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Cardoso de Araújo, M, Baumgart, C, Jansen, CT, Freiwald, J, and Hoppe, MW. Sex differences in physical capacities of German Bundesliga soccer players. J Strength Cond Res 34(8): 2329-2337, 2020-Sex differences in physical capacities of elite soccer players have received limited attention. Therefore, this study investigated sex differences in linear and nonlinear sprint, squat and countermovement jump, core endurance, as well as incremental and intermittent endurance capacities in German Bundesliga soccer players. A total of 76 field players (29 women) were tested for the mentioned anaerobic- and aerobic-related physical capacities in a noninterventional cross-sectional design. The largest sex differences were evident in the explosive- and intermittent endurance-related capacities, with women presenting largely to extremely largely lower values in sprints, jumps, and intermittent endurance (effect size [ES] ≥1.77, p < 0.01). The differences in the total core endurance, running velocity at 2 and 4 mmol·L capillary blood lactate (v2 and v4), maximal heart rate (HR) (ES ≤ 0.72, p ≥ 0.06), and distance covered during the incremental endurance test (ES = 1.09, p = 0.01) were trivially to moderately lower for women. However, women had small to moderately higher ventral and dorsal core endurance (ES ≤ 0.69, p ≥ 0.07) and largely higher relative HR at the lactate thresholds (ES ≥ 1.54, p < 0.01). The individual data of female players showed more variability. Some individual data of women overlapped those of men, most evident in the total core endurance and v2. The findings indicate that there are sex differences in physical capacities according to the underlying amount of anaerobic and aerobic energy supply. The sex specificities should be considered to optimize training and testing procedures for soccer players.

One of the major problems facing the elderly spine is the occurrence of vertebral fractures due to low bone mass. Although typically attributed to osteoporosis, disc degeneration has also been suggested to play a role in vertebral fractures. Existing bone adaptation theories and simulations may explain the biomechanical pathway from a degenerated disc to an increased fracture risk. A finite element model of a lumbar segment was created and calibrated. Subsequently the disc properties were varied to represent either a healthy or degenerated disc and the resulting bone adaptation was simulated. Disc degeneration resulted in a shift of load from the nucleus to the annulus. The resulting bone adaptation led to a dramatically reduced density of the trabecular core and to an increased density in the vertebral walls. Degeneration of just the nucleus, and in particular the dehydration of the nucleus, resulted in most of this bone density change. Additional annulus degeneration had much less of an effect on the density values. The density decrease in the trabecular core as seen in this study matches clinical observations. Therefore, bone remodeling theories can assists in explaining the potential synergistic effects of disc degeneration and osteoporotis in the occurrence of vertebral fractures., (Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.)

Ultraviolet radiation (UVR) is the principal cause of cutaneous malignant melanoma (CMM). However, the relation between CMM and UVR exposure is not clear. We present the trends of population exposure to UVR and conduct a time-series analysis of the relation between UVR exposure and incidence of CMM. Data on CMM incidence were obtained from the Finnish Cancer Registry. Clothing coverage of the body was scored from archival photographs and the proportion of uncovered skin was used as a measure of solar exposure. Information on the number of sunny resort holidays, duration of annual holidays, and sunscreen sales were obtained from various sources. Exposed skin area doubled from 1920 to 1985. The average duration of annual holidays increased 30-fold. The number of sunny resort holidays and the sales of sunscreens increased rapidly from 1980. CMM was most strongly associated with solar exposure of 5-19 years earlier. There is a considerable decrease in clothing coverage during the 20th century. UVR exposure preceding CMM occurrence 4 years or less does not appear relevant, whereas the period 5-19 years prior to CMM occurrence might be the most relevant period. However, findings of ecological studies may not be applicable at the individual level.

Background: A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris., Objectives: To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX., Methods: Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well., Results: The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3.4 mg week-1 (phase (II) and 2.6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle)., Conclusions: The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased.

Data on DNA repair rates of specific types of DNA lesions are very limited in humans in situ. Rate of repair of UV-induced DNA damage was followed in the skin of 17 volunteers up to 3 weeks of UV exposure, using a (32)P-postlabelling technique for the determination of specific photoproducts. The subjects of skin phototypes I and IV were exposed to 40 mJ/cm(2) of solar simulating radiation on buttock skin, and biopsies were taken at 0 h, 48 h and 3 weeks of exposure for the analysis of two cyclobutane pyrimidine dimers, TT=C and TT=T, and two 6-4 photoproducts, TT-C and TT-T, as trinucleotides. Repair rates were heterogeneous for different photoproducts. T=T dimers were repaired slower than C=T dimers, and 2.3-9.0% of the initial T=T damage remained unrepaired after 3 weeks, and was detectable in 16/17 subjects. The identity of the identified photoproducts was confirmed by a photochemical reversion assay. Damage level correlated with skin types, type I being more sensitive than type IV in an age-matched comparison. This is the first time the persistence of defined human DNA damage is demonstrated up to 3 weeks. Long-lasting DNA damage increases the likelihood of mutations.

The development of cutaneous malignant melanoma (CMM) and its precursor lesions, melanocytic nevi, has been linked to sun exposure. Cyclobutane pyrimidine dimers (CPDs) are the majority of DNA lesions induced by sun exposure. In our study, we investigated if CMM patients have impaired ability to repair CPDs in skin as well as in melanocytic nevi. The repair kinetics were followed up to 3 weeks after exposure to 40 mJ/cm(2) of solar simulating radiation. Altogether 12 CMM patients and 10 healthy controls were included in our study. Buttock skin biopsies were taken at 0 hr, 48 hr and 3 weeks after UV exposure, whereas melanocytic nevi and surrounding skin biopsies were taken only at 0 hr and 3 weeks. The CPD levels were measured by a (32)P-postlabeling method. The results showed that the repair rate of CPDs in neither the skin nor the nevi was significantly different between the CMM patients and the control group. For both groups, the repair rate of TT = C was faster than that for TT = T. The important finding is that about 10% of the initial TT = T damage remained unrepaired after 3 weeks, and was detectable in normal epidermis as well as in nevi of all subjects. We also found that the amount of TT = C and TT = T at 0 hr in nevi was significantly lower than that in surrounding skin (Wilcoxon rank sum test, p < 0.05)., (Copyright 2002 Wiley-Liss, Inc.)

Recent studies on the immunosuppressive effects of ultraviolet radiation (UVR) and the related resistance to infections in rodents and humans are presented. The waveband dependency of trans-to-cis isomerisation of urocanic acid in the stratum corneum and the role of DNA damage in UVR-induced erythema and immunosuppression were investigated to further elucidate the underlying mechanisms. Furthermore, human experimental studies on UVR-induced immunomodulation were performed. It appeared that the doses needed to suppress various immune parameters in humans (e.g. NK activity, contact hypersensitivity) were higher than those needed in experiments in rodents. Still, extrapolation of experimental animal data to the human situation showed that UVR may impair the resistance to different systemic infections at relevant outdoor doses. In observational human studies we aimed to substantiate the relevance of UVR for infections in humans. It was shown that sunny season was associated with a slightly retarded but clinically non-relevant antibody response to hepatitis B vaccination. Furthermore, sunny season appeared to be associated with a small decline in the number of CD4+ T-helper cells in a cohort of HIV-infected persons and a higher recurrence of herpes simplex and herpes zoster in a cohort of renal transplant recipients. However, in a study among young children a higher exposure to solar UVR was associated with a lower occurrence of upper respiratory tract symptoms. As disentangling the effects of UVR from other relevant factors is often impossible in observational studies, concise quantitative risk estimations for the human situation cannot be given at present.

Melanocytic nevi are localized benign proliferations of melanocytes. The number of nevi has been shown to be the major risk marker for the development of cutaneous melanoma. This study compares the induction of photoproducts in nevi and in surrounding skin after exposure to solar-simulating radiation. Cyclobutane pyrimidine dimers (TT=T and TT=C) and 6-4 photoproducts (TT-T and TT-C) were measured in 20 nevi and 20 surrounding skin samples obtained from 14 subjects, using a 32P-postlabeling method. The amount of all four types of photoproducts in nevi was found to be 3-5-fold lower than that in surrounding skin, and the difference was statistically significant (paired t test, p < 0.01). In nevi, the photoproduct level was significantly associated with the color of nevi (the lowest level in the darkest color of nevi; r = -0.86, p < 0.01 for TT=T; r = -0.68, p < 0.01 for TT=C). Our findings suggest that the magnitude of the DNA damage is not a sole risk marker for the development of cutaneous melanoma.

Forty-four Finnish volunteers who were previously studied with regard to the repair rate of UV-specific cyclobutane pyrimidine dimers in the skin were genotyped for XPD polymorphisms at codons 312 (exon 10 G-->A, Asp-->Asn) and 751 (exon 23 A-->C, Lys-->Gln). The repair rate was measured at 24 h for two different cyclobutane dimers. The data did not show consistent XPD genotype-specific differences in DNA repair rates among all subjects. The combined exon 10 AA and exon 23 CC genotype was associated with an approximately 50% depression of repair rate but this was of borderline statistical significance. However, the exon 23 C allele was associated with depressed repair among subjects aged 50 years or older and the result was consistent with both dimers.

Ultraviolet irradiation influences natural killer cell function both in vitro and in vivo. The postulated ultraviolet photoreceptor in the epidermis, urocanic acid, has been reported to depress the cytotoxic activity of human natural killer cells. Therefore, this study investigated whether this would occur through specific second messengers, using a radioimmunoassay for intracellular adenosine 3',5'-cyclic monophosphate (cAMP) and Fluo-3 staining plus flow cytometry for free calcium. Both isolated lymphocytes and enriched CD16+ cells were used. A combination of the trans- and cis-isomers of urocanic acid (200 microg/ml) induced cAMP in both CD16+ and CD16- cells, but individual, stereospecific effects were not demonstrable. Urocanic acid did not induce significant changes in calcium levels in lymphocytes, or natural killer cells alone or conjugated to K562 target cells. Evidently, the biochemistry of urocanic acid-mediated natural killer-cell modulation is complex, and the cellular receptor(s) and specific signal transduction pathway(s) mediating the biological effects of urocanic acid remain elusive.

It has been postulated that Langerhans cells (LC) provide tolerogenic signals in the local impairment of cutaneous immune functions and antigen-specific tolerance induced by UV radiation. Studies in vitro and ex vivo have indicated that UV radiation may down-regulate the expression of costimulatory molecules on LC, leading to reduced antigen-presenting function. In contrast, we recently observed an up-regulatory stage in the number of human epidermal LC with induced expression of B7 costimulatory molecules 12-24 h after solar-simulating UV radiation (SSR) in vivo. To examine the apparent discrepancy between the observed human LC responses in vitro, ex vivo and in vivo, we compared the three protocols in a parallel fashion. The intact skin as well as skin explants and epidermal cell suspensions from the same individuals were irradiated with a single erythematogenic dose of SSR. The expression of cell surface markers in the epidermal cells was analysed with flow cytometry 24 h later. The number of CD1a+/HLA-DR+ LC increased post-SSR in vivo by a factor of 2.8+/-0.4, whereas in irradiated skin explants ex vivo or in cell suspensions in vitro, reduced numbers were seen. HLA-DR expression intensities were found to have increased on DR+ and CD1a+/DR+ cells in vivo. Similarly, SSR induced B7-2 (CD86) expression in CD1a+ cells significantly in vivo (P=0.031) but reduced the expression ex vivo or in vitro. We conclude that the early up-regulatory stage of human LC number and membrane markers, recorded at 24 h after a single exposure to SSR, is exclusively an in vivo phenomenon.

The 32P-postlabeling method was applied to measure directly the levels and repair rates of specific cyclobutane pyrimidine dimers and 6-4 photoproducts in 10 basal cell carcinoma patients and 10 controls matched on age, skin type, and gender after exposure to 400 J per m2 of solar simulating radiation on previously unexposed buttock skin. The results showed an identical level of photoproducts at 0 h after solar simulating radiation in the basal cell carcinoma group and the control group. Erythemal response correlated with the repair of cyclobutane pyrimidine dimers within 24 h in both groups, i.e., repair was faster in those with a strong erythemal reaction. The basal cell carcinoma patients showed a somewhat slower repair of photoproducts in skin compared with the controls, but the result was not significant. Photoproducts formed at the TTC sites were repaired faster than those at the TTT sites for both cyclobutane pyrimidine dimers and 6-4 photoproducts in the basal cell carcinoma group and in the controls.

Ultraviolet radiation (UVR)-induced photoproducts can be measured by a number of methods. The newly developed 32P-postlabelling method is feasible in molecular epidemiological studies due to its sensitivity, specificity and little amount DNA needed. We applied the 32P-postlabelling method to investigate the induction and repair of photoproducts (cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts) after UVR in human skin in situ and studied the effects of age, skin type and gender. The study included 30 subjects aged 32-78 years. The photoproduct induction levels varied 7- to 15-fold between the individuals tested. All four types of photoproducts were induced at a higher frequency in the older population (>/=50 years) than in the younger population (<50 years). Individuals with skin type I and II had a higher CPD induction frequency than individuals with skin type III and IV. In both cases, the differences in thymidylyl (3'-5') thymidylyl (3'-5')-2'-deoxycytidine induction reached statistical significant levels (p<0.05). Photoproduct repair rates 24 h and 48 h after UV irradiation showed a large inter-individual variation. No clear effects of age, skin type or gender on DNA repair could be detected. Our data suggest that UV-induced DNA photoproduct levels increase with age.

The DNA lesions induced by ultraviolet radiation include cyclobutane pyrimidine dimers and 6-4 photoproducts. We investigated whether cutaneous melanoma patients have an impaired ability to repair their ultraviolet-induced photolesions. Seventeen patients with melanoma and 13 healthy controls took part in this study. Both groups received a dose of 40 mJ per cm2 Commission Internationale de l'Eclairage of solar simulating radiation on previously unexposed buttock skin. Skin biopsies were taken at 0 h, 24 h, and 48 h after ultraviolet exposure. A 32P-postlabeling method was used to measure both cyclobutane pyrimidine dimers and 6-4 photoproducts in skin. Cyclobutane pyrimidine dimers and 6-4 photoproduct levels did not differ in the melanoma patients from those in the control group at any time point post-ultraviolet radiation. The repair rate of cyclobutane dimer TT=C was faster than that for TT=T both at 24 h and 48 h postirradiation in both groups, providing evidence of site-specific repair (p < 0.05). We conclude that patients with melanoma have a normal ultraviolet-induced DNA repair capacity in skin in situ.

The relationship of epidermal urocanic acid concentration and photoisomerization reactivity to human skin cancer was studied. Twelve cutaneous malignant melanoma patients, 10 basal cell carcinoma patients and 22 healthy matched controls were enrolled in the study. A solar simulating ultraviolet irradiator was used for phototesting the minimal erythema dose. Using the Finn Chamber technique, urocanic acid was sampled from the healthy skin of the upper back, prior to and after exposure to suberythemal UV doses. The mean values of total and trans-urocanic acid were higher in basal cell carcinoma patients than in controls, but this difference was not statistically significant. No corresponding phenomenon was evident in the case of cutaneous malignant melanoma patients and their controls. Photoisomerization induced by irradiation with 1 mJ/cm2 CIE (Commission Internationale de l'Eclairage) was statistically significantly lower in cutaneous malignant melanoma patients than in controls (p=0.04). A similar trend was seen in basal cell carcinoma patients vs. their controls, but the difference was not significant.

We examined systemic effects of whole-body UVB irradiation on human peripheral blood phagocytes. We found that 24 h after a single erythemal dose of UVB radiation two phagocyte functions, adhesion and phagocytosis, were reduced by 50%. This functional suppression was accompanied by a significant decrease in the expression of complement receptors (CR1 and CR3) and IgG Fc receptors (FcRII and FcRIII). The greatest reduction (47%) was observed in CR3, which is important for both adhesion and phagocytosis. A kinetic analysis showed that both CR1 and CR3 levels started to decrease 15 min after the UVB exposure, reaching the lowest levels at 4.5- and 24-h time points, respectively. The down-modulation of CRs after whole-body UVB exposure was not due to a defective receptor synthesis or translocation from internal stores to plasma membrane because the maximal CR levels in stimulated cells were not affected by UVB. No change in the serum soluble ICAM-1 was detected after UVB, which rules out CD1 1b epitope masking by sICAM-1. UVB did not release low-receptor-density myeloid progenitor cells from storage pools into circulation. Interleukin 10, a mediator of UVB-induced immunosuppression, was unable to modulate CR expression in vitro. When seven suberythemal whole-body UVB exposures were given repeatedly within 2 weeks, a significant decrease in CR expression was seen, which was greatest after three irradiations. Our data suggest that an exposure to UVB has systemic effects in humans which, possibly due to the down-modulation of preexisting cell-surface receptors, suppress some important functions of circulating phagocytic cells.

Objectives: To examine the long-term outcome of polymorphous light eruption (PLE) in a large patient population and to evaluate associated conditions, especially lupus erythematosus, during the course of the disease., Design: A questionnaire-based follow-up study an average of 32 years after onset of PLE. The study was complemented by clinical examination of the patients with PLE similarly studied 16 years earlier or now reporting equal or worse PLE symptoms compared with the 1978-1979 follow-up or any symptoms suggesting an autoimmune disease., Setting: A dermatologic clinic in a university hospital., Patients: Ninety-four of the original cohort of 138 patients with PLE (87% of living patients) returned the questionnaire, and 46 (84%) of the 55 patients invited volunteered for clinical examination., Intervention: None., Main Outcome Measures: Clinical characteristics of PLE and clinical laboratory findings referring to associated diseases, especially lupus erythematosus., Results: Twenty-three (24%; 95% confidence interval [CI], 16%-34%) of the 94 patients were cured, 48 (51%; 95% CI, 41%-62%) experienced milder symptoms, and 23 (24%; 95% CI, 16%-34%) experienced equal or worse symptoms than in the 1978-1979 follow-up. At least 1 autoimmune disease was diagnosed at some point in 14 patients (15%; 95% CI, 12%-29%) (in 13 [18%] of the female patients) and lupus erythematosus specifically in 2 (2%; 95% CI, 0%-7%) (in 2 [3] of the female patients). The prevalence of a thyroid disease was 14% (13 patients) (95% CI, 8%-23%)., Conclusion: Polymorphous light eruption is a long-standing slowly ameliorating disease with some tendency to development of autoimmune disease or thyroid disorder, especially in female patients, but the risk for lupus erythematosus is not increased.

UV light is considered an important contributor to skin cancer, but methods have been lacking to quantify specific UV-induced lesions in human skin in situ. We applied a newly developed 32P-postlabeling technique to measure specific UV-induced cyclobutane dimers and 6-4 dipyrimidine lesions in the skin of healthy volunteers. At a dose of 400 J/m2, solar-simulated radiation caused at least 20 cyclobutane dimers/10(6) nucleotides, which is much higher than any known DNA adducts induced by specific external chemical exposure in human target tissues. This may explain why patients with DNA repair syndromes, such as xeroderma pigmentosum, preferentially develop skin cancer. We applied the 32P-postlabeling technique to study rates of DNA repair in healthy individuals. The obtained data indicated a base sequence dependence of the repair process. The applied method has potential for the study of DNA repair as a determinant of individual susceptibility to skin cancer.

Ultraviolet (UV) radiation impairs cutaneous immune functions and induces antigen-specific tolerance both locally at the irradiated skin site, as well as at distant skin sites and systemically. It has been postulated that in the local model, altered Langerhans' cells (LC) provide tolerogenic signals, and studies in vitro have indicated that UV radiation may down-regulate the expression of co-stimulatory molecules on the surface of these cells. To examine the effect of UV radiation on LC co-stimulatory molecules in vivo, we irradiated human volunteers with erythematogenic doses of solar-simulating UV radiation (SSR), and analyzed the expression of cell surface markers in dermatome skin samples obtained 1-72 h post-irradiation. For flow cytometric analysis, epidermal cell (EC) suspensions were prepared and double labeled with monoclonal antibodies against CD1a or HLA-DR, and B7-1 (CD80), B7-2 (CD86), ICAM-1 (CD54), ICAM-3 (CD50), LFA-3 (CD58), E-cadherin, or integrin-beta4 (CD104). In unirradiated control skin samples, keratinocytes (KC) expressed high levels of E-cadherin. LC expressed high levels of both E-cadherin and ICAM-3, and low levels of B7-2, LFA-3, ICAM-1, and integrin-beta4. Following SSR, a triphasic reaction pattern was seen: an immediate, down-regulatory phase prevailing 2-6 h post-irradiation, when the number of DR+ and CD1a+ cells were temporarily reduced; a delayed, up-regulatory phase in which the number of LC was increased and the expression intensities of CD1a, HLA-DR, B7-1, and B7-2 were strongly up-regulated, maximally evident 12-24 h after irradiation, but no more seen at 48 h; and a late phase at 72 h, in which an influx of monocytes and a concomitant rise in DR+ cells was recorded. We conclude that to understand real-life cutaneous UV immunology, studies in vitro need to be complemented with studies in vivo. In the case of LC, the effects of erythematogenic UV radiation in vivo on human LC B7 co-stimulatory molecules include an up-regulatory stage.

We have studied the influence of variations in allergen concentration and UVA dosaging on the results of photopatch testing with the Scandinavian standard photopatch series in 29 patients with photocontact and/or contact allergy to 1 or several of the allergens in that series. Photocontact test reactions were more sensitive to allergen dilution than plain contact test reactions. Even dilution from the standard 5% to 2.5% significantly reduced para-aminobenzoic acid photocontact test reactions. Reducing the UVA dose from the standard 5 J/cm2 to 2.5 or 1 J/cm2 in 2 out of 5 cases turned a significant (++) reaction into a doubtful one (+). Increasing the standard UVA dose of 5 J/ cm2 to 20-40 J/cm2 turned a single + photocontact reaction to trichlorcarbanilide and a single 1 + plain contact reaction to chlorhexidine into ++ reactions. In the majority of cases, however, neither photocontact nor plain contact test reactions were augemented by UVA doses up to 80 J/cm2. We conclude that a UVA dose of 5 J/cm2 is sufficient for eliciting photocontact allergic test reactions, and that a reduction of either the UVA dose level or the standard allergen concentrations of the Scandinavian photopatch test guidelines may cause loss of significant photocontact test reactions in a proportion of the cases.

The anamnestic skin phototypes (ASP) I-IV of 22 Caucasian volunteers wee compared with their phototested skin phototypes (PSP) using solar simulating, broadband UV radiation. The Commission Internationale de l'Eclairage (CIE)-weighted (i.e. erythemally effective) minimal erythema doses (MED) for solar simulating radiation varied from 20 mJ/cm2 (PSP type 1) to 57 mJ/cm2 (PSP type 4). In only 11 of 21 volunteers did the ASP (I-IV) and PSP (1-4) classifications coincide, and the MED values of the volunteers within the different ASP groups (I-IV) overlapped considerably. To compare the reactivity to erythematogenic radiation of different wavelengths, narrowband monochromator irradiations were performed at 298 nm, 310 nm and 330 nm. The CIE-weighted MED values at these wavelengths (20-80 mJ/cm2) corresponded well with those obtained in the broadband testing. Our results indicate that, with classification by interrogation, Caucasian skin can reliably be classified into only two subtypes, corresponding to Fitzpatrick phototypes I-III and phototype IV, respectively. A classification into four sensitivity types can be achieved by phototesting, only. We propose that the concept of ASP should be used with caution. The concept of PSP 1-4 should be favored.

In the present study we have measured the concentrations of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in preovulatory follicular fluid (FF) samples obtained from patients undergoing ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin. In 13 of the 24 (54%) FF samples obtained from 20 patients, TNF-alpha was detected. In contrast, IL-1 beta was observed in none of the 16 samples assessed. In the samples with detectable levels of TNF-alpha, the mean concentration was 40.1 pg/ml (range 20-74 pg/ml). In addition, we found an association between the presence of TNF-alpha in the FF and the serum level of 17 beta-estradiol (E2) and progesterone (P). The E2 and P levels were significantly lower in patients with detectable levels of TNF-alpha in FF than in patients with no detectable TNF-alpha in FF. In summary, the present study shows the presence of TNF-alpha and the absence IL-1 beta in hyperstimulated human preovulatory FF. In addition, our results show an association between the presence of TNF-alpha in FF and low E2 and P levels in serum, suggesting a role for TNF-alpha in the regulation of human steroidogenesis.

To assess the role of interleukin-1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha) in the physiological host defence mechanisms against malignancies, the production of these cytokines in sera, ascitic and cyst fluids and in the tumour tissues of patients with benign or malignant ovarian tumours was studied. IL-1 beta was found neither in the sera nor in the ascitic fluids of these patients. It was also virtually absent from the cyst fluid samples. However, a mean value of 790 pg IL-1 beta/g tumour was found. Like IL-1 beta, TNF alpha was virtually absent in the serum samples. It was, however, detectable in the ascitic and cyst fluids and tumour tissues. The TNF alpha concentrations were highest in the tumour tissues, with a mean level of 328 pg/g tumour. When comparing the level of IL-1 beta and TNF alpha in patients with benign tumours to that seen in patients with malignant tumours, no differences in production were observed, regardless of the origin of the test samples. Our results indicate the production of IL-1 beta and TNF alpha in patients with ovarian tumours. More importantly, the finding that the production of these cytokines in patients with benign tumours is similar to that in patients with malignant tumours supports the conclusion that the production of these cytokines is more a nonspecific indicator of an inflammatory process than a specific response to a malignant process.

Twenty-three patients with chronic urticaria were treated with cinnarizine, dexchlorpheniramine and placebo in a double-blind, crossover trial. Compared to placebo treatment both cinnarizine and dexchlorpheniramine caused a statistically significant improvement in the clinical symptoms (p less than 0.01). The two active drugs were found to be equally effective; however, cinnarizine was better tolerated. Both drugs appear to be useful in the treatment of chronic urticaria.

When 125 patients with generalized pruritus were followed up for 6 years, 66% reported continuing pruritus. In four patients a malignancy had been identified at the time of the initial examination, and four other patients developed malignancies during the follow-up period. Seven of the patients died of the malignancy during the follow-up period. This incidence of malignancies does not differ significantly from the value expected in a general population, matched for age and sex. However, two of the cancers were lymphomas, and this incidence is significantly (p less than 0.01) higher than that expected in a similarly matched population. As a whole our study indicates that no significant overall increase of malignant neoplasms is to be expected in patients with generalized pruritus and, therefore, any general efforts for cancer follow-up screening seem unwarranted in patients with pruritus.

The possible modulating effect of previous nickel sensitization on subsequent cobalt sensitization, and vice versa, was studied in a guinea pig model, using an open epicutanous induction protocol. Challenge tests were made by both topical and systemic routes. Controls included animals sensitized to only one of the metals. Animals sensitized with both metals seemed to react more readily in patch testing to either allergen, as compared to mono-sensitized animals. Systemic challenge with cobalt revealed a significantly (p less than 0.05) higher reaction rate (70%) in animals originally sensitized to cobalt and subsequently to nickel, as compared to the reaction rate (20%) in cobalt mono-sensitized animals. The reverse order of double-sensitization (nickel first, cobalt subsequently) led to an intermediate cobalt sensitization rate (50%). These experimental data corroborate clinical findings which have indicated a mutual enhancing effect of nickel and cobalt contact sensitization in man, and provide an animal model for studying the underlying immunological processes.

An in-depth allergy history was obtained from 830 consecutive patients who were subjected to intravenous radiographic contrast medium (RCM) examinations. During the RCM examination 47 patients reacted with symptoms of hypersensitivity. In 26 of these (55.3%) a positive previous allergy history had been obtained. Although this finding was statistically significant, its practical value is severely hampered by the lack of selectivity, many of RCM non-reactors also giving positive allergy histories. A positive history of a previous reaction to RCM or to penicillin, however, was found to have more specificity in predicting a forthcoming hypersensitivity reaction to RCM.

In a double-blind trial patients with atopic eczema received either oral evening primrose oil (EPO) (n = 14) or placebo (n = 11) for 12 weeks. In the EPO group a statistically significant improvement was observed in the overall severity and grade of inflammation and in the percentage of the body surface involved by eczema as well as in dryness and itch. Patients in the placebo group showed a significant reduction in inflammation. The patients receiving EPO showed a significantly greater reduction in inflammation than those receiving placebo. Evening primrose oil caused a significant rise in the amount of dihomogammalinolenic acid in the plasma phospholipid fatty acids. Plasma levels of TXB2, 6-keto-PGF1 alpha and PGE1, and the amount of TXB2 released into serum during clotting were not altered by evening primrose oil.

There is increasing evidence that derivatives of 20-carbon polyunsaturated fatty acids, the eicosanoids, play an important role in the inflammatory responses of the human skin. To better understand the metabolic fate of fatty acids in the skin, the effect of ultraviolet B (UVB) irradiation (280-320 nm) on the distribution and release of 14C-labeled arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture was investigated. Ultraviolet B irradiation induced the release of all three 14C-labeled fatty acids from the phospholipids, especially from phosphatidylethanolamine, and this was accompanied by increased labeling of the nonphosphorus lipids. This finding suggests that UVB induces a significant liberation of eicosanoid precursor fatty acids from cellular phospholipids, but the liberated fatty acids are largely reincorporated into the nonphosphorus lipids. In conclusion, the present study suggests that not only arachidonic acid but also dihomo-gamma-linolenic acid, and eicosapentaenoic acid might be involved in the UVB irradiation-induced inflammatory reactions of human skin.

Human keratinocytes in culture were labelled with 14C-dihomo-gamma-linolenic acid, 14C-arachidonic acid or 14C-eicosapentaenoic acid. All three eicosanoid precursor fatty acids were effectively incorporated into the cells. In phospholipids most of the radioactivity was recovered, in neutral lipids a substantial amount, and as free unesterified fatty acids only a minor amount. The most of the radioactivity was found in phosphatidylethanolamine which was also the major phospholipid as measured by phosphorous assay. The incorporation of dihomo-gamma-linolenic acid and arachidonic acid into lipid subfractions was essentially similar. Eicosapentaenoic acid was, however, much less effectively incorporated into phosphatidylinositol + phosphatidylserine and, correspondingly, more effectively into triacylglycerols as compared to the two other precursor fatty acids. Once incorporated, the distribution of all three precursor fatty acids was relatively stable, and only minor amounts of fatty acids were released into the culture medium during short term culture (two days). Our study demonstrates that eicosanoid precursor fatty acids are avidly taken up by human keratinocytes and esterified into membrane lipids. The clinical implication of this finding is that dietary manipulations might be employed to cause changes in the fatty acid composition of keratinocytes.