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1.
J Neonatal Perinatal Med ; 16(2): 227-234, 2023.
Article in English | MEDLINE | ID: mdl-37092239

ABSTRACT

PURPOSE: Infection with COVID-19 during pregnancy has been associated with a hypercoagulable state. It is unknown if maternal COVID-19 infection results in congenital anomalies secondary to intrauterine vascular accidents. This study sought to determine if the rate of in-utero vascular complications (intestinal atresia and limb abnormalities) that may be attributable to the hypercoagulable states associated with COVID-19 and pregnancy increased after the onset of the pandemic. METHODS: Pregnancy, neonatal, and congenital defect data from a single academic medical center and the partner's children's hospital were collected and compared to the period prior to onset of the pandemic. A subanalysis including pregnant woman 18 years or greater with documented COVID-19 infection during gestation between March 2020-2021 was performed. RESULTS: Rates of intestinal atresia did not differ prior to or after the onset of the pandemic (3.78% vs 7.23%, p = 0.21) nor did rates of limb deficiency disorders (4.41% vs 9.65%, p = 0.09). On subanalysis, there were 194 women with COVID-19 infection included in analysis: 135 (69.6%) were positive during delivery admission and 59 (30.4%) were positive earlier in their pregnancy. There was one infant born with intestinal atresia. CONCLUSION: We report a low incidence of congenital anomalies in infants born to mothers with COVID-19 infection. It remains unclear if the impact of COVID-19 on the coagulative state augments the normal pro-thrombotic state of pregnancy; ongoing surveillance is warranted.


Subject(s)
COVID-19 , Intestinal Atresia , Pregnancy Complications, Infectious , Pregnancy , Infant, Newborn , Infant , Child , Humans , Female , COVID-19/complications , COVID-19/epidemiology , Incidence , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome
2.
Int J Cosmet Sci ; 43(2): 201-210, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33289148

ABSTRACT

OBJECTIVE: Sunscreens play a major role in the EU sun protection strategy in order to prevent humans from UV light-induced skin damage. In recent years, the demand for high-quality sunscreen products including aspects of broad range and photostability of the UV protection, showing good spreadability onto human skin and excellent sensorial properties during and after application has increased. Environmental aspects are considered. Sunscreens are complex compositions, with UV filters being the key element in the formulations reaching up to about 30% in content in the final product. Some of these ingredients, however, may be regarded as hazardous for the aquatic environment. Nevertheless, the aquatic ecosystem represents only a single environmental compartment, which may be impacted by UV filters. Therefore, the EcoSun Pass (ESP) tool was developed in order to assess the overall environmental impact of UV filters in combination with its efficacy (Sun Protection Factor, SPF and UVA Protection Factor, UVA-PF). METHODS: For that purpose, at first 24 of the EU-approved UV filters for sunscreen applications were evaluated for their environmental hazard profiles. Nine example UV filter compositions representing both SPF 30 and 50 were evaluated for ecofriendliness using the ESP tool. RESULTS: The results revealed that two out of four SPF 30 compositions are considered as ecofriendly. Likewise, from the SPF 50 two out of five did meet the criteria for ecofriendliness. Furthermore, the results showed that most ecofriendly example formulations have also the lowest overall UV filter content in the product, based on the use of highly innovative and least hazardous UV filters. CONCLUSION: These results demonstrate that the tool is applicable to various formulations being present on the market and thus allows for a selection of most ecofriendly and efficient UV filters to be used in sunscreens.


OBJECTIF: les écrans solaires jouent un rôle majeur dans la stratégie de protection solaire de l'UE, afin de protéger les êtres humains contre les lésions cutanées causées par les rayons ultraviolets. Au cours des dernières années, la demande pour des écrans solaires de haute qualité a augmenté, notamment ceux ayant une bonne capacité d'étalement sur la peau humaine, d'excellentes propriétés sensorielles pendant et après l'application, une plage large et démontrant la photostabilité de la protection anti-UV. Les aspects environnementaux sont pris en compte. Les écrans solaires ont des compositions complexes, les filtres UV étant l'élément clé des formulations, avec une présence jusqu'à près de 30 % dans le contenu du produit final. Toutefois, certains de ces ingrédients peuvent être considérés comme dangereux pour l'environnement aquatique. Néanmoins, l'écosystème aquatique ne représente qu'un seul compartiment environnemental pouvant être affecté par les filtres UV. Par conséquent, l'outil EcoSun Pass (ESP) a été développé afin d'évaluer l'impact environnemental global des filtres UV, ainsi que leur efficacité (facteur de protection solaire, FPS et facteur de protection UV-A, UVAPF). MÉTHODES: dans ce but, les profils de risque environnemental de 24 des filtres UV approuvés dans l'UE, pour les applications d'écran solaire, ont d'abord été évalués. Le respect de l'environnement de neuf exemples de compositions de filtres UV, représentant les FPS 30 et 50, a été évalué à l'aide de l'outil ESP. RÉSULTATS: les résultats ont révélé que deux des quatre compositions de FPS 30 sont considérées comme écologiques. De même, deux écrans solaires sur cinq ayant un indice FPS 50 répondaient aux critères de respect de l'environnement. De plus, les résultats ont montré que la plupart des exemples de formulations écologiques contiennent également la plus faible teneur globale en filtres UV ; elles sont basées sur l'utilisation de filtres UV hautement innovants et les moins dangereux. CONCLUSION: ces résultats démontrent que l'outil est applicable à diverses formulations présentes sur le marché, et qu'il permet donc d'utiliser une sélection des filtres UV les plus écologiques et efficaces dans les écrans solaires.


Subject(s)
Sunscreening Agents , Ultraviolet Rays , Humans , Sun Protection Factor
3.
Vaccine ; 29(7): 1399-407, 2011 Feb 04.
Article in English | MEDLINE | ID: mdl-21195805

ABSTRACT

Plasmid DNA (pWRG7079::MOMP) expressing the major outer membrane protein of a human Chlamydia trachomatis serovar E strain was tested for the ability to induce an immune response and protect against experimental genital infection with the same serovar. The vaccine was tested in pigs, as they are genetically and physiologically related to humans and suitable for studying C. trachomatis infection of the genital system. To increase the immune response, GM-CSF, LTA and B and CpG motives were used as adjuvants. GM-CSF was administered seven days before immunization, while the other adjuvants were administered together with the vaccine. Ten pigs were randomly divided into two groups. One group received an intravaginal primo-vaccination and a booster of 500 µg pWRG7079::MOMP, while the other group received the placebo vaccine pWRG7079. All animals were challenged with 10(8) TCID(50) of C. trachomatis serovar E. Pigs immunized with the DNA vaccine showed significantly less macroscopic lesions, vaginal excretion and chlamydial replication in the genital tract, as compared to placebo-vaccinated controls. However, infection could not be completely cleared.


Subject(s)
Bacterial Outer Membrane Proteins/immunology , Bacterial Vaccines/immunology , Chlamydia Infections/prevention & control , Porins/immunology , Vagina/microbiology , Adjuvants, Immunologic/administration & dosage , Administration, Intravaginal , Animals , Antibodies, Bacterial/blood , Antibody Specificity , Bacterial Outer Membrane Proteins/administration & dosage , Bacterial Shedding , Bacterial Vaccines/administration & dosage , Cell Proliferation , Chlamydia Infections/immunology , Chlamydia trachomatis/immunology , Cytokines/immunology , Female , Leukocytes, Mononuclear/immunology , Porins/administration & dosage , Swine , Vaccines, DNA/administration & dosage , Vaccines, DNA/immunology , Vagina/immunology
4.
J Neuroendocrinol ; 14(1): 56-63, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11903813

ABSTRACT

To investigate the role of brain glucocorticoid (GR) and mineralocorticoid receptors (MR) in centrally evoked blood pressure responses, the effects of intracerebroventricular (i.c.v.) administration of angiotensin II and vasopressin were studied in adrenalectomized rats with and without corticosterone or aldosterone replacement. Five groups were examined: (i) Adrenalectomy (ADX); (ii) ADX + a subcutaneously implanted 20-mg corticosterone pellet (low corticosterone); (iii) ADX + 100 mg corticosterone pellet (high corticosterone); (iv) ADX + 6 microg/24 h aldosterone via Alzet minipump (Aldo); and (v) Sham adrenalectomy (Sham). Pressor responses to 150 ng angiotensin II and 50 ng vasopressin i.c.v. were determined in freely moving rats using biotelemetry. The results show that, compared to sham rats, ADX rats showed significantly reduced pressor responses. This reduction of the pressor response to angiotensin II could be reversed and even further enhanced by replacement of the ADX rats with high corticosterone concentrations. In contrast, with aldosterone, a depressor type response was observed. Corticosterone replacement could not restore the pressor response to vasopressin. We conclude that the pressor response to centrally administered vasoactive substances is substantially attenuated by removal of the adrenals and that, in the case of angiotensin II, this is due to the lack of high concentrations of circulating corticosterone occupying both MR and GR. However, predominant MR occupancy appears to play an opposite role and attenuates the angiotensin II-induced pressor response.


Subject(s)
Angiotensin II/pharmacology , Blood Pressure/drug effects , Corticosterone/physiology , Vasopressins/pharmacology , Adrenalectomy , Animals , Corticosterone/blood , Drinking Behavior/drug effects , Heart Rate/drug effects , Male , Rats , Rats, Wistar , Receptors, Glucocorticoid/drug effects , Receptors, Mineralocorticoid/drug effects
5.
Tree Physiol ; 22(2-3): 213-7, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11830418

ABSTRACT

Although it is generally accepted that the rate of accumulation of biomass declines as forests age, little is known about the relative contributions to this decline of changes in net primary production (NPP) and tree mortality. We used 10-15 years of observations of permanent plots in three small watersheds in and near the H.J. Andrews Experimental Forest, Oregon, to examine these issues. The three watersheds are of similar elevation and potential productivity and support young (29 years at last measurement), mature (approximately 100 years) and old (approximately 400 years) forest dominated by Pseudotsuga menziesii (Mirb.) Franco and Tsuga heterophylla (Raf.) Sarg. Accumulation of tree bole biomass was greatest in the young stand, reaching approximately 7 Mg ha-1 year-1 in the last measurement interval. Bole biomass accumulation was relatively constant (approximately 4-5 Mg ha-1 year-1) in the mature stand, and there was no net accumulation of bole biomass in the old-forest stand. The NPP of boles increased with time in the young stand, from approximately 3 to approximately 7 Mg ha-1 year-1, but was nearly constant in the mature and old-forest stands, at approximately 6 and 3-4 Mg ha-1 year-1, respectively. Mortality increased slowly in the young stand (from < 0.1 to 0.3 Mg ha-1 year-1), but fluctuated between 1-2 and 2-6 Mg ha-1 year-1 in the mature and old-forest stands, respectively. Thus, declining biomass accumulation with stand age reflects, in approximately equal amounts, both decreasing NPP and increasing mortality.


Subject(s)
Biomass , Pseudotsuga/physiology , Trees/physiology , Ecosystem , Oregon , Plant Stems/physiology , Tsuga/physiology
6.
Eur J Pharmacol ; 430(1): 87-91, 2001 Oct 26.
Article in English | MEDLINE | ID: mdl-11698067

ABSTRACT

Intracerebroventricular (i.c.v.) administration of the glucocorticoid receptor antagonist 17beta-hydroxy-11beta(4-dimethylamino-phenyl)17alpha-(1-propynyl)estra-4,9dien-3one (RU38486) in conscious rats slowly increased systolic blood pressure as assessed with the indirect tail cuff method. However, direct measurement of blood pressure in freely moving rats did not reveal changes in blood pressure after i.c.v. injection of this antagonist either in the light or in the dark phase. In the present study, the hypothesis is tested that aspects of the tail cuff procedure, involving heat (30 min, 32 degrees C) and brief restraint stress, are necessary conditions to detect the glucocorticoid receptor-mediated cardiovascular effect. Freely moving rats equipped with a telemetric transmitter to directly measure heart rate and blood pressure were injected i.c.v. with either the glucocorticoid receptor or the mineralocorticoid receptor antagonist and were either left undisturbed for 24 h, or were subjected to the tail cuff procedure at 1.5, 6.5 and 23.5 h after injection. Then after 30-min warming and during brief restraint, blood pressure and heart rate showed a rapid increase. The mineralocorticoid receptor antagonist administered i.c.v. did not affect these stress-induced increases in cardiovascular responses. The glucocorticoid receptor antagonist i.c.v. significantly increased the heart rate and pressor response at 24 h. In the undisturbed rats, neither basal heart rate nor blood pressure were affected by either antagonist during the circadian cycle. In conclusion, the blockade of central glucocorticoid receptor causes a long-lasting facilitation of the stress-induced pressor and heart rate response, which does not require a 2-week training to the condition of heat and stress.


Subject(s)
Mifepristone/pharmacology , Receptors, Glucocorticoid/antagonists & inhibitors , Spironolactone/analogs & derivatives , Stress, Physiological/physiopathology , Animals , Blood Pressure/drug effects , Circadian Rhythm , Heart Rate/drug effects , Hot Temperature , Injections, Intraventricular , Male , Rats , Rats, Wistar , Restraint, Physical , Spironolactone/pharmacology , Stress, Physiological/etiology , Time Factors
7.
Am J Surg Pathol ; 25(8): 1039-46, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11474288

ABSTRACT

Accurate diagnosis of micrometastases in sentinel lymph nodes of cutaneous melanoma is critical for proper clinical management. S-100 protein and HMB-45 are the traditional immunomarkers widely used for this purpose. However, the interpretation of micrometastases by these markers is difficult with significant reduction in the diagnostic accuracy. S-100 protein demonstrates immunoreactivity for other nonmelanoma cells and obscures nuclear details, which are crucial for the interpretation of single cell metastases. We compared the new melanoma markers, Melan-A (clone A103) and MART-1 (clone M2-7C10), with S-100 protein and HMB-45, by examining 77 formalin-fixed paraffin-embedded sections of sentinel lymph nodes from 13 cases of primary cutaneous melanoma. CD68 (PG-M1) and hematoxylin-eosin-stained sections were also studied. Four pathologists interpreted the staining pattern after concealing the identity of each immunomarker. Az values (area under receiver operating characteristic curve) with receiver operating characteristic curve were higher with Melan-A (0.9742) and MART-1 (0.9779) compared with S-100 protein (0.8034) and HMB-45 (0.8651), demonstrating a higher diagnostic accuracy with Melan-A and MART-1 with superior detection of melanoma micrometastases. Melan-A and MART-1 showed sharp cytoplasmic immunoreactivity, almost exclusively restricted to the melanoma cells. Therefore, Melan-A and MART-1 are recommended for the evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma as a routine alternative to S-100 protein and HMB-45.


Subject(s)
Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Melanoma/diagnosis , Skin Neoplasms/pathology , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Antigens, Neoplasm , Humans , Lymph Nodes/chemistry , MART-1 Antigen , Melanoma/chemistry , Melanoma/secondary , Melanoma-Specific Antigens , Neoplasm Proteins/analysis , Observer Variation , ROC Curve , Reproducibility of Results , S100 Proteins/analysis , Sentinel Lymph Node Biopsy , Skin Neoplasms/chemistry
8.
Psychophysiology ; 38(3): 490-9, 2001 May.
Article in English | MEDLINE | ID: mdl-11352138

ABSTRACT

We developed a new model of psychological "open-field" stress in freely moving rats. Blood pressure and heart rate of the rats were measured by radiotelemetry and behavior analyzed by video tracking software. Open-field exposure induced marked increases in blood pressure and heart rate. Repeated daily exposure induced pressor responses that were slightly higher on Day 4 when compared to Day 1. Pretreatment with the beta1-adrenoceptor antagonist atenolol inhibited the tachycardia whereas the ganglion blocker pentolinium inhibited the pressor response, indicating involvement of the sympathetic nervous system. Pretreatment with diazepam prevented the novelty stress-induced pressor response and reduced the tachycardia. These results show that the psychological stress of exposing rats to an open field induces marked cardiovascular effects that are mediated by sympathetic hyperactivity. This model is unique in that it focuses on psychological stress and allows concomitant measurement of blood pressure, heart rate, and behavior in freely moving rats.


Subject(s)
Behavior, Animal/physiology , Blood Pressure/physiology , Heart Rate/physiology , Animals , Behavior, Animal/drug effects , Blood Pressure/drug effects , Heart Rate/drug effects , Male , Motor Activity/drug effects , Motor Activity/physiology , Rats , Rats, Wistar
10.
Med Phys ; 28(12): 2518-21, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11797955

ABSTRACT

One of our linear accelerators is equipped with a free-movable treatment couch. An additional projects was to develop a system that first protects the free-movable couch against collisions, secondly build a remote control for moving the couch from outside the treatment room and finally implement this remote control/limitation system in an automatic position algorithm using an electronic portal image. The latter has been the subject of an on-going departmental investigation on intra-fractional correction of set-up errors. A few years ago, we developed a limitation system to protect both the table and the accelerator against collisions. In this paper we describe the second part of this project, the remote control system.


Subject(s)
Equipment Design , Particle Accelerators/instrumentation , Radiotherapy/instrumentation , Algorithms , Biophysical Phenomena , Biophysics
11.
Am J Dermatopathol ; 22(5): 443-6, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11048982

ABSTRACT

Cutaneous Crohn disease, sometimes called metastatic Crohn disease or Crohn disease with cutaneous involvement, is a rare complication of Crohn disease in which granulomatous lesions involve skin separated from gastrointestinal lesions by normal tissue. We report two cases of cutaneous Crohn disease presenting in young males with erythematous, nontender swelling of the scrotum. One of the young males presented erythematous, nontender swelling of the penis as well. In one case, cutaneous Crohn disease represented the primary presentation. The original biopsy in this case showed unusual areas of degeneration of dermal connective tissue forming cystic cavities. The diagnostic biopsies in both cases showed sarcoidal granulomas with an associated superficial and deep perivascular mixed infiltrate including eosinophils. On endoscopy, both patients showed lesions of active Crohn disease in the colon. Because changes that would suggest cutaneous Crohn disease may not be present on the initial biopsy, unusual presentations and negative cultures may warrant a second biopsy. A high index of suspicion and open communication with the clinician are essential to diagnose this disease.


Subject(s)
Crohn Disease/pathology , Penile Diseases/pathology , Skin Diseases/pathology , Testicular Diseases/pathology , Adolescent , Adult , Colitis/diagnosis , Humans , Male
12.
Clin Cancer Res ; 6(4): 1337-41, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10778960

ABSTRACT

Doxorubicin is a very effective antitumor agent, but its clinical use is limited by the occurrence of a cumulative dose-related cardiotoxicity, resulting in congestive heart failure. 7-Monohydroxyethylrutoside (monoHER), a flavonoid belonging to the semisynthetic hydroxyethylrutoside family, has been shown to protect against doxorubicin-induced cardiotoxicity when administered i.p. at a dose of 500 mg/kg five times/week in combination with a weekly i.v. dose of doxorubicin. Such a dosing schedule would be very inconvenient in clinical practice. We therefore investigated a dosing schedule of one administration of monoHER just before doxorubicin. The electrocardiogram was measured telemetrically in mice after the combined treatment of doxorubicin (4 mg/kg, i.v.) with one dose of monoHER (500 mg/kg, i.p., administered 1 h before doxorubicin) for 6 weeks. These data were compared with the five times/week schedule (500 mg/kg, i.p., administered 1 h before doxorubicin and every 24 h for 4 days). The increase of the ST interval was used as a measure for cardiotoxicity. It was shown that 500 mg/kg monoHER administered only 1 h before doxorubicin provided complete protection against the cardiotoxicity. This protection was present for at least 10 weeks after the last treatment. Because of the short half-life of monoHER, these results suggest that the presence of monoHER is only necessary during the highest plasma levels of doxorubicin.


Subject(s)
Antineoplastic Agents/pharmacology , Doxorubicin/pharmacology , Heart/drug effects , Hydroxyethylrutoside/pharmacology , Animals , Antineoplastic Agents/adverse effects , Doxorubicin/adverse effects , Drug Administration Schedule , Electrocardiography , Flavonoids/pharmacology , Heart/physiopathology , Male , Mice , Mice, Inbred BALB C , Myocardium/pathology , Weight Gain/drug effects
13.
Kidney Int ; 57(4): 1329-36, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10760063

ABSTRACT

Mineralocorticoid receptors (MRs) expressed in limbic neurons, notably of hippocampus, retain both aldosterone and corticosterone. Basal concentrations of corticosterone already substantially occupy the limbic MR type, suggesting that in hippocampal neurons, MR activity rather than ligand bioavailability is rate limiting. The periventricular region expresses MRs involved in the control of salt homeostasis, which are aldosterone selective because of the presence of 11beta-hydroxysteroid dehydrogenase. MR is in hippocampal CA1, CA2, and dentate gyrus colocalized with glucocorticoid receptors (GRs). Both receptor types mediate in a coordinate manner the corticosterone action on information processing critical for behavioral adaptation and associated neuroendocrine responses to stress. MRs operate in proactive mode determining the sensitivity of the stress response system, while GRs facilitate recovery from stress in reactive mode. On the neuronal level, MR-mediated action maintains a stable excitatory tone and attenuates the influence of modulatory signals. In contrast, GR-mediated effects suppress excitability transiently raised by excitatory stimuli. MR is also involved in control of autonomic outflow and volume regulation. This was demonstrated by the effect of an MR antagonist, which was administered centrally, because mdr P-glycoproteins hamper the access of synthetic steroids to the brain. The MR antagonist attenuates pressor responses to a stressor, such as experienced during tail sphygmography. Diuresis and urinary electrolyte excretion are increased after the MR antagonist, but this effect is abolished after bilateral denervation of the kidney. It is presently unknown in which brain cells the MR-mediated effects on these aspects of central cardiovascular regulation occur.


Subject(s)
Brain/physiology , Receptors, Mineralocorticoid/physiology , Animals , Brain/metabolism , Hippocampus/physiology , Neurosecretory Systems/physiology , Receptors, Mineralocorticoid/metabolism , Receptors, Steroid/metabolism
14.
Anticancer Res ; 20(6B): 4483-7, 2000.
Article in English | MEDLINE | ID: mdl-11205292

ABSTRACT

Cardiotoxicity, a side-effect that can occur after treatment with an anticancer drug, has severe clinical implications. Therefore, a model is desired to screen new anticancer drugs or drug combinations for possible cardiotoxic side-effects. In the present study we tested the applicability of the electrically stimulated isolated mouse left atrium model using a wide range of anticancer drugs with known cardiotoxicity. It appeared that the cardiotoxicity observed in our model, i.e. the negative or positive inotropic effects of the drugs on the isolated atrium, corresponded with the observed cardiotoxicity in animals and/or humans. It is therefore concluded that our model can be used to wam for possible cardiotoxic side-effects of anticancer drugs in vivo.


Subject(s)
Aminoglycosides , Antineoplastic Agents/adverse effects , Atrial Function, Left/drug effects , Myocardial Contraction/drug effects , Animals , Anti-Bacterial Agents/adverse effects , Atrial Function, Left/physiology , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Dose-Response Relationship, Drug , Doxorubicin/adverse effects , Drug Evaluation, Preclinical , Etoposide/adverse effects , Male , Mice , Mice, Inbred BALB C , Mitomycins/adverse effects , Mitoxantrone/adverse effects , Models, Animal , Myocardial Contraction/physiology , Quaternary Ammonium Compounds/adverse effects
15.
Br J Dermatol ; 141(4): 731-5, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10583128

ABSTRACT

Verrucae vulgares frequently induce nail dystrophy when infection of the nail matrix occurs. Classic periungual warts are easily recognized by the experienced physician. We report a very unusual presentation of human papillomavirus (HPV) infection of the nail matrix and nail bed involving all 20 nails in an otherwise immunocompetent patient. Viral typing by in situ hybridization revealed HPV type 57. To our knowledge, this is the first association between dystrophy of all 20 nails and HPV infection. However, as the ease of HPV typing improves, a variety of previously unrecognized cutaneous lesions is likely to be associated with HPV infection.


Subject(s)
Nail Diseases/virology , Papillomaviridae , Papillomavirus Infections/pathology , Tumor Virus Infections/pathology , Aged , Female , Humans
16.
Biochem Pharmacol ; 56(8): 935-43, 1998 Oct 15.
Article in English | MEDLINE | ID: mdl-9776303

ABSTRACT

The antioxidant activity of flavonoids is believed to be caused by a combination of iron chelation and free radical scavenging activities. Several authors have attempted to separate the iron chelation and scavenging activity of flavonoids in order to study these processes individually. There are, however, several contradictions in the literature, and the outcome largely depends on the experimental conditions and the type of assay used. In order to investigate the contribution of iron chelation to the antioxidant activity of flavonoids, we determined the antioxidant activity of a group of flavonoids from several subclasses in an iron-independent (azobisamidinopropane, [ABAP]) lipid peroxidation (LPO) process and compared them with data from an iron-dependent (Fe2+/ascorbate) LPO process, which we determined earlier. These LPO data were compared with oxidation potentials, which were earlier found to have a good correlation with the scavenging activity of flavonoids. For most flavonoids, it was found that there was no difference between the LPO assays, indicating that iron chelation is either a constant factor among the flavonoids or is not significant in these types of assays. The IC50 values in the iron-independent LPO assay showed an excellent correlation with the oxidation potentials (Ep/2). Therefore, it can be concluded that for the majority of flavonoids tested, iron chelation does not play a role in the antioxidant activity in microsomal lipid peroxidation.


Subject(s)
Antioxidants/metabolism , Flavonoids/metabolism , Iron Chelating Agents/pharmacology , Amidines/metabolism , Animals , Binding, Competitive , Free Radical Scavengers/metabolism , Linear Models , Lipid Peroxidation/physiology , Male , Mice , Mice, Inbred BALB C
17.
J Am Acad Dermatol ; 39(2 Pt 1): 239-45, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9704836

ABSTRACT

BACKGROUND: The histologic discrimination of melanoma in situ of sun-damaged skin (MIS) from chronically sun-damaged skin (SDS) can sometimes be difficult using accepted criteria. OBJECTIVE: We evaluated these entities by means of morphometry and multifactorial analysis. METHODS: We measured the number and area of melanocyte nuclei, melanocyte nucleoli, stratum spinosum keratinocyte nuclei, and papillary dermal lymphocyte nuclei from hematoxylin-eosin-stained slides representing 38 cases of MIS and 18 cases of SDS matched for age, sex, and site with a high-resolution digital imaging and analysis system. RESULTS: Multiple logistic regression analysis correctly classified 100% of the cases using the number of melanocytes per 0.5 mm and the maximum melanocyte nuclear area divided by the maximum keratinocyte nuclear area. The strongest results were achieved measuring approximately 1 mm of epidermis. CONCLUSION: Morphometry and multifactorial analysis can distinguish MIS from SDS. Morphometric analysis of melanocytic proliferations may be useful at the margins of surgical resections.


Subject(s)
Hutchinson's Melanotic Freckle/pathology , Melanoma/pathology , Skin Neoplasms/pathology , Sunburn/pathology , Aged , Chronic Disease , Diagnosis, Differential , Female , Humans , Logistic Models , Male , Middle Aged , Skin/pathology , Statistics, Nonparametric
18.
Clin Cancer Res ; 3(10): 1747-54, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9815559

ABSTRACT

The cumulative dose-related cardiotoxicity of doxorubicin is believed to be caused by the production of oxygen- free radicals. 7-Monohydroxyethylrutoside (monoHER), a semisynthetic flavonoid and powerful antioxidant, was investigated with respect to the prevention of doxorubicin-induced cardiotoxicity in mice and to its influence on the antitumor activity of doxorubicin in vitro and in vivo. Non-tumor-bearing mice were equipped with a telemeter in the peritoneal cavity. They were given six weekly doses of 4 mg/kg doxorubicin i.v., alone or in combination with either 100 or 250 mg/kg monoHER i.p., 1 h prior to doxorubicin administration and for the following 4 days. Cardiotoxic effects were measured from electrocardiogram changes up to 2 weeks after treatment. Protection against cardiotoxicity was found to be dose dependent, with 53 and 75% protection, respectively, as calculated from the reduction in the increase in the ST interval. MonoHER and several other flavonoids with good antioxidant properties were tested for their antiproliferative effects in the absence or the presence of doxorubicin in A2780 and OVCAR-3 human ovarian cancer cells and MCF-7 human breast cancer cells in vitro. Some flavonoids were directly toxic at 50 and 100 microM, whereas others, including monoHER, did not influence the antiproliferative effects of doxorubicin at these concentrations. The influence of monoHER was further tested on the growth-inhibitory effect of 8 mg/kg doxorubicin i.v., given twice with an interval of 1 week in A2780 and OVCAR-3 cells that were grown as s.c. xenografts in nude mice. MonoHER, administered 1 h before doxorubicin in a dose schedule of 500 mg/kg i.p. 2 or 5 days per week, was not toxic and did not decrease the antitumor activity of doxorubicin. It can be concluded that monoHER showed a dose-dependent protection against chronic cardiotoxicity and did not influence the antitumor activity of doxorubicin in vitro or in vivo.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Antioxidants/pharmacology , Cardiomyopathies/prevention & control , Doxorubicin/pharmacology , Flavonoids/pharmacology , Hydroxyethylrutoside/pharmacology , Kaempferols , Animals , Antibiotics, Antineoplastic/therapeutic use , Antibiotics, Antineoplastic/toxicity , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Antioxidants/toxicity , Breast Neoplasms/pathology , Cardiomyopathies/chemically induced , Catechin/administration & dosage , Catechin/pharmacology , Catechin/therapeutic use , Chelation Therapy , Cystadenocarcinoma, Serous/pathology , Dose-Response Relationship, Drug , Doxorubicin/therapeutic use , Doxorubicin/toxicity , Drug Interactions , Electrocardiography , Female , Flavonoids/administration & dosage , Flavonoids/therapeutic use , Flavonoids/toxicity , Flavonols , Free Radical Scavengers , Free Radicals , Humans , Hydroxyethylrutoside/therapeutic use , Iron , Iron Chelating Agents/administration & dosage , Iron Chelating Agents/pharmacology , Iron Chelating Agents/therapeutic use , Iron Chelating Agents/toxicity , Mice , Mice, Nude , Molecular Structure , Neoplasm Transplantation , Ovarian Neoplasms/pathology , Quercetin/administration & dosage , Quercetin/analogs & derivatives , Quercetin/pharmacology , Quercetin/therapeutic use , Quercetin/toxicity , Razoxane/administration & dosage , Razoxane/pharmacology , Razoxane/therapeutic use , Razoxane/toxicity , Rutin/administration & dosage , Rutin/pharmacology , Rutin/therapeutic use , Rutin/toxicity
19.
Chem Res Toxicol ; 9(8): 1305-12, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8951233

ABSTRACT

Flavonoids are a group of naturally occurring antioxidants, which over the past years have gained tremendous interest because of their possible therapeutic applicability. The mechanism of their antioxidant activity has been extensively studied over several decades. However, there is still much confusion about the molecular mechanism of radical scavenging and the relationship between structure and activity. Therefore, we have calculated the heat of formation and the geometry of both the parent compound and the corresponding radical using the ab initio program GAMESS. We have compared their differences in energy in order to gain insight into the stability of the radical and the ease with which it is formed. We have also investigated the spin density of the radical, to determine the delocalization possibilities. These calculated data were compared with experimental data from ESR (hyperfine coupling constants) and electrochemical oxidation (Ep/2) and were found to be in good agreement. By comparing the geometries of several flavonoids, we were able to explain the structural dependency of the antioxidant action of these compounds. The extremely good antioxidant activity of the flavonols could be explained by the formation of an intramolecular hydrogen bond.


Subject(s)
Antioxidants/chemistry , Flavonoids/chemistry , Chemical Phenomena , Chemistry, Physical , Computer Simulation , Electron Spin Resonance Spectroscopy , Hydrogen-Ion Concentration , Oxidation-Reduction , Structure-Activity Relationship
20.
Free Radic Biol Med ; 20(3): 331-42, 1996.
Article in English | MEDLINE | ID: mdl-8720903

ABSTRACT

Flavonoids, a group of naturally occurring antioxidants and iron chelators, might be used as cardioprotective agents in doxorubicin-induced cardiotoxicity, which is believed to be caused by the formation of oxygen free radicals. To investigate the underlying molecular mechanism, we tested a large group of flavonoids from all major structural subclasses on their ability to inhibit doxorubicin (enzymatically)-induced and Fe2+/ascorbate (nonenzymatically)-induced microsomal lipid peroxidation (LPO) and to chelate Fe2+. In addition, we measured half peak oxidation potentials (Ep/2). LPO inhibition data gave a good qualitative correlation with the oxidation potentials. Most flavonoids tested chelated Fe2+, but there were large differences in the chelating capacity. For good scavenging activity, a catechol moiety on ring B is required. The 3-OH moiety can function as a chelation site and can also be oxidized. The 3-OH group in combination with a C2 C3 double bond, increases the scavenging activity. Fe2+ chelation only plays a role in the LPO inhibition by less active scavengers. Chelation can then raise the activity to the level of the most active scavengers, possibly by site-specific scavenging. It can be concluded that Ep/2 values and iron chelating activity can almost completely describe the LPO inhibiting behaviour of the flavonoids.


Subject(s)
Antioxidants/chemistry , Antioxidants/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Lipid Peroxidation , Microsomes/metabolism , Animals , Ascorbic Acid , Ferrous Compounds , Free Radicals , Iron/metabolism , Iron Chelating Agents/pharmacology , Mice , Mice, Inbred BALB C , Microsomes/drug effects , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Molecular Structure , Myocardium/metabolism , Regression Analysis , Structure-Activity Relationship
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