Fateful triad of reactive oxygen species, mitochondrial dysfunction and lipid accumulation is associated with expression outline of the AMP-activated protein kinase pathway in bovine blastocysts.

Low cryotolerance is considered as the major drawback of in vitro-produced bovine embryos and is frequently associated with a triad encompassing increased cytoplasmic lipid accumulation, enhanced levels of reactive oxygen species (ROS) and mitochondrial dysfunction. The aim of the present study was to explore the role of the AMP-activated protein kinase (AMPK) pathway in the process resulting such phenotypes. Comparative analysis under different environmental conditions revealed downregulation of AMP-activated protein kinase cytalytic subunit 1alpha (AMPKA1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1A) and carnitine palmitoyltransferase 1 (CPT1) genes and upregulation of acetyl-CoA carboxylase α (ACC). In contrast, the presence of fatty acids within the culture medium resulted in a distinct molecular profile in the embryo associated with enhanced levels of ROS, mitochondrial dysfunction and elevated lipid accumulation in bovine embryos. Because AMPKA1 regulates PGC1A, CPT1 and ACC, the results of the present study reveal that AMPK in active its form is the key enzyme promoting lipolysis. Because AMPK1 activity is, in turn, controlled by the AMP : ATP ratio, it is possible to speculate that excessive uptake of exogenous free fatty acids could increase cellular ATP levels as a result of the disturbed ß-oxidation of these external fatty acids and could therefore bypass that molecular feedback mechanism. Subsequently, this condition would cause enhanced generation of ROS, which negatively affect mitochondrial activity. Both enhanced generation of ROS and low mitochondrial activity are suggested to enhance the accumulation of lipids in bovine embryos.

Molecular signatures of bovine embryo developmental competence.

Assessment of the developmental capacity of early bovine embryos is still an obstacle. Therefore, the present paper reviews all current knowledge with respect to morphological criteria and environmental factors that affect embryo quality. The molecular signature of an oocyte or embryo is considered to reflect its quality and to predict its subsequent developmental capacity. Therefore, the primary aim of the present review is to provide an overview of reported correlations between molecular signatures and developmental competence. A secondary aim of this paper is to present some new strategies to enable concomitant evaluation of the molecular signatures of specific embryos and individual developmental capacity.

G6PDH-activity in equine oocytes correlates with morphology, expression of candidate genes for viability, and preimplantative in vitro development.

Efficiencies for in vitro production of equine embryos are still low due to highly variable developmental competences of equine immature oocytes. In contrast to the equine, in vitro developmental competence of immature oocytes has been predicted successfully by the activity of glucose-6-phosphate dehydrogenase (G6PDH) indicated by brilliant cresyl blue (BCB) dye in a range of different species. Therefore, the aim of the present study was to test the association between G6PDH activity in equine oocytes with: (1) cumulus morphology and oocyte properties in terms of diameter and volume; (2) maturational competence; (3) gene expression of certain molecular markers; and (4) in vitro embryo development after intracytoplasmic sperm injection. Equine oocytes were exposed to BCB stain and were classified as BCB+ or BCB- according to their ability to convert the dye from blue to colorless. Additionally, BCB+ and BCB- oocytes were subclassified as having a compact (Cp) or expanded (Ex) cumulus complex. As a result, BCB+ oocytes had a greater proportion of expanded cumulus oocyte complexes compared with BCB- oocytes (71.2% vs. 49.5%). Moreover, we observed a significant difference in oocyte diameter and volume between BCB+ and BCB- oocytes irrespective of cumulus morphology. BCB+ oocytes reached a higher maturation rate compared with BCB- oocytes (59.0% vs. 28.7%). Regarding the analyzed candidate genes, relative transcript abundance was significantly different for nine genes. The expression of eight genes was significantly higher (P < 0.05) for BCB+ oocytes, including ATPV6E, IF-3, TFAM, DNMT1, STAT3, Aurora-A, ODC1, and CKS2 whereas BCB- oocytes showed higher in expression of COX1. These results are in line with the observed developmental competence. Cleavage rate (45.9% vs. 29.0%) and percentage of embryos that reached the blastocyst stage (9.2% vs. 1.4%) were significantly higher for embryos derived from BCB+ oocytes compared with BCB- oocytes. In conclusion, the present study provides evidence that G6PDH-activity in immature equine oocytes is a useful predictor for subsequent in vitro developmental competence.

The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol.

BACKGROUND: Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half-life. OBJECTIVES: To determine if isotretinoin (13-cis-RA), its main metabolite 4-oxo-isotretinoin (4-oxo-13-cis-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined. PATIENTS/METHODS: Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self-administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4-oxo-isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse-phase high-performance liquid chromatography. RESULTS: Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4-oxo metabolite or the all-trans compounds was chromatographically detectable in any of the patients' plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies. CONCLUSIONS: The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long-term isotretinoin treatment. After ceasing long-term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.

Less skin irritation from alcohol-based disinfectant than from detergent used for hand disinfection.

BACKGROUND: The benefit of alcohol-based disinfectant used on normal skin has been debated. OBJECTIVES: The objective of the present study was to compare the effects of repeated exposure to an alcohol-based disinfectant, a detergent and an alcohol-based disinfectant/detergent alternately for 10 days, including noninvasive measurements in the evaluation. Skin reactivity in irritated skin after a 4-week interval was also evaluated. MATERIALS AND METHODS: Detergent, disinfectant and alternate disinfectant and detergent were applied twice daily every 10 min for 1 h to the ventral upper arms and forearms of 17 healthy volunteers. A control area was included. After 4 weeks an SLS patch was applied to each area. Irritant reactions were quantified with a visual score recording and measurements of transepidermal water loss (TEWL) and skin colour were performed on days 1, 5, 11, 38 and 40. RESULTS: On day 5 the detergent caused a higher visual score than either disinfectant applied alone or alternate disinfectant and detergent, P < 0.05. On day 11 detergent and alternate disinfectant and detergent caused a higher score than disinfectant, P < 0.05. An increased irritant response for detergent compared with disinfectant alone and alternate disinfectant and detergent was confirmed by TEWL evaluations on days 5 and 11, P < 0.001, while no significant difference was found by colour measurement. After 4 weeks, when evaluated by colour measurement, significantly less response to the SLS patch was found on the disinfectant-treated area compared with the control area and detergent area, and a similar trend was found for TEWL, although it was not statistically significant. CONCLUSION: Alcohol-based disinfectant caused less visible skin irritation and less skin barrier disruption than the use of detergent. The alternate use of detergent and disinfectant caused less irritation than the use of detergent, and a possible interaction between the two irritants was not indicated. After 4 weeks there was a tendency for decreased skin reactivity in the skin areas which had 4 weeks previously been exposed to disinfectant.

The hand eczema severity index (HECSI): a scoring system for clinical assessment of hand eczema. A study of inter- and intraobserver reliability.

BACKGROUND: There is a need for a standardized clinical grading system for a more objective and accurate assessment of the severity of hand eczema (HE). OBJECTIVES: To develop and validate a scoring system called the hand eczema severity index (HECSI) designed for clinical assessment of HE. METHODS: Twelve dermatologists (observers) assessed 15 HE patients twice, with an interval of 30 min. The study was performed blinded for the observers, and only the hands and wrists of the patients were visible to the observers. Agreement between the observers was determined by using the intraclass correlation coefficient (ICC), which is the correlation between (single) ratings of the same patient. RESULTS: ICC for total HECSI score was 0.79 at the first assessment and 0.84 at the second assessment. ICC for intraobserver agreement was 0.90. CONCLUSIONS: Overall excellent agreement existed for both inter- and intraobserver reliability and the scoring system is suggested for use in future clinical studies on HE. Because HECSI is an entirely objective assessment of clinical signs, in addition, inclusion of patient-rated symptoms should be considered.

Methyldibromoglutaronitrile in leave-on products elicits contact allergy at low concentration.

BACKGROUND: The rapidly increasing level of contact allergy to methyldibromoglutaronitrile (MDBGN) in Europe is of concern. In April 2003, the EU Commission prohibited the use of MDBGN in leave-on cosmetic products, such as creams and lotions, until a level of safe use can be defined. Industry risk assessment has indicated that such a safe level could be 50-100 p.p.m. OBJECTIVES: To determine whether 50 p.p.m. or 100 p.p.m. could be tolerated by MDBGN-sensitized individuals, and to evaluate if the risk for elicitation of MDBGN allergy is higher for a leave-on product with a high lipid content than for a product with a low lipid content. METHODS: Eighteen volunteers with contact allergy to MDBGN and 10 healthy controls were exposed to repeated open application tests (ROATs) with two moisturizers with a high and a low lipid content, respectively, both containing MDBGN at a concentration of 50 p.p.m. The ROATs were performed on the left and the right side of the neck for 14 days, or until a positive reaction was seen. If a positive reaction did not develop within the first 14 days, two analogous moisturizers containing 100 p.p.m. MDBGN were applied for a further 14 days. Clinical assessments were done on days 2, 3, 7, 14, 21 and 28 or when a reaction developed. RESULTS: Eleven of 18 (61%) subjects developed dermatitis on the test area, of whom 10 developed a positive reaction to the 50 p.p.m. moisturizer, seven having a positive reaction on day 2 or 3. Reactions to the low-lipid moisturizer were the more frequent. All participants used more of the low-lipid moisturizer than the high-lipid moisturizer. The controls all had negative ROATs. CONCLUSIONS: Even 50 p.p.m. cannot be regarded as a safe concentration for use and the prohibition of MDBGN is scientifically well founded.

Stationary equilibria of two fluid plasmas having significant, internal, static electric fields.

New steady-state equilibria of two-species, collisionless plasmas have been found for symmetrical systems by varying the total energy subject to Maxwell's equations, momentum moment equations, and adiabatic equations of state, without imposing a quasineutrality condition. Electrons are confined by magnetic forces and ions by internal, electrostatic forces due to charge separation. The scale length for one-dimensional plasmas is characterized by the electron skin depth. Minimum average beta values are approximately one-half. Space and laboratory applications are discussed.

Prevention of work related skin problems: an intervention study in wet work employees.

AIMS: To evaluate the effect of implementation of an evidence based skin care programme for wet work employees as part of an occupational health and safety management system. METHODS: 375 wet work employees were included in a prospective randomised controlled trial, allocated to either intervention (n = 207) or control (n = 168). The intervention group was exposed to a skin care programme during the five month study period. The intervention included an educational programme for a group of frontline employees, who underwent formalised training, and subsequently introduced the information to their colleagues. As part of the intervention a skin care policy including written instructions was established at each workplace. Both groups answered a test quiz, completed questionnaires on behaviour and symptoms, and underwent clinical examination of their hands before and after the five month period. RESULTS: No difference between the intervention and the control group was found at baseline with respect to clinical symptoms or behaviour. Evaluation after the five months of intervention revealed a significantly higher information level on skin care in the intervention group compared to the control group, a significant change in behaviour in the intervention group but not in the control group, and significantly less skin symptoms as evaluated clinically in the intervention group but not in the control group. No significant difference was found for self reported skin problems. CONCLUSIONS: The intervention was successful with respect to information level (knowledge), behaviour, and clinical symptoms. Implementation of a skin care programme as part of an occupational health and safety management system is recommended as a prophylactic measure for employees in wet occupations.

Reversible MRI changes in a patient with uremic encephalopathy.

A 19-year-old patient on chronic ambulatory peritoneal dialysis experienced severe neurologic disturbances caused by uremia. Increased signal intensity was seen bilaterally in the cortical and subcortical areas of the occipital and parietal lobe on cranial magnetic resonance imaging (MRI). Insufficient peritoneal dialysis efficacy was documented and the patient was switched from peritoneal to hemodialysis. Cranial MRI indicated a marked regression of the lesions to nearly normal, confirming the diagnosis of uremic encephalopathy.

[Acute renal failure due to rhabdomyolysis in McArdle's disease following binge drinking with seizures]. / Alkoholabusus mit Krampfanfall als Auslöser einer Rhabdomyolyse mit akutem Nierenversagen bei McArdle-Syndrom.

HISTORY AND ADMISSION FINDINGS: A 36-year-old gardener was admitted for tonic-clonic seizures after binge drinking. The next days he developed massive rhabdomyolysis with acute renal failure. Past medical history was unremarkable except for a similar episode of acute renal failure 14 years ago. At that time he had consumed alcohol as well. Furthermore, the patient complained of exercise-related painful muscle cramping and swelling. INVESTIGATIONS: The serum creatinine peaked at 8.5 mg/dl, blood urea at 126 mg/dl and the maximal level of serum creatinine kinase was 108 300 U/l. Because of the massive rhabdomyolysis and the patient inverted question marks past medical history a metabolic myopathy was suspected and a muscle biopsy was performed. Histochemical staining of muscle frozen sections for phosphorylase revealed no activity which is typical for myophosphorylase deficiency (McArdle inverted question marks disease). Additional biochemical analysis of the muscle biopsy specimen confirmed the diagnosis. TREATMENT AND COURSE: By vigorous intravenous hydration and forced alkaline diuresis, the patient had a sufficient urinary output and lacked uremic signs. The serum creatinine and urea fell continuously and reached normal levels after 6 weeks. At that time serum creatinine kinase was still elevated (867 U/l), which is typical for McArdle inverted question marks disease. Avoiding alcohol, a new episode of rhabdomyolysis and acute renal failure did not occur. CONCLUSIONS: Besides exercise alcohol is likely to be a further possible trigger of rhabdomyolysis and acute renal failure in McArdle inverted question marks disease. Postulated mechanisms by which alcohol induces muscle injury include direct muscle toxicity and inhibition of gluconeogenesis, as these patients are probably more dependent on the gluconeogenetic pathway for muscle cell metabolism.

Effect of moisturizers on skin susceptibility to irritants.

Moisturizers are used for the treatment of dry and irritated skin. The benefit of moisturizers when used on normal skin has recently been challenged, since an earlier study indicated that the increased hydration that follows long-term use of moisturizers on normal skin may facilitate penetration of irritants. The aim of the present study was to evaluate short-term use of 2 different moisturizers used on normal skin: cream A (high lipid content) and B (moderate/low lipid content). Nineteen healthy volunteers applied the moisturizers on the upper arm/forearm 3 times daily for 5 days, while the other upper arm/forearm served as symmetrical control. The day after moisturizer treatment was stopped the skin was challenged with a patch test of sodium lauryl sulphate. Skin reactions were evaluated by bioengineering measuring methods and clinical scoring. Skin response to sodium lauryl sulphate was increased on moisturizer-treated arms compared to controls for one of the moisturizer (cream A), while this was not statistically significant for the other moisturizer (cream B). Data confirm previous indications that some moisturizers when used on normal skin may increase skin susceptibility to irritants.

[Clinic admission?--but not without my child!]. / Klinik?--Aber nicht ohne mein Kind!

Since the end of the 1990s the Westfälische Klinik Lengerich has offered an inpatient psychiatric treatment of an psychiatric ill parent--combined with a pedagogic attendance of the child taken along. The following article describes our experience in that matter, from a ward concentrated on psychotherapy. In selected examples supposed patterns of interaction--following the specific disease--are represented from both the psychotherapeutic und the pedagogic point of view. In practice our plan of treatment and attendance has proved successful for the wellbeing of the patients and their children. Remains to be hoped that--despite difficulties in organisation which will have to be overcome--similar offers can be made in regional psychiatric attendance.

Binocular vision recovery in bilateral keratoplasty.

PURPOSE: To determine the benefit of bilateral penetrating keratoplasty with regard to binocular vision. METHODS: We compared patients who underwent corneal transplantation bilaterally with patients who had successful corneal transplantation in one eye and corneal disease in the other eye. Specifically, changes in fusion, stereopsis, and binocular vision function were analyzed. A questionnaire regarding performance of daily tasks was given. RESULTS: Patients with bilateral keratoplasty performed better in all the analyzed functions. Fusion was achieved by 81.25% in the unilateral group versus 100% in the bilateral group (p = 0.15). Stereopsis was present more in the bilateral group (100% vs. 62.5%, p = 0.008) and the quantity of stereopsis was significantly better in the bilateral group (121 seconds of arc vs. 1,284 seconds of arc, p = 0.014). 88.8% of the patients subjectively improved in daily activities after second eye surgery. CONCLUSION: There are objective and subjective improvements after bilateral penetrating keratoplasty.

Prevention of work-related skin problems in student auxiliary nurses: an intervention study.

The present study was designed as an intervention study to investigate whether an educational programme was efficient in preventing work-related skin problems on the hands. 107 student auxiliary nurses (61 in the intervention group and 46 in the control group) were followed during the first 10 weeks of their initial practical training in county hospitals. The intervention group was given an educational programme before the practical training started. For evaluation the participants had questionnaires, clinical examination of the hands, measurement of transepidermal water loss (TEWL) and patch testing. The use of hand disinfectants, which was discouraged in the educational programme, was significantly lower in the intervention group as compared to the control group (p=0.002). 48% of the intervention group and 58% of the control group had aggravation of skin problems during practical training (p>0.05). Use of hand disinfectant agents was significantly associated with aggravation of skin problems (p=0.016). A significant increase in TEWL for the control group (p<0.005), but not for the intervention group, was seen after 10 weeks of practical training. In conclusion, the present intervention study shows promising results from the use of an educational programme.

Can it be a "sin" to understand disease? On "genes" and "eugenics" and an "unconnected connection".

Particularly, but not exclusively, in Germany, concerns are uttered as to the consequences of modern biotechnological advances and their range of applications in the field of human genetics. Whereas the proponents of this research are mainly focussing on the possible knowledge that could be gained by understanding the causes of developmental processes and of disease on the molecular level, the critics fear the beginnings of a new eugenics movement. Without claiming a logical relationship between genetic sciences and eugenics movements, it is nevertheless suggested in this article that a connection between both can become established when the distinction between scientifically validated statements on one hand and guiding hypotheses and assumptions on the other hand is blurred, as is observed particularly when scientists report their results to the public. This claim is demonstrated in comparisons between the current state of scientific knowledge on the role of genes in development and causation of diseases, and the way this is presented to the public. It is required that a debate on biotechnology should include reflections on the validity of claims made by scientists.

Effect of different moisturizers on SLS-irritated human skin.

Moisturizers are widely used to treat irritant contact dermatitis (ICD). Their use is, however, not well-documented and standardized models for testing skin care products are needed to acquire documentation of their efficacy. The present study was undertaken to evaluate the effect of 6 commonly-used moisturizers on the recovery of irritated human skin. No commercial interests were involved in the study. 36 healthy volunteers had patch tests with SLS 0.5% applied on their forearms/upper arms for 24 h. After irritation of the skin, all volunteers had a moisturizer applied on one forearm/upper arm, respectively, 3 x daily for the following 5 days. The other forearm/upper arm served as an untreated control. Each moisturizer was tested on 12 volunteers and each volunteer tested 2 moisturizers at the same time. Evaluation was done on days 1, 3 and 8 by transepidermal water loss, electrical capacitance, laser Doppler flowmetry, DermaSpectrometry and clinical scoring. All 6 moisturizers were found to accelerate regeneration of the skin barrier function when compared to irritated non-treated skin. The most lipid-rich moisturizers improved barrier restoration more rapidly than the less lipid-rich moisturizers. We suggest this experimental model for further moisturizer efficacy testing.