Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 61
Filter
1.
Pneumologie ; 76(12): 855-907, 2022 Dec.
Article in German | MEDLINE | ID: mdl-36479679

ABSTRACT

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.


Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Humans
2.
J Eur Acad Dermatol Venereol ; 35(10): 1963-1975, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34077579

ABSTRACT

Exposome factors that lead to stressed skin can be defined as any disturbance to homeostasis from environmental (meteorological factors, solar radiation, pollution or tobacco smoke) and/or internal exposure (unhealthy diet, hormonal variations, lack of sleep, psychosocial stress). The clinical and biological impact of chronic exposome effects on skin functions has been extensively reviewed, whereas there is a paucity of information on the impact of short-term acute exposure. Acute stress, which would typically last minutes to hours (and generally no more than a week), provokes a transient but robust neuroendocrine-immune and tissue remodelling response in the skin and can alter the skin barrier. Firstly, we provide an overview of the biological effects of various acute stressors on six key skin functions, namely the skin physical barrier, pigmentation, defences (antioxidant, immune cell-mediated, microbial and microbiome maintenance), structure (extracellular matrix and appendages), neuroendocrine and thermoregulation functions. Secondly, we describe the biological and clinical effects on adult skin from individual exposome factors that elicit an acute stress response and their consequences in skin health maintenance. Clinical manifestations of acutely stressed skin may include dry skin that might accentuate fine lines, oily skin, sensitive skin, pruritus, erythema, pale skin, sweating, oedema and flares of inflammatory skin conditions such as acne, rosacea, atopic dermatitis, pigmentation disorders and skin superinfection such as viral reactivation. Acute stresses can also induce scalp sensitivity, telogen effluvium and worsen alopecia.


Subject(s)
Dermatitis, Atopic , Exposome , Adult , Aggression , Environmental Exposure , Humans , Skin
3.
Psychoneuroendocrinology ; 86: 134-143, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28957772

ABSTRACT

To study pathogenic stress-effects in health and disease, it is paramount to define easy access parameters for non-invasive analysis of biological change in response to stress. Hair samples successfully provide this access for the study of hypothalamus-pituitary-adrenal axis (HPA) changes. In this study, we assess the hair expression and corresponding epigenetic changes of a neurotrophin essential for autonomic nervous system function and mental health: brain derived neurotrophic factor (BDNF). In three independent studies in healthy academic volunteers (study I: German students, N=36; study II, German academic population sample, N=28; study III: Mexican students, N=115), BDNF protein expression or BDNF gene (BDNF) histone acetylation was determined. Simultaneously, mental distress and distress-associated somatic complaints were assessed by self-report. In study I, we found a negative correlation between hair-BDNF protein level and hair-cortisol as well as between hair-BDNF and somatic complaints, while hair-cortisol correlated positively with mental distress. In study II, we found a negative correlation between H4 histone acetylation at the BDNF gene P4-promoter and somatic complaints. Regression analysis confirmed confounder stability of associations in both studies. In study III, we confirmed study I and found lower hair-BDNF protein level in volunteers with high somatic complaints, who also reported higher mental distress during the end of term exams. The results indicate that BDNF protein levels can be detected in clipped hair and are associated with somatic complaints and stress in life. In addition, we concluded that plucked hair can provide material for the study of epigenetic changes in stress-affected tissues. These tools can prove valuable for future studies on distress, both under experimental and field conditions.


Subject(s)
Brain-Derived Neurotrophic Factor/analysis , Stress, Physiological/physiology , Acetylation , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Epigenesis, Genetic , Female , Hair/chemistry , Hair/metabolism , Hippocampus/metabolism , Histones/metabolism , Humans , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Male , Nociceptive Pain , Pilot Projects , Pituitary-Adrenal System/metabolism , Promoter Regions, Genetic/genetics
4.
Hautarzt ; 64(6): 402-9, 2013 Jun.
Article in German | MEDLINE | ID: mdl-23760540

ABSTRACT

Stress and skin-an inseparable pair, this is how many of our patients perceive it and even clinicians are willing to integrate psychosomatic aspects into their recommendations if nothing from the somatic repertoire provides sufficient treatment. How the stress reaches the skin however is still an enigmatic matter to most lay people and professionals alike. Interestingly, psychoneuroimmunological research since the 1970s has produced a flood of valuable data. We now know that stressors, be it biochemical or psychoemotional, always elicit a neuroendocrine stress reaction with consequences for the immune response and therefore especially chronic inflammatory skin diseases. Here we employ allergic inflammation/atopic dermatitis and psoriasis as instructive model diseases to discuss basic mechanisms of molecular psychosomatic effects on chronic inflammation. The aim is to enhance pathogenetic understanding and open the door for the development and employment of integrated therapeutic concepts in dermatology.


Subject(s)
Cytokines/immunology , Neuroimmunomodulation/immunology , Skin Diseases/immunology , Skin Diseases/psychology , Skin/immunology , Stress, Psychological/immunology , Stress, Psychological/psychology , Humans , Models, Immunological , Skin Diseases/diagnosis , Stress, Psychological/diagnosis
5.
Br J Dermatol ; 167 Suppl 2: 105-10, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22881595

ABSTRACT

The diagnosis of skin cancer imposes a great stress on our patients. Ultraviolet (UV) radiation-induced skin cancers are on the rise and frequently occur in younger patients and unexposed sites despite improved protective behaviour. Environmental factors and lifestyle habits have changed greatly in the last century and in addition to UV radiation exposure, psychosocial stressors and physical inactivity may play a role in the rising tumour incidence. With environmental stressors such as UV radiation they share the capacity to change the stress reaction. So far research into the interaction between stress, cancer and psychosocial intervention has generated some interesting results with respect to improvement of quality of life and the function of the hypothalamic-pituitary-adrenal axis, the sympathetic axis and natural killer cells. These results hint at a suppressive effect of chronic stress on cellular immunity and the importance of a sufficient length and intensity of any psychosocial intervention for it to be effective. Nevertheless, the evidence remains inconclusive and does not take into account the findings of current psychoneuroimmunological research. This research has demonstrated the importance of a third stress axis along which neurotrophins and neuropeptides are effective. Along this axis, regulatory mechanisms may contribute to suppress tumoricidal immune responses. This may be instrumental in the establishment of an immune response that promotes tumour progression and holds important implications for integrated therapeutic strategies. However, research into the psychoneuroimmunological benefits of psychosocial intervention is largely missing, and future interdisciplinary research is warranted for understanding and further promoting improved quality of life and psychological as well as physical well-being after psychosocial intervention.


Subject(s)
Skin Neoplasms/psychology , Chronic Disease , Humans , Neurosecretory Systems/immunology , Psychoneuroimmunology , Psychotherapy/methods , Skin Neoplasms/immunology , Skin Neoplasms/therapy , Social Support , Stress, Psychological/immunology , Stress, Psychological/prevention & control
6.
Clin Exp Allergy ; 38(2): 283-90, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18070153

ABSTRACT

BACKGROUND: Asthma is a chronic disease defined by airway inflammation, increased airway hyperresponsiveness and episodes of airway obstruction. Although there are abundant clinical and experimental data showing that stress may worsen asthma, the mechanisms linking stress to asthma are not well understood. By inducing a pro-inflammatory cytokine milieu, stress might enhance airway inflammation in bronchial asthma. We therefore investigated the correlation of stress perception and the cytokine profile of circulating lymphocytes in humans. METHODS: Allergic asthmatic patients and healthy controls were evaluated for perceived level of stress, demographic and lung function data. Whole blood cells were obtained and stimulated by mitogen to assess intracellular IL-4, IFN-gamma and TNF-alpha by flow cytometry. Neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were measured in serum. RESULTS: Asthmatic patients showed significantly higher percentages of TNF-alpha-producing T cells than healthy controls. Only in asthmatic patients was stress perception correlated with percentages of TNF-alpha-producing T cells and serum BDNF levels, while forced expiratory volume in 1 s (% predicted) was negatively correlated to BDNF. CONCLUSION: The results of our study support the hypothesis that stress deteriorates bronchial asthma by inducing a pro-inflammatory cytokine profile in allergic asthmatics. Stress management might provide a supplement therapy of allergic asthma.


Subject(s)
Asthma/immunology , Cytokines/blood , Nerve Growth Factors/blood , Respiratory Hypersensitivity/immunology , Stress, Physiological/complications , Adult , Aged , Asthma/diagnosis , Brain-Derived Neurotrophic Factor/blood , Female , Humans , Male , Middle Aged , Nerve Growth Factor/blood , Respiratory Hypersensitivity/diagnosis , Stress, Physiological/diagnosis , T-Lymphocytes/immunology
7.
Horm Metab Res ; 39(2): 110-24, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17326007

ABSTRACT

Neurotrophins regulate cutaneous innervation, act as growth and motility factors on structural skin cells such as keratinocytes and fibroblasts, modulate cutaneous immune function and even serve as stress mediators in skin biology. The multilayered neurotrophin interaction with skin biology through high affinity specific tyrosinekinase receptors and the Janus-faced p75 receptor, which depending on ligand and co-receptor expression can serve as a low-affinity pan-neurotrophin receptor or a high affinity proneurotrophin receptor, guaranties this neuroendocrine peptide family a central position in the control of skin homeostasis in health and disease. It is a challenging task for future research efforts to integrate our knowledge on differential neurotrophin expression patterns and signaling pathways into complex concepts of neuroendocrine tissue remodeling and pathogenetic processes. In addition, we need to improve our understanding of the role of neurotrophin processing enzymes, associated co-receptors and intracellular adaptor molecules in specific cutaneous cell populations to design precise interaction tools for research and treatment. Such tools will allow us to utilize this ancient growth factor family in the management of neurotrophin responsive pathogenetic pathways and cutaneous diseases such as neurogenic inflammation, peripheral nerve degeneration, wound healing, atopic dermatitis or psoriasis.


Subject(s)
Homeostasis , Nerve Growth Factors/physiology , Skin Diseases/etiology , Skin Physiological Phenomena , Antigen Presentation/physiology , Cell Death , Humans , Lymphocyte Activation/physiology , Metabolic Diseases/etiology , Models, Biological , Nerve Tissue Proteins/physiology , Neutrophil Infiltration/physiology , Oncogene Proteins/physiology , Receptors, Nerve Growth Factor/physiology , Signal Transduction , Wound Healing/physiology
8.
J Neuroimmunol ; 184(1-2): 113-26, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17222461

ABSTRACT

The skin develops probably the densest and most complex innervation of all mammalian organs, consisting of sensory and autonomic nerves loaded with a plethora of neuropeptides and neurotransmitters. Skin innervation, as well as the expression patterns of neurotrophins and their receptors, is subject to dramatic changes during not only morphogenesis but also adult tissue remodeling under physiological or inflammatory conditions. Bilateral neuroimmune interactions are the basis of adaptive responses to tissue remodeling (such as hair cycling), psycho-emotional stress or skin inflammation. Dermatitis and hair loss may be exacerbated by stress-induced neurogenic inflammation. In addition, selected inflammatory skin diseases are associated with increased innervation. Finally, inflammatory cytokines influence the cutaneous expression of neurotrophins, as well as neurotrophin-induced neurite outgrowth following axotomy. Here, we review key studies on bilateral neuroimmune interactions in the skin under both healthy and disease conditions to provide a basis for future research on the role of inflammation in peripheral nerve regeneration.


Subject(s)
Inflammation , Nerve Regeneration/physiology , Neuronal Plasticity/physiology , Skin Physiological Phenomena , Skin , Animals , Humans , Skin/cytology , Skin/immunology , Skin/innervation , Stress, Psychological/immunology , Stress, Psychological/pathology , Stress, Psychological/physiopathology
9.
Eur J Appl Physiol ; 98(2): 124-31, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16941179

ABSTRACT

Recent research has demonstrated that lymphocyte apoptosis sensitivity appears to be related to training status and exercise intensity. This work investigated the effect of prolonged, submaximal treadmill running on percentage (%) apoptosis, % necrosis and DNA strand breaks in lymphocytes and related these to changes in total lymphocyte and blood cortisol concentrations in well-trained runners. Venous blood samples (n = 14) were taken immediately before (PRE), immediately after (IPE) and 3 h after (3PE) 2.5 h of treadmill running at 75% of VO2 max from eight well-trained male endurance athletes (age 34.2 +/- 2.44 years) and analysed for cellular content and serum cortisol concentrations. Lymphocytes were isolated from whole blood and % apoptotic and necrotic cell were detected by flow cytometry using Annexin V-FITC and propidium iodide uptake. DNA strand breaks were measured by single-cell gel electrophoresis. Despite a significant (P < 0.001) exercise-induced increase in mean serum cortisol concentrations and reduction in lymphocyte counts, the mean % Annexin-V positive cells (13.3 +/- 6.78 in PRE, 11.3 +/- 5.51 in IPE and 12.8 +/- 6.75 in 3PE samples) were not significantly different at the three time-points (P > 0.05). Mean DNA strand breaks in the lymphocytes also did not change significantly (P > 0.05) rising from 25.7 +/- 2.16 to 26.9 +/- 1.89 and 27.1 +/- 1.38 microm in IPE and 3PE samples, respectively. The exercise-induced changes in total blood lymphocyte counts and cortisol concentrations did not result in a significant change in % apoptotic lymphocytes or DNA strand breaks in the endurance-trained athletes during this prolonged, submaximal exercise.


Subject(s)
Apoptosis/physiology , DNA Damage/physiology , Lymphocytes/physiology , Physical Endurance/physiology , Physical Exertion/physiology , Physical Fitness/physiology , Running/physiology , Adult , Cells, Cultured , Humans , Lymphocytes/cytology , Male , Middle Aged
10.
Article in English | AIM (Africa) | ID: biblio-1269784

ABSTRACT

Background: The ever-increasing prevalence of chronic lifestyle-associated diseases has resulted in greater awareness of the importance of preventative medicine and its incorporation as an integral component of modern undergraduate medical curricula. As excessive dietary intake and physical inactivity are widely acknowledged as leading risk factors for the onset of chronic lifestyle-associated diseases; the promotion of a healthy lifestyle is regarded as a priority for today's primary care physicians. For this reason; it was deemed appropriate by the designers of the problem-based learning (PBL) curriculum; which was introduced at the Nelson R. Mandela School of Medicine in 2001; to include a six-week Nutrition theme early in the medical students' five-year curriculum. This study set out to determine the impact of this theme; which included a specific focus on the importance of nutrition in avoiding lifestyle-associated disorders; on the dietary awareness and lifestyle of the 2004 intake of medical students.Methods: First-year medical students (n = 213) spent the first six weeks of their curriculum (following an orientation period) engaged in a problem-based learning Nutrition theme; which included active; personalised learning experiences such as analysing their own dietary intakes and recording their personal anthropometric measures. They were questioned two weeks after conclusion of the theme regarding (i) the impact of the theme on their dietary awareness and lifestyles; (ii) whether they had; since the start of the theme; shared their newly acquired insights with others; and (iii) the extent to which they recalled their personal measured anthropometric data and calculated kilojoule (kJ) intakes derived during the practical sessions.Results: Nearly 84 of the students responded to the anonymous survey (n = 178). A greater awareness of their personal dietary intake following the completion of the Nutrition theme was acknowledged by 88.2( n = 157); while 65.1 (n = 116) reported improvements to their general lifestyle. Eighty-five percent reported having counselled family members and friends about diet and lifestyle-related issues in the eight-week period since the start of the theme. While recall of body mass indices was higher (p 0.01) in females (85.8) than in males (61.5 ); recall of daily kJ intakes was independent of gender. Unsolicited mention by the students surveyed in this study of components of the South African Food-based Guidelines and recent alternative food pyramids suggests that these models were recognised as health priority areas by this student cohort.Conclusion: The introduction of a Nutrition theme at the start of the problem-based medical learning curriculum appeared to have impacted significantly on the dietary awareness and lifestyles of the students surveyed; with a tendency among students to share this awareness with others. From the open-ended responses of the students; the findings of this study appear to confirm that medical students appreciated learning about their own health factors; and that personalising the information made the learning experience more valuable to them. Attitudinal changes and apparent internalisation of the newly acquired nutritional awareness were reflected by the high percentage of students who acknowledged that they had advised others within the two-week period following the completion of the theme. This augurs well for the potential preventative counselling practices of these future medical graduates. It will; however; be of interest to survey this student cohort longitudinally to establish whether their changed perceptions have a longer term impact and result in attitudes and practices that support preventative health care


Subject(s)
Chronic Disease , Feeding Behavior , Life Style , Nutritional Physiological Phenomena , Problem-Based Learning , Students
11.
J Hered ; 96(5): 614-7, 2005.
Article in English | MEDLINE | ID: mdl-16135703

ABSTRACT

This study tested the hypothesis that gibberellin levels were responsible for the superior growth habit of hybrids (i.e., heterosis). If this were true, plants reduced in their capacity to produce gibberellin, such as maize plants homozygous for dwarf1 (d1), should display a lesser heterotic response. The d1 mutation was introgressed into two inbred lines of maize, B73 and Mo17, for seven generations. Plants segregating for the dwarf phenotype were produced both by self-fertilizing the introgressed inbred lines and by making reciprocal crosses between them to produce hybrids. Measurements were made of several physical traits. The results indicated that the hybrid dwarf plants experienced no loss of heterosis relative to their normal siblings. These results exclude the possibility that modulation of bioactive gibberellins is a major underlying basis of the heterotic response.


Subject(s)
Genes, Plant/genetics , Gibberellins/genetics , Hybrid Vigor/genetics , Hybridization, Genetic , Zea mays/genetics , Crosses, Genetic , Zea mays/growth & development
12.
J Sports Med Phys Fitness ; 44(3): 315-21, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15756172

ABSTRACT

AIM: Haematological response to the 2001 downhill Comrades Marathon was compared in high (>120 km/w in training; 3 weeks of pre-race taper) and low (<80 km/w in training; 2 weeks of pre-race taper) training status groups. METHODS: Full blood counts, differential lymphocyte counts (CD3, CD4, CD8, CD19, CD56), serum cortisol, C-reactive protein (CRP) and creatine kinase (CK) were measured in blood samples donated 21 hours before and 16 hours after a 90 km ultramarathon. RESULTS: Despite significantly faster mean race finishing time (8.03 h vs 10.53 h; p<0.001) and greater percentage incidence (55.6% vs 40%) of post-race upper respiratory tract infection (URTI) in the highly trained group, these faster runners did not show evidence of a slower post-race recovery in terms of total leukocyte, neutrophil, total or differential lymphocyte counts (p>0.05). CRP concentrations were, however, markedly higher in the slower, less trained group (65.3+/-10.7 vs 38.3+/-5.9; p<0.01). CONCLUSIONS: Despite greater systemic evidence of post-race muscle inflammation and an acute phase response in the slower runners in a downhill ultramarathon race, the haematological recovery of well trained runners who undergo a 3-week taper period prior to the ultramarathon is not different to that in less trained runners who spend almost 3 hours longer on the road. The higher prevalence of post-race URTI symptoms in the fast, well trained group does not appear to be related to lymphocyte recovery in peripheral blood.


Subject(s)
Physical Education and Training/methods , Recovery of Function/physiology , Running/physiology , Adult , C-Reactive Protein/analysis , Humans , Leukocyte Count , Male , Neutrophils/metabolism
13.
J Biol Chem ; 276(50): 47212-6, 2001 Dec 14.
Article in English | MEDLINE | ID: mdl-11581249

ABSTRACT

Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is known to play an important role in signal transduction and membrane trafficking. We show that one enzyme responsible for PIP(2) production, phosphatidylinositol-4-phosphate 5-kinase type 1beta (PIPKbeta), is essential for epidermal growth factor receptor (EGFR)-mediated endocytosis. Expression of murine PIPKbeta in NR6 cells expressing EGFR strikingly increased receptor internalization. Moreover, the kinase was shown to form an immunoprecipitable complex with EGFR. Expression of either a truncated kinase or a kinase dead mutant inhibited EGFR endocytosis and also blocked the membrane recruitment of PIPKbeta and both clathrin light chain and dynamin. Our results delineate a novel mechanism by which PIPKbeta regulates receptor-mediated endocytosis and receptor tyrosine kinase membrane traffic.


Subject(s)
Endocytosis , Epidermal Growth Factor/metabolism , Phosphotransferases (Alcohol Group Acceptor)/genetics , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Animals , Blotting, Western , Cell Line , Cell Membrane/metabolism , Clathrin/chemistry , Clathrin/metabolism , Cloning, Molecular , Dynamins , Electrophoresis, Polyacrylamide Gel , GTP Phosphohydrolases/chemistry , GTP Phosphohydrolases/metabolism , Mice , Microscopy, Confocal , Microscopy, Fluorescence , Mutation , Phosphotransferases (Alcohol Group Acceptor)/chemistry , Precipitin Tests , Protein Binding , Protein Isoforms , Receptor Protein-Tyrosine Kinases/metabolism , Sindbis Virus/genetics , Time Factors , Transfection
14.
Int J Sports Med ; 22(7): 537-43, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11590482

ABSTRACT

The effects of vitamin C supplementation on the alterations in the circulating concentrations of cortisol, adrenaline, interleukin-10 (IL-10) and interleukin-1 receptor antagonist (IL-1Ra) which accompany ultramarathon running were measured using immuno-chemiluminescence, radioimmunoassay and ELISA procedures. Forty-five participants in the 1999 Comrades 90 km marathon were divided into equal groups (n = 15) receiving 500 mg/day Vit C (VC-500), 1500 mg/day Vit C (VC-1500) or placebo (P) for 7 days before the race, on the day of the race, and for 2 days following completion. Runners recorded dietary intake before, during and after the race and provided 35 ml blood samples 15 - 18 hrs before the race, immediately post-race, 24 hrs post race and 48 hrs post-race. Twenty-nine runners (VC-1500, n = 12; VC-500, n = 10; P, n = 7) complied with all study requirements. All post-race concentrations were adjusted for plasma volume changes. Analyses of dietary intakes and blood glucose and anti-oxidant status on the day preceding the race and the day of the race did not reveal that carbohydrate intake or plasma vitamins E and A were significant confounders in the study. Mean pre-race concentrations of serum vitamin C in VC-500 and VC-1500 groups (128 +/- 31 and 153 +/- 34 micromol/l) were significantly higher than in the P group (83 +/- 39 micromol/l). Immediate post-race serum cortisol was significantly lower in the VC-1500 group (p < 0.05) than in P and VC-500 groups. When the data from VC-500 and P groups was combined (n = 17), immediate post-race plasma adrenaline, IL-10 and IL-1Ra concentrations were also significantly lower (p < 0.05) in the VC-1500 group. The study demonstrates an attenuation, albeit transient, of both the adrenal stress hormone and anti-inflammatory polypeptide response to prolonged exercise in runners who supplemented with 1500 mg vitamin C per day when compared to < or = 500 mg per day.


Subject(s)
Anti-Inflammatory Agents/blood , Ascorbic Acid/administration & dosage , Dietary Supplements , Epinephrine/blood , Hydrocortisone/blood , Running/physiology , Administration, Oral , Adult , Blood Cell Count , Blood Glucose/analysis , Dietary Carbohydrates , Female , Humans , Interleukin-10/blood , Male , Middle Aged , Receptors, Interleukin-1/antagonists & inhibitors , Vitamin A/blood , Vitamin E/blood
15.
J Invest Dermatol ; 117(2): 173-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11511291

ABSTRACT

Parathyroid hormone (PTH) related peptide (PTHrP) and the PTH/PTHrP receptor (PTH/PTHrP-R) show prominent cutaneous expression, where this signaling system may exert important paracrine and/or autocrine functions, such as in hair growth control. Chemotherapy-induced alopecia - one of the fundamental unsolved problems of clinical oncology - is driven in part by defined abnormalities in hair follicle cycling. We have therefore explored the therapeutic potential of a PTH/PTHrP-R agonist and two PTH/PTHrP-R antagonists in a mouse model of cyclophosphamide-induced alopecia. Intraperitoneal administration of the agonist PTH(1-34) or the antagonists PTH(7-34) and PTHrP(7-34) significantly altered the follicular response to cyclophosphamide in vivo. PTH(7-34) and PTHrP(7-34) shifted it towards a mild form of "dystrophic anagen", associated with a significant reduction in apoptotic (TUNEL+) hair bulb cells, thus mitigating the degree of follicle damage and retarding the onset of cyclophosphamide-induced alopecia. PTH(1-34), in contrast, forced hair follicles into "dystrophic catagen", associated with enhanced intrafollicular apoptosis. We had previously shown that an induced shift in the follicular damage-response towards "dystrophic catagen" mitigates cyclophosphamide-induced alopecia, whereas a shift towards "dystrophic catagen" initially enhanced the hair loss, yet subsequently promoted accelerated hair follicle recovery. Therefore, this study in an established animal model of chemotherapy-induced alopecia, which closely mimics human chemotherapy-induced alopecia, strongly encourages the exploration of PTH/PTHrP-R agonists and antagonists as novel therapeutic agents in chemotherapy-induced alopecia.


Subject(s)
Alopecia/drug therapy , Antineoplastic Agents, Alkylating/pharmacology , Cyclophosphamide/pharmacology , Parathyroid Hormone , Peptide Fragments , Alopecia/chemically induced , Animals , Apoptosis/drug effects , Cell Division/drug effects , Female , Hair Follicle/drug effects , Hair Follicle/pathology , Hormone Antagonists/agonists , Hormone Antagonists/pharmacology , In Situ Nick-End Labeling , Keratinocytes/drug effects , Keratinocytes/pathology , Mice , Mice, Inbred C57BL , Neoplasms/complications , Neoplasms/drug therapy , Parathyroid Hormone/agonists , Parathyroid Hormone/antagonists & inhibitors , Parathyroid Hormone/pharmacology , Peptide Fragments/agonists , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/pharmacology , Proteins/agonists , Proteins/antagonists & inhibitors , Proteins/pharmacology , Teriparatide/agonists , Teriparatide/analogs & derivatives , Teriparatide/antagonists & inhibitors , Teriparatide/pharmacology
16.
J Am Chem Soc ; 123(30): 7228-32, 2001 Aug 01.
Article in English | MEDLINE | ID: mdl-11472150

ABSTRACT

The singlet-oxygen ene reaction and the epoxidation by DMD of chiral oxazolidine-substituted alkenes, equipped with a free urea NH functionality and a conformationally fixed double bond, proceed in high like diastereoselectivity (up to >95:5); also a high regioselectivity was found for the (1)O(2) ene reaction. Capping of the free NH functionality by methylation erases this like selectivity for both oxidants and significantly reduces the regioselectivity in the ene reaction. These data demonstrate effective hydrogen bonding between the remote urea NH functionality and the oxidant that favors the like attack on the C-C double bond. For (1)O(2), the hydrogen bonding in the exciplex results in preferred hydrogen abstraction from the alkyl group cis to the directing urea functionality.

18.
J Org Chem ; 66(10): 3265-76, 2001 May 18.
Article in English | MEDLINE | ID: mdl-11348106

ABSTRACT

A wide range of enol carbonate, carbamate, and ester radical cations is characterized in solution by cyclic voltammetry and EPR spectroscopy. Preparative transformations using one-electron oxidants or anodic oxidation yield benzofurans after O-CO bond cleavage. Mechanistic investigations and direct detection of radical intermediates reveal that all enol radical cations undergo exclusively O-CO bond cleavage to provide alpha-carbonyl cations and acyl (or alternatively, alkoxyacyl and aminoacyl) radicals, respectively. The kinetics of the mesolytic fragmentation and the influence of nucleophilic additives have been determined using fast-scan cyclic voltammetry.

19.
Int J Sports Med ; 22(2): 120-6, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11281614

ABSTRACT

Supplementary vitamin C (2 x 500 mg tablets daily) or a matched placebo was administered to 10 and 6 ultramarathon athletes respectively for 7 days prior to participation in a 90 kilometer running event, as well as on the day of the race and for 2 days after its completion. Circulating concentrations of vitamins A, C and E, as well as those of leukocytes and platelets, myeloperoxidase, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF), cortisol, and creatine kinase were measured 16 hours before the race and at 30 min, 24 hours, and 48 hours after completion. Pre-race vitamin C concentrations in the supplemented group were unchanged after the race (118.2 +/- 15.9 and 115.9 +/- 11.9 micromol/l) while an increase was observed in the placebo group immediately post-race (85.8 +/- 11.9 to 107.4 +/- 18.8 micromol), with a return to pre-race values after 24 hours. Immediately on completion of the race transient elevations occurred in the concentrations of circulating neutrophils, monocytes and platelets, IL-6, cortisol, CRP, and creatine kinase in both groups. In the supplemented group the concentrations of CRP were significantly higher (p < 0.01) at each of the post-race time-points while those of cortisol were 30% lower immediately post-race. These observations provide evidence that supplementation with vitamin C may blunt the adaptive mobilization of this vitamin from the adrenals during exercise-induced oxidative stress and may be associated with an enhancement of the acute phase protein response and attenuation of the exercise-induced increase in serum cortisol.


Subject(s)
Acute-Phase Proteins/analysis , Ascorbic Acid/pharmacology , Hydrocortisone/blood , Physical Endurance , Running/physiology , Administration, Oral , Adrenal Glands/physiology , Adult , Dietary Supplements , Double-Blind Method , Humans , Male , Middle Aged , Oxidative Stress , Placebos
20.
J Org Chem ; 66(7): 2275-80, 2001 Apr 06.
Article in English | MEDLINE | ID: mdl-11281766

ABSTRACT

The oxidation of the 1-thiochromanones 1-3 by dimethyldioxirane (DMD) produced the corresponding sulfoxides 4-6 or sulfones 7-9; their relative amounts depended on the amount of oxidant used. A low diastereoselectivity was observed in the sulfoxidation of the 2-substituted 1-thiochromanones 2 and 3, due to the small steric differentiation during the DMD attack. An unusual reactivity pattern was found in the DMD oxidation of the 1-thiochromones 10-12, in that the sulfoxides 13-15 were more reactive toward the electrophilic oxidizing agent than the corresponding sulfides. The observed anomaly may be explained in terms of transannular stabilization of the transition structure (TS) for the sulfone formation, promoted through favorable conformational effects in the sulfoxide. Higher sulfoxide/sulfone ratios were found in solvents of greater hydrogen bond donor capacity, which is in accordance with the postulated stabilizing effect.


Subject(s)
Benzopyrans/chemistry , Chromans/chemistry , Epoxy Compounds/chemistry , Oxidation-Reduction , Oxides/chemistry , Stereoisomerism , Substrate Specificity
SELECTION OF CITATIONS
SEARCH DETAIL
...