EcoSun Pass: A tool to evaluate the ecofriendliness of UV filters used in sunscreen products.

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.

Multicenter methodology comparison of the FDA and ISO standard for measurement of in vitro UVA protection of sunscreen products.

In vitro standard methods are available and accepted worldwide to assess UVA protection of sunscreen products. Though, harmonisation of methods has made progress in the last decade, still two differing methods - one by FDA the other by ISO - are in use. In a multicentre study including 9 centres in Germany, 4 different commercial sunscreen products were assessed using both methods to discover their similarities and differences. UVA protection factor and Critical Wavelength were detected at various substrate type (sandblasted versus moulded PMMA plates), at different surface roughness of the plates as well as at different product application dose using two different irradiation spectra. Results: The strongest influence on UVA protection factor results from the surface roughness of the plates. Depending on the roughness (accepted range of 2 to 7 µm in the FDA method) a variability in the UVA protection factor of up to 25% was observed, while the much narrower definition of plate roughness by ISO (4.5 to 5.2 µm) had no relevant influence on the test results. Sandblasted plates in our assessment led to higher UVA protection factors and produced less scattered results compared to moulded plates. These differences were not pronounced. Application dose and spectra of the irradiation source were of negligible influence on UVA protection factor results for the investigated UV-filter combinations. The UVA protection factor which is the endpoint of the ISO method was found to be a parameter with a high potential to differentiate among different test products. The endpoint of the FDA method - the Critical Wavelength - was found to be an unambitious endpoint. Insensitivity to all described modifications of the method was observed. All investigated products performed similar and passed the Critical Wavelength criteria independent of method and parameters.

In vitro water resistance testing using SPF simulation based on spectroscopic analysis of rinsed sunscreens.

OBJECTIVE: Water resistance retention (WRR) is the third performance attribute of sunscreens. Today, the standardized method for testing WRR is performed in vivo. For screening purposes, an in vitro method is highly preferable. Up to now, however, available methods have failed in accurately predicting in vivo WRR. In this study, we examine a novel in vitro approach aimed at enhancing in vivo prediction of WRR. METHODS: We investigated two approaches, including a traditional procedure referred to as the 'plate method', which involves measuring in vitro sun-protection factor (SPF) before and after water immersion, and a new approach termed the 'solution method'. The latter employed a computational method to calculate the SPF using UV transmittance measurements of a sunscreen solution, obtained by rinsing the substrate without water immersion and with water immersion. It also had a model function for describing film irregularity. The aim was to avoid the effect of substrate-to-product affinity on the film distribution, which impacts the measured absolute value of the in vitro SPF occurring in the conventional approach. For both methodologies, we assessed two substrates for the sunscreen application based on different polymers, the widely used polymethylmethacrylate (PMMA) and the ethylene methacrylate acid copolymer (EMA). RESULTS: The agreement between in vivo and in vitro WRR values obtained from each of the four test conditions was analysed using different sunscreens. No correlation was found between in vivo and in vitro WRR using the plate method, independently of the plate type. In contrast, the solution method, using EMA plates, revealed a significant correlation between in vivo and in vitro results, with an especially high correlation for in vivo non-water-resistant sunscreens. The results of two operators were comparable. The solution method was unsuitable for PMMA plates. CONCLUSION: Despite the small discrepancy remaining between WRR values obtained from the in vitro solution method and in vivo method, which itself shows variability in results, this work provided a new insight into the in vitro testing of water resistance of sunscreens.

[Circadian rhythm : Influence on Epworth Sleepiness Scale score]. / Zirkadianer Rhythmus : Einfluss auf den Punktwert der Epworth-Schläfrigkeits-Skala.

BACKGROUND: The Epworth Sleepiness Scale (ESS) is frequently used to determine daytime sleepiness in patients with sleep-disordered breathing. It is still unclear whether different levels of alertness induced by the circadian rhythm influence ESS score. OBJECTIVE: The aim of this study is to investigate the influence of circadian rhythm-dependent alertness on ESS performance. MATERIALS AND METHODS: In a monocentric prospective noninterventional observation study, 97 patients with suspected sleep-disordered breathing were investigated with respect to daytime sleepiness in temporal relationship to polysomnographic examination and treatment. The Karolinska Sleepiness Scale (KSS) and the Stanford Sleepiness Scale (SSS) served as references for the detection of present sleepiness at three different measurement times (morning, noon, evening), prior to and following a diagnostic polysomnography night as well as after a continuous positive airway pressure (CPAP) titration night (9 measurements in total). The KSS, SSS, and ESS were performed at these times in a randomized order. RESULTS: The KSS and SSS scores revealed a circadian rhythm-dependent curve with increased sleepiness at noon and in the evening. Following a diagnostic polysomnography night, the scores were increased compared to the measurements prior to the night. After the CPAP titration night, sleepiness in the morning was reduced. KSS and SSS reflect the changes in alertness induced by the circadian rhythm. The ESS score war neither altered by the intra-daily nor by the inter-daily changes in the level of alertness. CONCLUSION: According to the present data, the ESS serves as a reliable instrument to detect the level of daytime sleepiness independently of the circadian rhythm-dependent level of alertness.

Changes in body weight and obesity status in German adults: results of seven population-based prospective studies.

BACKGROUND/OBJECTIVES: The objective of this study was to quantify body weight changes in German adult populations during the past decades. SUBJECTS/METHODS: Longitudinal analysis of seven cohort studies covering different age ranges between 18 and 83 years. Baseline examinations were between 1994 and 2007 and follow-up durations between 4.0 and 11.9 years. For each study, mean change in body weight per year and 10-year change in body mass index (BMI) classification were analyzed. For the middle age group of 45-64 years, meta-analysis was conducted to obtain an overall estimate for Germany. RESULTS: Among men weight gain was highest in the youngest participants and decreased with advancing age. Among women weight gain was on a stable high level among those younger than 45 years and decreased at older age. Within 10 years, 30-40% of middle-aged participants with normal baseline weight became pre-obese or obese and 20-25% of those with pre-obesity at baseline became obese, whereas >80% of persons who were obese at baseline remained obese over time. The estimated average weight change in adults aged 45-64 years was 0.25 (95% confidence interval (CI): 0.18-0.33) kg/year among men and 0.24 (0.17-0.30) kg/year among women. CONCLUSIONS: We could observe a moderate weight gain over the past years in German middle-aged populations of 0.25 kg/year. Obesity prevention needs to be targeted to specific subgroups in the population, especially to younger adults, who seem to be most vulnerable for gaining weight. Obesity intervention needs to be improved, as the majority of obese adults remained obese over time.

Educational level and chronic inflammation in the elderly--the role of obesity: results from the population-based CARLA study.

This study aimed to assess the mediating role of anthropometric parameters in the relation of education and inflammation in the elderly. Cross-sectional data from the population-based CARdio-vascular Disease, Living and Ageing in Halle study were used after excluding subjects with a plasma level of high-sensitive C-reactive protein (hsCRP) above 10 mg L(-1) (916 men/760 women remaining). Education was categorized in accordance with International Standard Classification of Education. As inflammation parameters, the soluble tumour necrosis factor type 1 (sTNF-R1), hsCRP and interleukin 6 (IL-6) were taken into account. Anthropometric parameters were the body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHeR). We used covariate adjusted mixed models to assess associations. Effect measures were the natural indirect effect (NIE), controlled direct effect and total effect (TE). Education was associated with sTNF-R1, hsCRP and IL-6 in men, and sTNF-R1 and hsCRP in women. Anthropometric parameters correlated with all inflammation parameters after covariate adjustment. BMI and WHeR were strong mediators of educational differences in sTNF-R1 (percentage of NIE of TE: 28% in men; 33% in women) and hsCRP (percentage of NIE of TE: 35% in men; 52% in women), while WHR was the weakest mediator. General obesity mediates roughly one-third of the association of education with chronic inflammation in the elderly.

L-lysine dose dependently delays gastric emptying and increases intestinal fluid volume in humans and rats.

BACKGROUND: Novel sensory inputs for the control of food intake and gastrointestinal (GI) function are of increasing interest due to the rapid increase in nutrition-related diseases. The essential amino acid L-lysine was demonstrated to have a selective impact on food intake, gastric emptying, and intestinal transit in rats, thus indicating a potential novel direct sensory input to assess dietary protein content and quality. The aim of this study was to assess translational aspects of this finding and to investigate the dose-dependent effect of L-lysine on human and rat GI function. METHODS: L-lysine doses from 0-800 mg in rats and 0.5-7.5 g in humans were analyzed for their effect on gastric emptying and GI secretion. Human GI function was assessed non-invasively using magnetic resonance imaging (MRI), rat data were acquired using standard lethal measurement methods. L-lysine dose dependently delayed gastric emptying and stimulated GI secretion in rats as reflected by residual phenol red content and increased gastric wet weight. KEY RESULTS: The dose-dependent delay in gastric emptying observed in rats was confirmed in humans with an increase in halftime of gastric emptying of 4 min/g L-lysine, p < 0.01. Moreover, a dose-dependent increase in intestinal fluid accumulation was observed (0.4 mL/min/g L-lysine, p < 0.0001). No effect on alkaline tide, glucose concentration, hematocrit, or visceral sensations was detected. CONCLUSIONS & INFERENCES: This translational study demonstrates comparable dose-dependent effects of intragastric L-lysine on GI function in humans and rats and suggests a broader role for individual amino acids in the control of GI motility and secretion in vivo.

Lowering heart rate with an optimised breathing protocol for prospectively ECG-triggered CT coronary angiography.

OBJECTIVES: The aim was to prospectively characterise the effect of the level of breath-hold on heart rate in CT coronary angiography (CTCA) with prospective electrocardiogram (ECG) triggering and its impact on coronary artery attenuation. METHODS: 260 patients (86 women; mean age 59 ± 11 years) underwent 64-slice CTCA using prospective ECG triggering. Prior to CTCA, heart rates were recorded during 15 s of breath-hold at three different levels of inspiration (normal, intermediate and deep). The inspiration level with the lowest heart rate was chosen for actual CTCA scanning. Coronary artery attenuation was measured, and the presence of backflow of contrast material into the inferior vena cava (as an indicator of increased intrathoracic pressure) was recorded. RESULTS: The mean heart rate at breath-hold was significantly different for the three inspiration levels (normal, 60 ± 8 bpm; intermediate, 59 ± 8 bpm; deep, 57 ± 7 bpm; p<0.001). The maximum heart rate reduction in each patient at breath-hold averaged 5.3 ± 5.1 bpm, and was observed at a normal inspiration depth in 23 (9%) patients, at an intermediate inspiration depth in 102 (39%) patients and at deep inspiration in 135 (52%) patients. Overall, there was no association between the level of breath-hold and coronary vessel attenuation (p-value was not significant). However, the backflow of contrast material into the inferior vena cava (n = 26) was found predominantly at deep inspiration levels (p<0.001), and, when it occurred, it was associated with reduced coronary attenuation compared with patients with no backflow (p<0.05). CONCLUSION: The breath-hold level to best reduce heart rate for CTCA should be individually assessed prior to scanning because a mean heart rate reduction of 5 bpm can be achieved.

In vitro sun protection factor: still a challenge with no final answer.

In the past, several attempts have been made to develop in vitro methods for determining protection against UV radiation. To date however, there is no broadly accepted method. Various known and unknown parameters influence the transmission measurements of scattering films, such as the multifaceted compositions of sunscreens, the technical limitations of measurement devices as well as the difficulty to apply very thin films of sunscreen in a reproducible manner throughout different laboratories. In vitro data were measured in this multicenter study to compare possible methodologies and strategies for an in vitro approach to the sun protection factor (SPF). This publication will not present a final in vitro SPF test method, but it will point out which technical side effects may influence such a method. Influential factors such as the quality of spectrophotometer used, the amount of product applied, pretreatment of samples, time and temperature of equilibration, size of the measured surface, the application process or the calculation on the basis of standardized data are presented and discussed. Finally, a reduction of the standard deviations within single laboratories could be realized for in vitro SPF testing, but no improvement of the interlaboratory comparison was obtained. The development of a valid and reliable SPF in vitro test still remains a challenge, and further work is necessary to develop a satisfactory method.

Sun protection factors: world wide confusion.

The Sun Protection Factor (SPF) is a very popular instrument in the marketing of sunscreens. Unfortunately it is often not understood how sunscreens work and where the limitations of the SPF are. A lot of aspects of the SPF are confusing, e.g. the race for higher and higher numbers, the effect on SPF when less sunscreen is applied and if sunscreen should be used at all because they may block the Vitamin D synthesis. All this has a negative impact on compliance by the consumer or patient which is the most important influence factor in sun protection. This paper explains how sunscreens work, how the SPF is determined and where the limitations of the current methods exist. The dynamic view of 'UV radiation applied' and the 'UV dose transmitted' through the sunscreen onto the skin as well as onto a substrate in vitro help in the understanding and are also promising approaches in the in vitro assessment. A variation of the in vitro assessment of a sunscreen is the in silico calculation based on the absorption spectrum of the UV filters and an assumption about the irregular sunscreen film on the skin. The sunscreen simulator program can be used to determine how the SPF is affected by applying smaller amounts of sunscreen. Besides the SPF, UVA protection is also discussed. The degree of UVA protection determines the quality of the overall UV protection, whereas the SPF is an indication of the quantity of protection. Furthermore other protection factors such as IPF, iSPF, RSF and p53, and the inhibition of the Vitamin D3 synthesis by sunscreens are also discussed. In conclusion it is shown that the accuracy and robustness of the SPF and other Protection Factors will improve significantly with the availability of true broad-spectrum sunscreens rather than conventional UVB-biased sunscreens, because uniform protection profiles lead to protection independent of the action spectrum of the endpoint and the UV-radiation source.

First head-to-head comparison of effective radiation dose from low-dose 64-slice CT with prospective ECG-triggering versus invasive coronary angiography.

BACKGROUND: Reduction of radiation burden of multidetector computed tomography coronary angiography (CTCA) has remained an important task. OBJECTIVE: To compare effective radiation dose of low-dose 64-slice CTCA using prospective ECG-triggering versus diagnostic invasive coronary angiography (CA). METHODS: 42 patients referred for elective invasive CA owing to suspected coronary artery disease (CAD) were prospectively enrolled to undergo a low-dose CTCA without calcium scoring within the same day before CA. Dose-area product of diagnostic invasive CA and dose-length product of CTCA were measured, converted into effective radiation dose and compared using Mann-Whitney U tests. In addition, accuracy of CTCA to detect CAD (coronary artery narrowing > or =50%) was assessed using invasive CA as standard of reference. On an intention-to-diagnose basis all non-evaluative vessels were included in the analysis and censored as positive. RESULTS: The estimated mean effective radiation dose was 8.5 (4.4) mSv (range 1.4-20.5 mSv) for diagnostic invasive CA, and 2.1 (0.7) mSv (range 1.0-3.3 mSv) for CTCA (p<0.001). 19 patients (42.9%) had no CAD by invasive CA. 40 (95.2%) patients have been correctly classified as having CAD (23/23) or no CAD (17/19). Over 97% (551/567) of segments were evaluable. Vessel-based analysis revealed sensitivity, specificity, positive and negative predictive value of 94.2% (CI 0.8% to 1.0%), 94.8% (CI 09% to 1.0%), 89.0% (CI 0.8% to 1.0%), 97.4% (CI 09% to 1.0%) and an accuracy of 94.6%. CONCLUSIONS: Low dose CTCA allows evaluation of CAD with high accuracy, but delivers a significantly less effective radiation dose to patients compared to diagnostic invasive CA.

Phase behavior of aqueous mixtures of 2-phenylbenzimidazole-5-sulfonic acid and cetyltrimethylammonium bromide: hydrogels, vesicles, tubules, and ribbons.

We studied the phase behavior and aggregation in mixed aqueous solutions of the anionic UV-absorber 2-phenylbenzimidazole-5-sulfonic acid sodium salt, PhBSA (Na salt), and the cationic surfactant cetyltrimethylammonium bromide, CTAB. The mixtures of the two components behave similarly to catanionic surfactant mixtures. The samples on the PhBSA-rich side have low viscosity and are turbid. The turbidity, due to uni- and multilamellar vesicles (SUVs and MLVs), increases with the mole ratio of CTAB. The interbilayer distance inside the MLV changes with the mole ratio of the two components from a few 10 nm for the 7:3 (molar ratio of PhBSA, Na salt, to CTAB) system to practically zero for the 5:5 mixture. The latter mixture forms a precipitate within less than 1 h. With the exception of the 5:5 mixture, all samples on the PhBSA-rich side are stable for many days. After that period, within one more day, the turbid vesicle phases are transformed into more or less clear hydrogels. We found that the gelation is due to the formation of very long stiff tubules about 14 nm in diameter, which is independent of the mixing ratio of the samples. The hydrogels and the tubules melt around 45 degrees C. On the CTAB-rich side, the 4:6 sample behaves like the 6:4 sample, whereas at 3:7 a precipitate was found to form shortly after mixing. At still smaller PhBSA (Na salt) to CTAB ratios, only clear, viscoelastic solutions are found that do not change with time. We determined the micellar structures in the samples by cryo-TEM and by SAXS. The rheological properties of the hydrogels and of the viscoelastic samples were characterized by oscillating rheological measurements. DSC measurements indicated that the tubules are in a semicrystalline state and melt at around 45 degrees C. The semicrystalline bilayer of the tubules seems to have a 1:1 composition of PhBSA to CTAB. The excess PhBSA seems to be adsorbed on the tubules. It is assumed that the stiffness of the bilayer of the vesicles and the stiffness of the tubules are due to the stiffness of the PhBSA molecule.

Influence of applied quantity of sunscreen products on the sun protection factor--a multicenter study organized by the DGK Task Force Sun Protection.

It is often debated that the protection against solar-induced erythema under real conditions is dependent upon the amount of sunscreen applied. It is believed that when too little is applied a lower sun protection than indicated on the label will result. The aim of this study was to quantify this effect. In this multicenter study, the influence of three different amounts (0.5, 1.0, 2.0 mg/cm(2)) of three commercial sunscreen products in three reliable test centers was investigated according to the test protocol of The International Sun Protection Factor Test Method. The main result was a linear dependence of the SPF on the quantity applied. Taking into consideration the volunteer-specific variations, an exponential dependence of confidence interval of the in vivo SPF and amount applied was found. The highest amount applied (2.0 mg/cm(2)) was linked to the lowest confidence intervals. Thus, from the point of view of producing reliable and reproducible in vivo results under laboratory conditions, the recommendation of this multicenter study is an application quantity of 2.0 mg/cm(2).

In vivo and in vitro assessment of UVA protection by sunscreen formulations containing either butyl methoxy dibenzoyl methane, methylene bis-benzotriazolyl tetramethylbutylphenol, or microfine ZnO.

The UVA-attenuating properties of the three UVA filters butyl methoxy dibenzoyl methane (BMDBM), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT), and microfine zinc oxide (ZnO), are compared. For this purpose persistent pigment darkening (PPD) as an in vivo method as well as different in vitro approaches like the UVA/UVB ratio, the critical wavelength, and the Australian standard have been used. For the case of the UVA/UVB ratio and the critical wavelength the behaviour was also assessed after irradiation with 10 minimal erythemal doses (MED). Sunscreen formulations were manufactured containing either one of these UVA filters or combinations of one UVA filter and a constant amount of UVB filter. The concentration of the respective UVA filter was varied. BMDBM was dissolved in the oil phase of the formulations. MBBT, which is produced as particulate organic UVA-filter dispersion with average particle size smaller than 200 nm, was added to the aqueous phase. The microfine ZnO was incorporated into the oil phase. If no additional UVB filters were present, UVA/UVB ratio and critical wavelength stayed almost constant, independent of UVA-filter content. With constant levels of additional UVB filters these parameters increased with UVA-filter concentration. In contrast to the behaviour of the UVA/UVB ratio, which appeared to be a sensitive measure for the UVA protection in relation to UVB protection in almost the whole ranges of UVA-filter concentrations, the critical wavelength approached saturation already at low UVA-filter levels. The UVA-protection factors (UVA-PF) obtained from the in vivo studies increased with the concentration of the UVA filter in the formulations. Formulations, which showed UVA-PFs > or = 4 in most cases met also the conditions of the Australian Standard. An irradiation dose of 2.5 kJ m(-2) (10 MED) induced significant decreases of UVA/UVB ratio or critical wavelength only with some BMDBM formulations, indicating a loss of UVA protection in those cases.

The importance of both an early orchidopexy and germ cell maturation for fertility.

Delayed orchidopexy for undescended testes has been associated with abnormal testicular histology, but the effect on later fertility is unknown. We aimed to establish the importance of the first postnatal maturational step-ie, the transformation of gonocytes into Ad (dark) spermatogonia on fertility. We matched histological findings of the testes from 31 patients who had undergone an early orchidopexy with their total number of sperm. If Ad spermatogonia were present, 17 (94%) of 18 (95% CI 72.7-99.9) of the men had a total sperm count of 40 x 10(6)/ejaculate or greater. By contrast, despite successful early surgery, if Ad spermatogonia were absent, 12 (92%) of 13, (64.0-99.8) patients had abnormal spermiograms. Thus, the transformation of gonocytes into Ad spermatogonia is crucial for male fertility.

Nitrogen metabolism and bone metabolism markers in healthy adults during 16 weeks of bed rest.

BACKGROUND: The associations between nitrogen metabolism and bone turnover during bed rest are still not completely understood. METHODS: We measured nitrogen balance (nitrogen intake minus urinary nitrogen excretion) and biochemical metabolic markers of calcium and bone turnover in six males before head-down tilt bed rest (baseline), during 2, 10, and 14 weeks of immobilization, and after reambulation. RESULTS: The changes in nitrogen balance were highest between baseline and week 2 (net change, -5.05 +/- 1.30 g/day; 3.6 +/- 0.6 g/day at baseline vs -1.45 +/- 1.3 g/day at week 2; P<0.05). In parallel, serum intact osteocalcin (a marker of bone formation) was already reduced and renal calcium and phosphorus excretions were increased at week 2 (P <0.05). Fasting serum calcium and phosphorus values and renal excretion of N-telopeptide (a bone resorption marker) were enhanced at weeks 10 and 14 (P <0.05-0.001), whereas serum concentrations of parathyroid hormone, calcitriol, and type I collagen propeptide (a marker of bone collagen formation) were decreased at week 14 (P <0.05-0.01). Significant associations were present between changes of serum intact osteocalcin and 24-h calcium excretion (P <0.001), nitrogen balance and 24-h phosphorus excretion (P <0.001), nitrogen balance and renal N-telopeptide excretion (P <0.05), and between serum osteocalcin and nitrogen balance (P <0.025). CONCLUSIONS: Bone formation decreases rapidly during immobilization in parallel with a higher renal excretion of intestinally absorbed calcium. These changes appear in association with the onset of a negative nitrogen balance, but decreased bone collagen synthesis and enhanced collagen breakdown occur after a time lag of several weeks.

Importance of early postnatal germ cell maturation for fertility of cryptorchid males.

PATIENTS/METHOD: Twenty-seven adults who underwent an orchidopexy before 2 years of age have recently had their spermiograms analyzed. RESULTS: Sixty-three percent of them had a normal sperm count; their germ cells had undergone the second stage of maturation and adult dark (Ad) spermatogonia were present at the time of surgery 20-25 years earlier. In contrast, 37% of them were infertile despite a seemingly successful orchidopexy; they had impaired second-step germ cell maturation and Ad spermatogonia were absent at orchidopexy. CONCLUSIONS: Transformation of gonocytes into Ad spermatogonia is crucial for fertility. This underscores the importance of a testicular biopsy at orchidopexy in order to identify those who could benefit from early LH-RH treatment after orchidopexy.

Intralipid-based short-term total parenteral nutrition does not impair small intestinal mucosa-related cellular immune reactivity in the healthy rat.

BACKGROUND: The lipid component of total parenteral nutrition (TPN) has reportedly been associated with trophic effects on the intestinal mucosa and suppressive effects on the immune system. METHODS: We have challenged these hypotheses using a 7-day TPN rodent model comparing the effects of isocaloric, isonitrogenous lipid-based (TPN-lipid, 50% of calories as long-chain triacylglycerol) and carbohydrate-based TPN (TPN-CH, 100% of calories as carbohydrates) on mucosal morphology and immune function. Enterally fed animals were included to establish a baseline for immunologic read-outs. The study was performed in healthy, metabolically stable animals to avoid interference by septic or trauma-related stress factors. RESULTS: Both TPN regimens resulted in a significantly smaller weight gain (TPN-lipid, 29.8 +/- 4.0 g; TPN-CH, 30.3 +/- 4.4 g) compared with enterally fed reference animals (49.2 +/- 3.2 g; p = .007), with no difference in nitrogen balance between the TPN groups. Mucosal sucrase activity was significantly lower in both TPN groups (TPN-lipid, 8.8 +/- 1.0 x 10(-7) katal per gram (kat/g) of protein; CH: 11.9 +/- 1.6 x 10(-7) kat/g of protein) compared with enteral feeding (17.4 +/- 0.9 x 10(-7) kat/g of protein; ANOVA: p = .0007). Morphometric analysis of the small intestine revealed no differences between the two TPN groups although a significantly depressed villus height in the TPN-lipid group could be observed in comparison to enterally fed reference rats (TPN-lipid, 0.47 +/- 0.02; TPN-CH, 0.50 +/- 0.01; enteral, 0.56 +/- 0.02 mm; ANOVA: p = .0298). Light and electron microscopy revealed a normal surface architecture in all three groups of rats. Cellular immune reactivity was evaluated using a novel specific immunization protocol: animals were immunized against OVA 4 weeks before TPN. OVA-induced lymphoproliferative responses and phenotypic data from draining popliteal and mesenteric lymph nodes were evaluated after the different regimens. Results did not differ among the three groups. CONCLUSIONS: In healthy rodents, short-term lipid-based and carbohydrate-based TPN regimens lead to limited mucosal atrophy with preserved surface architecture compared with enteral feeding. However, peripheral and mesenteric cellular immune responsiveness after both TPN regimens remained comparable to enterally fed reference animals. Therefore, mesenteric and systemic cellular immune reactivity does not appear to be impaired by lipid-based or carbohydrate-based TPN.

Characterization of the human liver fructose-1,6-bisphosphatase gene promoter.

Fructose-1,6-bisphosphatase (FBPase; EC 3.1.3.11), an important gluconeogenic enzyme, catalyses the hydrolysis of fructose 1, 6-bisphosphate to fructose 6-phosphate and P(i). Enzyme activity is mainly regulated by the allosteric inhibitors fructose 2, 6-bisphosphate and AMP. Although some observations about hormonal regulation of the enzyme have been published, the FBPase promoter has not been studied in detail. Here we report an in vitro characterization of the FBPase promoter with respect to the elements that are required for basal promoter activity. Transient transfection of H4IIE rat hepatoma cells, combined with site-directed mutagenesis, demonstrated that an enhancer box, three GC-boxes and a nuclear factor kappaB (NF-kappaB)-binding element are important for hepatic FBPase promoter activity. These elements are found in the region located between -405 to +25 bp relative to the transcription start site. Electrophoretic-mobility-shift assays and supershift analysis confirmed that upstream stimulatory factor 1 (USF1)/USF2, specificity protein 1 (Sp1)/Sp3 and NF-kappaB respectively bind to these sites. The present study provides the basis for a more comprehensive screening for mutations in FBPase-deficient patients and for further studies of the transcriptional regulation of this gene.