3-5-fold more sensitive to the chemotherapy given than AFP producing cells. Treatment response versus DDP dose appeared to be bi-phasic, but with no significant change in treatment efficiency within the given range of DDP doses.     

A longitudinal study of semen quality in pesticide spraying danish farmers

It was hypothesized that occupational exposure to pesticides during a spraying season causes changes in semen quality that might be detected in a longitudinal study. We analyzed the within-person changes in semen quality and reproductive hormones across a spraying season in groups of farmers using and not using pesticides. A total of 248 men collected two semen samples (participation rate: 32%). The median sperm concentration declined significantly from the first to the second sample in both groups, but there was no statistical difference in the decline between the two groups, unadjusted or adjusted. Only minor changes were found in sperm morphology, vitality, motility, sperm chromatin denaturation (SCSA), and reproductive hormones, and the differences in changes between the two groups were nonsignificant, or, in the opposite direction to the expected. There was no relation between the changes in sperm parameters in relation to pesticide exposure variables. In conclusion, use of pesticides by Danish farmers is not a likely cause of short-term effects on semen quality and reproductive hormones.     

Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options.

Malfunction of the male reproductive system might be a sensitive marker of environmental hazards, the effects of which may extend beyond reproductive function. The testis is more vulnerable to heat and ionising radiation than any other organ of the body and several xenobiotics are known to disrupt spermatogenesis after low level exposure. Studies of environmental impact on human health are often most informative and accurate when carried out in the workplace where exposures can be high and easy to document. Semen analysis provides readily obtainable information on testicular function. The main advantages in comparison with functional measures such as fertility rates and time taken to conceive are the possibilities to examine men independently of marriage and pregnancy, to find changes of fecundity with different exposures within the same person and to detect adverse effects when no alteration of fertility is yet taking place. In the implementation of an occupational sperm study considerable attention must be paid to logistic issues. A mobile laboratory unit for initial semen preparation and processing may in some situations increase worker compliance and the quality of sperm cell motility. The cross sectional design which has been used in almost all male reproductive studies so far has several severe limitations including selection bias because of differential participation, difficulties in defining a suitable reference group, and lack of information about the time dimension of the cause-effect relation. The longitudinal design deals adequately with most of these constraints. Semen samples are collected before, during, and possibly after exposure to the risk factor of interest and causal inferences are based upon change of semen variables within a man over time rather than upon differences between men. The logistics of the longitudinal study may benefit from pre-employment health examinations to enrol newly hired workers and require fewer participants to obtain comparable statistical power. In conclusion, andrological methods and epidemiological designs are available for the implementation of valid studies concerned with environmental impact on human testicular function. Occupational sperm studies should probably not be the first choice when the objective is initial screening of environmental impact on fertility but should be implemented when their is a need to corroborate or refuse earlier evidence that specific exposures have impact on testicular function.