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This prospective study evaluated the relationship between fecal markers of intestinal inflammation and cystic fibrosis (CF)-associated abdominal symptoms. These were assessed using the CFAbd-Score, a CF-specific patient-related outcome measure developed and validated, following FDA guidelines. In feces from patients with CF (n = 41) and healthy volunteers (n = 27), concentrations of fecal calprotectin (FC), M2-pyruvate kinase (M2-PK), interleukins IL-1ß, IL-6, IL-8, and neutrophilic elastase (NE) were measured. Abdominal symptoms during the 2 preceding weeks were recorded using the CFAbd-Score. This patient-reported outcome measure (PROM) for assessment of the multi-organic abdominal involvement in CF includes 28 items in five domains. Inflammatory parameters FC, IL-1ß, M2-PK, and NE in feces, as well as CFAbd-Scores resulted significantly higher in CF patients than in healthy controls (all P< 0.01). Furthermore, significant differences between both groups were found for pain-symptoms, disorders of bowel movement, impaired quality of life, as well as disorders of eating and appetite. With 83% sensitivity and 74% specificity, FC was the most reliable measure for CF-related intestinal inflammation, which, in the CFAbd-Score, was associated to significantly higher rates of abdominal pain, as well as to general quality of life items such as gastrointestinal-related impaired sleep and frustration. Using the CFAbd-Score as a CF-specific PROM for identification and quantification of abdominal symptoms revealed that abdominal pain and impaired quality of life are associated with intestinal inflammation in CF.

AbstractAntimicrobial organic-inorganic hybrids based on amphiphilic dendritic hyperbranched polyethylenimine with zinc were prepared. To study their property profile and potential as an antimicrobial modifier they were incorporated via melt extrusion into cast films or injection molded into plates of polyamide (PA). The antimicrobial efficacy, bacterial adhesion, cytotoxicity and blood compatibility of the respective PA composites were investigated as a function of material composition and morphology. It could be demonstrated that the polymers with the developed zinc-hybrids possess a high antimicrobial efficacy as well as good cyto- and hemo-compatibility in vitro. Furthermore, they showed reduced bacterial adhesion. Finally, it can be stated that the developed zinc-hybrids are suitable as advanced additive agents for the production of antimicrobial polymer materials with promising properties particular for various medical applications.

Negative pressure wound therapy (NPWT) has advanced the management of the open abdomen and other wounds. However, using the correct wound filler is essential as the material needs to convey a heterogeneous pressure distribution and create the pressure gradients required to drain interstitial fluid and remove wound exudate. This study compared the differences in fluid distribution during NPWT using a large-pore PU-foam dressing (Suprasorb®CNP foam), drainage film (Suprasorb®CNP drainage film) and a specialized NPT dressing system (KCI ABThera™ NPT system) in vitro.

Chronic wounds, such as venous, pressure, and diabetic ulcers, are difficult to heal and represent a rising social and economical problem. Compared to acute wounds, non‐healing wounds contain elevated levels of neutrophil elastase, pro‐inflammatory cytokines (IL‐1β, IL‐6, IL‐8), and matrix metalloproteases (MMP‐2, MMP‐9, MMP‐13) as well as free radicals. Their overproduction perpetuates the inflammatory phase resulting in severe tissue damage and degradation of growth factors. Consequently, wound closure is prevented and the wound remains non‐healing for month or even years. The increasing numbers of patients suffering from wounds that fail to heal are a significant challenge for health care professionals. Wound dressings play an important role in the entire management of these wounds. New materials and treatment strategies are needed to improve wound care. Recent advances in the field of biomaterials and their medical applications indicate the significance and potential of various natural polymers in the development of novel classes of wound dressings. Native polymers are an ideal source for bio‐active wound dressings because of their availability and biocompatibility. Hence, several studies have been conducted to explore the influence of wound dressings consisting of collagen, oxidized regenerated cellulose, bacterial cellulose, chitosan, or alginate on the destructive milieu in chronic wounds.

The application of bacterial cellulose as a dressing for chronic and burn wounds has been described as beneficial for healing. However, this study and other tests have shown that bacterial cellulose has no significant influence on the biochemical state of chronic wounds. Such wounds persist in the inflammatory phase of the normal healing process and fail to heal. Exudates from non-healing wounds show elevated levels of proteolytic enzymes, cytokines and reactive oxygen species (ROS), leading to a reduced concentration of growth factors and proteinase inhibitors and to a degradation of tissue and severe damage. Thus, the reduction of protein degrading enzymes and proinflammatory interleukins as well as scavenging of ROS appears to be a suitable way to support the healing process. The aim of the present study was to improve the positive features of bacterial cellulose as wound dressing by incorporation of collagen type I into the cellulose pellicle. The research focussed on the possible in situformation of a composite of bacterial cellulose and collagen type I. This biomaterial is able to reduce the amount of selected proteases and interleukins significantly and possesses a distinct antioxidant capacity as well.The application of bacterial cellulose as a dressing for chronic and burn wounds has been described as beneficial for healing. However, this study and other tests have shown that bacterial cellulose has no significant influence on the biochemical state of chronic wounds. Such wounds persist in the inflammatory phase of the normal healing process and fail to heal. Exudates from non-healing wounds show elevated levels of proteolytic enzymes, cytokines and reactive oxygen species (ROS), leading to a reduced concentration of growth factors and proteinase inhibitors and to a degradation of tissue and severe damage. Thus, the reduction of protein degrading enzymes and proinflammatory interleukins as well as scavenging of ROS appears to be a suitable way to support the healing process. The aim of the present study was to improve the positive features of bacterial cellulose as wound dressing by incorporation of collagen type I into the cellulose pellicle. The research focussed on the possible in situformation of a composite of bacterial cellulose and collagen type I. This biomaterial is able to reduce the amount of selected proteases and interleukins significantly and possesses a distinct antioxidant capacity as well.

AbstractTo prove the relative potency of melatonin as a radical scavenger in UV-irradiated leukocytes, it was compared to other antioxidative substances such as trolox and vitamin C. Human leukocytes were isolated from EDTA whole blood and incubated with melatonin, trolox and vitamin C. The experiments were performed in a wide concentration range from 0.1 nMto 1 mMand in a small concentration range from 0.5 to 2 mM(mel), 5 mM(trolox) and 10 mM(vit. C). Irradiation was performed with UV-light (280-360 nm) at a dose of 750 mJ/cm2. Radical formation was measured by the chemiluminescence technique. The maximum effect of radical suppression was seen at a concentration of 10 nM(p = 0.003) and 1 mMmelatonin (p < 0.001) and vitamin C (p = 0.002; p < 0.001), respectively. ROS suppression by trolox was only significant at 1 mM(p < 0.001). In the small concentration range, a linear dose-response relationship was found and melatonin showed the strongest radical suppression (IC50= 0.21 mM) followed by vitamin C (IC50= 0.26 mM) and trolox (IC50= 1.03 mM).Copyright © 2002 S. Karger AG, Basel

Abstract. Purpose: Matrix metalloproteinases (MMPs) are a family of structurally related zinc-dependent endopeptidases that are able to degrade extracellular matrix components. MMPs play a role in tumor invasion and tumor metastasis. MMP-2 (also known as gelatinase A) is expressed in human melanoma cells. Methods: In this study, we measured MMP-2 in 337 serum probes of 166 melanoma patients with a recently developed enzyme immunoassay and compared these data with the tumor stage, presence of metastases, and the levels of S100beta and soluble intracellular adhesion molecule-1 (sICAM-1) in serum. Results: The mean levels were (189.2±50.8) ng/ml for MMP-2, (263.2±74.1) ng/ml for sICAM-1, and (0.424±1.568) U/ml for S100beta. There was a statistical significant correlation of MMP-2 with sICAM-1 (P=0.05) and S100beta (P=0.01). The mean MMP-2 levels (in ng/ml) in patients with metastatic melanoma were 196.4±54.0 versus 182.6±46.9 in non-metastasizing melanoma (P=0.037). However, there was no significant difference in MMP-2 levels between the different tumor stages. Conclusion: Determination of MMP-2 serum levels is of limited value as a tumor marker in melanoma, though there are higher levels in the more advanced disease.

Reactive oxygen species (ROS) are presumed to be involved in inflammatory UV reactions of the skin. This in vitro study was performed to investigate the suppressive effect of melatonin in interleukin‐3 (IL‐3) stimulated leukocytes. Neutrophilic granulocytes were isolated from EDTA‐treated whole blood and placed in a phosphate‐buffered saline (PBS) containing IL‐3. Cell suspensions were either treated with PBS (control) or with increasing doses of melatonin (0.1, 0.5, 1, 2, 3, 5, 7.5, 10 mmol). One PBS solution was left unirradiated and the other nine solutions (PBS and melatonin) were irradiated with 750 mJ/cm2UVB light (280–360 nm, max: 310 nm). Radical formation was measured by the chemiluminescence technique. UV‐irradiated leukocytes showed a 5‐fold higher radical formation than unirradiated leukocytes. Melatonin, in increasing doses in powers of ten, led to a maximum suppression of free radicals at 10 nmol (P=0.01) and 1 mmol melatonin (P=0.001), showing a biphasic, non‐linear, dose–response relationship. Melatonin, given in amounts of 0.1–10 mmol, led to a direct dose‐dependent suppression of ROS. Radical formation was suppressed significantly in a range from 0.5 to 10 mmol (P=0.001). Melatonin is known to function as a radical scavenger and antioxidant; some of these melatonin effects may be receptor independent, while others may be receptor dependent.

Background:Both interferon alfa and extracorporeal photochemotherapy have been shown to be effective in primary cutaneous T-cell lymphomas (CTCLs). However, no prospective trial has been published on the combination of both treatments, although retrospective investigations suggested a better efficacy than for either interferon or extracorporeal photochemotherapy. Objective:Our purpose was to evaluate the efficacy and toxicity of combined interferon alfa-2a with extracorporeal photochemotherapy in a prospective controlled trial. Methods:A prospective controlled study was performed. Fourteen patients (all male) aged 38 to 72 years with CTCL of the mycosis fungoides type, stage IIa/IIb, and a 72-year-old male patient with a Ki-1 lymphoma were treated twice a month for 6 months with extracorporeal photochemotherapy using oral 8-methoxypsoralen as photosensitizer in combination with interferon alfa-2a subcutaneously 3 times a week in the maximal tolerable dosage (ie, up to 18 × 106U). The effects were investigated by a skin score, staging, histologic score (density of the T-cell infiltrate; from 0 = absent to 3 = heavy), immunohistology, and laboratory investigations including total peripheral T-cell count, CD4/CD8 ratio, and soluble interleukin 2 receptor (sIL-2R). Results:After 6 months, best response was a complete response (CR) in 4 patients, a partial response (PR) in 3, and a stable disease (SD) in 7 of 14 patients (overall response rate [CR + PR] 50%). In responders the time to best response was 4.3 ± 1.4 months. The skin score decreased from 22.5 ± 8.1 to 15.1 ± 11.0 (P< .001), the histologic score decreased from 2.57 ± 0.51 to 1.21 ± 0.80 (P< .001). In the lesional skin the percentage of CD4 cells decreased from 75% to 51% (P= .038) and Ki-67-positive cells decreased from 6.7% to 2.4% (P= .001). The total T-cell count/μL decreased from 1018.9 ± 557.1 to 667.9 ± 417.9 (P= .012), and the CD4/CD8 ratio also decreased from 1.88 ± 0.92 to 1.51 ± 0.67 (P= .038). The sIL-2R levels did not change significantly during the first 4 months of treatment. Among patients of stage IIa the response rate was 60% in contrast to only 25% of those in stage IIb. Side effects were seen temporarily, ranging from grade 0 to grade 3. There was no need for additional therapy, but interferon dose was decreased because of side effects. After 1 year of follow-up the total response rate was 46.2% (6 of 13 patients): 5 of 9 with stage IIa(55.6%) and 1 of 4 with stage IIb (25.0%). Conclusion:These results indicate that patients with CTCL stage IIa can achieve a total response rate of 56% with combined interferon alfa-2a and extracorporeal photochemotherapy. Responders seem to experience their best response within the first 6 months of treatment. The treatment is well tolerated and does not cause severe side effects. (J Am Acad Dermatol 2001;44:253-60.)

Because the primary aim of adjuvant therapy for melanoma is not curative, all the possible aspects of quality of life have to be considered. One aspect of increasing importance is fertility. The effect of adjuvant interferon α‐therapy for malignant melanoma on male fertility has not been systematically investigated. In the present study, twelve male patients with primary cutaneous melanoma (pT3, 4; N0; M0) who were taking adjuvant low‐dose interferon α2b (3 times 3 mio U/week) for one year were included. Inhibin B—an established marker of male fertility—was measured with an immunosorbent assay before and after one year of interferon α‐therapy to investigate whether this treatment has any influence on fertility. The results were compared with those from normal controls (n=40). The mean serum inhibin B concentration in melanoma patients before interferon therapy was 225.4 ± 112.5 pg/mL; after treatment the level was 229.6 ± 82.0 pg/mL. This difference was not statistically significant (p>0.05). The serum inhibin B concentration in controls was 201.5 ± 17.1 pg/mL, which was not statistically different from either untreated or interferon‐treated melanoma patients (p>0.05). We conclude that low‐dose interferon α does not have a significant (negative) effect on inhibin B or male fertility.

S100 protein is well established as a diagnostic tool in malignant melanoma immunohistology. In this study we measured S100 in serum with a recently developed luminometric immunoassay with a detection limit of 0.02 g/l. By measuring S-100 in a group of apparently healthy individuals a mean value of 0.031 0.026 g/l was found. In the reference group, serum S100 was below 0.12 g/l in all cases. To assess the sensitivity of the assay we investigated serum S-100 levels in 371 serum samples of 315 patients with histological proven malignant melanoma at different disease stages. Staging was performed according to the German Society of Dermatology classification. Significant differences were observed between the control group and stages IIb (P = 0.01) and IV (P = 0.001). In tumour-bearing patients of stages IIIb and IV, the difference was highly significant (P < 0.0001). S100 > 0.20 g/l helps to distinguish between tumour-free and tumour-bearing patients with a specificity of 97.0% and a sensitivity of 64.6%. Our results demonstrate the serum S100 is of limited value as a melanoma marker. However, it has clinical significance for identifying tumour-positive patients in advanced malignant melanoma stages III and IV.