Konzentration intravenös applizierter gammaglobulin-präparate in der hundehaut

Zusammenfassung Die chemische Modifikation von Standardgammaglobulin durch enzymatische Spaltung (Pepsin) oder Stabilisierung (-Propiolacton) beeinflußt Elimination, Fragmentierung und Organverteilung des intravenös applizierten Gammaglobulins. Untersuchungen mit radioaktiv markierten allogenen und xenogenen Gammaglobulin-Präparaten an 36 Hunden zeigten, daß das pepsingespaltene Gammaglobulin am schnellsten fragmentiert und eliminiert wurde. Dabei fand sich für die Konzentration aller Gammaglobuline in der Haut ein wesentlich langsamerer Abfall als im Blut. Die höchsten Hautkonzentrationen nach 10 Tagen fanden sich für-Propiolacton-Gammaglobulin mit 6,2 ± 1,6 µg/g Haut bei einer Blutkonzentration von 7,9 ± 0,9 µg/ml.

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Concentration of intravenously administered gammaglobulin preparations in dog skin

Summary Chemical modification of standard gammaglobulin with enzyme treatment (pepsin) or stabilization (ß-propiolactone) is able to influence elimination, fragmentation and organ distribution of intravenously administered gammaglobulins as shown in 36 dogs after i.v. application of allogenic and xenogenic gammaglobulin preparations. Pepsin-gammaglobulin was eliminated and fragmented most rapidly. Gammaglobulin concentrations of all preparations in the skin showed as slower decrease than comparable blood concentrations. The highest skin concentrations 10 days after i.v. application were found for -propiolactone gammaglobulin with 6.2 ± 1.6 µg/g compared to a blood level of 7.9 ±0.9 µg/ml.

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Die Autoren danken Jutta Krumbach und Susanne Pfeffer für hervorragende technische Assistenz     

ANDROGENETIC ALOPECIA IN MEN: THE SCALE OF THE PROBLEM AND PROSPECTS FOR TREATMENT

While the precise incidence of androgenetic alopecia is unknown, it is universally acknowledged to be the most common hair problem in men. Balding is generally associated with ageing; consequently, the desire to prolong a youthful appearance inevitably leads to demands for effective treatments. Further, changing attitudes in modern society have resulted in people becoming concerned about their appearance and less tolerant about conditions that might be alleviated by medical intervention. The importance of hair loss upon quality of life has been underestimated by the medical profession. Clinicians failing to accept hair loss as an important medical problem ignore the real distress suffered by a significant proportion of those affected. New options for treatment that selectively target the metabolic pathways involved in the balding process are showing promise. The first generation of such drugs, Propecia, is now available in some countries and other molecules are currently under development.     

Positron emission tomography detected thyroid incidentaloma

We describe the case of a 48-year-old woman who presented with a thyroid lesion incidentally detected on positron emission tomography/computed tomography for a suspicious lung lesion. Subsequent clinical examination and investigations revealed a 3cm nodule in the left lower pole of the thyroid. Fine needle aspiration was indeterminate for malignancy. A left hemithyroidectomy was performed and histology confirmed a benign thyroid adenoma with an incidental micropapillary carcinoma. The literature regarding the best management for thyroid incidentalomas remains uncertain and, as such, each patient must be managed on an individual basis.     

Intense pulsed light vs. pulsed‐dye laser in the treatment of facial acne: a randomized split‐face trial

Background Various laser and light therapy have been increasingly used for the treatment of acne vulgaris. Patients and methods Twenty patients with facial acne were treated using intense pulsed light (IPL) on one side of the face and pulsed dye laser (PDL) on the other to compare the efficacy and safety of IPL and PDL. Treatment was performed 4 times at 2‐week intervals. Treatment effectiveness was determined using lesion counts, acne severity, patient subjective self‐assessments of improvement, and histopathological examinations, which included immunohistochemical staining for transforming growth factor‐β (TGF‐β). Results Numbers of total acne lesions decreased following both treatments. For inflammatory lesions such as papules, pustules and nodules, IPL‐treated sides showed an earlier and more profound improvement than PDL‐treated sides. However, at 8 weeks after the 4th treatment, a rebound aggravation of acne was observed on IPL‐treated sides. On the contrary, PDL produced gradual improvements during the treatment sessions and these improvements lasted 8 weeks after the 4th treatment. Non‐inflammatory lesions as open and closed comedones also showed improvement following both treatments and PDL‐treated sides showed better improvement as the study proceeded. Histopathological examinations showed amelioration in inflammatory reactions and an increase in TGF‐β expression after both treatments, which were more prominent for PDL‐treated sides. Conclusion Both PDL and IPL were found to treat acne effectively, but PDL showed a more sustained effect. TGF‐β might play a key role in the resolution of inflammatory acne lesions.     

Non‐ablative 1550‐nm erbium‐glass and ablative 10 600‐nm carbon dioxide fractional lasers for acne scars: a randomized split‐face study with blinded response evaluation

Background Non‐ablative 1550‐nm erbium‐doped fractional photothermolysis systems (FPS) and 10 600‐nm carbon dioxide fractional laser systems (CO₂ FS) have been effectively used to treat scars. Objective We compared the efficacy and safety of single‐session treatments of FPS and CO₂ FS for acne scars through a randomized, split‐face, evaluator‐blinded study. Methods Eight patients with acne scars were enrolled in this study. Half of each subject’s face was treated with FPS and the other half was treated with CO₂ FS. We used a quartile grading scale for evaluations. Results At 3 months after the treatment, the mean grade of improvement based on clinical assessment was 2.0 ± 0.5 for FPS and 2.5 ± 0.8 for CO₂ FS. On each side treated by FPS and CO₂ FS, the mean duration of post‐therapy crusting and scaling was 2.3 and 7.4 days respectively and that of post‐therapy erythema was 7.5 and 11.5 days respectively. The mean VAS pain score was 3.9 ± 2.0 with the FPS and 7.0 ± 2.0 with the CO₂ FS. Conclusion We demonstrated the efficacy and safety of single‐session acne scar treatment using FPS and CO₂ FS in East Asian patients. We believe that our study could be used as an essential reference when choosing laser modalities for scar treatment.     

Influence of indomethacin and L-cysteine on histamine and peptidoleukotriene release from superfused tracheas taken from guinea pigs passively sensitized with IgG1 and IgE antibodies.

We have previously reported differences in mediator release during equivalent levels of antigen (Ag)-induced smooth muscle contraction of guinea pig pulmonary tissues after passive sensitization with IgG1 versus IgE antibodies (Abs). In the present study, we have examined the influence of indomethacin (5 x 10(-6) mol/L) and L-cysteine (3 or 10 mmol/L) on mediator release from superfused trachea taken from guinea pigs passively sensitized with IgG1 or IgE Ab 1 day before in vitro studies. Tissues were challenged with Ag (oxazolone-human serum albumin conjugate), and contractions and superfusate histamine and peptidoleukotrienes were monitored at discrete time intervals thereafter. Superfusate mediator contents were determined by spectrophotofluorimetry (histamine) and RAST (peptidoleukotrienes). The profiles of peptidoleukotrienes were examined with high-pressure liquid chromatography. At equivalent levels of contraction, significantly less histamine and peptidoleukotrienes were found in superfusate samples after sensitization with IgE Abs. None of the drug pretreatments significantly altered Ag-induced histamine release after IgG1 or IgE sensitization. Indomethacin resulted in an increase in total measurable peptidoleukotrienes found only after IgG1 receptor activation, but it did prolong tracheal contractions with both Abs. L-cysteine, 10 mmol/L, resulted in an increase in total measurable superfusate peptidoleukotriene content under all experimental conditions. The percentage increase in peptidoleukotriene content from that found without drug pretreatment was larger in the case of IgE compared to IgG1 sensitization. During early time periods, after Ag challenge, measurable peptidoleukotriene levels in superfusate samples were similar for both Abs in the presence of L-cysteine, 10 mmol/L. These data suggest that there is a differential pattern of peptidoleukotriene metabolism after activation of IgG1 versus IgE receptors in guinea pig trachea.     

Adult rat myocardial slices: A tool for studies of comparative cardiotoxicity

The applicability of myocardial slices in comparative cardiotoxicity studies was investigated using the known cardiotoxicants allylamine (AAM) and doxorubicin (DOX). Precision-cut adult rat myocardial slices are a recently developed in vitro system. Previously, it has been demonstrated that myocardial slices are viable for up to 24 hr in organ culture. Myocardial slices exhibited a concentration- and time-dependent loss of viability in response to exposure to AAM or DOX (10⁻⁷, 10⁻⁶ or 10⁻⁵ ) during 24 hr in culture, as assessed by biochemical parameters including protein synthesis, ATP content, lipid peroxidation and the loss of the cytosolic enzyme creatine kinase. Protein synthesis and ATP content were sensitive indicators of slice viability, while lipid peroxidation was affected only by 10⁻⁵ DOX. Myocardial slices appear to be a useful in vitro system for the study of the cardiotoxic potential of chemicals. The maintenance of normal cellular architecture makes myocardial slices uniquely attractive for these studies.     

3，4－二羟基苯乙酮对老年大鼠血小板膜磷脂成分的影响

ＤＨＡＰ１００ｍｇ·ｋｇ－１·ｄ－１，ｐｏ，持续１０周，可使老龄大鼠血小板膜磷脂（ＰＬ）含量增加，膜磷脂与膜胆固醇比值（ＰＬ／Ｃ）相对增高；血小板磷脂成分——磷脂酰乙醇胺（ＰＥ）和磷脂酰胆碱（ＰＣ）含量也有明显增加（ｐ＜０．０１），但血小板膜总脂及膜胆固醇含量无明显变化（Ｐ＞０．０５）。本实验结果提示：ＤＨＡＰ对血小板功能的影响可能与其抑制血小板膜磷脂降解、改变血小板膜组分有关。     

Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers.

BACKGROUND: Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. PURPOSE: This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. METHODS: IgG1 monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas--21 sporadic and 76 familial (hereditary)--from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. RESULTS: Nuclear p53 protein was observed in 16% of the 31 in situ carcinomas, 22% of the 172 sporadic carcinomas, 34% of the 50 tumors from patients with familial breast cancer, 52% of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. CONCLUSIONS: Immunohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation.